Part 3: Injuries and Untoward Events

INTRODUCTION

The assessment and management of infants who are described, by a parent or other caregiver, as having had a frightening, perhaps life-threatening, event is a challenging problem for clinicians. The fear that the infant may experience additional episodes, perhaps a fatal one, heightens the anxiety level of both families and medical professionals.

DEFINITION

Prior to 1986, parent/caregiver-reported acute events in infants were commonly referred to as an aborted crib death or near-miss sudden infant death syndrome (SIDS). However, in 1986, a National Institutes of Health (NIH) Consensus Development Conference on Infantile Apnea and Home Monitoring recommended use of a newly defined term: apparent life-threatening event (ALTE). The consensus conference defined an ALTE as “an episode that is frightening to the observer and that is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually limpness), choking, or gagging.” In addition, it was recommended that previously used terminology such as aborted crib death or near-miss sudden infant death syndrome be abandoned to avoid implication of a causal association between this type of spell and SIDS.

Apparent life-threatening events were described in the Consensus Development Conference statement as a “chief complaint that describes a general clinical syndrome.” Although the definition of an apparent life-threatening event appeared straightforward, in practice, determining whether or not an infant experienced an ALTE has been extraordinarily difficult for clinicians, and it has frequently led to hospital admissions and testing of questionable value. In response to this dilemma, in 2016, a clinical practice guideline was published by the American Academy of Pediatrics (AAP), which suggested using event characteristics, rather than the term ALTE, to describe events and suggested new terminology, brief resolved unexplained events (BRUE), be used for events that met specific characteristics. The definition of a BRUE is a sudden, brief (ie, < 1minute), and now resolved episode with at least 1 of the following: cyanosis or pallor; absent, decreased, or irregular breathing; marked change in tone (hyper- or hypotonia); and altered responsiveness. In addition, criteria were provided to risk stratify infants having events that met the BRUE criteria, and management guidelines were provided for infants who met criteria to be considered low risk.

INCIDENCE

Since the terminology is newly developed, there are no data on the incidence of BRUE. Data regarding the incidence of ALTEs are also limited, due to the imprecise manner in which this terminology has been applied. However, the incidence of ALTE was estimated to be 0.05% to 1% in population-based studies. Some perspective on the occurrence of idiopathic ALTE can be obtained from the Collaborative Home Infant Monitoring Evaluation (CHIME study), which was conducted at 5 medical centers (located in Cleveland, Toledo, Chicago, Los Angeles, and Honolulu) during the mid-1990s. This study included a systematic review of infants who presented with diagnoses consistent with ALTE and found that a typical urban medical center hospital provides care for about 1 case of possible ALTE each week and that approximately 20% of such cases will be considered an idiopathic ALTE.

CLINICAL PRESENTATION

Most commonly, infants are no longer experiencing respiratory or circulatory dysfunction by the time they are first seen by medical professionals. Even in cases in which an emergency medical team has been called, the signs commonly have resolved by the time emergency medical technicians arrive. In some cases, during a routine well-child visit, a parent may describe an event that was witnessed days or weeks in the past.

Among the most difficult tasks for the clinician is to identify the events that the infant actually experienced. The ability of the caretakers to provide an accurate history is diminished by the fact that they may have been frightened to the point of panic. The situation may be further confounded by circumstances such as a dark room, clothes or covers obscuring the view of the infant, or inexperience evaluating infant behavior.

If the infant has current symptoms or abnormal vital signs (eg, cough, respiratory symptoms, or fever), or if there is a likely diagnosis suggested by the history and physical (eg, gastroesophageal reflux, feeding difficulties, or airway abnormality), then the event is not a BRUE and the evaluation and management should be guided by the specific findings. If the infant is well appearing, and meets the criteria provided above, then the event should be considered a BRUE, and evaluation and management should be based on risk stratification criteria. Infants experiencing an event meeting the BRUE criteria are considered at lower risk if there are no specific concerns raised by the history and physical (eg, family history of sudden cardiac death or subtle, nondiagnostic social feeding or respiratory problems) and they meet the following low-risk criteria: age > 60 days, at least 32 weeks’ gestation and corrected gestational age at least 45 weeks, no CPR given by a trained medical provider, event lasted < 1 minute, first-time event.

EVALUATION

Infants Meeting Lower-Risk BRUE Criteria

For infants who meet the BRUE criteria and are in the lower-risk category, the AAP clinical practice guideline should be followed. Caregivers should be educated about BRUE and engaged in shared decision-making to guide evaluation, disposition, and follow-up, and resources for CPR training should be offered to the caregiver. Depending on the circumstances, it may be appropriate to obtain pertussis testing or a 12-lead electrocardiogram (ECG). The guideline recommends that clinicians should not obtain laboratory studies such as white blood cell (WBC) count, blood culture, cerebrospinal fluid (CSF) analysis or culture, serum electrolytes, blood urea nitrogen (BUN), creatinine, ammonia, blood gasses, urine organic acids, plasma amino acids or acylcamitines, chest radiograph, echocardiogram, electroencephalogram (EEG), or studies for GER. Clinicians also should not initiate home cardiorespiratory monitoring and should not prescribe acid suppression therapy or antiepileptic medications. In addition, the guidelines states that clinicians need not obtain viral respiratory tests, urinalysis, blood glucose, serum bicarbonate, serum lactic acid, laboratory evaluation for anemia, or neuroimaging, and need not admit the patient to the hospital solely for cardiorespiratory monitoring.

Infants Meeting Higher-Risk BRUE Criteria, with Persistent Symptoms or With Findings Suggesting A Diagnosis

The relatively small number of infants who meet higher-risk BRUE criteria or who have symptoms or other findings suggesting an underlying explanation for the event should receive a careful investigation, directed by the specific findings to identify a cause. Recognizing that most of the signs potentially relate to disturbed breathing, the initial focus in an evaluation is often directed at assessing respiratory function unless there are other cues in the history. Examples include respiratory infection, especially respiratory syncytial virus; seizures; tumors of the central nervous system; gastroesophageal reflux; drug-induced respiratory depression; poisoning; postanesthetic depression; upper airway obstruction; arrhythmias; inborn errors of metabolism; and child abuse (eg, Munchausen syndrome). Based on the results of the history and physical examination, clinicians should identify those conditions that require further investigation. Table 113-1 lists the tests commonly used in the evaluation of these infants. Diagnoses may include infections, gastroesophageal reflux, and seizures. In addition, among infants who were born prematurely, while no specific etiology may be identified, BRUE episodes may be attributable to persistent apnea of prematurity. In some cases, it may be possible to document features that suggest an immature respiratory control based on physiological recordings; however, no prognostic value of these recordings has been demonstrated.

PROGNOSIS

For infants in whom a cause for the event is identified, the prognosis is determined by the particular diagnosis and by the ability to successfully provide treatment. In those cases in which the event is associated with prematurity, no further episodes are usually observed beyond the 43 to 44 weeks postconception age. Although premature infants have a higher rate of sudden unexpected death than do term infants, the occurrence of apnea has not been shown to add to this risk.

Among infants with an event meeting the lower-risk BRUE criteria, the prognosis is believed to be very good, with little data to suggest that subsequent episodes are likely to occur or that an underlying diagnosis might have been missed due to limiting the observation period or testing performed. However, outcome data based on use of the newly published AAP clinical practice guideline are not yet available. Among infants with a BRUE that falls into the higher-risk category, data from studies among the heterogeneous group of infants considered to have had an ALTE do not provide convincing evidence that these infants are at increased risk for neurodevelopmental problems. Controlled follow-up studies have reported a slight increase in subtle neurologic abnormalities at 1 to 3 years post-ALTE and an increased frequency of breath-holding spells; however, no differences were observed at 10 years. The rate of recurrent ALTE episodes or subsequent death is not well studied but appears to be less than 5%. One common problem in understanding the prognosis of recurrent ALTE is the difficulty in disentangling child abuse from other causes. Although, the proportion of ALTE cases that may be attributable to child abuse is unknown, such cases have been well documented. Factors that increase the suspicion of child abuse include recurrent ALTE requiring cardiopulmonary resuscitation, history of SIDS or ALTE in siblings, and episodes that occur only in the presence of a single caretaker. Infants who have ALTE features suggestive of child abuse are at particularly high risk of recurrent episodes or death.

MANAGEMENT

In the majority of cases that meet the lower-risk BRUE criteria, the AAP clinical practice guideline should be followed: Families need reassurance with a clear explanation of why no further intervention is needed and, if appropriate, need advice regarding childcare practices that will decrease the likelihood of recurrence (eg, proper feeding technique to reduce choking). Although there is often reluctance on the part of both families and clinicians to accept simple reassurance and counseling, there is no evidence that these episodes are associated with increased risk of morbidity or mortality. In this setting, undertaking an extensive workup that may be both intrusive and expensive has little justification and may heighten, rather than reduce, anxiety. Alternatively, when the event meets the higher-risk BRUE criteria, or the suspected underlying diagnosis warrants it, hospitalization is appropriate, and the results of the inpatient evaluation, as described above, along with the ongoing clinical course will dictate subsequent management strategies.

Home cardiorespiratory monitoring is a potential management option that is controversial. Standard home cardiorespiratory devices detect when the heart rate falls below or above a preset range or when there is no chest wall movement for a preset length of time. Most currently used monitors also record waveforms during events (documented monitoring), which can facilitate diagnosis and decisions about when to stop monitoring. Oxygen saturation measurements can be included on some monitors if specifically requested. Although there have not been studies demonstrating a therapeutic benefit from home cardiorespiratory monitoring, in selected cases, monitor recordings may provide some diagnostic value, or may provide reassurance that clinically important events are not occurring. It should be noted that standard cardiorespiratory monitoring typically detects only chest wall movement and heart rate, and there may be circumstances (eg, suspected obstructive apnea) in which monitoring oxygen saturation by pulse oximetry may be more appropriate than cardiorespiratory monitoring. The decision regarding potential use of a home cardiorespiratory monitor should be made on a case-by-case basis after considering with the family the potential benefits, uncertainties, and stresses involved. Circumstances in which home cardiorespiratory monitoring may be considered would include premature infants with recurrent episodes of apnea and bradycardia, or infants with unstable airways or chronic lung disease.

Infants who experience multiple events are at very high risk for substantial morbidity, including death. In such cases, it is critical to identify the underlying cause, so that appropriate intervention can be initiated. The most common causes of recurrent events include infections, seizures, gastroesophageal reflux, and child abuse. Of these, the most difficult and the most important to diagnose is child abuse. However, an appropriate index of suspicion and a careful look for features consistent with abuse can be lifesaving. In cases of multiple events, where a specific diagnosis cannot be identified, use of a home monitor with memory may be of value in determining whether the events described are in fact genuine and, if they are genuine, to define physiologic changes that occur during the event.

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MANAGEMENT OF THE INTOXICATED PATIENT

Morbidity and mortality from childhood poisoning have decreased in the last few decades. This decrease can be credited to the development of poison control centers with a sophisticated poison management database, new governmental regulations, widespread use of child-resistant enclosures for medications, safer packaging for consumer products, public education and anticipatory guidance, and a growing understanding of the environmental and pharmacologic foundations of toxicology.

In particular, poison control centers, if available, provide immediate and expert advice from trained specialists in poison information to aid the practitioner in the management of poisoned patients, with particular reference to decontamination, antidotes, or other medical treatment; selection of appropriate laboratory tests; and enhanced drug elimination.

Poison Prevention

The goal of poison prevention programs is to prevent pediatric poisoning through legislation and educational strategies; medication safety, such as parental anticipatory guidance regarding medication; and household safety during well-child visits. Brochures and other poison prevention materials can be obtained from local poison centers or through national bodies and legislative initiatives, such as the Poison Prevention Packaging Act (in the United States) have been instrumental in decreasing the impact of childhood poisoning.

Epidemiology

Young children usually have little difficulty finding toxic substances, which can result in accidental poisoning. Personal-care products and cleaning substances are the most common agents involved in household intoxications, although pharmaceutical products are responsible for the majority of fatalities. Analgesics are the most common pharmaceutical exposure.

There are fewer adolescent exposures reported to poison centers compared with younger children, but most adolescent poisonings are intentional and involve greater amounts of toxins, often with multiple agents, and with delayed presentation for medical attention. As a consequence, adolescent poisonings often result in more serious toxicity.

Evaluation of the Poisoned Patient

A presumptive diagnosis can often be made using information from the history, vital signs, and physical examination before extensive laboratory results are available. The type of toxin, timing, amount, and route of exposure are ascertained by asking the patient, family members, or other sources, and are critical to guiding therapy. The circumstances of the exposure and history of psychiatric illness help determine the risk for intentional harm. Potentially toxic household products such as automotive and cleaning products should not be overlooked. Paramedics and first responders provide important information about the scene of exposure and progression of the patient’s signs and symptoms.

Discussion with the Poison Center

The value of a discussion with the local poison center cannot be overstated in terms of identification of substances through diagnostic tests, but also in piecing together the puzzle of unusual toxidromes and, equally importantly, in guiding immediate and longer term investigations and therapeutic interventions.

Toxidromes

Toxidromes or “toxic syndromes,” are characteristic physical findings that indicate the presence of a specific category of toxins (Table 114-1). Toxidromes are especially helpful when the patient has been exposed to a single toxin. Exposure to multiple substances can obscure the clinical diagnosis, whereas other disease processes may mimic the toxidromes. Stimulation or inhibition of specific central or autonomic receptors results in the classic toxidromes (Fig. 114-1).

Laboratory Evaluation

Basic laboratory evaluation provides valuable information for the diagnosis and management of the poisoned patient. An arterial blood gas demonstrating an acid–base disturbance, and calculation of the anion gap (Na⁺ – [Cl^– + HCO₃^–]) can narrow the differential diagnosis (Table 114-2). An elevated anion gap suggests the presence of an unidentified negatively charged molecule in the serum, which may represent a toxin or a byproduct of the intoxication, such as lactate.

If there is an unexplained metabolic acidosis, obtaining serum osmolarity, electrolytes, blood urea nitrogen (BUN), and glucose, and then calculating the osmolar gap (measured serum osmolarity – calculated serum osmolarity; normal is less than 10) can aid in diagnosis. The calculated osmolality is estimated by

An elevated osmolar gap indicates the presence of a low-molecular-weight and osmotically active substance such as methanol or ethylene glycol in the blood. An elevated anion gap metabolic acidosis accompanied by an elevated osmolar gap suggests toxic alcohol poisoning. A normal osmolar gap does not eliminate the possibility of toxic alcohol poisoning if the alcohol has already been converted into toxic metabolites.

Quantitative blood tests are ordered for specific drugs or toxins whose serum concentration can guide therapy or predict toxicity. In cases of unknown ingestions, serum acetaminophen and salicylate levels are obtained because these poisonings are common and early diagnostic clues may be absent.

Toxicology screens should only be ordered when the result is expected to influence patient management. The history and clinical toxidrome are usually adequate to narrow the differential diagnosis and guide management decisions. Comprehensive blood or urine toxicology screens have a longer turnaround time and qualitatively detect only 40 to 100 specific drugs. They will not affect emergency management but may be helpful to the admitting physicians when the patient’s diagnosis remains unclear and the clinical course is complicated.

Radiology

Abdominal radiographs aid in the visualization of radio-opaque substances such as bezoars, radio-opaque medications (ie, ferrous sulfate pills), metals, and drug-filled packets. Serial abdominal radiographs may be useful to assess adequacy of gastrointestinal decontamination in such patients.

Resuscitation and Stabilization

Initial treatment follows the same principles applied to other life-threatening conditions. Decreased respiratory effort, airway obstruction, and severe respiratory distress are indications for endotracheal intubation and mechanical ventilation. If there is suspicion of opioid intoxication, judicious use of an opioid antagonist may restore normal breathing, precluding the need for endotracheal intubation. Intravenous access should be obtained promptly, and cardiovascular dysfunction corrected with intravenous fluids and pharmacologic support. Appropriate monitoring includes measurement of temperature, respiratory rate, oxygen saturation, heart rate, blood pressure, and serial electrocardiograms.

Decontamination

The goals of decontamination are to prevent the absorption of a toxin into the systemic circulation either internally from the gastrointestinal tract or externally from the skin or eyes, and this should be performed as early as possible.

Ocular and Dermal Decontamination

Immediate and thorough irrigation with tap water or normal saline may ameliorate injury following ocular and dermal exposures. Contact lenses should be removed and irrigation of the eyes performed rapidly to prevent ocular damage. The patient’s clothing, jewelry, and other items should be removed for dermal decontamination, and care is required to protect healthcare staff from secondary toxin exposure.

Syrup of Ipecac

This is a potent emetic that is no longer recommended as a home remedy for ingestions. The efficacy of syrup of ipecac in improving clinical outcomes remains unproven, and its use may delay the use of other decontamination techniques such as activated charcoal.

Activated Charcoal

Activated charcoal administered into the gastrointestinal tract binds most toxins, decreasing systemic absorption. It is ineffective for iron and other metals, lithium and other small ions, cyanide, alcohols, and most caustics. The dose of activated charcoal is 1 g/kg by mouth or via nasogastric tube for children and 50 to 100 g for adolescents and adults. If a nasogastric tube is necessary, consideration must be given as to whether the expected benefit exceeds the risk. Patients with protracted vomiting are not candidates for activated charcoal, and those with decreased consciousness or undergoing sedation should not receive charcoal unless the airway has been protected with an endotracheal tube, to protect from life-threatening aspiration.

Gastric Lavage

Orogastric lavage can be considered in patients who present to medical attention within 1 to 2 hours after ingestion of a potentially lethal toxin. It is not routinely recommended for all overdose patients due to the risk of complications, including visceral perforation, tracheal placement of the orogastric lavage tube, and aspiration of vomit. This should not be performed in patients with depressed mental status and an unprotected airway and ingestion of a caustic or hydrocarbon. A large-bore lavage tube (pediatrics, 16–28 Fr; adults, 36–40 Fr) is placed orogastrically with the patient in the left lateral decubitus position to optimize gastric decontamination and reduce the risk of aspiration. The stomach is lavaged with 50 to 250 mL aliquots of water or saline until clear of residual toxin.

Whole Bowel Irrigation

Whole bowel irrigation reduces the absorption of ingested toxins by decreasing gastrointestinal transit time. Polyethylene glycol electrolyte solution is administered via nasogastric tube at rates of 25 to 40 mL/kg/hour for children and 1.5 to 2 L/hour for adults until rectal effluent is clear. This should be stopped if no rectal effluent occurs after several hours. Indications include ingestion of delayed-release medications, substances not adsorbed by charcoal, or drug-filled packages in drug smugglers (“body packers”).

Enhanced Elimination

Enhanced elimination procedures hasten the excretion of toxins from the systemic circulation at a rate greater than endogenous clearance.

Multiple-Dose Activated Charcoal

Multiple-dose activated charcoal enhances elimination and decontaminates the gastrointestinal tract by (1) disrupting enterohepatic recirculation of the toxin, (2) utilizing the intestinal mucosa as a dialysis membrane (“gut dialysis”) to draw the toxin from the bloodstream into the intestinal lumen, and (3) binding any toxin present in the gut. It enhances elimination of substances that undergo enterohepatic recirculation such as phenobarbital, quinidine, theophylline, carbamazepine, and dapsone as well as substances that can form bezoars such as salicylates. The dose of activated charcoal without cathartic administration is 0.5 to 1 g/kg by mouth or via nasogastric tube every 4 hours. It should be discontinued if ileus develops. Complications include charcoal aspiration, formation of charcoal bezoars, and intestinal obstruction.

Urinary Alkalinization

Urinary alkalinization enhances the elimination of drugs that are weak acids (ie, salicylates) by trapping the ionized drug in the renal tubule, where it is subsequently excreted in the urine (Fig. 114-2). Sodium bicarbonate is administered in a dose of 1 to 2 mEq/kg intravenously followed by a continuous infusion titrated to a urinary pH of 7.0 to 8.0. Hypokalemia must be corrected because it impedes urinary alkalinization as potassium is reabsorbed in exchange for hydrogen ions.

Extracorporeal Methods

Extracorporeal methods of removing toxins include hemodialysis, continuous hemofiltration, and hemoperfusion, and are typically used in severe cases; in patients in whom there is impairment of the natural mechanism of elimination, who are deteriorating despite maximal supportive care; in toxins with delayed effects; or if a blood level of the toxin is associated with severe toxicity or death.

Hemodialysis is effective for toxins with small volumes of distribution (< 1.0 L/kg), low molecular weight, and low protein binding (eg, salicylates, theophylline, methanol, barbiturates, ethylene glycol, and lithium). Continuous hemofiltration techniques such as continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHD) can be used for the removal of molecules up to 40 kDa. The advantages of CVVH and CVVHD are that they can be performed in hemodynamically unstable patients and can be performed over a prolonged period of therapy. Hemoperfusion is similar to hemodialysis except for substitution of the dialysis membrane by a cartridge containing an adsorbent material such as charcoal, and is more effective for larger molecules because there is no ultrafiltration. Despite these advantages, the use of hemoperfusion has declined in recent years due to the short shelf life of the cartridges and the technical difficulty of the procedure. Hemoperfusion does not correct acid–base or fluid balance, or electrolyte abnormalities.

Antidotes

Antidotes prevent or reverse the effects of poisoning. Most are dispositional antidotes that decrease toxicity by altering absorption, distribution, metabolism, or elimination. Competitive antagonists interfere with the toxin binding to receptor sites. Physiologic antagonists alter the physiologic effect of the toxin. Antidotes are available for a very limited number of poisonings and do not replace meticulous supportive care and good clinical judgment. The risks and benefits of each antidote must be carefully considered.

Disposition after Toxin Exposure

Asymptomatic patients with a potential toxic exposure are observed for at least 4 to 8 hours from the time of exposure. If symptoms develop, the patient is admitted to the hospital for further evaluation and management. Any patient with severe toxicity will require admission to an intensive care unit. A longer observation period is required for toxins with delayed onset of action, such as sustained-release products, agents with toxic metabolites, and drugs with delayed distribution into the tissue compartment. Cellular injury may begin early with delayed onset of overt symptoms, such as with acetaminophen.

All pediatric exposures require social evaluation to determine home safety and provide poison prevention education. Patients may have been intentionally poisoned as a form of physical abuse or for purposes of sexual exploitation. Any intentional overdose warrants psychiatric evaluation of suicidal intent. Patients with chemical dependency should be referred to an appropriate treatment program.

PHARMACEUTICAL AGENTS

Acetaminophen

Acetaminophen (N-acetyl-p-aminophenol, or APAP), a widely used analgesic and antipyretic agent, is responsible for 10% of all calls to poison control centers. After therapeutic dosing, acetaminophen undergoes glucuronidation and sulfation in the liver prior to urinary and bile excretion (Fig. 114-3). A small percentage is oxidized in the hepatocytes by the cytochrome P450 system of CYP oxidases to produce N-acetyl-p-benzoquinoneimine (NAPQI), a highly reactive 2-electron species that can act as an oxidant and thus is highly cytotoxic. N-acetyl-p-benzoquinoneimine is eliminated by conjugation to the reduced form of glutathione (GSH), and the resulting APAP-GSH conjugate is eliminated as mercapturic acid and cysteine conjugates. After an overdose, however, the amount of NAPQI generated can exceed the capacity of this detoxification mechanism. N-acetyl-p-benzoquinoneimine then accumulates in the hepatocytes and toxicity ensues. Acute ingestion of more than 150 to 200 mg/kg in children or 7.5 g in adults is potentially hepatotoxic. Chronic or subacute overdose also results in liver injury.

The clinical presentation of acute acetaminophen toxicity is described in 4 phases. Phase 1 occurs during the first few hours after ingestion and is characterized by gastrointestinal symptoms of nausea, vomiting, and abdominal pain, but some patients are asymptomatic. Phase 2 is known as a quiescent phase and occurs within 24 hours, as the acute gastrointestinal symptoms subside. The onset of hepatotoxicity is manifested by upper-right quadrant abdominal tenderness and elevation of laboratory markers of liver injury such as transaminases and prothrombin time (PT). Phase 3 is the period of maximal hepatotoxicity, usually occurring within 72 to 96 hours. In mild cases, spontaneous recovery occurs. In severe cases, fulminant hepatic failure is manifested by coagulopathy, encephalopathy, and coma. Fatalities typically occur between 3 and 5 days because of multiorgan failure, hemorrhage, respiratory failure, sepsis, and cerebral edema. Phase 4 is the period of hepatic recovery, which may take a week or longer, depending on the severity of the liver injury.

Treatment decisions are guided by plotting the serum acetaminophen concentration on the Rumack-Matthew nomogram (Fig. 114-4) at 4 hours or more after a single acute ingestion. The nomogram is not used to predict toxicity after subacute overdose or multiple ingestions over a prolonged time period. Antidotal therapy with N-acetylcysteine (NAC) is initiated if the acetaminophen level is above the lower (possible hepatotoxicity) line on the nomogram, and should be started within 8 to 10 hours of drug ingestion because its efficacy for preventing fulminant hepatic failure diminishes thereafter.

NAC functions both as a glutathione precursor to replenish depleted glutathione stores and as a glutathione substitute that directly binds to NAPQI. In addition, NAC facilitates the sulfation pathway of acetaminophen metabolism. NAC comes in both oral and intravenous preparations. The United States Food and Drug Administration’s (FDA) approved oral NAC protocol consists of a loading dose of 140 mg/kg followed by 17 subsequent doses of 70 mg/kg administered every 4 hours over a 72-hour period. Treatment may be discontinued at 24 hours if there has been no elevation of liver transaminases and acetaminophen is no longer detectable in the serum. There are several intravenous NAC regimens that have been utilized, including 21-, 36-, and 48-hour protocols. The commonly used 21-hour protocol consists of a loading dose of 150 mg/kg administered over 1 hour, followed by an additional 50 mg/kg over the next 4 hours, and a subsequent 100 mg/kg over the next 16 hours. Repeated 100 mg/kg doses over 16 hours can be administered if the patient continues to have significantly elevated liver transaminases.

Laboratory monitoring includes measuring the serum acetaminophen level, liver transaminases, electrolytes, BUN, creatinine, and PT. Patients with severe hepatotoxicity require early evaluation for liver transplantation.

Anticoagulants

Warfarin was initially used as a rodenticide before its therapeutic applications were recognized. These compounds inhibit vitamin K, a cofactor required for the synthesis of coagulation factors II, VII, IX, and X. The typical clinical scenario for warfarin ingestion would be a toddler who has ingested a small amount of rodenticide. In this situation, no significant anticoagulation is expected, and no interventions are required. In contrast, larger ingestions with suicidal intent or chronic exposures may result in poisoning. The anticoagulant effect will not be seen until the circulating clotting factors have been degraded, which may take 1 to 2 days. Excessive anticoagulation results in ecchymoses, bleeding gums, subconjunctival hemorrhage, hematemesis, melena, or hematuria. In severe cases, intracranial hemorrhage or gastrointestinal bleeding is life threatening. The duration of effect after a single dose of warfarin is 2 to 7 days, whereas coagulopathy from superwarfarin poisoning often persists for months due to an extremely long elimination half-life.

Laboratory monitoring includes evaluation of coagulation, in particular the PT and international normalized ratio (INR). A normal PT 48 hours after ingestion rules out poisoning. Severe hemorrhage is treated with fresh-frozen plasma, packed red blood cells, and other blood products, as needed. Administration of vitamin K₁ (phytonadione), often as repeated doses for prolonged coagulopathy, allows regeneration of clotting factors, but peak effect may take 24 hours or longer. Vitamin K₁ is recommended for documented coagulopathy but should not be administered prophylactically because it will mask the development of toxicity and make the end point of treatment difficult to assess.

Anticonvulsants

Carbamazepine, phenobarbital, phenytoin, and valproic acid are frequently responsible for acute intoxications and are discussed here because serum concentrations are available rapidly from the laboratory to aid in patient management. Newer anticonvulsants are becoming more common. However, serum concentration measurements are not rapidly available, and overdoses are typically managed with nonspecific supportive care.

Carbamazepine

Carbamazepine is a central nervous system sodium channel inhibitor. Toxic manifestations after an overdose are similar to those produced by tricyclic antidepressants (TCAs), with which carbamazepine is structurally related, resulting in central nervous system depression, anticholinergic effects, and myocardial sodium channel inhibition. Induction of vasopressin secretion may result in the syndrome of inappropriate secretion of antidiuretic hormone. Carbamazepine toxicity is characterized by neurologic abnormalities, including nystagmus, ataxia, dysarthria, myoclonus, and dystonia, and at higher levels (above 40 mg/dL) results in coma, respiratory depression, and seizures. Cardiovascular disturbances include tachycardia, hypotension, myocardial depression, and cardiac conduction abnormalities, such as prolongation of the QRS complex and QT interval. Mydriasis, hyperthermia, ileus, and other signs of cholinergic inhibition may occur.

Monitoring after a significant ingestion should include obtaining a serum carbamazepine level every 4 to 6 hours until a downward trend is established. Serum electrolytes should be checked for hyponatremia, and electrocardiogram monitoring helps detect cardiotoxicity. Treatment is supportive. Enhanced elimination procedures may be considered in patients with severe toxicity that is not responsive to standard supportive care.

Phenobarbital

Barbiturates depress central nervous system function by enhancing the neuronal inhibition mediated by γ-aminobutyric acid (GABA). Supratherapeutic serum phenobarbital levels are associated with progressive ataxia, dysarthria, nystagmus, sedation, coma, hypothermia, and respiratory depression. Decreased sympathetic tone results in bradycardia and hypotension. Serial phenobarbital levels should be obtained until they are decreasing and the patient’s symptoms are improving. Treatment is supportive. Enhanced elimination may benefit patients with severe toxicity refractory to supportive care.

Phenytoin

Phenytoin and fosphenytoin are nonsedating at therapeutic doses. Phenytoin decreases the activity of neuronal voltage-dependent sodium channels, resulting in suppression of seizures. Excessive doses result in ataxia, nystagmus, diplopia, dysarthria, confusion, coma, and respiratory depression. Cardiotoxicity has not been reported following oral overdoses of phenytoin, although rapid intravenous administration may cause bradycardia and hypotension.

Phenytoin is poorly water soluble, and the intravenous preparation requires a solution of 40% propylene glycol and 10% ethanol at a pH of 12. Rapid infusion (> 50 mg/min phenytoin) results in myocardial depression and decreased systemic vascular resistance largely caused by the propylene glycol. Local irritation and tissue damage may be caused by the propylene glycol and the alkaline pH of the intravenous formulation. Fosphenytoin is a water-soluble product that is converted to phenytoin following intravenous administration. It is buffered to a pH of 8 to 9 and does not contain propylene glycol, allowing rapid intravenous administration (up to 150 mg/min of phenytoin equivalents). However, excessive doses of fosphenytoin have been reported to cause myocardial depression.

Serial serum phenytoin levels should be obtained until a downward trend is documented. Management is supportive. Multiple-dose activated charcoal may enhance the elimination of phenytoin, but is usually not necessary because of the success of supportive care alone.

Valproic Acid

Valproic acid inhibits voltage-gated sodium channels and increases GABA levels in the central nervous system, resulting in central nervous system depression. In addition, valproic acid interferes with fatty acid metabolism by causing carnitine deficiency, impaired mitochondrial β-oxidation, and disruption of the urea cycle.

Patients with valproic acid toxicity can present with confusion and lethargy that may progress to coma, cerebral edema, and respiratory failure. Severe toxicity includes hypotension, metabolic acidosis, hypernatremia, hypocalcemia, pancreatitis, hepatic injury, hyperammonemia, renal insufficiency, and bone marrow suppression. Elevated ammonia levels result in valproate-induced hyperammonemic encephalopathy, characterized by altered mental status, focal neurologic abnormalities, and seizures.

Serial valproate levels should be obtained until a downward trend is established and the patient’s symptoms are improving. Other useful laboratory studies include blood gas analysis, complete blood count, serum electrolytes, glucose, BUN, creatinine, calcium, liver transaminases, bilirubin, PT, lipase, amylase, lactate, ammonia, and carnitine. Treatment with carnitine is recommended if hyperammonemia, hepatotoxicity, or carnitine deficiency is present. Enhanced elimination techniques may be considered in patients with severe toxicity.

Antipsychotics

The antipsychotic medications are classified as typical or atypical. The typical antipsychotics (eg, haloperidol, thioridazine, promethazine, mesoridazine, and chlorpromazine) were introduced in the 1950s but were associated with serious adverse effects, including extrapyramidal syndromes (particularly dyskinesia in children), tardive dyskinesia, and neuroleptic malignant syndrome (NMS). The atypical antipsychotics were developed to overcome these shortcomings. Examples of atypical agents include aripiprazole, olanzapine, clozapine, quetiapine, ziprasidone and risperidone.

The clinical presentation of mild intoxication with atypical antipsychotics includes confusion, sedation, vagolysis, and orthostatic hypotension with reflex tachycardia. Severe overdoses result in coma, seizures, respiratory arrest, and hypothermia or hyperthermia. Cardiovascular effects include hypotension due to impaired myocardial contractility and peripheral vasodilation, as well as widened QRS complex and QTc interval prolongation resulting in ventricular arrhythmias including torsade de pointes.

Extrapyramidal dystonic reactions include tremor, rigidity, bradykinesia, and spasms of the muscles of the eyes (oculogyric crisis), face, tongue, lips, jaw, neck (torticollis), abdomen (tortipelvis), and spine (opisthotonus). NMS is a life-threatening condition characterized by altered mental status, muscular rigidity, hyperthermia, and autonomic dysfunction.

Diagnosis is based on the clinical presentation. Quantitative blood levels are not routinely available. Comprehensive urine toxicology screens may detect only phenothiazines. Continuous electrocardiogram monitoring is essential to detect cardiac conduction abnormalities and dysrhythmias.

Management is primarily supportive. Specific interventions include sodium bicarbonate for treatment of myocardial sodium channel blockade and QRS interval prolongation, and magnesium infusion and cardioversion or defibrillation for ventricular arrhythmias. Dystonic reactions are treated with diphenhydramine or benztropine. Management of NMS requires aggressive cooling measures, intravenous hydration, advanced airway management as indicated, and intravenous benzodiazepines for sedation and muscle relaxation. Dantrolene (a muscle relaxant) may be of benefit if there is severe malignant hyperpyrexia, particularly in the setting of pending or actual rhabdomyolysis.

β-Blockers and Calcium Channel Blockers

β-Adrenergic blocker (BB) and calcium channel blocker (CCB) medications are discussed together because of similarities in clinical presentation and management after overdose. Many of these similarities are due to their common effect of inhibiting the influx of calcium into myocardial cells, where it participates in physiologic signaling and other critical processes. Severe poisoning is difficult to treat and is associated with significant morbidity and mortality.

β-Blockers inhibit the binding of catecholamines to β-adrenergic receptors. Blockade of cardiac β₁-adrenergic receptors results in decreased chronotropy and inotropy, and the blockade of noncardiac β₂-adrenergic receptors antagonizes bronchial and smooth muscle relaxation, and also causes hypoglycemia by inhibition of glycogenolysis and gluconeogenesis.

Calcium channel blockers inhibit the influx of calcium through the L-type calcium channels of myocardial cells, resulting in decreased chronotropy and inotropy. Antagonism of similar vascular smooth muscle calcium channels results in coronary and peripheral vasodilation. Additionally, calcium-mediated insulin release from pancreatic β-islet cells is inhibited, preventing myocardial cells from utilizing glucose as an energy source, resulting in further myocardial dysfunction. The resulting shock state resembles diabetic ketoacidosis, with hyperglycemia and acidemia.

The hallmark of BB and CCB poisoning is cardiovascular depression and shock, with bradycardia, heart block, impaired cardiac contractility, and hypotension. Altered mental status is usually caused by cerebral hypoperfusion, but in the case of β-blockers may also be caused by hypoglycemia. β-Blockers that cross the blood-brain barrier and have membrane-depressant effects, such as propranolol, may cause coma, convulsions, and respiratory arrest. Noncardiac effects of CCBs include nausea, vomiting, and hyperglycemia. Global hypoperfusion may result in angina or myocardial infarction, cerebral ischemia, hepatic dysfunction, renal failure, and metabolic acidosis.

Diagnosis of BB and CCB poisoning is based on the history and clinical presentation, especially bradycardia and hypotension. β-Blocker poisoning may cause hypoglycemia, whereas CCB poisoning typically results in hyperglycemia. Studies that are helpful in assessment and management include electrolytes, glucose, BUN, creatinine, blood gas analysis, and electrocardiogram monitoring. A rapid bedside cardiac echocardiogram is useful to assess myocardial function. Patients with severe poisoning may require invasive monitoring to guide management.

Gastric lavage and administration of activated charcoal may be helpful early in patients with large recent ingestions. If the patient already has significant bradycardia, hypotension, or altered mental status, resuscitative procedures take precedence. Whole-bowel irrigation and multiple-dose activated charcoal should be considered in patients with ingestion of sustained-release preparations. General supportive measures include atropine for bradycardia and intravenous fluids for hypotension. Calcium and catecholamines should be used initially but may be ineffective after calcium channels and β-adrenergic receptors are inhibited. Glucagon is a specific antidote for β-blocker poisoning and has been used with some success in calcium channel blocker overdose as well. Glucagon produces positive inotropic and chronotropic effects by stimulating adenyl cyclase and opening calcium channels independent of the β-adrenergic receptor activation. Vasopressin improves blood pressure and increases the response to catecholamines. Hyperinsulinemia/euglycemia therapy improves myocardial contractility in calcium channel blocker overdose, often when other pharmacologic therapy has failed. It is postulated that this therapy corrects the impaired myocardial substrate utilization caused by calcium channel blocker–induced hypoinsulinemia, resulting in improved carbohydrate metabolism and increased myocardial contractility. Intravenous fat emulsion (IFE) therapy has been recently used to manage severe calcium channel blocker overdose. Although the mechanism is not well understood, it has been theorized that IFE sequesters lipophilic toxins such as CCBs in an intravascular lipid channel. This may decrease the distribution of the CCB into the tissue and result in the redistribution of the toxic drug back into the lipid channel. When pharmacologic therapy has failed, cardiopulmonary bypass or extracorporeal membrane oxygenation may be lifesaving.

Clonidine

Clonidine is a centrally acting antihypertensive that is also prescribed for conditions such as attention-deficit/hyperactivity disorder and drug withdrawal. Clonidine binds to inhibitory presynaptic α₂-adrenergic receptors in the medulla, resulting in decreased sympathetic outflow from the central nervous system.

The hallmark of intoxication is generalized sympathetic depression. Neurologic manifestations are similar to the opioid toxidrome and include pinpoint pupils, hypotonia, sedation, coma, hypothermia, respiratory depression, and apnea. Cardiovascular toxicity is manifested by bradycardia, decreased cardiac output, and hypotension.

Although clonidine poisoning mimics the opioid toxidrome, it does not reliably respond to naloxone. Sinus bradycardia does not require treatment unless it is associated with hypotension and poor perfusion. Atropine will often improve heart rate and cardiac output. Persistent hypotension is treated with intravenous fluids and catecholamine infusion. Coma and respiratory depression may require advanced airway management. Gastrointestinal decontamination is usually not indicated because of rapid onset of symptoms and good outcome with supportive care.

Cyclic Antidepressants

TCAs were developed to treat depression in the 1950s, but TCA overdoses caused severe toxicity, resulting in many poisoning deaths. The selective serotonin reuptake inhibitors (SSRIs) were introduced in the 1980s and have a better safety profile than the TCAs. TCAs inhibit the reuptake of biogenic amine neurotransmitters in the central nervous system, including norepinephrine, dopamine, and serotonin. In overdose, other mechanisms result in toxicity, including antagonism of muscarinic cholinergic receptors, α₁-adrenergic receptors, serotonin receptors, histaminic H₁ and H₂ receptors, GABA_A receptors, and myocardial fast sodium channels.

Patients with significant TCA ingestions usually manifest symptoms within 30 to 60 minutes, and life-threatening toxicity within 6 hours. The most common cause of death is cardiovascular toxicity. Inhibition of myocardial fast sodium channels causes slowed phase 0 ventricular depolarization, decreased contractility, widened QRS and QT intervals, and ventricular arrhythmias including torsades de pointes. Severe hypotension is caused by norepinephrine depletion, α₁-adrenergic receptor blockade, myocardial depression, and dysrhythmias. Muscarinic cholinergic receptor blockade results in sedation, coma, myoclonus, and seizures. Other anticholinergic effects include tachycardia, hyperthermia, mydriasis, ileus, urinary retention, diminished sweating, and dry mucus membranes. Seizures are also caused by inhibition of GABA_A receptors.

SSRIs do not usually cause severe toxicity except in large overdoses. However, excessive serotonergic activity may result in the life-threatening serotonin syndrome. Some SSRIs cause additional toxicity via inhibition of dopamine and norepinephrine reuptake and antagonism of α₁-adrenergic receptors. Some agents also have sodium and potassium channel inhibition causing QRS and QTc prolongation. Significant SSRI overdose results in nausea, ataxia, and sedation. Coma and respiratory depression may occur, particularly when alcohol or other sedating drugs are also involved. Some agents, such as buproprion, may cause tremor, agitation, and seizures. Cardiovascular effects include sinus tachycardia, hypotension, and cardiac conduction disturbances, but are usually not life threatening.

Serotonin syndrome is caused by excessive stimulation of serotonin 5-HT_2A and possibly 5-HT_1A receptors. This often occurs when an SSRI is combined with another drug with serotonergic activity, but it has been reported in patients taking single or multiple SSRIs. Its manifestations include agitation, altered mental status, coma, incoordination, myoclonus, hyperreflexia, tremor, muscle rigidity, diarrhea, diaphoresis, and hyperthermia. Patients may only exhibit a few of the symptoms, making the diagnosis challenging. Deaths are caused by hyperthermia, rhabdomyolysis, lactic acidosis, disseminated intravascular coagulation, and multiorgan failure.

Diagnosis of cyclic antidepressant poisoning is based on the history and clinical presentation. In the patient with an unknown ingestion, the combination of anticholinergic signs, coma, seizures, hypotension, and a widened QRS interval strongly suggests TCA poisoning. Because of the potential lethality of TCA poisoning, gastrointestinal decontamination procedures are considered for patients who present early after an overdose. Patients presenting later with severe symptoms are unlikely to benefit from such procedures.

The management of cyclic antidepressant poisoning is mainly supportive. Intravenous access and cardiac monitoring should be immediately established. Endotracheal intubation is indicated if significant central nervous system depression is present. Hypotension should be treated with rapid crystalloid infusion and pharmacologic support. Norepinephrine is recommended because of its predominant α₁-mediated vasoconstrictive effects. Seizures are treated aggressively, and anticonvulsants that enhance GABA, such as benzodiazepines or barbiturates, are usually effective. It is important to monitor the QRS interval, and prolongation is associated with seizures (> 100 ms) and ventricular arrhythmias (> 160 ms). Ventricular dysrhythmias and hypotension are treated with serum alkalinization and sodium loading. Increasing the extracellular sodium concentration helps overcome the sodium channel blockade caused by TCAs, and serum alkalinization diminishes drug binding to the fast sodium channel. A QRS interval greater than 100 milliseconds, ventricular dysrhythmias, or intractable hypotension should be treated with intravenous sodium bicarbonate in a dose of 1 to 2 mEq/kg, aiming for a pH between 7.45 and 7.55. Use of hypertonic saline (3% NaCl) to increase the extracellular sodium concentration may also be considered in difficult cases. Ventricular dysrhythmias that fail to respond to sodium bicarbonate may be treated with lidocaine, a class IB antiarrhythmic agent. Although lidocaine theoretically can worsen ventricular dysrhythmias, it has been used safely in TCA poisoning. Phenytoin (another class IB antiarrhythmic agent) should not be used and may worsen ventricular dysrhythmias. Patients with cardiogenic shock who fail to respond to maximal therapeutic interventions are candidates for extracorporeal life support, such as cardiopulmonary bypass or extracorporeal membrane oxygenation to support the patient until the TCA is eliminated and cardiotoxicity abates.

Serotonin syndrome is diagnosed when characteristic symptoms occur in the setting of serotonergic medication use and other etiologies are excluded. Treatment consists of immediate withdrawal of any offending drugs and supportive care that focuses on decreasing hyperthermia and muscular rigidity. Effective measures include external cooling, intravenous hydration, and benzodiazepines or neuromuscular blockade to achieve muscle relaxation. Case reports support cyproheptadine to treat serotonin syndrome owing to its inhibitory effects at 5-HT_1A and 5-HT_2A serotonin receptors.

Digoxin and Cardiac Glycosides

Digoxin is still used at times to treat congestive heart failure (CHF) and control ventricular rate in supraventricular tachydysrhythmias. The narrow therapeutic index of digoxin increases the risk of toxicity during therapeutic administration. Other sources of exposure include unintentional and intentional overdose, as well as ingestion of plants (ie, foxglove, oleander, and lily of the valley) and other natural sources of cardiac glycosides.

Digoxin produces its therapeutic effects through inhibition of the sodium-potassium–adenosine triphosphatase (Na⁺/K⁺-ATPase) pump, resulting in an increase in intracellular sodium and an increase in extracellular potassium. The increased intracellular sodium inhibits efflux of calcium through the Na⁺/Ca²⁺ antiporter at the cell membrane. The result is an increase in intracellular calcium that results in improved inotropy. Digoxin also enhances vagal tone, decreasing the rate of depolarization and conduction through the sinoatrial and atrioventricular nodes, and increasing the refractory period. Digoxin poisoning results in excessive increases in intracellular calcium with oscillatory disturbances of membrane potential, resulting in ectopy and tachydysrhythmias.

The clinical presentation of acute digoxin poisoning includes cardiac and noncardiac features. The noncardiac effects include gastrointestinal manifestations such as nausea, vomiting, and diarrhea; neurologic manifestations such as confusion, headaches, weakness, and seizures; and visual manifestations such as blurred vision, scotoma, and xanthopsia. The cardiac effects of digoxin poisoning are the primary, potentially fatal concern. Prolongation of the PR interval, with bradycardia and varying degrees of atrioventricular block can result in life-threatening bradyarrhythmias. Additionally, increased myocardial automaticity and excitability can result in atrial, junctional, and ventricular ectopy, and tachyarrhythmias.

The serum digoxin level must be interpreted with caution. The correlation between clinical effects and digoxin level is based on the steady state concentration, so the level is more helpful in predicting chronic rather than acute toxicity. Although the therapeutic range for serum digoxin is usually between 0.5 and 2 ng/mL, up to 10% of patients in this range may demonstrate toxicity. Digoxin demonstrates a biphasic distribution pattern following acute overdose. Serum levels will initially be elevated without clinical toxicity because distribution into the tissues occurs over many hours. Digoxin levels 10 times greater than the therapeutic serum concentration can be seen in patients during the first few hours after acute overdose without apparent toxicity. Similar concentrations in a patient with chronic toxicity would be fatal. Serum digoxin concentrations then decline as the drug is distributed into the tissues and eliminated by the kidneys, and it is during this phase that toxicity may begin.

Management of digoxin poisoning begins with standard supportive care and continuous electrocardiogram monitoring. Intravenous access is obtained, and blood is analyzed for serum digoxin, electrolyte, creatinine, calcium, and magnesium concentrations.

The treatment of choice for serious digoxin poisoning is intravenous administration of digoxin-specific Fab antibody fragments. Indications include life-threatening dysrhythmia, conduction delay, hyperkalemia (> 5 mmol/L), cardiogenic shock, or cardiac arrest due to digoxin overdose. Other indications include a high likelihood of progression to life-threatening digoxin toxicity, such as ingestion of more than 4 mg or 0.1 mg/kg in a child, ingestion of more than 10 mg in an adult, serum digoxin level greater than or equal to 15 ng/mL at any time or greater than or equal to 10 ng/mL 6 hours after ingestion, or rapidly progressive signs and symptoms of digoxin poisoning. Dosing of digoxin-specific Fab, in theory, is dose dependent, but relies on accurate knowledge of amount ingested and cannot be guided by blood levels. It is more practical to administer an empiric dose of 10 to 20 vials of digoxin-specific Fab for acute overdose, repeating as needed to reverse life-threatening toxicity. A lower dose is recommended for chronic digoxin poisoning to reduce the toxic effects by neutralizing a fraction of the digoxin while maintaining therapeutic benefits in the patient with underlying cardiac disease. Empiric dosing of digoxin-specific Fab for chronic poisoning is 1 to 2 vials for children and 3 to 6 vials for adults, titrated to clinical effect. Following administration of digoxin-specific Fab, total serum digoxin levels increase dramatically because digoxin is pulled from the tissue compartment into the intravascular space, where it is bound by the Fab fragments and inactivated. The kidneys then excrete this complex. Measurement of free serum digoxin levels may be helpful in guiding further therapy.

A crucial aspect in the treatment of digoxin poisoning is the management of electrolyte homeostasis. Hyperkalemia is a consequence of digoxin poisoning and may be treated with sodium bicarbonate or dextrose and insulin but the use of calcium is contraindicated, as this can further increase dysrhythmias. Although digoxin initially causes an elevated extracellular potassium concentration, serum potassium concentrations often fall precipitously following digoxin-specific Fab and must be checked frequently. Hypokalemia is especially dangerous in digoxin poisoning because it exacerbates cardiotoxicity. A fall in serum potassium concentration from 3.5 mEq/L to 3 mEq/L increases cardiac sensitivity to digoxin by approximately 50%. Patients with chronic digoxin toxicity are often hypokalemic because of concomitant treatment with diuretics. Significant hypokalemia should be corrected cautiously, especially in the patient with renal insufficiency.

Magnesium is a cofactor for the Na⁺/K⁺-ATPase pump. Hypomagnesemia potentiates digoxin-induced cardiotoxicity and inhibits correction of hypokalemia. Patients who are on chronic digoxin therapy may be hypomagnesemic because of concurrent diuretic use. Intracellular magnesium depletion may be present despite a normal serum magnesium concentration. Magnesium replacement is indicated for patients with digoxin-related cardiotoxicity, hypokalemia, and documented hypomagnesemia. Caution is again advised in the patient with renal insufficiency.

Gastrointestinal decontamination may be considered for recent acute ingestions. Activated charcoal binds to digoxin, decreasing gastrointestinal absorption. Digoxin poisoning results in conduction delays and increased vagal tone, and therefore induced emesis and gastric lavage are avoided because vagal stimulation may induce bradydysrhythmias.

Iron

Iron is an important cause of severe childhood poisoning. Its toxic effects are mediated primarily by free-radical production, resulting in multiorgan injury.

The first stage of iron poisoning results from direct gastrointestinal toxicity and is characterized by nausea, vomiting, diarrhea, and abdominal pain. Hematemesis and hematochezia may also occur. The second stage is the latent stage, which usually occurs 6 to 24 hours after ingestion and is characterized by lethargy, tachycardia, and metabolic acidosis. The third stage is shock and systemic toxicity, with circulatory collapse, hypovolema and gastrointestinal bleeding, lethargy, seizures, or coma, which can occur very rapidly after a massive ingestion or up to 24 hours after a moderate ingestion. The fourth stage is acute hepatic failure, which can occur 2 to 3 days after ingestion. The fifth stage refers to later mechanical complications resulting from the initial corrosive gastrointestinal injury, such as gastric outlet obstruction and small intestinal strictures. These may manifest 2 to 8 weeks following ingestion.

Diagnosis is based on a history of iron ingestion and the presence of consistent signs and symptoms, especially gastrointestinal distress or shock. The absence of symptoms within the first 6 hours excludes serious iron toxicity. The amount of elemental iron ingested and peak levels 4 hours after ingestion correlate with toxicity (Table 114-3). Concomitant investigations should include blood gas analysis, electrolytes, glucose, renal and liver functions, and coagulation studies. Abdominal radiographs may identify iron tablets, concretions, or free air in the abdomen.

Intravenous chelation with deferoxamine should be considered for any patient with a serum iron level greater than 500 μg/dL or signs of significant toxicity such as metabolic acidosis and hypoperfusion. Deferoxamine binds iron with high affinity, forming ferrioxamine (deferoxamine-iron) that is eliminated by the kidneys. The classic vin rosé coloration of the urine does not always occur despite significant iron toxicity. Therapy may be discontinued when systemic toxicity resolves and serum iron levels return to normal.

Whole bowel irrigation is recommended when iron tablets are seen on radiographs of the gastrointestinal tract. Serial abdominal radiographs are obtained to document elimination of the iron tablets. Surgery may be required to excise adherent iron concretions that cannot be removed with whole bowel irrigation. Although hemodialysis does not enhance elimination of iron, it may be necessary to remove the ferrioxamine complex in patients with renal failure.

Opioids

Opioids are categorized as natural opiates derived from the Papaver somniferum, the opium poppy (ie, morphine, codeine), semisynthetic opioids (ie, heroin, hydrocodone), and synthetic opioids (ie, fentanyl, meperidine). Opiate receptor activation results in analgesia, euphoria, sedation, respiratory depression, miosis, gastrointestinal dysmotility, and pruritus.

The classic opioid toxidrome consists of coma, respiratory depression, and miosis. Other effects include bradycardia, hypotension, hypothermia, ileus, decreased muscle tone, and hyporeflexia leading to apnea, cardiovascular collapse, and death. Noncardiogenic pulmonary edema occurs, especially with heroin overdoses. Seizures are associated with certain opioids such as meperidine, propoxyphene, and tramadol.

Diagnosis should not be difficult when the opioid toxidrome is present and improvement occurs with administration of the opioid antagonist naloxone. Urine toxicology screens can confirm recent use of certain opioids. Serum acetaminophen and salicylate levels should be obtained because many prescription opioids are combined with these analgesics.

Initial management is focused on support of the airway and ventilation. Early administration of naloxone may obviate the need for definitive airway management. The primary goal is reversal of respiratory depression, which usually improves rapidly after naloxone. High-potency opioids such as fentanyl may require higher doses. Altered mental status and respiratory depression will not be effectively reversed if other sedative-hypnotic drugs are also contributing to toxicity.

A useful starting dose of naloxone for the opioid-dependent patient is 0.1 mg intravenously followed by escalating doses every 1 to 2 minutes as needed to a maximum of 10 mg. Isolated opioid toxicity is unlikely if there is no improvement after 10 mg of naloxone.

Patients who initially respond to naloxone must be closely monitored for several hours because its duration of action is shorter than that of many opioids. Return of respiratory depression requires additional doses or continuous infusion of naloxone and hospital admission.

Salicylates

The primary therapeutic mechanism of action of salicylates is decreased biosynthesis of prostaglandins via inhibition of cyclooxygenase, which results in their analgesic, antipyretic, and anti-inflammatory properties. The pathophysiology of salicylate poisoning is complex because of the multiple mechanisms of toxicity (Table 114-4).

Acid–base disturbances are characteristic of salicylate toxicity. Stimulation of the medullary respiratory center results in hyperpnea and primary respiratory alkalosis. However, an elevated anion gap metabolic acidosis also begins early and worsens as the poisoning progresses. Blood gas analysis demonstrates early respiratory alkalosis, followed by mixed respiratory alkalosis and metabolic acidosis. The respiratory alkalosis may be blunted if the patient also has salicylate-induced pulmonary edema, severe central nervous system toxicity, or coingestion of another agent that results in respiratory depression.

Fluid and electrolyte abnormalities are always present with significant salicylate poisoning. Dehydration results from vomiting, hyperventilation, hyperthermia, diaphoresis, and diuresis associated with obligatory excretion of Na⁺, K⁺, and HCO₃^– as a response to the respiratory alkalosis. Hyperglycemia is often present early as increased energy demand promotes glycolysis and gluconeogenesis. Later, increased metabolic demands exceeding the supply of glucose result in hypoglycemia. Neuroglycopenia may occur even in the presence of a normal serum glucose concentration.

Central nervous system toxicity is manifested by lethargy, delirium, seizures, coma, and respiratory depression. Acidemia contributes to central nervous system toxicity because it decreases salicylate dissociation and promotes the ingress of salicylate into the brain. Hyperthermia, cerebral edema, respiratory failure, and cardiovascular collapse ultimately result in death.

Diagnosis is based on the history of salicylate exposure as well as characteristic laboratory and clinical findings, and is confirmed by serum salicylate levels. Blood gases, electrolyte, renal function, and glucose levels should be monitored closely. Measurement of the serum salicylate concentration confirms the diagnosis and helps predict severity of toxicity but must be evaluated in the context of the patient’s clinical examination and laboratory results as well as other factors such as time elapsed since ingestion, formulation of the salicylate, and adequacy of decontamination. Serial salicylate levels are needed because of the possibility of delayed absorption from sustained-release products or tablet concretions in the gastrointestinal tract.

Treatment of salicylate poisoning begins with meticulous correction of fluid, electrolyte, and acid–base disturbances. Dehydration requires fluid resuscitation to restore adequate circulating volume, tissue perfusion, and urine output. Excessive hydration should be avoided as it increases the risk of pulmonary and cerebral edema. Potassium is added to maintenance fluids to replace ongoing losses. Dextrose is provided even if the patient is normoglycemic, because increased metabolic demands often result in neuroglycopenia.

Sodium bicarbonate is a specific treatment for salicylate poisoning for 2 main reasons. First, sodium bicarbonate increases the serum pH and favors movement of salicylate from the central nervous system and other organs into the serum compartment. Second, alkalinization of the urine favors excretion and enhanced elimination of salicylate. Intravenous sodium bicarbonate is indicated when the patient is symptomatic and the serum salicylate level is greater than 40 mg/dL. Hypokalemia must be corrected to achieve urinary alkalinization. The goal of sodium bicarbonate therapy is a urinary pH of 7.5 to 8 and a serum pH of 7.4 to 7.5. Frequent salicylate, blood gas, electrolyte, and urine pH determinations guide therapy.

In cases of severe intoxication (levels > 100 mg/dL), or if there is renal failure, profound acid–base imbalance, or progressive clinical deterioration, hemodialysis can be used to eliminate salicylate and correct fluid, electrolyte, and acid–base disturbances. Gastrointestinal decontamination with activated charcoal binds salicylate, preventing systemic absorption. Multiple-dose activated charcoal is recommended in salicylate poisoning because of delayed absorption from sustained-release preparations or salicylate concretions. The end points of therapy are resolution of symptoms, normalization of electrolyte and acid–base disturbances, and serial salicylate levels that remain less than 25 mg/dL after sodium bicarbonate therapy has been discontinued.

Sulfonylureas

Sulfonylureas can cause prolonged and severe hypoglycemia following an acute overdose. The sulfonylurea family includes acetohexamide, carbutamide, chlorpropamide, glibornuride, gliclazide, glimepiride, glipizide, gliquidone, glyburide, tolazamide, and tolbutamide. They bind to receptors on pancreatic β cells, stimulating release of insulin. They also enhance peripheral insulin sensitivity and reduce gluconeogenesis.

Early signs and symptoms of hypoglycemia are secondary to the associated catecholamine release and include anxiety, tremor, diaphoresis, tachycardia, and vomiting. Neuroglycopenia results in confusion, lethargy, coma, and seizures. Permanent brain injury or death is the consequence of severe and prolonged hypoglycemia.

The diagnosis of sulfonylurea poisoning is based on history of ingestion and clinical manifestations of hypoglycemia. Serum concentrations are not rapidly available. Supportive care, immediate treatment with intravenous dextrose, and hospitalization are indicated for significant hypoglycemia. The agent of choice for treating sulfonylurea overdose is octreotide, a semisynthetic long-acting analog of somatostatin that inhibits the release of insulin from the pancreas, reduces dextrose requirements, and prevents rebound hypoglycemia in patients with sulfonylurea poisoning. The starting dose is 4 to 5 μg/kg/day divided every 6 hours intravenously or subcutaneously in children and up to 50 to 100 μg every 6 hours in adults. Persistent hypoglycemia may necessitate more frequent dosing or continuous infusion. Most significant sulfonylurea poisonings will require 24 hours of octreotide therapy and another 24 hours of observation after therapy is discontinued to monitor for recurrent hypoglycemia.

Blood glucose should be monitored frequently in asymptomatic patients who may have ingested a sulfonylurea. The patient should be allowed normal access to food and liquids. Patients who do not develop hypoglycemia within 8 hours of ingestion are probably safe to discharge home, although some experts recommend 24-hour hospital observation for all patients. Intravenous dextrose is not indicated in euglycemic patients because it masks the onset of hypoglycemia, makes it difficult to ascertain whether the patient is dependent on intravenous dextrose, and prolongs the observation period. Excessive dextrose stimulates release of insulin, which results in rebound hypoglycemia.

ENVIRONMENTAL AND HOUSEHOLD TOXINS

Carbon Monoxide

Carbon monoxide (CO) is an odorless gas produced by incomplete combustion of carbon-containing material. Common sources of exposure include house fires, automobile exhaust, and improperly ventilated water heaters, stoves, furnaces, fireplaces, and space heaters. Inhalation of CO is the leading cause of poisoning death in the United States.

CO causes cellular hypoxia via several mechanisms. First, CO binds to hemoglobin with an affinity 250 times greater than that of oxygen, forming carboxyhemoglobin (COHb). This results in decreased oxyhemoglobin saturation and oxygen delivery to the tissues. Second, the formation of COHb shifts the oxyhemoglobin dissociation curve to the left, further diminishing release of oxygen to the tissues. Third, CO binds to cytochrome oxidase, impairing cellular respiration and oxidative metabolism. In addition, CO binds to myoglobin, resulting in myocardial depression, hypotension, dysrhythmias, and cardiac arrest.

The diagnosis of CO poisoning is readily suspected in the patient found unconscious in a house fire or running automobile. However, the diagnosis is difficult when the patient presents with nonspecific symptoms after an unrecognized exposure. Mild to moderate CO exposures present with malaise, nausea, vomiting, dyspnea, headache, dizziness, and confusion. Such patients are often misdiagnosed with influenza or gastroenteritis. Severe poisoning is characterized by syncope, seizures, coma, cardiorespiratory depression, and death.

Once suspected, the exposure can be confirmed by determining the COHb level from a blood gas sample using co-oximetry. There is a correlation between COHb levels and clinical presentation (Table 114-5). However, if significant time has elapsed since exposure, the COHb level will underestimate the initial severity of the poisoning. Metabolic acidosis is an indicator of the severity of cellular hypoxia and ischemia. In cases of CO poisoning, arterial co-oximetry should be performed, which directly measures oxygen saturation and specifically detects COHb. Routine blood gas analysis may reveal a normal partial pressure of oxygen (PO₂) because dissolved oxygen is unaffected by COHb and transcutaneous pulse oximeters give false normal readings because they do not distinguish between oxyhemoglobin and COHb.

In addition to general supportive measures, the treatment of CO poisoning is aimed at reducing the amount of CO bound to hemoglobin, cytochrome oxidase, and myoglobin by administering the highest possible oxygen concentration to the patient as this reduces the half-life from approximately 4 hours in room air (21% oxygen) to 1 hour when the patient is on 100% oxygen. Hyperbaric oxygen treatment at 2 to 3 atm pressure can further decrease the COHb half-life to 20 to 30 minutes. Although the utility of hyperbaric therapy remains controversial because of conflicting research design and results, it should be considered for patients with significant CO poisoning (COHb levels > 25%, acute neurological symptoms or metabolic acidosis with pH < 7.20) if practical. The regional poison control center and hyperbaric chamber can help guide this decision, which is also based on distance from a hyperbaric center and the patient’s stability.

Caustics

Caustic agents are found in household products such as drain cleaners, oven cleaners, rust removers, toilet bowl cleaners, tile cleaners, and hair straighteners. They are capable of causing serious injury on contact with the skin, eyes, and gastrointestinal tract.

The most commonly encountered caustic agents are acids and alkalis. Acids denature proteins (coagulation necrosis), producing a firm coagulum that may limit tissue penetration. Acids often have a strong odor and cause immediate pain, which can limit the amount ingested. Alkalis dissolve proteins and saponify fats (liquefaction necrosis), resulting in deeper tissue penetration. Alkalis are often odorless and do not cause immediate pain on contact, which may allow ingestion of larger volumes. Strong acids (very low pH) and strong alkalis (very high pH) cause the greatest damage, but the severity of tissue injury is also determined by other factors such as duration of contact, volume of exposure, and physical state of the caustic substance.

Ingestion is the most common route of exposure. The complete absence of signs and symptoms after several hours usually indicates that significant injury has not occurred. However, the absence of oropharyngeal burns on physical examination does not completely rule out the possibility of esophageal or gastric injury. Patients with caustic burns usually report pain of the mouth, throat, chest, or abdomen. Young children manifest pain by crying, drooling, and refusing to swallow. Esophageal perforation usually causes severe mediastinitis. Gastric injury may result in hematemesis and epigastric or upper-left quadrant abdominal pain. Peritonitis and metabolic acidosis are ominous signs, correlating with severity of tissue necrosis, esophageal or gastrointestinal perforation, and sepsis.

Respiratory tract injury may occur via direct extension of esophageal burns or secondary to aspiration of the caustic while swallowing or vomiting. Upper airway edema may result in hoarseness, stridor, and catastrophic upper airway obstruction. Pulmonary involvement includes bronchospasm and pneumonitis.

Ocular exposure to caustic agents, especially strong alkalis, often results in severe damage. Initial findings include eye pain, blepharospasm, lacrimation, conjunctival injection, and edema. Necrosis and opacification of the cornea, lens, and anterior chamber lead to blindness. Dermal contact results in localized pain, erythema, blistering, and deeper necrosis when the exposure is severe.

The caustic substance should be identified with respect to pH, concentration, amount, and time of exposure. Immediate decontamination is of the utmost importance. Patients should be undressed, inspected for dermal exposures, and washed thoroughly with tepid water. In the case of ocular exposures, the eyes should be immediately irrigated. Tap water is usually readily available, and the eyes should be flushed under running water for a minimum of 15 minutes. In the emergency department, local anesthetic drops may be applied and each eye irrigated with at least a liter of saline. After thorough ocular decontamination, the pH of the tears should be checked with litmus paper or a urine dipstick. Further irrigation is indicated if the pH has not returned to approximately 7.4. Following irrigation, a Wood lamp and fluorescein dye are used to evaluate for corneal and conjunctival injuries. Ophthalmologic consultation should be obtained for all ocular caustic injuries.

Following ingestion of a caustic substance, gastrointestinal decontamination is of limited utility. The mouth should be rinsed thoroughly in patients with oral burns. Some experts recommend diluting the gastric contents by having the patient drink small volumes of water or milk. The placement of a small nasogastric tube to suction the stomach may be considered in recent and large intentional ingestions. Activated charcoal does not bind caustics and obscures endoscopy.

Imaging for serious caustic ingestions may include lateral neck, chest, and abdominal radiographs. Patients with respiratory distress require laryngoscopy to assess for airway burns. Immediate surgical consultation is required if esophageal or gastrointestinal perforation is suspected based on hypotension, mediastinitis, abdominal rigidity, sepsis, metabolic acidosis, and radiographic or endoscopic evidence.

Gastroenterology consultation is required for all caustic ingestions with signs and symptoms of injury. If the patient is stable, endoscopy should ideally be performed within the first 24 hours after ingestion to evaluate full progression of the burn. Endoscopic grading of the severity of esophageal injuries helps to guide subsequent management (Table 114-6). Antibiotics should not be administered prophylactically for mild injuries, but are indicated for patients with gastrointestinal perforation or signs of infection.

Hydrocarbons

Hydrocarbons are found in many common household and automotive products. They are derived from petroleum distillation and other sources, including coal tar, plant oils, and animal fats. Hydrocarbon exposures are a frequent cause of pediatric morbidity and mortality. Common clinical scenarios include toddlers who aspirate a liquid hydrocarbon and recreational inhalation of volatile hydrocarbons by adolescents.

Most hydrocarbons are poorly absorbed from the gastrointestinal tract after ingestion and lack systemic toxicity. The chief concern is pulmonary aspiration resulting in chemical pneumonitis. The risk for aspiration is determined by the hydrocarbon’s physical properties of viscosity and surface tension. Viscosity is the tendency to resist flow and is the best predictor of aspiration. Hydrocarbons with low viscosity have the highest risk for aspiration, while those with high viscosity are less likely to be aspirated. Surface tension is the cohesive force between molecules and defines the ability of the liquid to move along a surface. Hydrocarbons with low surface tension have a higher risk for aspiration. Volatility is the ability of a liquid to vaporize into a gas. Volatile hydrocarbons can displace alveolar oxygen, resulting in hypoxia. These compounds are easily absorbed across the alveolar-capillary membrane, resulting in systemic effects such as central nervous system depression.

The respiratory injuries caused by hydrocarbon aspiration are multifactorial. Irritation of the larynx and trachea results in coughing, choking, and laryngospasm. Spread of the hydrocarbon to the lower airways results in bronchospasm, bronchial inflammation, and necrosis. When the hydrocarbon reaches the alveoli, changes in pulmonary dynamics occur due to lipid solubilization and disruption of the surfactant layer, resulting in alveolar collapse and decreased compliance. Direct injury to lung parenchyma results in alveolar edema, exudates, and hemorrhage, with interstitial inflammation and necrosis leading to a further ventilation-perfusion mismatch and decreased compliance.

Cardiovascular toxicity is unusual after hydrocarbon ingestion or aspiration but is well described with inhalational abuse of halogenated or aromatic hydrocarbons. Sensitization of the myocardium to endogenous catecholamines results in ectopy, tachydysrhythmias, ventricular fibrillation, and sudden death. The term sudden sniffing death syndrome has been used to describe this phenomenon associated with inhalational solvent abuse.

Central nervous system depression following hydrocarbon aspiration is most commonly caused by hypoxia secondary to pulmonary injury. Systemic absorption of volatile hydrocarbons following inhalation or ingestion can result in central nervous system depression because of disruption of neuronal membranes. It is this alteration of mental status that is sought by the inhalant abuser. Chronic inhalational abuse of volatile hydrocarbons can result in irreversible white matter degeneration and dementia. Certain hydrocarbons, including camphor, halogenated hydrocarbons, aromatic hydrocarbons and hydrocarbons containing metals or pesticides, have systemic toxicities that may require consultation with a poison control center.

Most patients with hydrocarbon aspiration will have immediate symptoms of coughing, gagging, and choking. In mild cases, these symptoms may be transient, but patients with significant aspiration will have persistent coughing and tachypnea. Patients with severe aspiration present with severe respiratory distress, including coughing, grunting, bronchospasm, tachypnea, intercostal retractions, use of accessory muscles, cyanosis, agitation, and somnolence. Other patients may have more gradual development of respiratory distress.

Patients who remain asymptomatic for 6 hours after ingestion are unlikely to have pulmonary aspiration and may be safely discharged home with careful follow-up instructions. Symptomatic patients are admitted to the hospital for further observation and management. Persistent cough or tachypnea should be evaluated with a chest radiograph, which usually demonstrates pneumonitis. Pneumatoceles are a late finding, appearing on radiographs a week or 2 after the initial necrotizing pneumonitis. In patients with more significant respiratory distress, blood gas analysis may demonstrate hypoxemia and hypercarbia with a combined respiratory and metabolic acidosis. Empiric antibiotics are usually not recommended unless fever and leukocytosis develop later, suggesting bacterial superinfection. Corticosteroids are not helpful in limiting the pulmonary injury.

Patients with severe respiratory distress require immediate endotracheal intubation with mechanical ventilation and oxygenation. Decreased lung compliance necessitates increased positive end-expiratory pressures. Patients who fail these interventions may be candidates for extracorporeal membrane oxygenation to allow time for the lungs to heal.

The use of gastrointestinal decontamination following hydrocarbon ingestion is controversial because the primary risk is pulmonary aspiration. For these agents, gastric decontamination is not indicated because of the increased risk of aspiration. Some experts recommend gastric emptying for hydrocarbons with serious systemic toxicity, especially large intentional ingestions. However, the benefit of gastric emptying must be weighed against the risk of aspiration pneumonitis. Most ingestions occur in young children and are unintentional, resulting in smaller volumes ingested, reducing the need for gastric decontamination. Activated charcoal has poor adsorptive capacity for most hydrocarbons.

Methanol and Ethylene Glycol

Methanol and ethylene glycol are found in many consumer products. Ingestion of these toxic alcohols results in significant morbidity and mortality, but outcomes can be improved with early diagnosis and treatment.

Both alcohols derive their toxicity from the fact that they are metabolized by alcohol and aldehyde dehydrogenases into more toxic metabolites. The parent alcohol initially causes an elevated osmolar gap, followed by the gradual development of an elevated anion gap metabolic acidosis as toxic metabolites are formed. Later, the osmolar gap normalizes and severe anion gap metabolic acidosis predominates.

The toxic metabolite of methanol is formic acid, which causes metabolic acidosis as well as optic nerve and brain injury. The principal toxic metabolites of ethylene glycol are glycolic and oxalic acid. Glycolic acid is primarily responsible for the metabolic acidosis. Oxalic acid causes calcium oxalate precipitation in the kidney, leading to renal failure, and in the brain, resulting in altered mental status, coma, seizures, and cerebral edema. Widespread calcium oxalate precipitation may lead to severe hypocalcemia with seizures, prolonged QT interval on electrocardiogram, and ventricular dysrhythmias.

Suspected methanol and ethylene glycol ingestions must be taken with extreme caution because the lethal dose is very low. Initial symptoms include ataxia, altered mental status, and vomiting. Patients will subsequently exhibit Kussmaul respirations as metabolic acidosis develops. Both poisonings can result in coma, seizures, myocardial depression, and hypotension. Visual disturbances and blindness are specific to methanol, whereas renal failure, calcium oxalate formation, and hypocalcemia are specific to ethylene glycol poisoning.

The diagnosis of methanol or ethylene glycol poisoning is based on a careful history and interpretation of physical examination and laboratory data. Measurement of blood methanol and ethylene glycol levels confirms the diagnosis and guides therapy, but results may not be immediately available. Other helpful laboratory studies include serum osmolality, blood gas analysis, BUN, creatinine, electrolytes, calcium, glucose, and lactate. Elevated anion gap metabolic acidosis not due to lactate suggests toxic alcohol poisoning. Urinalysis may reveal calcium oxalate crystals due to ethylene glycol poisoning.

The treatment of methanol and ethylene glycol poisoning is aimed at preventing formation of toxic metabolites by blocking the activity of alcohol dehydrogenase. Two therapeutic options are available for the blockade of alcohol dehydrogenase: ethanol and fomepizole. The newer antidote fomepizole has many advantages over ethanol: It does not have the risk of inebriation or hypoglycemia, it can be intermittently dosed, and it does not require monitoring of serum concentrations or monitoring in the ICU setting, which make it the antidote of choice for toxic alcohol poisoning. The indications for fomepizole in the setting of suspected methanol or ethylene glycol poisoning are outlined in Table 114-7. Because the turnaround time for methanol and ethylene glycol levels may be long, the decision to start treatment with fomepizole must often be made based on clinical presentation, an elevated osmolar gap, or an elevated anion gap metabolic acidosis. The loading dose of fomepizole is 15 mg/kg intravenously (up to 1 g), followed by maintenance doses of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours thereafter.

Hemodialysis eliminates the toxic alcohol and its metabolites, and corrects fluid, electrolyte, and acid–base disturbances. The indications for hemodialysis are outlined in Table 114-7. Early nephrology consultation for hemodialysis is critical for seriously poisoned patients. Treatment with fomepizole and dialysis should be continued until serum methanol or ethylene glycol levels are negligible, the increased osmolar gap and anion gap metabolic acidosis are resolved, and the patient is clinically improved.

Methemoglobinemia

Methemoglobinemia occurs when hemoglobin is oxidized to form methemoglobin (MetHb) as a result of exposure to oxidizing drugs, nitrate-contaminated well water, or other oxidative stress, as well as to inhaled nitric oxide without an appropriate controlled delivery system. MetHb is unable to bind and transport oxygen, and the oxyhemoglobin dissociation curve is shifted to the left, further reducing oxygen delivery to the tissues. These effects are exacerbated when anemia is present. Many oxidizing agents also cause hemolysis secondary to oxidative effects on the cell membrane, especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Two enzyme systems are responsible for reducing MetHb back to normal hemoglobin (Fig. 114-5). The primary enzyme is nicotinamide adenine dinucleotide (NADH)-dependent MetHb reductase that utilizes NADH generated from glycolysis and performs 95% of this activity. The secondary enzyme is nicotinamide adenine dinucleotide phosphate (NADPH)-dependent MetHb reductase that relies on the G6PD-dependent hexose monophosphate shunt. This second enzyme system accounts for only 5% of normal activity but can be induced to rapidly reduce MetHb to hemoglobin. The antidote methylene blue increases the activity of this second NADPH-dependent pathway.

The signs and symptoms of methemoglobinemia result from cellular hypoxia. Clinical severity correlates with increasing MetHb levels as shown in Table 114-5. For a given MetHb level, the clinical effects will be more severe if the patient has concomitant anemia. Diagnosis depends on a high index of suspicion and history of exposure to oxidizing agents. Methemoglobinemia should be suspected in the cyanotic patient with no obvious cardiac or respiratory disease, whose cyanosis does not improve with oxygen and is out of proportion to the degree of respiratory distress. Infants presenting with gastroenteritis and methemoglobinemia may have severe metabolic acidosis and shock that is out of proportion to degree of dehydration.

The patient’s blood has a characteristic chocolate brown color. The diagnosis is confirmed by sending a blood sample to the laboratory for measurement of the MetHb level and blood gas analysis on a co-oximeter. Routine blood gas analysis does not detect MetHb, and as for COHb, incorrectly calculates normal oxygen saturation based on the measured PO₂ (which is normal). With significant cellular hypoxia, blood gas analysis demonstrates metabolic acidosis, and serum lactate is elevated secondary to anaerobic metabolism. The absorption spectrum of MetHb causes transcutaneous pulse oximeters to measure oxygen saturation incorrectly.

Patients with MetHb levels less than 20% usually improve simply with supportive care and removal of the oxidizing agent. More severely affected patients require treatment with methylene blue. A lower threshold for treatment is indicated in patients with anemia or cardiopulmonary disease. Methylene blue is a thiazine dye that increases the reduction of MetHb to Hb and ultimately reduces MetHb to Hb (Fig. 114-5). This pathway requires G6PD, and therefore, methylene blue may cause hemolysis in patients with G6PD deficiency. The dose of methylene blue is 1 to 2 mg/kg intravenously over 5 minutes, repeated in 30 minutes if the response is inadequate. Methylene blue will transiently cause a false decrease in oxygen saturation measured by transcutaneous pulse oximetry. Excessive doses of methylene blue (> 7 mg/kg) may actually cause methemoglobinemia. If the patient has not responded to a second dose of methylene blue, consider other problems such as G6PD deficiency or NADPH-dependent MetHb reductase deficiency. Exchange transfusion may be considered in patients with severe methemoglobinemia if methylene blue has failed or is contraindicated.

Organophosphorus and Carbamate Insecticides

Organophosphorus and carbamate insecticides prevent the breakdown of acetylcholine in the synaptic cleft by inhibiting the acetylcholinesterase (AChE) enzyme, resulting in continued stimulation of muscarinic, nicotinic, and central nervous system receptors. Carbamates form reversible bonds with AChE that undergo spontaneous hydrolysis with full return of AChE activity by 24 hours in most cases. Carbamate toxicity is shorter and less severe compared to organophosphorus compounds, which can permanently inhibit AChE, resulting in prolonged toxicity. The “aging” process during which the reversible bond becomes a stable covalent bond may take 24 to 72 hours. Infants are at increased risk of toxicity because they have decreased AChE activity compared to adults.

Organophosphorus and carbamate poisoning results in signs and symptoms of cholinergic excess, which are summarized in the cholinergic muscarinic and nicotinic toxidromes. The primary cause of death is respiratory failure. The pulmonary muscarinic effects include bronchorrhea and bronchospasm, whereas the nicotinic effects on skeletal muscle result in weakness, muscular incoordination, and fasciculations. The respiratory compromise is compounded by central nervous system cholinergic effects, including coma and seizures.

Diagnosis is based on history of exposure and clinical presentation consistent with cholinergic excess (muscarinic and nicotinic toxidromes). Plasma cholinesterase and red blood cell (RBC) cholinesterase activity are both decreased after organophosphorus poisoning. Plasma cholinesterase activity is a more readily available and sensitive measure of organophosphorus poisoning. A plasma cholinesterase level 20% to 50% of normal correlates with mild poisoning, 10% to 20% indicates moderate poisoning, and less than 10% is severe. Red blood cell cholinesterase activity is a more specific test for organophosphorus poisoning, but is not readily available in most hospitals. Plasma cholinesterase and RBC cholinesterase levels are not helpful with initial management and diagnosis of organophosphorus compound toxicity but aid management of prolonged toxicity. Cholinesterase measurements are not helpful after carbamate poisoning because the inhibition of cholinesterase activity is usually mild and transient.

The first priority of treatment is decontamination of the victim and protection of healthcare providers from secondary exposure. Resuscitation is focused on correcting respiratory dysfunction. Atropine is the initial antidote for organophosphorus and carbamate poisoning because it is a competitive antagonist of muscarinic acetylcholine receptors. The goal of atropinization is the reduction of pulmonary secretions, reversal of bronchospasm, and improvement in respiratory distress. The initial dose of atropine is 0.02 mg/kg intravenously up to 0.5 to 2 mg in adults, doubling the dose every 5 minutes until adequate oxygenation is achieved. Extremely high doses are required to overcome the cholinergic excess, and severely poisoned patients require frequent dosing or continuous intravenous infusion. Atropine has no effect at nicotinic receptors, and will not reverse nicotinic toxicity.

The second antidote for organophosphorus poisoning is pralidoxime chloride (2-PAM), which reactivates AChE, reverses both muscarinic and nicotinic effects, and reduces atropine requirements. Pralidoxime must be administered early for organophosphorus poisoning because the inhibition of AChE becomes irreversible over time. Pralidoxime is not necessary for carbamate poisoning because of rapid hydrolysis of the carbamate–AChE complex. The dose of 2-PAM is 25 to 50 mg/kg intravenously in children, up to 1 to 2 g in adults, over 15 to 30 minutes, repeated if there is no improvement in muscle weakness or fasciculations. Severely poisoned patients require repeat dosing or continuous infusion, which may be necessary for several days.

SUGGESTED READINGS

INTRODUCTION

Drowning is defined as a process resulting in primary respiratory impairment from submersion or immersion in a liquid medium. For drowning to occur, the face and airway must be immersed. Drowning is a major public health problem. According to the World Health Organization (WHO), there are 372,000 deaths per year worldwide attributed to drowning. More than 90% of these deaths occur in low- and middle-income countries. It is 1 of the 10 leading causes of death worldwide among people between 1 and 24 years of age. The full extent of the world’s drowning problem is underreported since statistics exclude intentional drowning and drowning deaths resulting from flood disasters, tsunamis, and water transport incidents.

In the United States, drowning is the leading cause of unintentional injury-related death among children 1 to 4 years of age, with a death rate of 2.4 per 100,000. Approximately 1 in 5 people who die from drowning are children aged 14 and younger. In 2014, there were 7701 emergency department visits for nonfatal unintentional submersions and 892 unintentional drowning deaths in US children 0 to 18 years of age. Fortunately, the death rate due to drowning in children is decreasing. The crude death rate due to unintentional drowning in children decreased from 1.17 per 100,000 in 2009 to 1.06 per 100,000 in 2014. Rates are highest in the southern United States. Most victims of nonfatal drowning do well, but about 5% to 10% of these incidents result in severe neurologic damage secondary to cardiac arrest. These are even more common when drowning occurs in open bodies of water.

Key risk factors for drowning are: a lack of barriers controlling exposure to bodies of water; lack of adequate, close supervision for infants and young children who are a drowning risk; poor swimming skills; low awareness of water dangers; and high-risk behavior, including consuming alcohol while engaging in water-related activities, especially among adolescents and young adults. Other risk factors include the failure to wear life jackets and seizure disorders. In low- and middle-income countries, transport on water and water crossings, lack of safe water supply, and flood disasters are additional risk factors. Drowning victims involved in natural disasters may also have associated traumatic injuries.

There are 2 peaks of incidence of drowning in children: The first is in the infant/toddler age group and occurs in bathtubs and swimming pools, and the second is in the adolescent age group and is frequently related to risk-taking behavior in swimming pools and during recreational water sports in natural bodies of water. Drowning rates are influenced by factors such as access to swimming pools, the motivation to learn how to swim, and participation in water-related recreational activities, as well as demographics. African-American children are at between 3- and 5-fold increased risk of drowning than children of similar ages of other racial or ethnic groups.

Among all US residents between the years 1999 and 2010, natural water was the most frequent drowning location, accounting for 47.2% of all unintentional drowning deaths (including deaths while boating), followed by other/unspecified places (26.8%), swimming pools (16.3%), and bathtubs (9.7%). Age is an important determinant of where a child drowns. Most infant drownings occur in bathtubs and large buckets, largely when children are left unsupervised. Most deaths due to drowning in toddlers occur in swimming pools. School-age children and adolescents are more likely to drown in natural water than swimming pools, and fatal submersions in boating accidents usually occur when individuals do not wear a personal flotation device or wear it improperly. Inadequate marine training and the use of alcohol also contribute to fatal boating incidents. Alcohol increases the risk of drowning by impairing judgment and performance and by causing disorientation and hypothermia, and although data is lacking, illicit drugs would likely have similar effects. Above ground pools without barrier fencing (they are outside the purview of local building codes) and entrapment in a drain of a swimming pool (particularly with hair being entangled or a body part “sucked in”) are also high-risk settings. Another dangerous situation may occur when swimmers hyperventilate before swimming underwater or try to hold their breath for long periods of time. This can render a swimmer unconscious (“shallow water blackout”), leading to drowning. Hyperventilation or breath-holding before diving or swimming decreases the body’s stores of CO₂ and the arterial partial pressure of carbon dioxide (PaCO₂), delaying the cerebral response to come to the surface to breathe. The blackout is caused by the drop in the arterial partial pressure of oxygen (PaO₂) in arterial blood gas, resulting in hypoxia and loss of consciousness under water. Underlying conditions such as epilepsy and autism increase the risk of drowning. No study has specifically studied developmental disabilities or attention-deficit/hyperactivity disorder as drowning risk factors. Undiagnosed malignant cardiac arrhythmias or propensity for these (eg, long QT syndrome), cardiomyopathy, or other subclinical cardiac diseases may lead to sudden cardiac events or cardiac arrest leading to drowning.

The relationship between swimming ability and drowning is complex and important. The ability to swim may or may not decrease drowning risk and does not completely protect against drowning. A proficient swimmer may have an elevated risk of drowning due to increased aquatic exposure and participation in potentially dangerous aquatic situations. Similarly, a good swimmer may suffer an immersion accident, which then becomes submersion due to fatigue, particularly in cold water. Even a strong swimmer may succumb rapidly due to hypothermia in icy water. Nevertheless, swimming lessons do reduce drowning risk in small children and it is possible for preschool-aged (24–42 months) children to develop the water-safety skills necessary to survive a fall into a home swimming pool after training.

TERMINOLOGY

Confusion exists around the terminology used to describe drowning events. Terms such as near-drowning, wet or dry drowning, active or passive drowning, silent drowning, or secondary drowning should be avoided. Instead, the Utstein style for classifying submersion injuries is recommended. The term drowned should be used to describe a person who has died from drowning. Drowning outcomes should be classified as death, no morbidity, or morbidity (further categorized as moderately disabled, severely disabled, vegetative state/coma, and brain dead).

PATHOPHYSIOLOGY

When a person begins to drown, water first enters the victim’s mouth and is either swallowed or spat out. The victim then voluntarily holds his/her breath. If water enters the oropharynx or larynx, there may be laryngospasm. The breath-holding and laryngospasm prevent respiration, and hypoxia, hypercarbia, and acidosis ensue. As the hypoxia worsens and laryngospasm abates, victims actively breathe in and aspirate water. Ultimately, there is loss of consciousness and apnea. The cardiovascular response begins with initial tachycardia followed by bradycardia, pulseless electrical activity, and finally, asystole. This whole process may take a few minutes but may be more protracted in hypothermic conditions. Drowning in cold or icy water confers protective effects on many organ systems, including the brain, through reductions in consumption, resulting in delayed cellular anoxia and adenosine triphosphate (ATP) depletion in a temperature-dependent manner. Cerebral oxygen consumption falls at least 5% for each 1°C reduction in temperature when the range of ambient temperature is between 37°C and 20°C. Cold water drowning results in a rapid fall in core temperature, particularly if there is associated aspiration, and this is the reason that seemingly miraculous anecdotal accounts exist of intact survival after hypothermic submersion accidents. Importantly, these conditions—even in the absence of vital signs—warrant prolonged resuscitative efforts (see also Chapter 102), though it is important to note that a recent study and meta-analysis did not observe a protective effect of colder water in drowning victims.

Aspiration of water into the alveoli leads to surfactant dysfunction and washout. Salt-water and fresh-water aspiration cause similar degrees of injury, although there may be differences in osmotic gradients. Regardless, there is disruption of the delicate alveolar-capillary membrane with attendant shifts in fluids, plasma, and electrolytes. The clinical picture is that of pulmonary edema with reduced lung compliance, ventilation-perfusion mismatch, atelectasis, and bronchospasm. Submersion victims may swallow large amounts of water. During resuscitation, they may vomit their stomach contents and aspiration into the lungs may occur, predisposing them to aspiration pneumonia.

Depending on when rescue occurs, and the timing of appropriate resuscitative measures, the patient may recover with or without subsequent therapy with resolution of hypoxia, hypercarbia, and acidosis. If the patient is not ventilated (or does not resume spontaneous effective respiration) soon enough, then profound hypoxemia will ensue and ultimately will lead to organ hypoperfusion and cardiopulmonary arrest. The most common organ failures within the first 24 hours of drowning are respiratory, followed by neurologic, cardiovascular, gastrointestinal, hematological, and least commonly, renal. Severely injured victims of submersion are at risk of multiorgan dysfunction due to severe hypoxia and hypoxic-ischemic brain injury or even brain death, as well as acute respiratory distress syndrome or sepsis syndrome attributable to aspiration pneumonia or nosocomial infections. Posthypoxic encephalopathy with or without cerebral edema is the most common cause of death in hospitalized drowning victims. While brain injury is 1 of the most common sequelae of drowning, it is also important to investigate the possibility of concurrent trauma or neurologic disease (eg, seizures resulting in loss of consciousness before drowning) as factors associated with this.

MANAGEMENT

The response to a drowning victim involves a multilevel approach from the initial water rescue and on-scene resuscitation to hospital transport to emergency room and in-patient resuscitation and care and rehabilitation. A universal Drowning Chain of Survival comprising 5 links that serve as a guide informing important lifesaving steps for lay and professional rescuers has been proposed. This chain of survival has the potential to greatly improve the chances of prevention, survival, and recovery from drowning. The 5 steps of the chain are prevent drowning, recognize distress, provide flotation, remove from water, and provide care as needed. A classification of the severity of submersion injuries, based on a retrospective review of 1831 adult cases of submersions of predominantly seawater rescues, has been proposed (Fig. 115-1). The clinical findings of the victims and interventions that were administered at the submersion scene were evaluated, and a treatment algorithm was developed. Patients are categorized into 6 subgroups based upon the severity of respiratory compromise at the submersion site. The grading is as follows:

• Grade 1 (normal lung auscultation with coughing) survival = 100%;

• Grade 2 (abnormal lung auscultation with rales in some lung fields) survival = 99%;

• Grade 3 (auscultatory evidence of acute pulmonary edema without arterial hypotension) survival = 95% to 96%;

• Grade 4 (evidence of acute pulmonary edema with arterial hypotension) survival = 78% to 82%;

• Grade 5 (isolated respiratory arrest) survival = 31% to 44%; and

• Grade 6 (cardiopulmonary arrest); survival = 7% to 12%.

It is uncertain whether this classification that was developed for adults would be applicable for children and infants, or whether similar results would be obtained if this scale were to be validated prospectively, although it does provide clinicians with a helpful prognostic guide.

Prehospital Management

Bystander rescue and resuscitation of drowning victims play an important role in positive outcome. The victim should be removed rapidly and safely from the water without placing the rescuer at undue risk. The potential rescuer should, if possible, instruct someone else to call for help while staying on-scene to provide assistance. He or she must watch where the victim is in the water, or ask a bystander to keep constant watch. If possible, the rescuer should provide some form of flotation to prevent submersion. Staying out of the water reduces the rescuer’s risk of drowning. Prompt resuscitation by safely removing the victim from the water as rapidly as possible is encouraged. Rescue breathing may begin while the victim is still in the water if doing so will not delay removing the victim from the water. Administering chest compressions in the water is not advised. Water does not act as an obstructive foreign body, so attempts to remove it by abdominal or chest thrusts or placing the person head down should be avoided. Doing so only delays the initiation of ventilation and increases the chances of vomiting. Upon removal of the victim from the water, cardiopulmonary resuscitation (CPR) is commenced if the victim is unresponsive or not breathing. For the lone rescuer, 5 cycles (about 2 minutes) of compressions and ventilations are administered before activating the emergency response system and getting an automated external defibrillator (AED). If 2 rescuers are present, the second rescuer is instructed to activate the emergency response system immediately and prepare the AED while the first rescuer performs CPR. Coexisting cervical spine injuries are in general rare, and so immobilization of the cervical spine is only recommended if there is a high-risk mechanism, such as diving into shallow water or an accident involving boating, waterskiing, or surfing. In an unwitnessed event, depending on depth of water and the age/abilities of the child, responders will often err on the side of caution with cervical spine protection. Regurgitation of stomach occurs in more than 65% of persons who require rescue breathing alone and in 86% of those who require CPR with chest compressions. Most patients will need suctioning of the oral cavity as soon as this is available.

Emergency Department

A majority of submersion victims recover spontaneously and fewer than 6% of all persons who are rescued by lifeguards need medical attention in a hospital. Successful resuscitation requires close attention to oxygenation, ventilation, circulation, and the prevention and treatment of hypothermia. For the spontaneously breathing patient with respiratory distress, 100% oxygen should be administered by a nonrebreathing mask or high-flow oxygen by nasal cannula, bilevel positive airway pressure (BiPAP), or continuous positive airway pressure (CPAP). Because of atelectasis, pulmonary edema, and intrapulmonary shunting, positive airway pressure can increase the functional residual capacity and improve lung compliance. Bronchospasm should be treated with nebulized or inhaled β-agonists such as albuterol or levalbuterol. Pulmonary edema and reduced lung compliance in severe cases will necessitate endotracheal intubation with positive pressure ventilation and positive end-expiratory pressure. Criteria for intubation are the presence of neurologic deterioration or an inability to protect the airway, the inability to maintain a PaO₂ above 60 mm Hg or oxygen saturation (SpO₂) above 90% despite supplemental oxygen, or a PaCO₂ above 50 mm Hg—all of which indicate actual or pending acute respiratory failure. If tracheal intubation is performed, this should be done as a rapid sequence procedure, avoiding bag-mask ventilation, and an orogastric tube should be placed to relieve stomach distension.

Survival after prolonged submersion and cardiac arrest in cold water is possible, so it is imperative that resuscitation continues until the patient has been warmed adequately. All wet clothing should be removed. A hypothermic patient will require rewarming using passive and active external rewarming (eg, application of warm blankets, heating pads, radiant heat, forced warm air), or active internal core rewarming (eg, warmed humidified oxygen via tracheal tube, irrigation of peritoneal and pleural cavities with warm fluids).

Antibiotics or steroids are not routinely indicated in victims of drowning. If the person remains unresponsive without an obvious cause, a toxicologic investigation and computed tomography of the head and neck should be considered. The administration of naloxone may be considered if opioid intoxication is suspected. In the acute phase, measurements of electrolytes, blood urea nitrogen, creatinine, and hematocrit are rarely helpful. Criteria for hospitalization include persistent dyspnea or hypoxia beyond 8 hours postsubmersion, and severe submersion injuries with unconsciousness, respiratory failure, and hypothermia.

Intensive Care Management

Respiratory System

The pathologic features are acute lung injury with acute respiratory distress syndrome, generally necessitating mechanical ventilation, as in the treatment of other types of acute lung injury. The manifestations of lung injury, pulmonary edema, and aspiration often progress over the first 24 hours, so weaning is generally withheld during this period. The patient should be monitored daily for fever, leukocytosis, persistent or new lung infiltrates, and a leukocyte response in the bronchoalveolar lavage. Early-onset pneumonia can occur due to aspiration of polluted water, endogenous flora, or gastric contents. Aspiration of swimming-pool water rarely results in pneumonia, whereas drowning in ponds or lakes significantly increases the risk of this. The risk of pneumonia increases during prolonged mechanical ventilation and may be detected by the third or fourth day of hospitalization, or later, when pulmonary edema has nearly resolved. A secondary pneumonia is often related to nosocomial pathogens. Empirical therapy should initially include broad-spectrum antibiotics, covering the most predictable Gram-negative and Gram-positive pathogens. Later, antibiotic therapy should be guided by the results of culture and sensitivity testing of bronchial secretions. There is no evidence supporting the use of steroids or exogenous surfactant for reducing pulmonary injury in victims of drowning.

In the most severe cases of acute lung injury with refractory hypoxemia, hypercarbia, or both, extracorporeal membrane oxygenation (ECMO) may be considered as it would for other etiologies of acute respiratory failure, in patients with predominantly single-organ (pulmonary) failure. ECMO also has been used as a temporizing measure with absence of early cardiac recovery after drowning associated with profound hypothermia.

Circulatory System

In most submersion victims, adequate oxygenation, crystalloid boluses, and measures to correct hypothermia lead to a stable hemodynamic status. Cardiac dysfunction may occur in severely injured victims, particularly those who have suffered significant cardiopulmonary arrest requiring CPR. In these patients, circulatory failure should be treated according to usual algorithms, including vasoactive medications, potentially utilizing echocardiography to assess function and fluid status, as well as response to interventions.

Neurologic System

Victims who are comatose or show signs of neurological injury should be closely monitored to prevent secondary neurologic injuries due to cerebral ischemia and edema, hypoxemia, fluid and electrolyte imbalance, acidosis, seizures, and postresuscitation rise in temperature. Usual protective measures to reduce elevated intracranial pressure (eg, elevation of the head of the bed, maintaining the head midline, avoiding noxious stimulation, careful blood gas, glucose and electrolyte control) should be routinely instituted as early as possible in this situation. While there is no evidence to support therapeutic hypothermia in these patients, controlled normothermia without allowing core temperature to increase to greater than 37.5°C should be a part of routine management, as hyperthermia is known to worsen preexisting anoxic brain injury. Placing the patient on a cooling blanket targeting normothermia will avoid unwanted swings in temperature in these vulnerable patients.

Other Systems

Sepsis and disseminated intravascular coagulation may occur during the first 72 hours after resuscitation. Renal insufficiency or failure is rare but can occur as a result of anoxia, shock, myoglobinuria, or hemoglobinuria. These sequelae will all require specific interventions, although in general are not primary determinants of prognosis.

OUTCOMES AFTER DROWNING: PROGNOSTIC INDICATORS

The longer term outcomes after drowning are largely determined by the degree of neurological injury, and this, in turn, is typically related to whether or not there has been a cardiac arrest. Victims who arrive at a hospital without a perfusing cardiac rhythm who are subsequently successfully resuscitated are highly likely to have neurological injury unless they have been submerged in icy water. Neurological injury that is associated with cardiac arrest after submersion is typically severe and may progress to brain death or be otherwise unsurvivable. By contrast, other organ failures that occur are generally reversible.

Factors influencing survival and long-term morbidity include duration of submersion, water temperature, how promptly and effectively CPR was provided, and the subsequent interval prior to return of a perfusing cardiac rhythm. The issue of hypothermia in submersion accidents is an important one in northern climates. There are many case reports of intact neurological survival in children who have been submerged in icy water (below 5°C). This, of course, is biased literature, but is relevant when deciding when to terminate CPR in a drowned hypothermic patient because there may be a neuroprotective effect of rapidly induced hypothermia.

The strongest predictor of outcome in victims of drowning is the duration of submersion victims is submersion duration. However, time estimates of the duration of submersion are notoriously inaccurate. Many of the events are unwitnessed, so the time between the actual submersion and being found is often unknown. Additionally, a caregiver may minimize the time because of feelings of guilt that may be related to lack of supervision of the victim at a vulnerable time. With that in mind, a meta-analysis revealed that favorable outcome was associated with shorter compared to longer submersion durations. For submersion duration of less than 5 to 6 minutes, the risk ratio was 2.9; for less than 10 to 11 minutes, it was 5.1; and for less than 15 to 25 minutes, it was 26.9. Favorable outcomes were also seen with shorter emergency medical service response times (risk ratio = 2.8) and salt water versus fresh water submersion (risk ratio = 1.16). No differences in outcomes have been observed with the age of the victim, water temperatures, or witnessed versus unwitnessed drownings.

Long-Term Outcomes in Survivors

A good health-related quality of life is achieved in a majority of submersion victims who survive long term after a submersion event. However, as already stated, the overall quality of life is dependent on submersion time. Mean quality-of-life scores were significantly lower in victims for whom the submersion time exceeded 10 minutes compared to patients with shorter submersion times. Additionally, neurological dysfunction and a lower full-scale intelligence quotient (FSIQ) may occur long term in seriously injured submersion victims. In a study, cognitive or neurologic deficits were detected in 17 of 21 subjects, although 11 of them were reported to have a full recovery at hospital discharge. The study revealed that 57% of the drowned and resuscitated children had neurological dysfunction and 40% had a low FSIQ. The median estimated submersion time of the subjects with normal FSIQ was 3.5 minutes, which was significantly shorter than for those with an FSIQ less than 80, 12.5 minutes. Therefore, neurological and neuropsychological long-term follow-up of pediatric submersion victims is highly recommended.

PREVENTION

The prevention of drowning is the mainstay in reducing the burden of injuries associated with submersions. Safety interventions are grouped based on their ability to change the environment, the individual at risk, or the agent of injury (water).

Water Safety

Recommended water safety measures include:

1. Adult supervision of young children around any body of water is vitally important. Because drowning occurs quickly and quietly, adults should not be involved in any other distracting activity (such as reading, playing cards, talking on the phone or texting, or mowing the lawn) while supervising children, even if lifeguards are present. A responsible adult should be designated to be a “water watcher” to monitor young children while in the bath and when children swim or play in or around water. For preschool children, “touch supervision,” which involves an adult being close enough to reach the child at all times, is recommended. Older children should use the buddy system. Swimming with a friend and selecting swimming sites that have lifeguards when possible are recommended.

2. Since epilepsy is a known risk factor for drowning, these patients should have one-on-one supervision around water, including swimming pools, take showers instead of bathing in a tub, and wear life jackets when boating. Children with autism spectrum disorders and developmental delay should be closely supervised around water.

3. All children should learn to swim. While formal swimming lessons can begin at age 4 years of age, water survival skills could be taught to toddlers between 1 and 4 years of age. More research is needed to determine which types of swimming instruction and water-survival skills are most effective in preventing drowning in young children of various ages. Nevertheless, constant and careful supervision of children who are in and around water should always occur.

4. Immediate CPR at the site of a submersion incident can be lifesaving. Parents and caregivers should be trained in basic life support.

5. Approved personal flotation devices (PFDs) should be used. Air-filled or foam toys, such as water wings, noodles, or inner tubes are not life jackets and are not designed to keep swimmers safe.

6. The consumption of alcoholic beverages should be avoided before or during swimming, boating, or water skiing or while supervising children. Swimmers should not hyperventilate before swimming underwater or try to hold their breath for long periods of time.

7. Knowledge of the local weather conditions is important prior to swimming or boating. Strong winds and thunderstorms with lightning strikes can be dangerous.

8. Lifeguards at swimming pools and beaches serve to make them safer by monitoring the aquatic environment, enforcing rules and regulations, and educating swimmers about safety and injury prevention.

Home Swimming Pools

The best method to prevent submersions in unsupervised young children is to install fencing that completely isolates the pool area from the house and yard; this type of fencing has been shown to decrease the rate of pool-immersion injuries among young children by more than 50%. Fences should be at least 4 feet high, and no opening under the fence should be more than 4 inches. Vertical members of the fence should be less than 4 inches apart to keep a child from squeezing through them, and there should be no footholds or handholds that could help a young child climb the fence. Self-closing and self-latching gates that open outward with latches that are out of reach of children are also required. The latch should be placed at least 54 inches above the bottom of the gate. It is also advisable to remove floats, balls, and other toys from the pool and surrounding area immediately after use so that children are not tempted to enter the pool area unsupervised. Additional barriers, such as automatic door locks and alarms to prevent access to the pool area, are helpful. Pool covers and pool alarms are not recommended as a substitute for isolation pool fencing. In order to prevent drain entrapments and entanglement in swimming pools and spas, the use of special drain covers, safety vacuum-release systems, filter pumps with multiple drains, and a variety of other pressure-venting filter-construction techniques are required.

Natural Bodies of Water

When boating in natural bodies of water, it is essential to use life jackets approved by the US Coast Guard or an equivalent. This is important regardless of the distance to be traveled, the size of the boat, or the swimming ability of the boater. Life jackets can reduce risk for weaker swimmers, too. At the beach, bathers should know the meaning of and obey warnings represented by colored beach flags. These may vary from 1 beach to another. Water that is discolored and choppy, foamy, or filled with debris and moving in a channel away from shore may indicate a rip current. If caught in a rip current, the swimmer should first swim parallel to shore and then, once free of the current, should swim diagonally toward the shore.

SUGGESTED READINGS

INTRODUCTION

Trauma is the number 1 cause of mortality and morbidity for children even in the developed world, and major resources are still needed to prevent and treat traumatic injuries. Between 1 month and 18 years of age, one-half of all deaths in children are the result of a traumatic injury. Trauma accounts for more deaths in children in this age range than all forms of cancer, heart disease, and infections combined. The objectives of this chapter will be to review the differences between adults and children in regard to mechanism of injury and physiologic response; discuss pathophysiology and the initial management of the trauma victim; and outline common injuries involving various organ systems.

Most infants and children with traumatic injuries are seen in the emergency department with nearly half of the facilities being adult centers rather than pediatric-specific trauma facilities. This underscores the importance of education of community emergency department, family, and pediatric specialists. Not surprisingly, the significantly injured child requires evaluation and management skills that may not be available in every emergency department. Caregivers may have less experience with their care and an understanding of the initial management and stabilization of these patients and their safe and timely transfer to the higher level of care needed for definitive management.

CHILDHOOD TRAUMA

The often invoked maxim that children, and especially infants and young children, are not small adults applies also to understanding and treating traumatic injuries. The differences involve anatomical and physical characteristics, physiological and psychological responses, and even the very mechanisms by which trauma occurs. Adult practitioners often need to be reminded that, for instance, children have greater surface ratio of area to mass than do adolescents or adults. This results in greater dissipation of heat and water, which may compound the effects of other traumatic injuries. The head of an infant or small child encompasses a much larger percentage of the total body than that of adults and subjects children to higher rates of brain and skull injuries. The child’s skeleton exhibits greater elasticity than that of the adult and is therefore more likely to tolerate compression and visceral injury without fractures. A vast majority of childhood injuries are passive and result from blunt trauma and thus tend to involve multiple organs. Yet children tend to experience better outcomes compared to adults with the same mechanism of injury because of factors such as the occurrence of fewer bone fractures and the lack of comorbid disorders. It is important to remember that, while a recovery of function and quality of life after blunt injury is common, physical function tends to remain lower than age-matched norms at 6 months postinjury, and often the childhood trauma victim and his or her family bears the consequence of that injury for a lifetime.

Trauma Scores

A common language that objectively describes injuries and their consequences is very useful in the frenzied circumstances that are the norm in the trauma management process. The Glasgow Coma Scale (GCS) and Injury Severity Scale (ISS) have been mainstays in the assessment and subsequent review of outcomes in pediatric trauma patients. Additional scoring systems are used widely for pediatric trauma and include the Pediatric Trauma Score (used for triage of new patients), the Abbreviated Injury Score (primarily used for classification of the patient for research and comparison purposes), and the Trauma and Injury Severity Score (allows an estimation of the probability of survival).

Trauma Management

The evaluation and management of the injured child is best performed using a standard protocol. The Advanced Trauma Life Support (ATLS) protocol is widely used and establishes 3 sequential events: the primary Survey, the secondary survey, and a definitive care phase.

Primary Survey

The primary survey is performed immediately on arrival to the emergency department and may be completed in the first several minutes (Table 116-1). Seminal to this phase is the rapid assessment of vital functions followed by the appropriate resuscitation measures without progression until that portion of the primary survey has been confirmed or corrected.

The reality of trauma assessment and management is that it is frequently a team effort with multiple parallel actions, but it is meaningful to consider the actions as a series of single steps. It is critical not to progress from 1 of the steps until you have completed the assessment and any needed interventions. As an example, when assessing the airway (A), if the patient does not have a secure airway and the patient needs to be intubated, this must occur before moving on to breathing (B), and so on. The assessments and interventions related to the primary survey must identify life-threatening conditions and provide the needed emergent therapies. Thus, these must be rapid and decisions must be made with the available evidence. This does not allow at time for definitive treatment or diagnosis, but rather limited assessment and stabilizing treatment for life-threatening conditions.

Assessment of Vital Functions

Early on in the primary survey, there must be assessment of vital functions, including declaration of a working weight. The airway and breathing are first in line in the primary survey. In children, inadequate oxygenation and ventilation are the most common causes of cardiac arrest after trauma. In every case, the mouth should be opened and the pharynx examined for foreign material or loose teeth. Secretions should be cleared and, if the child is unconscious, a jaw thrust maneuver or insertion of an oral airway may be used to prevent upper airway obstruction. Supplemental oxygen should be given. The presence of persistent respiratory distress or insufficient respiratory effort is usually an indication for tracheal intubation, which should be performed efficiently by the most experienced individual. Bag and mask ventilation can often provide adequate ventilation even in the most difficult circumstances and is preferable to unskilled tracheal intubation, particularly if laryngeal or tracheal injuries are suspected. Additional specialty aids for intubation include video-assisted direct laryngoscopy, such as the glide scope, or applying a laryngeal mask airway. These devices, when used by experienced providers, can be lifesaving for the difficult airway.

If intubation has failed and adjuncts have only partially supported delivery of oxygen, a surgical airway may be necessary. If the patient has a suspected injury and no stridor but apparent upper airway obstruction, after several unsuccessful attempts of endotracheal intubation, a cricothyroidotomy is the next step. A tracheostomy attempted outside of the operating room (OR), particularly in a small child, can be a very difficult procedure, and is not the treatment of choice in this situation. Rarely, in the circumstance where there is a suspected laryngeal crush injury and stridor, consideration should be given to proceeding directly to a cricothyroidotomy without attempted endotracheal intubation because of the risk of creating a false passage in placing the airway via an endotracheal route.

After airway patency is assured, attention should move to other aspects of respiratory function. Palpation and auscultation are used to determine whether the trachea is in the midline. Auscultation for breath sounds should be completed and they should be heard well bilaterally. A tracheal shift or a decrease of breath sounds on 1 side of the chest may indicate a pneumothorax or hemothorax. If the patient is stable, a chest radiograph should be obtained to establish the origin of the findings.

If there is a shift of the trachea away from the side of absent breath sounds in the setting of hemodynamic instability, then a tension pneumothorax is suspected and emergent treatment is indicated. This can be carried out by simply placing a needle into the pleural space through the second intercostal space at the midclavicular line. This allows relief of the tension and provides an opportunity to place a chest tube for continued evacuation of air. Chest tube placement or tube thoracostomy is the appropriate treatment for a traumatic accumulation of gas or liquid in the pleural space. In a small infant, a 12- to 14-French chest tube is appropriate. In an older child, an 18- to 24-French chest tube is preferable. A larger-bore chest tube is more appropriate if a hemothorax is suspected. A pigtail-type catheter may both allow for adequate evacuation of air and fluid and provide some improved comfort associated with smaller-diameter tubes. Prior to placing the chest tube, clinicians should consider the level of the diaphragm on that side of the chest to avoid injuring abdominal organs. Placement of the chest tube should be anterior to the midaxillary line at the level of the fourth intercostal space. It is best placed in this location to prevent the patient from lying on the tube. The use of a metal obturator with a very sharp, pointed end should be avoided because of the high risk of injury to the lungs or vascular organs. The chest tube should be placed to suction using a Pleur-evac chamber to measure output and assess for air leak. A chest film should be obtained to confirm evacuation of the pneumothorax and assess for position of the tube. Regular reassessment of chest tube positioning, patency, and drainage or bubbling are extremely important aspects of management of these patients.

Rib fractures are less frequently seen in the young child compared to older children and adults. Typically, they require little treatment aside from pain control and assessment of the respiratory effort. However, a child with several contiguous rib fractures may have a flail chest, a condition characterized by a paradoxic inward movement of a portion of the chest during inspiration. This reduces both the functional residual capacity and the tidal volume, requiring positive pressure ventilation if the respiratory effort is inadequate.

A sucking chest wound involves a penetrating injury that allows air to enter the chest during inspiration. The resulting pneumothorax can be prevented from becoming larger by placing a flap valve dressing over the injury until a chest tube can be inserted and the chest wall can be subsequently repaired.

The next step in the primary survey is assessing the adequacy of tissue perfusion (see Chapter 107). A number of physical signs, including tachycardia, pallor, cool extremities, confusion, combativeness, or a decreased blood pressure, can reflect inadequate perfusion. The presence of poor perfusion should raise the suspicion of hypovolemic shock. After hemorrhage, blood pressure is usually maintained until the child loses 20% of the blood volume; thus, hypotension is a late manifestation of a significant injury. The capillary refill time provides a quick assessment of perfusion, provided that the patient is not cold. Initial management of shock includes infusion of crystalloid in the amount of 20 mL/kg as a bolus. Rapid assessment for the location of blood loss should be completed and initial attempts at hemorrhage control may include direct pressure on a wound or open fracture, placement of a pelvic binder or sheet to stabilize a bleeding pelvic fracture, or surgical assessment or consideration of transfer for large volume hemorrhage from a chest tube or evidence of an intra-abdominal injury. In the child with severe shock (hypotension, tachycardia, poor perfusion), consideration for early blood transfusion or utilization of a massive transfusion protocol has been associated with less coagulopathy.

Completion of the primary survey requires a rapid assessment of the entire patient, including neurologic function. The cervical collar, which is often applied prior to arrival, should be temporarily removed to carry out the neck examination. An examination of the back and all other locations that are difficult to see (eg, armpits and perineum) must be completed. It is necessary to remove all clothing to complete this assessment. It is particularly important to establish at this point whether the child has any lateralizing neurological signs that suggest an intracranial space-occupying lesion or spinal cord injury.

A critical consideration of the pediatric trauma patient is the rapid loss of body heat and susceptibility to hypothermia, which can be associated with coagulopathy, physiologic dysfunction, and death. Thus, the critically injured child and the environment may require active interventions to prevent heat loss and cooling, including environmental temperature control, avoiding unnecessary exposure, warm forced air or warming blankets, and active warming through the infusion of warm fluids.

Intravenous Access

It has become the norm that any child with a significant traumatic injury should have 2 intravenous (IV) lines. If there is an injury involving the abdomen, then at least 1 of the lines should be in an upper extremity or neck. The ideal IV access is a large-bore peripheral IV placed in the upper extremity. Attempts should first be made to place an ideal IV, although this may be challenging in the young child, particularly if hypovolemic. In such conditions, successful placement of a small-bore peripheral intravenous line may gain precious time for the initial resuscitation. A larger-gauge catheter can be inserted later under less pressing circumstances. If peripheral intravenous access cannot be achieved within several minutes, alternative methods of access should be attempted (see Chapter 100) including intraosseous access and, if skilled personnel are available, insertion of a central venous catheter either percutaneously or by surgical venotomy. Subclavian vein access in the trauma patient, particularly in one who is hypotensive or hypovolemic, can be particularly challenging if the clinician has not had significant experience in placing these lines. Additionally, it carries the potential consequence of an iatrogenic pneumothorax or hemothorax. Also, central venous pressure monitoring in the emergency department is unnecessary in the majority of pediatric trauma victims.

After vascular access is established, fluid resuscitation can be initiated accompanied by frequent reassessment of hemodynamic function (heart rate, blood pressure, state of alertness, capillary refill). A urinary catheter can be a valuable measure of organ perfusion, and consideration of placement in a major trauma patient after assessment for urethral injury is mandatory.

Secondary Survey

The secondary survey includes a history and a complete head-to-toe examination of the child with a focus on specific organ systems. The mnemonic AMPLE assists in obtaining a rapid and complete history by focusing on Allergies, Medications, Past illnesses, Last meal, and Events and environment involved with the injury. In the secondary survey, the evaluation, testing, and interventions should be individualized for each patient. Every part of the body should be palpated, the chest and abdomen auscultated, and the patient log rolled to examine the back and to perform a rectal examination.

Head and Neck

The presumption that every patient may have suffered a cervical spine injury has become integral to initial trauma management. Cervical stabilization is thus 1 of the first steps of stabilization and must be continued until cervical injury can be adequately excluded. Immobilization of the cervical spine is usually carried out by prehospital personnel and can be achieved with appropriately sized Philadelphia or Aspen collars or by using sandbags on either side of the head and applying tape over the sandbag and the forehead of the patient. A foam cervical collar will not adequately stabilize the neck. A caregiver can stabilize the cervical spine by holding both mastoids and mandibles in a manner that prevents flexion–extension and lateral movements. If the child is awake and cooperative, the absence of pain or other findings upon careful, full-range mobilization of the neck is usually sufficient to exclude injury. However, physical examination alone cannot exclude a spinal injury in (1) a patient who is uncooperative or unresponsive, (2) the young child unable to give a meaningful or reliable response to questions, or (3) the patient with a significant distracting painful injury elsewhere. Pain with neck movement, tenderness to palpation of the cervical vertebrae, a detectable cervical spine deformity, or a neurologic abnormality referable to the neck are all good reasons to continue immobilization and protection of the cervical spine and to obtain specialized imaging studies and neurosurgical consultation if available.

The assessment and management of acute neurological injuries are discussed elsewhere. Inspection and palpation of the head focuses on the detection of eye and ear injuries, and craniofacial fractures. Crepitus usually indicates a communication between the sinuses and the subcutaneous tissue through a facial bone fracture. Tenderness over the maxilla and mandible, and malocclusion also indicate facial bone fractures. Rhinorrhea or otorrhea suggest a spinal fluid leak through a fracture at the base of the skull.

Examination of the neck and cervical spine includes palpation to identify tenderness, mobilization to assess range of motion, a motor and sensory examination, evaluation of reflexes, and appropriate imaging studies. Difficulty in carrying out this examination is most commonly the result of an altered level of consciousness and/or lack of ability to cooperate because of the patient’s age, or the distracting effects of other injuries. Signs of airway obstruction, hoarseness, stridor, crepitus, or significant soft tissue swelling are alerts for a possible airway injury.

In patients who have undergone stabilization of the neck with a collar, examination of the cervical spine requires the removal of the collar. This may require manual stabilization of the neck during the exam in patients who are unconscious or uncooperative. After inspecting for injury, the cervical spine is palpated. Selecting which patients should undergo evaluation of the cervical spine using imaging has been evaluated in a multicenter study under the direction of the Pediatric Emergency Care Applied Research Network (PECARN). They identified 8 factors that were predictive of cervical spine injuries in children: altered mental status, focal neurologic deficits, complaint of neck pain, torticollis, substantial torso injury, predisposing condition, diving, and high-risk motor vehicle crash. These factors should be considered when deciding which patients should be cleared without imaging. In the author’s experience, if there is pain on palpation or if there is a deformity or swelling, the cervical collar is reapplied and an imaging study should be performed, especially when there is substantial torso injury or high-energy injury mechanism. If no abnormality on examination is noted and no pain elicited, the patient is asked to rotate the head and neck to each side, move it laterally, and then flex and extend it. If movement is limited or pain occurs, the collar is reapplied and imaging studies are indicated. If again no pain or abnormality is noted, the patient’s cervical spine has been “cleared” and no diagnostic imaging is needed. As above, the decision process is more difficult if, for any reason but usually for loss of consciousness or lack of cooperation, the cervical spine cannot be “cleared” using these criteria. Because of the differences in the body habitus of children, a plain cervical spine series may be all that is required in the awake patient with cervical pain or in a child unable to cooperate with an exam as a way to exclude major cervical anomalies in the initial evaluation. Computerized tomography (CT) examination is infrequently needed but may provide a practical method to assess for neck injuries in children. It is important to recognize, however, that a normal neck CT scan does not eliminate the need to perform a functional examination of the neck once it is possible to obtain patient cooperation. Magnetic resonance imaging (MRI), without CT, may eventually be required to exclude an injury in the patient with persistent pain.

Chest

More than 80% of thoracic injuries in children are caused by blunt trauma. The incidence decreases to slightly less than 60% in adolescents. In the patient with blunt chest injuries, the most common cause of death is a head injury; in patients with penetrating chest injury, the death is most often caused by the chest injury itself.

The majority of thoracic injuries can be handled well with supplemental oxygen, tube thoracotomy, and analgesia. Approximately 5% to 10% of all blunt chest injuries may require a thoracotomy. Immediate life-threatening conditions, which should be identified and stabilized during the primary survey, include complete airway obstruction, tension pneumothorax, massive hemothorax, cardiac tamponade, and penetrating cardiac injury. Also potentially life-threatening conditions include pulmonary contusion, myocardial contusion, aortic disruption, diaphragmatic rupture, tracheobronchial disruption, and esophageal perforation. Indications for emergent thoracotomy in the OR include a penetrating wound to the heart or aorta, continued significant intrathoracic bleeding from other source (≥ 3–4 mL/kg/hour), an imaging study indicating an injury to the aorta or other large vessel, a pneumothorax with an open chest wall injury, a large continuing air leak indicative of a bronchial injury, cardiac tamponade, impalpable pulses with closed chest compression, diaphragmatic rupture, and esophageal perforation. Emergent thoracotomy in the emergency department (ER thoracotomy) has an exceedingly low survival rate and very few indications, especially in the patient who is the victim of blunt trauma. This therapy should only be considered if one has the skills, experience, and ability to definitively manage any identified injuries.

Abdomen

The secondary survey of the abdomen includes inspection, palpation, percussion, auscultation, and the use of imaging studies as needed. Abdominal blunt trauma carries an increased risk of injuring multiple organs. The presence of a “seat belt” sign, a linear abdominal wall ecchymosis, is indicative of a rapid deceleration mechanism of injury. This deceleration can often cause significant intra-abdominal injuries. The combination of a seat belt injury and significant tenderness on palpation should cause a high degree of suspicion for injuries of the abdominal viscera.

A nasogastric tube should be placed to decompress the stomach if distended. If there is any evidence of a mid-face fracture, the tube should be placed via an orogastric route to avoid the possibility of the tube being misplaced into the cranial cavity. Distention of the stomach alone can cause pain and even respiratory compromise.

The presence of a pelvic fracture should raise suspicions of a concomitant retroperitoneal or urethral injury. Urethral injury is common in males and should be suspected if there is blood in the urethral meatus or a high-riding prostate on rectal examination. If there is a significant suspicion to a urethral injury, a retrograde urethrogram should be performed before inserting a Foley catheter. Contemporary evaluation of the abdomen often includes an abdominal and pelvic computerized tomography scan. With the new generation of helical scanners, a full abdominal examination can be carried out in minutes. Radiological assessment should only be performed, however, once the patient is sufficiently stable. Peritoneal lavage is now used in very limited circumstances, because the presence of free blood in the abdominal cavity is no longer considered an automatic indication for surgery. For the same reason bedside ultrasound or the focused assessment with sonography for trauma (FAST) exam is of limited value in the stable pediatric patient.

The spleen and the liver are 2 of the abdominal organs most commonly injured. The conservative management of childhood splenic and liver injuries is common practice today. A multicenter study of pediatric level I trauma centers conducted by the pediatric research consortium ATOMAC+ has provided an evidence-based guideline that was validated in a prospective review of patients with blunt liver and spleen injuries (Fig. 116-1). This guideline is based on the assessment of the hemodynamic stability of patients regardless of injury grade. This is in contrast to previous guidelines that were grade based. Major decision points include initial assessment of the patient’s hemodynamic stability and normal values, response to volume resuscitation, and measurement of blood counts. Intervention is indicated for patients with ongoing blood loss and hemodynamic stability. Use of interventional radiology techniques for control of hepatic or splenic sources of bleeding are becoming more common, but frequently are only available at specialized pediatric trauma centers. Indications for surgery include unstable hemodynamics unresponsive to blood transfusion and interventional control techniques for hemorrhage.

Injuries to the pancreas are often the result of a blunt injury, such as those caused by the handlebar of a bicycle, rapid deceleration in a motor vehicle accident, a fall, or intentional child abuse. Penetrating pancreatic injuries are rare and most commonly associated with gunshot injuries. Because of the location of the pancreas and regardless of mechanism, there are often coexisting injuries to the stomach, duodenum, kidneys, or spine. The diagnosis is made on the basis of laboratory studies (elevation in amylase and lipase) and imaging studies (a CT scan demonstrating pancreatic edema, hematoma, or disruption). A penetrating injury of the abdomen with a pancreatic injury requires laparotomy. A blunt injury with stable vital signs and no peritonitis should undergo dedicated cross-sectional imaging. Injuries with a high likelihood of disruption of the pancreatic duct are better managed operatively if the injury can be characterized within the first 24 to 48 hours from injury. This approach reduces the number of interventions, shortens the length of stay, and decreases the time to complete resolution of the injury. The decision to defer operation is usually prompted by a blunt injury, lack of peritonitis, and imaging showing no obvious pancreatic disruption. Nonoperative treatment consists of bowel rest, intravenous nutrition, and administration of octreotide as needed to decrease pancreatic exocrine secretions. A decision to change from nonoperative management to operative intervention is based on the development of peritonitis, persistent amylase/lipase elevations, and fever. A pancreatic pseudocyst is a known later complication of pancreatic trauma, often associated with an elevation in lipase and amylase. The pseudocyst is initially managed nonoperatively, but if still present for over 6 weeks, consideration should be given to internal drainage to the stomach or small bowel.

Intestinal injuries can occur throughout the bowel. The ligament of Treitz and the ileocecal valve are 2 vulnerable points because shear forces tend to tear the bowel at the points where it is tethered to the abdominal wall. Additional mechanisms that can cause a tear in the mesentery or perforation of the small bowel are related to compression against the spine by a force against the anterior abdominal wall. This type of injury may be associated with a Chance fracture of the spine, a fracture along a transverse plane in the vertebral body. The duodenum is also often injured when compressed between the abdominal wall and the spine. A duodenal hematoma can be diagnosed by an upper gastrointestinal (GI) contrast study or an abdominal CT scan and in older children is generally managed conservatively. A duodenal injury in children younger than 5 years of age is highly associated with inflicted injury and should raise suspicion by providers. These inflicted injuries have a higher likelihood of requiring operative intervention (53% of all cases).

Microscopic hematuria in a patient with a normal CT scan does not itself warrant admission, and outpatient follow-up is reasonable. An abnormal CT scan or macroscopic hematuria are indications for hospital admission. If the CT scan shows a major blood extravasation or nonvisualization of renal flow, arteriography is indicated. If the vasculature is normal, the renal injury can be managed as with other solid organ injuries. However, operative intervention is required if hypertension or hemodynamic instability occurs. Bladder rupture can be identified on cystogram and CT scan and requires operative intervention if the perforation is intraperitoneal. Extraperitoneal bladder ruptures can be managed with transurethral catheter drainage.

Nonaccidental Trauma

This subject is covered extensively elsewhere. In the evaluation of the trauma patient, the suspicion of child abuse should be kept in mind. This is particularly true if any or several of the following are noted: (1) a discrepancy between the history and the degree of injury, (2) a prolonged interval from injury to treatment, (3) a history of repeated similar injuries, (4) an inappropriate parental response, or (5) a changing history given by the caretaker.

BURNS

Burn injuries are the third most common cause of death due to trauma in children in the United States, accounting for 2500 deaths and over 10,000 cases of severe, permanent disability annually. Many of these injuries are preventable. The majority of hospital admissions of pediatric burn patients are children younger than 2 years of age. Burns are often caused by hot liquids in younger children, particularly those under 3 years of age, and by fire in older children and adults. The initial resuscitation has a fundamental role, particularly in the case of large–surface-area burns. The outcome for the burned patient is related to the magnitude of the injury, and is influenced substantially by the quality of the care provided. Patients with significant burn injuries are best cared for in a burn center. Survival rates in pediatric burn victims with 40% to 60% body surface area (BSA) burns have been reported to be as high as 100%, and with 60% to 100% BSA, burn survival is 86%.

Burns can be categorized as the result of thermal, electrical, chemical, or radiation injury. The majority of burns in children have a thermal mechanism. Developmental differences in BSA-to-body mass ratio and thickness of the skin account for most differences in the response to a burn injury between infants, children, and adults. The child has a larger BSA-to-body mass ratio in comparison to an adult. A 1–year-old weighing 10 kg has one-seventh the body mass of an adult and one-third the BSA of an adult. Accordingly, the child has a larger evaporative fluid loss and greater difficulty maintaining temperature regulation. The child’s skin is not as thick as the adult’s, and thus can burn more deeply after the same duration of contact with a comparable heat source.

The severity of tissue damage after a burn is related to several factors: (1) temperature of the heat source responsible for the burn, (2) duration of exposure, (3) area of the body burned, and (4) age of the patient. Burns to the palms of the hand and soles of the feet tend to be less deep than similar burns to other parts of the body because of the relative thickness of the epidermis in those areas. Likewise, while a shoulder burn may require a skin graft because of the depth of burn, a facial burn after a similar exposure may heal spontaneously, because the rich blood supply of the face limits the injury by dissipating heat more rapidly from that area.

The Assessment of Burn Surface and Depth

The accurate determination of the burned surface area is an integral part of burn-wound management. In adults, the rule of nines is a simple and accurate way of estimating this surface. Each upper extremity and each of the anterior or posterior surfaces of the chest, abdomen, and lower extremities represents 9% of the total body surface. Unfortunately, the same rule is not applicable to children. The head and neck of a child younger than 1 year of age accounts for 21% of the BSA. The modified Lund and Browder BSA chart (Fig. 116-2) can be used to estimate the percent of the BSA involved in a burn. Except in “stocking-glove” burns that extend from the tip of an extremity to the trunk, it is often necessary to approximate the magnitude of involvement of a body part. Especially in the case of irregular burns, it is also useful to know that the palm of a child represents approximately 1% of the BSA.

Burn depth is categorized as either partial or full thickness. Partial-thickness burns involve the epidermis and portions of the dermis. This corresponds to the older nomenclature of first-degree burns, which are exemplified by sunburn, and second-degree burns, which are characterized by a red or mottled appearance, blisters, edema, and a weeping, moist surface. Because of involvement of the dermal nerve endings, they are both painful to the touch and sensitive to cold air. Partial-thickness burns are subclassified as superficial or deep partial-thickness burns. Superficial partial-thickness burns tend to heal spontaneously over 7 to 14 days postinjury. Deep partial-thickness burns may heal spontaneously, but over a longer period of time, and may require tangential excision and skin grafting. Full-thickness or third-degree burns involve all skin layers. Their color can be variable. The tissue appears dry and inelastic, and the area is insensitive. Full-thickness burns will not heal spontaneously. As a rule, they require excision and skin grafting. Small full-thickness burns may heal by wound contracture. In some burns, the central portion is full thickness and the peripheral portion is partial thickness. In rare cases, the burns may extend into the deep tissues underneath the skin. These deep burns are associated with increased resuscitative needs and complications.

Management of the Burned Patient

Immediate Treatment

The first step of immediate burn care is to make sure that there is no ongoing injury. If there is any clothing or object that may still be a significant source of heat, it should be immediately removed from the patient. Jewelry should also be removed from the area and the burn should be wrapped with a clean, dry cloth. Cold liquids should not be applied to burns larger than 1% or 2% of the BSA because the cold can result in diminished local perfusion, which may worsen the injury. Instead, the burns should be dressed with clean, moist dressings and the patient kept warm. The patient should be made as comfortable as possible, and rapid transport should be arranged to a local hospital for immediate resuscitation and stabilization. Criteria for transfer to a burn center are given in Table 116-2.

Fluid Resuscitation

Intravenous access should be obtained in any patient with a burn greater than 10% BSA, and fluid resuscitation should be initiated. If needed, the IV may be placed through burned tissue. A calculated burn resuscitation volume has shown benefits. However, the guideline is to achieve a urine output of 1 mL/kg/hour in young children and 30 to 50 mL/hour in adolescents. A Foley catheter should be inserted to monitor urinary output. If there is a perineal burn, bladder catheterization should be performed before edema formation makes this difficult.

Airway and Lung Injuries

Any patient with a potential for a smoke-inhalation injury requires a rapid physical examination with special attention to the integrity of the airway and to gas exchange. Carbonaceous material in the oropharynx, nasopharynx, or sputum should be noted. Pharyngeal burns, stridor, significant bronchorrhea, dyspnea, or decreased arterial oxygen saturation are indications of airway or lung injuries. Supplemental oxygen should be given. Any concern about airway patency should be addressed by cannulating the trachea before edema makes endotracheal intubation difficult. Bronchoscopy can confirm the presence of carbonaceous material below the vocal cords. Arterial blood gas and carboxyhemoglobin levels should be determined.

Three important complications are associated with smoke-inhalation injuries: carbon monoxide poisoning, thermal injury to the upper respiratory tract, and chemical injury by combustion products to the lower respiratory tract. Carbon monoxide intoxication should be suspected in any patient who has been exposed to combustion products, especially if the exposure occurred in a closed environment and if the patient has an altered state of consciousness or signs of poor oxygen delivery, such as a metabolic acidosis.

Thermal burns can affect the pharynx, the nasopharynx, and the upper airway, causing edema and mucosal sloughing. Direct thermal injuries are rare below the glottis, although steam may carry sufficient heat to cause burns in the trachea and bronchi. Inhalational injuries in the subglottic airways are almost invariably due to chemical damage to the lower respiratory tract, including the bronchi, terminal bronchioles, and alveoli. Their severity varies from bronchial irritation causing cough, increased mucus production, and bronchospasm to more serious alveolar-capillary disruption resulting in respiratory failure.

In patients with burns greater than 25% to 30% of their BSA, pulmonary edema is a common complication, independent of smoke inhalation. Its mechanism involves fluid overload, hypoalbuminemia, and systemic inflammation initiated by the burn. Infection of the respiratory tract is common and carries a high morbidity and a significant mortality risk. Respiratory failure resulting from any of the aforementioned mechanisms occurs in more than half of the children who die as a result of their burns.

Fluid Resuscitation

Fluid resuscitation within the first 24 hours can be done with crystalloid alone, crystalloid and colloid, or hypertonic saline. Each regimen has its rationale and proponents. The majority of burn centers favor a crystalloid resuscitation based on an initial intravenous infusion of 4 mL of Ringer lactate solution per kilogram of body weight per percent of BSA burned. In addition, the patient should receive maintenance fluid. Half of the calculated resuscitation fluid is given in the first 8 hours of the resuscitation and the remaining half in hours 9 through 24. In the course of the treatment, the volume of Ringer lactate infusion is adjusted to maintain urine output at 1 mL/kg/hour. The initial fluid calculation is a guide to fluid management. The adequacy of fluid resuscitation is manifested by an appropriate urine output. In this manner, the patient’s homeostatic mechanisms are used to guide the therapy and to avoid over- and underhydration. Patients who are unable to attain a rate of 1 mL/kg/hour despite increasing the volume of resuscitation should have a deeper injury suspected. Tissue edema of the burn wound, although unavoidable, can cause complications of its own. A partial-thickness burn of the back may progress to a full-thickness burn because of dependent edema. This is particularly true if the patient is resuscitated with excessive amounts of fluid.

In patients with myoglobinuria or hemoglobinuria, a larger urine output is desirable and consideration should be given to the administration of sodium bicarbonate to raise urine pH. The use of a diuretic during the resuscitative phase is rarely indicated and should be avoided.

A number of metabolic disturbances can occur with fluid resuscitation. Metabolic acidosis is most often due to inadequate perfusion and is best treated by increasing fluid volume. Hyperkalemia can be seen in patients with electrical burns and is a consequence of red blood cell breakdown. Moderate hyponatremia can occur at all stages of stabilization due to intracellular shift of sodium and natriuresis, and can be partly attributed to crystalloid resuscitation. If the patient is symptomatic, the judicious use of hypertonic saline may be indicated in experienced hands.

Circumferential Burns

Circumferential burns deserve specific attention because they have a potential to cause additional vascular or respiratory derangements. In the case of an extremity injury, burned skin and subcutaneous tissue do not expand to accommodate swelling in the extremity, limiting venous outflow. Continued arterial inflow causes edema in the distal portion of the extremity, eventually occluding the arterial vessels. Arterial inflow is then compromised. Cyanosis, paresthesia, weakness, or a decreased or absent pulse can be observed and are indications for escharotomy involving both sides of the fingers, toes, feet, hands, arms, or legs. For circumferential burns to the chest, a limited tidal volume or chest rise and blood–gas exchange abnormalities should prompt similar action. The chest escharotomy consists of bilateral vertical incisions in the midaxillary line and a transverse costal incision. The escharotomy can be done at the bedside because these burns are full thickness in nature and the skin is insensitive.

Burn-Wound Management

Initial treatment consists of debridement of the wound injury and application of a topical silver-containing antimicrobial such as silver sulfadiazine (Silvadene). Daily wound care involves either whirlpooling and wound debridement of the burn eschar or applying a silver salt product and leaving it on the burns for several days. After this, the burn is assessed for signs of spontaneous re-epithelialization and formation of capillary buds, followed by the reapplication of the antimicrobial, assessment of mobility, and wrapping. Sedation facilitates aggressive wound debridement and alleviates the anxiety and discomfort associated with this type of repetitive care.

The use of split-thickness skin grafting is often indicated in full-thickness and deep partial-thickness burns. An early decision to carry out tangential excision of the burn and split thickness skin grafting has the advantage of a lower risk of infection, shorter hospitalization, and improved outcome. After several days of burn-wound assessment, a determination of whether the burn will heal spontaneously can usually be made.

Nutrition

Burn patients have perhaps the largest caloric needs of any single group of pediatric patients. In a child who has suffered a large BSA burn, the caloric needs may be 50% greater than the calculated basal needs for body weight or surface area. Additionally, the protein requirements are increased to nearly 2 g/kg/day due to significant loss through the affected tissues. Many patients will not ingest a sufficient amount of calories orally. In addition, because of the need for daily burn-wound debridement and procedural sedation, the patient may not ingest nutrients for a number of hours before or after the debridement procedure. The use of enteral feeding via a nasogastric tube is an excellent method for supplying the appropriate caloric needs and carries a much lower risk of morbidity when compared to intravenous nutrition. Enteral feedings can be started as soon as 24 hours after the burn. If enteral feedings cannot be used, central parenteral nutrition is indicated. Central intravenous access can be challenging if the areas typically used for access are burned. Rotating intravenous access for total parenteral nutrition is a common technique with variable success in reducing the risk of bacteremia. A central line bundle and dressing protocol should be followed and the catheters removed as soon as possible to reduce the risk of bacteremia.

Infections

Infections are the major cause of death and a major cause of morbidity in burn patients. The infections can be divided into 3 types: (1) primary wound or graft infection; (2) bacteremia and catheter-related sepsis; and (3) infections at other sites (lung, urinary tract). In children, risk of infection is increased in inhalation injuries, burns greater than 30% BSA, and full-thickness burns.

The type of bacterial flora that colonizes burn injuries changes with time. In the first week, Gram-positive organisms predominate. By week 2, Gram-negative organisms increase in frequency and number. By week 3, infections due to fungal organisms and antibiotic-resistant organisms are often found. There has been no proven benefit of using prophylactic intravenous antibiotic therapy in burn patients.

In contrast, the use of topical antimicrobials is well documented to be efficacious in burn-wound management. Almost all of the topical antimicrobial agents have silver as the antimicrobial agent. There has been an evolution over the past 40 years in the use of various topical agents for burn care. Silver nitrate was associated with a marked decrease in burn-wound infection and improved survival with its use. However, difficulty with dressing changes, staining, and metabolic complications were noted. For the past 3 decades, silver sulfadiazine is the topical agent used most frequently throughout the United States because it affords good Gram-positive and Gram-negative coverage and it is relatively easy to apply. A disadvantage to its use is the development of leukopenia in a small number of patients. It is often unclear whether this is the result of using the silver sulfadiazine or infection. Sulfamylon is an alternative agent that has the advantage of better penetration of the burn eschar. It is of particular benefit in ear burns, where the cartilage may be involved. Its disadvantages are that it acts as a carbonic anhydrase inhibitor and that it may be painful for the patient. More recently, a series of silver impregnated products, for example Aquacel Ag (Convatec) and Acticoat (Smith and Nephew) have become available and have been associated with excellent results in burn-wound care. This family of topical agents often has greater ease of use than silver sulfadiazine. They come in sheets, are easier to apply, and can be left in place for a number of days. This decreases both the amount of caregiver time needed for wound care and the number of times the patient must be sedated and exposed to discomfort with dressing changes.

A major principle in burn care is to obtain coverage of the burn wound. This can be achieved by spontaneous re-epithelialization or by graft coverage. Most superficial partial-thickness burns heal spontaneously and do not require skin grafting for a satisfactory cosmetic result. Tangential excision of the burn eschar and split-thickness skin grafts are indicated in children with full-thickness burns and deep partial-thickness burns. Tangential excision removes the dead burn tissue to the point that capillary bleeding is identified. The recipient bed is then usually covered with a meshed graft (1.5:1, 3:1, or 6:1) of approximately 14/1000-inch thickness. The meshing allows for expansion of the skin graft, an important consideration in the patient with an extensive burn. In addition, it prevents the accumulation of fluid between the native tissue base and at the graft, which would hinder graft adherence. The cosmetic result declines as more widely meshed grafts are used.

A major research interest for decades in the field of burn injury has been in the area of biological dressings. Ideally, the patient’s own skin would and should be used. However, in large–surface-area burns, there is often not enough skin. The use of cultured epidermal autografts began in 1985. This technique consists of taking a portion of skin from a patient and growing that tissue in culture. Large sheets of autograft can be harvested and applied to a recipient bed on the patient. However, the tissue is very fragile and the cost of producing the cultured autografts is high. Another technique is to place a combination of a thinner (6/1000 to 7/1000 inch) split-thickness skin graft and a donor dermal base (AlloDerm) on the recipient site. This allows for earlier reharvesting of a graft from the same donor site of the burn patient and affords good coverage for a deep burn.

In patients where there is a clear need for wound coverage but not enough tissue available for skin grafting, cadaveric homograft or porcine xenograft can be used as a temporary biological dressing. These types of grafts would typically be recognized as foreign tissue by an immunocompetent recipient and rejected in 4 to 5 days. In patients with significant burns, there often is a degree of immune dysfunction and these grafts may last for up to 10 to 14 days. Biological dressings decrease the risk of infection based on the same principle as do grafts. They also decrease fluid loss and discomfort with dressing changes, while allowing spontaneous epithelialization of the native skin. They can be used in patients in whom (1) there is not enough native skin to cover a burn and coverage is needed until sufficient skin is available for grafting, (2) there is a burn-wound infection and a split-thickness skin graft is likely to become infected, and (3) there is a reasonable likelihood that the wound will epithelialize spontaneously and thus will not require a skin graft, but prompt coverage is desirable.

Prevention of Burns

As with other injuries in children, there are ample opportunities for avoidance of burn injuries through educational processes. Burn injuries in children younger than 3 years of age are often caused by hot liquids, and not fires. This age group compromises the majority of pediatric burn injuries. Therefore, prevention in this population could potentially significantly decrease the number of burns seen in children.

In children younger than 6 months of age, burns due to hot liquids often occur because of a parent carrying both a child and a cup containing hot liquids such as coffee or tea. As the child becomes a toddler, their curiosity can lead to burn injuries because of the home not being “burn safe.” Parents are often well educated in terms of child proofing various rooms in the house, so that the child does not tumble down a flight of stairs or pull a lamp off of a table. The 2 rooms that carry the highest risk or burns in children are the kitchen and bathroom. Any electrical cord hanging off a counter affords the opportunity for the child to pull on the cord and thus pull the coffee pot, electric fryer, or electric slow cooker, and its contents, onto himself or herself. Likewise, allowing a bathtub to be filled with warm or hot water with an unsupervised child carries significant risk of burn injury. During the summer months, the child is at risk for injuries in the area of outdoor cooking appliances such as barbecue grills and campfires. Fortunately, the incidence of electrical burns has markedly decreased over the past 30 years with the use of much better insulation for electrical wiring of home products.

In children older than 5 years of age, burn wounds are more commonly caused by fire. Again, there are excellent educational opportunities. Fire-related injuries are often due to children playing with matches or other combustible products. These types of injuries are very predictable, with burn injuries from fireworks being a common example. Suspicion of abuse is also necessary in the when there are delays to seeking care or the pattern of injury does not fit the provided history.

ANIMAL AND HUMAN BITES

Between 80% and 90% of all bites are inflicted by dogs and 5% to 15% by cats. The remainder involve humans or a variety of species including rodents, bats, and other wild animals. Bites merit consideration either because they involve substantive tissue injuries or because of the potential for the transmission of zoonosis to the victim.

Dog Bites

Approximately 5 million dog bites occur in the United States annually. Of these, approximately 800,000 require medical attention. More than half occur in children and the incidence is highest in 5- to 9-year-old boys, decreasing with age and severity thereafter. Over 75% of the dogs causing the injury either belong to the child’s family or a neighbor.

All pediatric dog bite victims should be treated as trauma patients. The force of a dog’s bite not only may result in soft tissue laceration or puncture, but also may cause bone fractures. The upper extremity is the most commonly injured area, particularly in older children, whereas the head and neck are more frequently involved in children younger than 4 years of age. Facial and neck wounds can be associated with mandibular fractures, intracranial injuries, and cervical spine injuries.

After a bite, the wounds should be thoroughly cleaned, debrided of devitalized tissue, and copiously irrigated. Tetanus toxoid should be administered when immunization status is unknown or out of date. Options regarding wound management include primary, delayed, and secondary closure. The decision is based on the amount of wound contamination, the degree of tissue loss, and the length of time since the injury. Particularly in wounds involving the face, the infectious risks of early closure need to be weighed against the potential for a poor cosmetic result if the wound is allowed to close without suture repair. Infection occurs in one-third of pediatric hand wounds, despite appropriate initial therapy, prompting the recommendation of antibiotic prophylaxis in most cases. Amoxicillin/clavulanate provides good coverage for many of the organisms isolated.

Education has been shown to decrease the number of dog bite injuries. Common recommendations rooted in common sense include avoiding contact with strange dogs; not leaving young children alone at home with a dog; and teaching children, if they are old enough, of the need to respect a dog’s territory, particularly while the dog is feeding or protecting her pups.

Cat Bites

Although cat bites are less common than dog bites, they appear to carry a higher risk of infection. Pasteurella multocida is the most common organism; it is isolated from 20% to 80% of all infected cat bites and from the mouth of 90% of the cats tested. Cat scratch fever is caused by Bartonella henselae, which can be transmitted by a cat bite or scratch from the cat’s claw and is discussed in detail elsewhere (see Chapter 252).

The injured area is typically much smaller than in a dog bite. Treatment principles, however, are the same in regard to initial management, assessment, and infection prevention and treatment. Since the vast majority of cat bites are not deep or associated with tissue loss, wounds are typically left open. A significant index of suspicion is appropriate for the patient who develops subsequent fever or lymphadenopathy. This may be indicative of an abscess or cat scratch disease.

Human Bites

Human bites are considered to be the third most common bite wound following dog and cat bites. The true incidence is unknown; many cases are not reported because they involve only minor injury or because the patient or family does not wish to admit the mechanism of injury. The bite can be either accidental or purposeful, and can range from minor to serious. Some wounds do not involve an occlusive bite and result from an accidental or purposeful impact against another person’s teeth. Over one-half of bite wounds occur in the upper extremity and 10% to 20% involve the head and neck area. Human oral flora includes potentially infectious species of both aerobic and anaerobic organisms, and the overall risk of infection is at least as high as with dog bites.

Bite Wound Evaluation and Care

Evaluation of bite injuries includes a history of the event; a pertinent medical history; assessment of the vulnerability of the patient to infection, very particularly for tetanus and rabies (see Chapters 284 and 316); and a detailed examination of the wound. In cases where presentation is delayed, there often is an increased likelihood of infection. The initial evaluation should note and document the following: wound size and depth; type of wound (eg, abrasion, puncture, avulsion, laceration) and whether there is any tissue loss; where appropriate, motor and sensory function of the affected area; and signs of infection, such as pain, swelling, erythema, drainage, red streaking, or fever.

Bite wounds resulting in a superficial abrasion or contusion need no further treatment after cleaning and evaluation. With more extensive wounds, if exploration appears appropriate or if there is any concern regarding neurovascular abnormalities, a surgical consultation should be obtained. Potential complications include abscess formation, joint penetration, fracture, tendon disruption, tenosynovitis, osteomyelitis, and a paronychia. A decision to close the wound is best made by an experienced clinician and should consider factors such as the degree of contamination, length of time since the injury, signs of infection, the location of the wound, the degree of tissue loss, and whether the patient is immunocompromised. For example, a facial wound with tissue loss may be best treated with wound closure or approximation and an antibiotic therapy, while a hand wound that is 24 hours old with signs of infection may be better treated by leaving the wound open, elevating the extremity, and administering parenteral antibiotics.

SUGGESTED READINGS

INTRODUCTION

Numerous terrestrial and marine animals may envenomate humans, with children overrepresented among the victims^*. Treatment, in some cases, may include mechanical ventilation and intensive cardiovascular support, as well as the application of specific therapies and, in some cases, the administration of antivenom. This chapter describes some of the more common animals, their toxins, and the injuries that they cause, and outlines treatment appropriate for each. Snakebites and scorpion stings cause most deaths and morbidity. Envenomation is, for most clinicians, rarely encountered, but if missed, may have catastrophic effects on the victims. It is therefore important to have a high index of suspicion for envenomation, when circumstances and clinical presentation would suggest that this is a possibility, and also to seek advice early from experts in the field when treating these patients.

SNAKEBITE

Snakebite is most common among highly populated rural communities in tropical developing countries. The annual incidence of snakebites, according to the World Health Organization, is 5 million bites leading to 2.5 million envenomations and 100,000 to 200,000 deaths, of which about 50,000 occur in India. Many more survivors have significant handicaps. A worldwide lack of antivenoms contributes to this neglected public health problem.

Medically significant venomous snakes are from 2 major families: the Elapidae and Viperidae. Elapids are front-fanged terrestrial snakes, including dangerous Australian snakes (taipan, brown, death adder, tiger, and black snakes); the cobras, mambas, and kraits of Asia and Africa; and the coral snakes of the Americas. Elapid venoms are highly neurotoxic with an additional cytotoxicity in some species, such as spitting cobras. Vipers, including the rattlesnakes of the Americas and vipers, have large front-folding fangs and venom that is, generally, less systemically toxic than that of the elapids, but is notable for inducing bite-site swelling and local tissue destruction.

VENOM

Snake venoms are complex mixtures of toxic and nontoxic substances, mostly proteins, that have neurotoxic, myotoxic, procoagulant, anticoagulant, cytotoxic, and hemolytic properties. Many are metalloproteinases and phospholipases.

DIFFERENTIAL DIAGNOSIS

The diagnosis may be unclear in young children or others unable to give a clear history (eg, those found unconscious) or bitten at night or in dense scrub where snakes may not be seen. The differential diagnoses of venomous snakebite include nonvenomous snakebite or a bite or sting by another venomous creature, stroke or head injury, neuropathy (eg, Guillain-Barré syndrome), metabolic disturbance, allergic reaction, toxin ingestion, or sepsis.

DIAGNOSIS OF ENVENOMATION

There should be a high index of suspicion for a diagnosis of envenomation when children become suddenly unwell in areas where snakes exist, alongside a constellation of localized and generalized clinical signs that may or may not include obvious puncture marks (Table 117-1).

Clinical Signs and Symptoms

Symptoms and signs of envenomation follow a predictable time sequence but may vary enormously according to body weight, amount of venom injected, age and state of health of the patient, time since the bite, prior bite history, and allergy status, as well as the site of the bite (Table 117-2). The effects of envenomation are specific to snake genera and species but biogeographical variation in venom within a species with some variation in clinical presentation is well known. Coagulation disturbances are common after many elapid and viper bites, although severe hemorrhage is infrequent. Myolysis is particularly prominent in envenomations from South American pit vipers, sea snakes, and Australian black snakes, whereas death adder and king cobra envenomations are specifically neurotoxic. Renal failure may result from myolysis or may be a primary effect after Russell’s viper and Bothrops envenomations. Bite-site swelling and tissue necrosis may be severe after Asian cobra and pit viper bites and may lead to a compartment syndrome and may even require limb amputation.

Investigations

A snake venom detection kit (SVDK) can be used to detect venom at either the bite site or in the urine or blood. However, this kit is only clinically applicable in Australia and Papua New Guinea. Significant morbidity can result from disseminated intravascular coagulopathy (DIC), rhabdomyolysis, primary or secondary renal impairment, and electrolyte imbalance after envenomation. Thus, routine laboratory investigations should include full coagulation and DIC studies (or, if unavailable, a 20-minute whole blood clotting test), renal function, urinalysis, and careful monitoring of electrolytes. A full blood count may reveal a mildly elevated white cell count as well as thrombocytopenia, which may occur in isolation or as part of DIC or microangiopathic hemolytic anemia. Cardiotoxicity (either primary or secondary to hyperkalemia associated with rhabdomyolysis) may also be present, and an electrocardiogram (ECG) should be performed and cardiac troponin measured if this is suspected.

TREATMENT OF VENOMOUS SNAKEBITE

First Aid

First aid is important prehospital and in-hospital, and all snakebites should be pre-emptively managed as potentially serious envenomations from the moment of first suspicion. While a significant number of venomous snakebites do not result in systemic envenomation because the snake injected no venom or only a small amount, the severity of envenomation cannot be predicted at the time of the bite. Since at least 95% of bites occur on the limbs and approximately 60% involve a lower limb, they are easily treated with first aid.

Some of the earlier, traditionally applied first-aid practices may have no benefit or may even be harmful. Venom may be injected quite deeply, and consequently, little venom is removed by incision or excision (cutting or sucking). These practices are not recommended, and indeed may be dangerous, particularly in the coagulopathic patient. The use of arterial tourniquet, especially for prolonged periods, may also be dangerous and is not recommended for any type of venomous bite or sting.

Pressure-Immobilization

Pressure-immobilization first aid was developed for Australian elapid envenomation. Immobilization without pressure remains a routine first-aid recommendation for crotalid and viper bites. In the pressure-immobilization technique (Fig. 117-1), a continuous, ideally elasticized, bandage is applied, as tightly as binding a sprained ankle, to the whole limb and then a splint applied to further prevent movement. Compression of lymphatic channels and inactivation of the muscle pump delays venom reaching the circulation and buys time for the victim to reach a hospital. Compression without immobilization is ineffective. If applied correctly, pressure-immobilization first aid may be safely left in situ for several hours.

The timing of removal of a pressure-immobilization bandage is important. Once an asymptomatic patient has reached a hospital stocked with appropriate antivenom, first-aid measures may be removed. If, on removal of first aid, the patient’s condition deteriorates, the bandages can be reapplied while antivenom is administered. If a patient arrives at a hospital with obvious envenomation but without pressure-immobilization, it should be applied.

Medical Treatment of Envenomation

The management principles are resuscitation, antivenom administration, and treatment of specific effects of venom. A careful history and examination should be undertaken with reference to the features of envenomation described above, as well as to any previous envenomations and allergies to antivenoms or to other venoms, and with reference to allergic illnesses and asthma. Samples for venom detection and for investigations should be obtained where appropriate and an attempt made to identify the genus of snake. The key question is whether or not to give antivenom, an issue that should be regularly reassessed, as envenomation is a highly dynamic situation reflecting ongoing absorption of venom (see “Choice of Antivenom,” below).

If the patient has not developed any symptoms or signs of envenomation, nor any indication of coagulopathy or myolysis by 4 to 6 hours after bite or removal of first aid, then it is unlikely that significant envenomation has occurred. However, the delayed onset of symptoms, particularly relating to neurotoxicity and rhabdomyolysis, may occur up to 24 hours after the bite or removal of first aid. Particular care is required if a neurotoxic elapid bite is suspected, as few early signs may be present. Overnight observation is highly desirable, especially if the victim is a young child or comes from a remote area. Envenomated patients should ideally be admitted to a hospital and observed for a period of at least 24 hours, depending on the clinical circumstances. Frequent neurological observations should be performed and pathology studies repeated regularly to monitor progression of the illness.

Local Effects

Viper envenomation causes local effects such as skin blistering, limb swelling, and tissue necrosis. Although progressive limb swelling is an indication for antivenom use, its effectiveness at reducing local venom effects remains controversial. The role of fasciotomy in North American crotaline (pit viper) envenomation causing limb swelling is controversial. Fasciotomy is generally considered unnecessary when crotaline antivenom has been administered but intracompartment pressures should be carefully monitored to guide surgical intervention. Local blistering may progress to full thickness skin necrosis over 3 to 7 days and is prone to infection.

Management of Coagulopathy and Hematologic Abnormalities

Envenomation can lead to a procoagulant state and thrombotic microangiopathic renal failure (for example, with Australian elapid venoms and Russell’s viper venom). In other cases, a consumptive coagulopathy and DIC-like state can result. Antivenom per se does not correct coagulopathy. After circulating venom has been neutralized, it may be 4 to 6 hours or longer before the hepatic production of intrinsic plasma clotting factors can normalize coagulation tests.

Whether to give or withhold coagulation factors—for example, in the form of fresh frozen plasma (FFP)—is a controversial question. While it does hasten the restoration of coagulation after antivenom in the treatment of Australian snake envenomation, the administration of FFP may exacerbate the effects of coagulopathy in the continued presence of venom. A lack of improvement in a victim’s clotting times on retesting may represent either insufficient antivenom or insufficient time for hepatic regeneration of clotting factors, while improvement in coagulation may represent the efficacy of antivenom or natural hepatic regeneration of clotting factors. While it is reasonable to withhold FFP unless coagulation restores itself within approximately 6 hours after antivenom administration, active bleeding or the risk for this according to coagulation studies, despite adequate quantities of antivenom, is an indication for factor replacement. Whole blood transfusion is reserved for significant anemia and hypovolemia. In North America, extrapolation from other hematologic conditions suggests that coagulopathy with parameters exceeding critical thresholds (international normalized ratio [INR] > 3, activated partial thromboplastin time [aPTT] > 50 seconds, platelets < 50,000/mm³, and fibrinogen < 75 mg/dL) is associated with a major bleeding risk of 1% over a few days and thus warrants coagulation factor replacement.

Neurotoxicity

Descending paralysis, starting with ptosis and external ophthalmoplegia and progressing to respiratory failure, are typical neurotoxic signs of envenomation. In severe cases resulting in respiratory failure, supplemental oxygen and endotracheal intubation with mechanical ventilation are indicated. If antivenom is delayed or if inadequate doses are given, recovery may take days or weeks.

Rhabdomyolysis and Renal Failure

Many factors, including circulatory shock, which can be, a direct toxic effect of venom, rhabdomyolysis, and coagulopathy, may contribute to the development of renal failure. Hyperkalemia secondary to rhabdomyolysis may be treated with calcium, insulin and glucose, salbutamol (albuterol), or ion-exchange resins. Hemodialysis may occasionally be required, particularly if there has been a delay in treatment with antivenom. In some cases, long-term renal morbidity may occur.

Shock and Cardiotoxicity

The etiology of shock may vary with the snake species and includes fluid sequestration into necrotic tissue, altered vascular permeability, autopharmacological phenomena, acute reactions to venom or antivenom, and cardiotoxicity that is either direct or secondary to hypoxemia or hypotension. The procoagulant state may be associated with myocardial ischemia and pulmonary hypertension. Acute systemic hypotension associated with procoagulopathy after Australian brown snakebite may be lethal.

Other Considerations

Spitting cobras of Asia and Africa and the South African rinkhals spray venom from their fangs into a victim’s eyes, potentially causing blindness (venom ophthalmia) with painful chemical conjunctivitis, corneal ulceration, anterior uveitis, and possible secondary infection. The eyes should be irrigated immediately with generous volumes of water followed by other treatment, such as cycloplegics, topical antibiotics, and analgesia.

All victims should receive appropriate tetanus prophylaxis, but antibiotic prophylaxis is only routinely warranted if the bite wound is contaminated. Other treatments include analgesia (though it is advisable to avoid sedating agents such as morphine, if possible), and early intervention with mobilization, splinting, and occupational and physical therapy are recommended to prevent secondary complications associated with immobility.

Antivenom

Presently, antivenom is the only specific clinical treatment for venomous snakebite. However, it does not immediately reverse the effects of venom and may not neutralize all effects, particularly if administration is delayed. Antivenoms are immunoglobulins or their fragments derived from plasma of animals immunized with venom. The choice of antivenom is determined by the genus or species of snake or by geographic location if unknown.

Indications

Antivenom should not be given for a positive result from a venom detection kit or for only the presence of bite marks, unless there are signs of systemic envenomation (neurological signs, abdominal symptoms, abnormal bleeding, coagulopathy, rhabdomyolysis, hematuria, or myoglobinuria) or progressive limb swelling and/or necrosis. If pressure-immobilization first aid is in place, the symptoms or signs of envenomation, including laboratory signs, may only become rapidly apparent when this is removed.

Choice of Antivenom

The correct choice is crucial. Antivenoms only neutralize the venoms used in their production. Generally, they provide little or no neutralization of other snake venoms. The correct antivenom should be based on unequivocal morphological identification of the snake, use of an SVDK (only available for Australia and Papua New Guinea), or on geographical location, combined with a specific clinical syndrome.

Identification of the snake aids with the selection of the appropriate antivenom and forewarns clinicians of expected effects. Formal identification by a highly experienced professional herpetologist is ideal. Sometimes, the snake is not seen, or is only glimpsed in retreat, rendering identification impossible or unreliable. In addition, especially concerning young children, a history may be vague or lacking. In all these circumstances, a contingency plan for choice of antivenom should be based on knowledge of local species. Bites by exotic snakes (ie, snakes from other countries or regions kept in zoos or private collections) are very problematic and hospitals should have contingency plans to urgently obtain an appropriate antivenom from local poison information centers.

The SVDK is a rapid 2-step enzyme immunoassay that uses antibodies to the venoms of major Australian snake genera. Venom from a bite-site swab or a blood or urine sample reacts with specific antibodies in different reaction wells, resulting in a rapid color change that indicates the snake group involved and thus helps to select the antivenom required. Bite-site swabs are the most reliable samples for use in an SVDK, provided the bite site has not been washed. Blood and urine samples are less reliable, although urine may be useful when presentation is delayed, or if the bite site cannot be identified. Although a positive SVDK test of blood or urine confirms that envenomation has occurred, it is not per se an indication to give antivenom. The information should be used in conjunction with clinical presentation, knowledge of snakes in the geographic area, and identification of snakes to determine whether to use an antivenom and, if so, which to use.

If a reliable identification of the snake cannot be made, then polyvalent antivenom or a selection of monovalent antivenoms that cover likely local species should be used. For example, in Australia, a combination of brown and tiger snake antivenoms is satisfactory for all snake envenomation in the state of Victoria, whereas tiger snake antivenom alone is satisfactory for the state of Tasmania. Elsewhere, polyvalent antivenom containing tiger, brown, black, death adder, and taipan antivenoms is required.

Administration of Antivenom

Snake antivenoms are given intravenously and should be administered with the guidance of experts. Antivenoms should be diluted in at least 100 mL of normal saline, 5% dextrose, or Hartmann (Ringer lactate) solution. The administration and dosing of antivenoms may vary according to the severity of the envenomation rather than the size of the patient, and should be guided by regional poison experts. Initial administration should be slow, while the patient is observed for signs of allergic reaction. If no reaction is observed, the infusion may be run over 15 to 30 minutes. Acute (within minutes or hours) and delayed (days to weeks) hypersensitivity can occur with antivenom administration. If the patient reacts to the antivenom, the rate may be slowed or the infusion ceased temporarily. If the reaction is severe, treatment with epinephrine, antihistamines, corticosteroids, or plasma volume expanders should be undertaken, as required. The decision to recommence antivenom should be based on the clinical state of the patient. A prior allergy to antivenom is not an absolute contraindication to subsequent administration. In the case of the patient with a known allergy to antivenom or to horse serum, the decision to withhold antivenom should be based on the severity of envenomation and availability of resuscitation facilities and skills.

Premedication for Antivenom

Premedication to reduce adverse reactions to antivenom is recommended. Premedication with subcutaneous (not intravenous or intramuscular) epinephrine is particularly recommended for polyvalent antivenom in a low-resource setting and for higher risk patients, such as those with equine allergy and asthma. Antihistamines are not recommended due to the ineffectiveness of promethazine in a randomized placebo-controlled trial in Brazil. Additionally, antihistamines may confound the effects of venom through their sedative and hypotensive actions.

Serum Sickness

Serum sickness, due to the deposition of immune complexes, is a recognized complication of the administration of foreign protein solutions such as antivenoms. Symptoms include fever, rash, arthralgia, lymphadenopathy, and a flu-like illness. It usually occurs 7 to 10 days after antivenom administration. The possibility of serum sickness, and the usual symptoms and signs, should be discussed with a patient prior to discharge, so that it may be recognized and treated early. It is common after administration of Australian snake antivenoms, irrespective of volumes or type of antivenom. Accordingly, prophylactic corticosteroids should be considered in all cases (eg, prednisolone 1–2 mg/kg daily for 5 days) and especially if the patient has a past history of exposure to equine protein.

Anticholinesterase Treatment

Anticholinesterase inhibitors such as neostigmine may assist in the emergency management of predominantly postjunctional neurotoxic envenomations, such as by the Philippine cobra and Papuan death adder, due to the curare-like actions of their neurotoxins.

SCORPION STINGS

Of approximately 1900 known species of scorpions, about 30 cause serious and life-threatening illness. Scorpion stings are the second most frequent cause of envenomation deaths, with about 3250 deaths annually from more than 1.2 million stings (0.27%). Scorpions are nocturnally active creatures in warm or hot dry climates within 45° latitudes of the equator.

VENOM

Scorpion venom is a complex mixture of mucopolysaccharides, hyaluronidase, serotonin, histamine, protease inhibitors, histamine releasers, and protein neurotoxins. In addition, the venom of some species contains potassium channel inhibitors, ryanodine-type calcium channel modulators, and inhibitors of the inactivation of voltage-gated sodium channels, resulting in a massive release of transmitters at sympathetic, parasympathetic, and neuromuscular receptors.

ENVENOMATION

Distinctive syndromes of severe envenomation are caused by members of a scorpion genera in 7 principal world regions: Mexico, southern American states (Texas, Arizona, New Mexico), South America (Brazil, Venezuela, Colombia, Argentina), India, Near and Middle East, north-Saharan Africa, Sahelian Africa, and South Africa (Table 117-3).

The principal life-threatening effects are cardiovascular and neurotoxic in most species; some species may also cause coagulopathy that is usually mild, and in some (eg, Centruroides sculpturatus), the effects are essentially confined to neurotoxicity. A systemic inflammatory response with cytokine release, kinin release, and complement activation may lead to multiorgan failure. Mortality is variable; for example, it has been reported in 8.9% of 685 child victims in Tunisia, 1.3% of 1212 child victims in Morocco, and 12.5% of 41 child victims in Egypt. Envenomation by Australian and European species are limited to local pain and mild systemic effects.

Neurotoxicity

Although pain is the universal feature of envenomation, usually requiring systemic or topical analgesia (lidocaine), a wide variety of other neurological symptoms and signs constitutes species-specific syndromes. Generally, envenomation may cause coma, convulsions, cerebral edema, external ophthalmoplegia, mydriasis, meiosis, agitation, rigidity, tremor, twitching, tongue and muscle fasciculation, respiratory failure, gastric and pancreatic hypersecretion, bradycardia, tachycardia, salivation, sweating, abdominal pain, vomiting, and priapism. Some species cause lethal cardiovascular failure. Rhabdomyolysis and renal toxicity are infrequent.

Cardiotoxicity

Acute biventricular failure occurs in 2 clinical phases due to combined catecholamine stress-induced, sudden (takotsubo-like) cardiomyopathy and direct cardiotoxicity. An early vascular phase is caused by profound vasoconstriction with increased ventricular afterload, impeded ventricular emptying, and increased ventricular filling pressures. Systemic hypertension and pulmonary edema are evident. A subsequent myocardial phase ensues due to coronary artery spasm or increase in coronary resistance, with consequent low cardiac output and systemic hypotension. Cardiac creatine kinase (CK-MB) enzymes and troponin levels are raised.

TREATMENT

Antivenom Therapy

The efficacy of scorpion antivenoms is variable and is related in part to the species of scorpion. Although antivenom reduces the levels of free circulating venom antigen, the clinical relevance of this is questionable. Moreover, the incidence of reactions to a specific antivenom may be significant, and therefore, its administration must be weighed against the degree of envenomation, local knowledge of species, and their effects and duration since envenomation.

Supportive Therapy

Supportive cardiovascular therapy is necessary in severe envenomation. Intensive monitoring and titration of vasoactive agents, along with judicious mechanical ventilation, are required. In early envenomation, catecholamine release causes hypertension, but this later culminates in cardiac failure and hypotension. A titratable vasodilator is desirable at least in the hypertensive phase of the syndrome and possibly later, in conjunction with an inotropic agent. When peripheral circulatory failure and pulmonary edema are present, mechanical ventilation and infusion of dobutamine markedly improve cardiac output, systemic arterial pressure, and right ventricular ejection fraction, while decreasing pulmonary artery occlusion pressure. Extracorporeal support of cardiac output may be necessary. Hydrocortisone does not improve outcome.

SPIDER BITE

Thousands of species of spiders exist in nearly all global environments. Consequently, spider bites are 1 of the most common problems in toxinology. Fortunately, in most cases, only transient local or radiating pain, bite-site redness, swelling, and itchiness occur. Since virtually nothing is known about the venom of the majority of spiders, the most appropriate approach to medical management is symptomatic. Few antivenoms exist. The most dangerous spiders include funnel-web spiders (Atrax or Hadronyche species), comb-footed spiders (Latrodectus species), Phoneutria, and the necrotizing species, the most important of which are the recluse or violin spiders (Loxosceles species). These require specific treatment.

FUNNEL-WEB SPIDER

More than 30 species of highly dangerous funnel-web spiders inhabit the eastern seaboard of Australia. Funnel-web spiders can cause death within 2 hours. Fortunately, severe envenomation is uncommon and no fatalities have occurred since the introduction of an antivenom in 1980. Identification of funnel-webs may be difficult because some resemble less dangerous trapdoor spiders. Any dark-colored or brown spider with a body length of 2 to 3 cm on the eastern seaboard of Australia should be regarded as a funnel-web. Capture and formal identification of the spider is helpful.

VENOM

While the venoms have many components, the key polypeptide neurotoxins of around 42 amino acids are the γ-atracotoxins (γ-ACTXs), which act by slowing sodium current inactivation. These toxins cause spontaneous repetitive generation of action potentials, triggering the release of excessive catecholamines and eventual exhaustion of predominantly sympathetic neurotransmitters and leading to a characteristic biphasic clinical syndrome. Acetylcholine is also released at neuromuscular junctions and in the autonomic nervous system.

ENVENOMATION

Local Effects

Funnel-web spider bites are painful—lasting for days to weeks because of direct trauma and acidity—and accompanied by local swelling and erythema. Although most bites by funnel-web spiders are confined to local effects, a severe systemic syndrome may ensue.

Systemic Effects

The cardiovascular effects are due to catecholamine excess and direct cardiac toxicity. The latter may not be reversed with antivenom. The syndrome of envenomation occurs in 2 phases:

• Phase 1 is characterized by perioral numbness; nausea and vomiting; gastric dilation; sweating, salivation, and lacrimation; and dyspnea, hypertension, and local and generalized muscle fasciculation or spasm.

• Phase 2 is characterized by hypotension, hypoventilation and apnoea, acute pulmonary edema, coma, and eventually irreversible cardiac arrest.

TREATMENT

Treatment should include appropriate respiratory and circulatory support, as well prompt application of a pressure-immobilization bandage to the affected limb, as for neurotoxic elapid snakebite. The bandage should only be removed when appropriate resuscitation can be given and antivenom is available. If available, antivenom should be given. If antivenom is not available, the pressure-immobilization bandage should be kept in place, because venom may be inactivated at the bite site. Specific additional therapies include atropine for excessive salivation and bronchorrhea, as well as muscle relaxants for muscle fasciculation and spasm. Asymptomatic patients may be discharged 4 hours after a bite or removal of first aid. Antitetanus status should be updated. Follow-up is needed for potential secondary infection.

COMB-FOOTED (WIDOW) SPIDERS

Comb-footed spiders of the family Theridiidae exist worldwide. The Latrodectus genus, including the widow, button, koppie, and redback spiders, are the most important causes of spider bites, but mortality is rare. Antivenoms are available. In Australia, more redback spider (L hasselti) antivenom is used than any other antivenom.

VENOM

The exact mechanism(s) by which the toxins of Lactrodectus spiders exert their clinical effects are poorly understood, as is the precise cause of rare fatalities. The key toxin, α-latrotoxin, forms calcium-permeable pores in presynaptic membranes and stimulates the release of catecholamines from sympathetic nerves and acetycholine from motor nerve endings.

ENVENOMATION

Bites by Lactrodectus spiders produce a recognizable syndrome called latrodectism that may necessitate antivenom. The untreated syndrome may persist for weeks or months. The bite is usually, although not always, painful. Visible puncture marks and local swelling are uncommon. The onset of symptoms and signs is highly variable, but progression is generally slow. Effects may persist for weeks or even months after an untreated bite. Signs and symptoms include local pain, swelling and lymphadenopathy, and local or generalized sweating. Systemic features include rash, fever, myalgia, neck spasm, migratory arthralgia, hypertension, tachycardia, nausea and vomiting, abdominal pain, headache, lethargy, and insomnia. Rare but lethal complications include myocarditis, rhabdomyolysis, and paralysis.

TREATMENT

Indications for antivenom include pain unrelieved by simple analgesia (eg, local application of ice or oral analgesics) and/or systemic symptoms or signs of envenomation such as vomiting, severe headache, abdominal pain and collapse, hypertension, arthralgia, or myalgia. When the clinical findings are atypical but the history is suggestive, a trial of antivenom may be helpful both diagnostically and therapeutically. Typically, antivenom is effective within the first 2 hours, but symptoms can reappear necessitating a further dose. Unlike most other antivenoms, the administration of widow or redback spider antivenom may be effective even several weeks after a bite. In general, premedication for acute hypersensitivity or steroids for delayed hypersensitivity are not recommended unless there is a history of horse allergy or prior exposure to equine immunoglobulin, which may predispose to acute or delayed allergic reactions.

BEE, WASP, AND ANT (HYMENOPTERA) STINGS

Most stings by Hymenoptera (bees, wasps, and ants) are mild and self-limiting. However, a life-threatening immediate hypersensitivity reaction (anaphylaxis) may occur for which the same treatment protocol should be adopted regardless of the responsible creature. In Australia, annual deaths from anaphylactic reactions to insect stings are approximately 0.1 per million population, approximately equal to snakebite deaths. By contrast, in the United States, annual deaths from Hymenoptera stings are 0.26 per million, which is 7 to 8 times more frequent than snakebite deaths.

The location of a single sting may cause a significant problem. For example, a pharyngeal sting may obstruct the airway, while a corneal sting may threaten vision. Multiple stings may also cause massive envenomation.

BEE STINGS

Within the superfamily Apoidea, subfamilies include the social bumble bees (Bombinae) and honey bees (Apinae). The common honeybee (Apis mellifera ligustica) is well established throughout the world and is an important cause of Hymenopteran stings. It does not tend to attack in a swarm, unlike the aggressive Africanized honey bee (Apis mellifera scutellata) that is responsible for mass envenomations in the Americas. Cases of massive bee envenomation (venom toxicity) are rare outside of those areas where the Africanized strain is endemic. While the majority of bee stings are trivial, rapid death may follow either mass stings or from anaphylactic reactions in hypersensitive individuals (even after a single sting). Most bee sting–related deaths occur in outdoor workers, especially farmers, truck drivers, and beekeepers (and their families, including children).

WASP STINGS

The majority of social wasps belong to 1 of the 2 subfamilies of Vespidae: Vespinae and Polistinae. The subfamily Vespinae includes 4 genera: Dolichovespula (yellow jackets), Vespula (common social wasps), Vespa (hornets, large potentially very dangerous wasps that inject more toxic venom, in larger quantities, than bees and smaller wasps), and Provespa. The subfamily Polistinae includes some species of the paper wasps of the genus Polistes. Vespinae are found in Eurasia, North America, and North Africa. The United States has 17 native species of yellow jackets, the exotic European hornet (Vespa crabro), and the European wasp (Vespula germanica). Vespula yellow jackets have spread and become well established in non-native regions such as Australia, New Zealand, South America, and South Africa. In northern Australia, serious wasp stings are generally due to native paper wasps. In Asia, deaths frequently occur in children and young adults from stings of Oriental and tropical Vespa wasps. Like bees, wasps are colony insects that construct large nests, often among the lower tree branches where they can be accidentally disturbed, provoking an aggressive swarm attack.

ANT STINGS

Ants (family Formicidae) are widespread, with approximately 8800 species worldwide. Relatively few species are medically important and these can be divided into 2 major groups, distinguished by the development of a venom injection apparatus. The first group gives an irritating bite, which is then sprayed with secretions from their abdominal glands. The second group causes painful true stings, injecting allergenic venom. These are typified by the jumper ants (Myrmecia species) in Australia and the fire ants (Solenopsis species) in the Americas. Other groups also cause occasional allergic reactions.

The red fire ant, S invicta, is of particular clinical significance. It forms super-colonies and is an aggressive, territorial species that swarms onto an intruder. Stings are multiple, usually in the tens or hundreds. Approximately one-quarter of patients stung will develop some degree of allergy. Numerous fatalities, but rarely among children, have occurred in the United States, where fire ants have become widespread since their introduction in the 1930s. They also now are established in Australia. Fire ant venom contains alkaloids known as piperidines, which produce a very painful burning sensation and cause a characteristic urticarious pustule at the sting site. Jumper ants inject enzymes, pharmacologically active substances, and allergenic proteins.

VENOMS

A typical wasp sting contains 2 to 20 μg of venom, which consists of active amines (serotonin, histamine, tyramine, catecholamines); histamine-releasing peptides or mastoparans; wasp kinins, which are pain-inducing molecules; and antigen 5 (the most active allergen). In addition, venoms contain several enzymes, including phospholipases, hyaluronidases, and cholinesterases that also contribute to the allergic response. The venom of some wasp species contain neurotoxins and acetylcholine. The potency of the venom varies greatly among species. Hornets have potent venom that can deliver lethal doses in as few as 50 to 200 stings. Social wasps have less potent venom and deliver smaller quantities.

In contrast, a single bee sting typically contains about 50 μg of venom consisting of enzymes, small proteins, and peptides and amines. Melittin, which hydrolyzes cell membranes, changing cell permeability and inducing pain, is the primary component of bee venom, making up 50% of the venom. Phospholipase A₂, a major allergen that also causes pain and hemolysis, is another component of bee venom. Additional components are hyaluronidase (a “spreading factor” that allows venom components to permeate tissue), amines (histamine, dopamine, norepinephrine), and peptide 401 (a mast cell degranulating peptide that triggers the inflammatory cascade). An estimated 500 to 1500 bee stings would deliver a lethal dose. Africanized honeybees deliver slightly less (but equally toxic) venom than European honeybees. Deaths due to venom toxicity have occurred within 4 hours but may be delayed until 7 to 9 days after stinging.

ENVENOMATION BY BEE, WASP, AND ANT STINGS

Simple bee, wasp, and ant stings in nonallergic individuals produce immediate burning pain, redness, and swelling at the sting site. Pain usually subsides over some hours, while redness and swelling resolve more slowly. With multiple stings, the effects are dramatically amplified, and systemic effects include headache, vomiting, thirst, pain, edema, discolored urine (hematuria and/or myoglobinuria), jaundice, and confusion. Rhabdomyolysis, intravascular hemolysis, coagulopathy, thrombocytopenia, metabolic disturbances, encephalopathy, liver dysfunction, and myocardial damage have also been reported. The inflammatory response may precipitate an acute coronary syndrome. Deaths from venom toxicity have been recorded in many countries, generally when there are more than 200, and usually approximately 500, bee stings but may also occur after as few as 25 to 30 wasp or hornet stings. Hospitalization is mandatory for victims receiving more than 10 stings. It is important to remember that children are at greater risk of toxicity due to the higher dose of venom per unit of body mass.

Systemic Allergy

Children with hypersensitivity to bee, wasp, or ant stings may develop rapid catastrophic anaphylaxis, causing death within minutes. Severe systemic reactions are less common in children than adults but the risk of recurrence persists for decades.

Large Local Reactions

In some patients, venom allergy may cause large local reactions. These may involve the swelling of the whole limb within 24 hours.

TREATMENT FOR BEE, WASP, AND ANT STINGS

Simple Stings

The stinger should be removed as soon as possible (by any effective method) to limit the amount of venom injected. The majority of single bee stings do not require treatment, although cold packs and oral analgesia are valuable. Wasps and ants do not leave their stinger behind; therefore, each individual insect may sting multiple times.

Large Local Reactions

Large local reactions usually respond well to symptomatic treatment with nonsteroidal anti-inflammatory agents and topical steroid creams. Oral steroids and antihistamines are often used.

Anaphylaxis

Treatment is based on administration of epinephrine (adrenaline) as definitive therapy supported by oxygen, β-agonists for bronchoconstriction, steroids, and intravenous fluid for hypotension. Individuals at risk of anaphylaxis from insect stings must carry and be taught to use autoinjectable intramuscular epinephrine available in numerous proprietary preparations. Most mortalities occur in victims with a known insect sting allergy. Patients with a history of anaphylaxis to bee or wasp venom and a positive skin test should also have maintenance immunotherapy (injection of small quantities of pure bee or wasp venom) for at least 3 to 5 years.

Multiple Stings

Patients with serious systemic effects may require resuscitation with circulatory support. In particular, renal function should be closely monitored, and in some cases, hemofiltration or long-term hemodialysis is necessary. As for other etiologies, tetanus status should be checked. In cases of multiple wasp stings, septicemia should be anticipated and antibiotic prophylaxis considered.

JELLYFISH STINGS

All 4 classes of the phylum Cnidaria (Hydrozoa, Scyphozoa, Cubozoa, Anthozoa) have nematocysts (stinging cells) and cause human envenomation. Three of the classes are described as jellyfish because of their gelatinous free-floating medusal life-cycle stage. Of these, Scyphozoa are true jellyfish, Cubozoa are box jellyfish, and Hydrozoa are hydroids. Large chirodropid (multi-tentacled) cubozoan jellyfish have killed or seriously injured numerous victims, while small carybdeid (single-tentacled) cubozoan jellyfish and some species of hydroids have caused occasional deaths.

CHIRODROPIDS

These large jellyfish have a box-shaped white or translucent bell, 20 cm by 30 cm weighing more than 6 kg, from whose 4 corners arise bundles of up to 15 translucent, extensile tentacles. The most prominent, or notorious, is Chironex fleckeri (Australian box jellyfish), which inhabits the waters of northern Australia and the Indo-Pacific region, including Vietnam, the Philippines, Malaysia, Thailand, and likely Indonesia. It has caused approximately 80 deaths in Australia.

The tentacles of mature specimens stretch 3 meters. The wide, ribbon-like tentacles are covered with millions of nematocysts, which discharge toxins via a penetrating everting thread or tube upon contact, much like a spring-loaded syringe. The threads have denticles that enable them to drill 1 mm into the dermis of human skin. As the tube everts and penetrates the skin, it releases venom directly into any transfixed capillaries, thus ensuring rapid toxicity.

VENOM

Toxic components of C fleckeri venom include hemolysins (causing hyperkalemia), dermatonecrotic factors, and protein components with probable direct cardiotoxicty as the result of membrane pore formation (porination).

ENVENOMATION

C fleckeri are rarely noticed by a victim before contact with tentacles, usually while wading or swimming in shallow water. The tentacles are easily torn from the jellyfish by the encounter and, in adhering to the victim’s skin, resemble earthworms of a pink, gray, or bluish hue. During the first 15 minutes, pain increases in mounting waves, despite removal of the tentacles. The victim may scream and become irrational. The lesions are distinctive and resemble marks made by a whip 8 to 10 mm wide, on which is a frosted ladder pattern that matches the bands of nematocysts on the tentacles. Whealing is prompt and massive. Edema, erythema, and vesiculation soon follow, and when these subside (after approximately 10 days), patches of full-thickness necrosis leave permanent scars. The severity of injury is related to size of the jellyfish and the extent of tentacle contact. Most stings are quite minor. The mechanism of death in humans is not known with certainty but case reports suggest a consequence of combined cardiovascular and respiratory failure.

ANTIVENOM

C fleckeri antivenom is the only jellyfish antivenom manufactured worldwide. It is concentrated immunoglobulin derived from the serum of sheep injected with C fleckeri venom. Each vial contains sufficient activity to neutralize 20,000 intravenous LD₅₀ mouse doses. Antivenom is used in about 10% of envenomations.

TREATMENT OF ENVENOMATION

The severity and rapidity of envenomation necessitate decisive action:

• Immediate first aid involves retrieval of victim from the water to avoid further contact with the creature(s) and to prevent drowning, basic life support, and inactivation of undischarged nematocysts by pouring vinegar (4–6% acetic acid) over adhering tentacles to prevent further envenomation. (Alcohol in any form, which discharges nematocysts, must not be used this purpose.)

• Advanced cardiopulmonary resuscitation should be performed on the beach, during transportation, and at the hospital, where extracorporeal life support and treatment for hyperkalemia may be required.

• Administer antivenom (3 vials of 17% ovine whole Ig).

Indications for Antivenom

Antivenom should be administered as soon as possible in the following circumstances:

• unconsciousness, cardiorespiratory arrest, hypotension, dysrhythmia, hypoventilation, difficulty swallowing, or speaking;

• severe pain (parenteral analgesia is also usually required), and

• possibility of significant skin scarring.

The initial dose is 3 vials infused intravenously, diluted 1 in 10 with a crystalloid solution.

LABORATORY DIAGNOSIS

The simplest and quickest way to confirm C fleckeri envenomation is to identify characteristic nematocysts on microscopic examination of a piece of ordinary transparent sticky tape approximately 4 to 8 cm long that has been applied to the sting site. The tape is applied to a lesion, stroked several times, removed, and with its sticky side up, affixed onto a glass slide. Microscopic examination of skin scrapings is an alternative. Nematocysts of C fleckeri and Chiropsella bronzie are difficult to distinguish.

PREVENTION

Swimming and wading should be restricted to the safe months of the year and to beaches enclosed by jellyfish-resistant nets (“stinger enclosures”). Protective “stinger suits” offer additional protection for swimmers.

CARYBDEIDS

Carybdeids are also box jellyfish: The bell is cubic but small, and from each of the 4 corners arises an arm (pedalium), usually bearing only a single tentacle. About 25 species exist in tropical Australian, Indo-Pacific, and Caribbean waters.

IRUKANDJI SYNDROME

Numerous small Carybdeid jellyfish cause a distinct syndrome that was initially observed in northern Australian waters but is now recognized worldwide. The syndrome was initially attributed to the sting of a near invisible jellyfish called Carukia barnesi. Its squarish bell is barely 12 mm wide with 4 tentacles up to 35 cm. Irukandji syndrome, attributed to other carybdeids, has been reported from many other regions including the Pacific Islands, Papua New Guinea, Hawaii, Fiji, Japan, China, Qatar, Thailand, Malaysia, and the Caribbean.

VENOM AND ENVENOMATION CAUSING IRUKANDJI SYNDROME

C barnesi venom contains a potent neuronal sodium channel modulator that releases high levels of catecholamines, causing tachycardia, increased cardiac output, and systemic and pulmonary hypertension. This hyperadrenergic state may explain some clinical features of Irukandji syndrome. The victim rarely sees the offending jellyfish but is often aware of a slight sting to the upper body. Although the sting may be unnoticed, the onset of symptoms forces the victim to leave the water. The sting is merely an oval area of barely perceptible erythema measuring about 5 cm by 7 cm. Irregularly spaced papules (“goose pimples”) up to 2 mm in diameter develop within 20 minutes and then fade but erythema may last several days.

From 5 minutes to 2 hours after the sting, but usually after about 30 minutes, a distinctive severe syndrome develops. Severe low back pain, cramping muscle pains, nausea, vomiting, profuse sweating, headache, restlessness, and agitation almost invariably occur, sometimes with hypertension. Abdominal pain is associated with spasm of the muscles of the abdominal wall, and cramps occur in limb muscles. Occasionally, cerebral edema causes loss of consciousness and acute cardiac failure occurs and manifests as pulmonary edema, poor contractility, low cardiac output, and raised cardiac enzymes. The onset of pulmonary edema is delayed, occurring after several to many hours. The mechanism of cardiac failure is probably secondary to hypertension and direct myocardial depression. Although hypertension may have been brief, it may cause an acute “stress” cardiomyopathy (Takotsubo cardiomyopathy) secondary to catecholamine release. Additionally, toxins may cause membrane poration with disruption of membrane function and accompanying rises in serum troponin levels.

Most stings do not cause serious illness but 2 fatalities have been attributed to unseen jellyfish causing Irukandji syndrome in northern Australia. In both, intracerebral hemorrhage was associated with severe hypertension.

TREATMENT

Pain relief is important. Repeated doses of intravenous or intramuscular opiates may be required, with care not to cause hypotension. Among victims of Irukandji syndrome, intravenous magnesium salts provide pain relief and a reduction in blood pressure. Otherwise, treatment is oxygen, diuretics, vasodilators, inotropic support, and mechanical respiratory support. Antihypertensive therapy may be required initially. Although infusions of phentolamine have been used successively, a more titratable nitrate infusion would be preferable.

OTHER JELLYFISH

Carybdea rastoni is a small jellyfish often found in swarms, with a very wide distribution in the western Pacific Ocean and most Australian and Japanese waters. The bell is approximately 2 to 3 cm in diameter and its tentacles trail 30 cm. Its purified protein toxins cause vasoconstriction (perhaps by release of catecholamines), release of prostaglandins, and contraction of smooth muscle. Tentacles bear ovoid nematocysts. Stings cause immediate pain with 4 linear lesions 10 to 20 cm in length and may blister. No specific management exists.

Alatina alata, or the Hawaiian box jellyfish, has a bell approximately 8 cm high and 5 cm wide and tentacles about 0.5 m long. Stinging causes moderate pain and may cause Irukandji syndrome. Immersion of the sting in hot water is analgesic. The venom causes poration of red cells and release of potassium with cardiovascular collapse.

Physalia physalis and Physalia utriculus (Portuguese Man-of-War, Blue Bottle) are found in all hot and temperate waters. They are easily identifiable jellyfish and are the most frequent cause of significantly painful jellyfish stings. Most stings are minor, and immersion of a stung limb in hot water provides pain relief. The main lethal toxin, physalitoxin, is a glycoprotein that causes cardiorespiratory collapse, and no antivenom exists. Three deaths have been attributed to the Atlantic P physalis on the southeast coast of the United States but no fatalities have been attributed to the Pacific P utriculus in Australia. In the few deaths that have been reported worldwide, victims were in cardiac arrest within minutes of contact with the tentacles.

FISH STINGS

Numerous fish have dorsal or pectoral spines that may inflict a traumatic wound made worse by deposition of venom.

STONEFISH

Species of the stonefish genus Synanceia are found throughout the whole Indo-Pacific region, including the north of Australia. Stonefish may easily be mistaken for a piece of rock or dead coral encrusted with marine growth. The venom apparatus is purely defensive, and plays no role in the capture of prey. Stonefish have 13 dorsal spines, each of which carries 2 basal venom glands. When disturbed, the spines become erect. When trodden upon, venom is forced out the tips of the spines into the victim’s foot.

VENOM

Venoms of all 3 species (S verrucosa, S horrida, and S trachynis) depress the cardiovascular and neuromuscular systems and have a direct effect on muscle. Less dangerous effects are hemolysis, an increase in vascular permeability, and effects due to a host of enzymes, including hyaluronidase. Experimentally, venom injected intravenously causes hypotension, respiratory distress and paralysis by direct myotoxicity. Various protein toxins have been isolated and been determined to be cytotoxins, to release acetylcholine and other transmitters, to cause myolysis, and to cause cardiovascular collapse by negative inotropic actions and vasodilation.

ENVENOMATION

Stings are extremely painful, which causes the victim to become irrational. The severity of the signs and symptoms is usually in direct proportion to the depth of penetration of the spine(s) and the number of spines involved. As well as local swelling and pain, muscle weakness and paralysis may develop in the affected limb, and shock may occur. Fatalities have occurred in Indo-Pacific regions, and a single death has been reported in Australia.

ANTIVENOM

Stonefish antivenom, an equine Fab′₂ preparation, neutralizes the venoms of S trachynis, S verrucosa, and S horrida. Vials contain approximately 2 mL, which will neutralize 20 mg of venom in vitro.

TREATMENT

The initial priority is pain relief. Relief in minor cases may be achieved by bathing or immersing the sting with warm to hot water. In severe cases, pain relief may only be obtained by the combined use of antivenom and opiate drugs. A local anaesthetic may be injected into the track of the sting and the surrounding area, but regional nerve block should be considered.

Antivenom, usually given intramuscularly (not in the region of the sting), is recommended for all cases, except those involving only a single puncture wound with only moderate discomfort. The initial dose of antivenom is determined by the number of spines and depth of penetration. One vial (2000 units of antivenom in 2 mL) is sufficient for every 1 to 2 spine punctures. In very severe cases, 3 or more vials may be required and the use of the intravenous route should be considered, particularly if the pain is widespread or the patient is in circulatory shock. Stonefish stings require fastidious wound toilet, regional analgesia, and appropriate antibiotics. Delayed presentation and suboptimal care may be associated with poor wound healing and problematic infection.

The injured limb should be comfortably immobilized. Administration of an antibiotic (eg, trimethoprim-sulfamethoxazole, third-generation cephalosporins, imipenem) that is active against pathogens found in salt or brackish water (Vibrio spp, Aeromonas spp, Plesiomonas spp) is recommended. Tetanus prophylaxis should be updated. Severe injuries may require early surgical debridement of dead tissue and drainage. Skin grafting may be necessary when antivenom has been delayed and when considerable ulceration exists. Sometimes a sting remains painful for months, or recurrent inflammation or discharge occurs. This is usually due to an embedded spine fragment, which is semitransparent and may be deeply embedded, and therefore, may be undetectable except by ultrasound examination and subsequent surgical exploration.

OTHER STINGING FISH

Numerous other fish with stinging spines of the families Scorpaenidae (scorpionfish), Synanceiidae, and Trachinidae exist in the world’s oceans and fresh waters. The mechanical penetration or laceration by their spines is painful and many also envenomate. Examples are the butterfly cod or lionfish (Pterois volitans), waspfish (Apistops caloundra), scorpion cod (Scorpaena cardinalis), South Australian cobbler (Gymnapistes marmoratus), fortescue (Centropogon australis), bullrout (Notesthes robusta), gurnard perch (Neosebastes pandus), goblinfish (Glyptauchen panduratus), ghoul (Inimicus caledonicus), and numerous catfish, weeverfish, rabbitfish, and spinefeet (Siganus lineatus and S spinus). Many envenomations occur among amateur collectors of Pterois volitans.

TREATMENT

Little is known about the nature of the venoms associated with the dorsal spines of the many stinging fish. There are no specific antivenoms for these, except for the possibility of using stonefish antivenom for lionfish and other closely related Scorpaenidae based on analogous venom pharmacology. Otherwise, the management of a wound is the same as for stonefish.

STINGRAYS

Stingrays have barbed tails that may inflict serious leg, abdominal, or chest wounds. Direct damage by penetration of the stinging barb is usually of greater importance than the introduction of the venom or a marine pathogen. A swimmer cruising the ocean floor is at risk of a serious chest wound when disturbing settled rays, as is the occupant of an open small boat when a ray leaps from the water surface.

Significant wounds require exploratory surgery because the wound track may contain a trail of glandular and integumentary sheath material as well as necrotic tissue. Penetrating wounds to the chest or abdomen, even when apparently minor, should be imaged or explored, because of likely damage to internal organs. Tetanus prophylaxis should be updated. The introduction of marine bacterial infection is possible after penetrating injury.

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INTRODUCTION

Acute upper airway obstruction is a common pediatric problem caused by a variety of disorders (Table 118-1). The degree of severity of obstruction is variable, depending upon the underlying problem and the size of the airway.

Acute respiratory failure involving the upper airways can be a life-threatening emergency that requires emergent action. Failure to rapidly assess and properly manage acute upper airway obstruction may lead to cardiopulmonary arrest in pediatric patients, who have less pulmonary reserve compared to adults. In this chapter, we will review pediatric upper airway anatomy and discuss the causes, presentation, evaluation, and management of acute upper airway obstruction.

PEDIATRIC AIRWAY CONSIDERATIONS

Compared to adults, pediatric patients have a larger occiput, larger tongue, shorter mandible, and prominent adenoids and tonsils (Fig. 118-1). These differences combine with a relatively smaller airway, lower functional residual capacity, higher peripheral airway resistance, and higher oxygen consumption to put infants and young children at higher risk for decompensation from an upper airway obstruction.

During inspiration, loose supraglottic tissues collapse inward due to negative inspiratory pressures and then freely enlarge on expiration. This yields characteristic inspiratory stridor in children with supraglottic disorders such as laryngomalacia and supraglottic stenosis. By comparison, the subglottic region is completely encircled by the cricoid cartilage, giving it a fixed size essentially unaffected by airway pressure. Thus, disorders in the subglottic region resulting in decreased lumen size typically produce biphasic stridor, as seen in croup or foreign body aspiration.

INFECTION

Croup

Etiology

Laryngotracheobronchitis, commonly known as croup, is a viral infection resulting in inflammation of the glottis and subglottis. This inflammation or edema produces a characteristic barking cough. Croup is both the most common cause of stridor and infectious cause of upper airway obstruction, affecting up to 5% of all children. The vast majority of cases occur between 6 months and 3 years of age, although croup can afflict older children. Croup has been associated with a number of different viruses, many of which are given in Table 118-2.

Clinical Presentation

The clinical presentation of croup may vary. Generally, the illness begins with a prodrome of nasal congestion and rhinorrhea, similar to other viral upper respiratory infections (URI). Fever usually occurs during the first 24 hours of illness. Within 12 to 48 hours, signs and symptoms of upper airway obstruction such as inspiratory stridor and the classic “barking seal” cough develop, with hoarseness appearing later. The illness may last 3 to 14 days, depending on the severity of the case.

Spasmodic croup typically affects children between 3 months and 3 years of age who are afebrile and previously well or had mild URI symptoms. This disorder usually has nighttime onset and is a noninfectious variant of croup. Affected children awake with sudden dyspnea, barking cough, and inspiratory stridor. Symptoms rapidly resolve, yet recurrence is common. Both allergens and gastroesophageal reflux have been implicated as potential etiologies.

Diagnosis

Croup is a clinical diagnosis based on the presence of a barking cough, stridor, and preceding viral URI. Laboratory assessment is typically not indicated. Radiographic examination of the soft tissues of the neck may assist in distinguishing between other causes of upper airway obstruction. In croup, the anteroposterior radiograph will show both subglottic narrowing and progressive tracheal narrowing as it reaches the subglottis. This is referred to as the “steeple sign,” and is due to mucosal edema below the vocal cords (Fig. 118-2).

Management

Croup is often a mild and self-limiting illness. Mild cases typically present with the barking cough, hoarseness, and stridor, only when agitated. One dose of oral corticosteroids, such as dexamethasone, and humidified air are recommended for these cases. However, there is some evidence to suggest that higher humidity air offers no benefit over lower humidity air. More severe cases may present with biphasic stridor, agitation, and increased work of breathing, even at rest. In addition to corticosteroid therapy, these patients may require inhaled racemic epinephrine, which has been shown to effectively decrease signs and symptoms of airway obstruction. The effects of racemic epinephrine are short-lived, therefore the possibility of recurrence of swelling and symptoms must always be considered. Patients who are administered inhaled epinephrine should be observed for a minimum of 2 to 3 hours after treatment in case of recurrence of airway symptoms. Patients who require repeated doses of racemic epinephrine may require hospitalization. The most severe cases cause significant upper airway obstruction, resulting in oxygen desaturations, cyanosis, and subsequent respiratory failure if not managed appropriately. In these cases, an advanced airway may be indicated if other less invasive interventions are unsuccessful in alleviating symptoms. As tracheal intubation may lead to subglottic stenosis after extubation, it must be performed judiciously.

Epiglottitis (Supraglottitis)

Etiology

Infection of the epiglottis may rapidly cause airway obstruction and is a true life-threatening emergency. Epiglottitis is described as an infectious process of the epiglottis and/or its associated structures and is more accurately termed supraglottitis. This process is classically caused by Haemophilus influenzae type B (HIB), leading to edema and inflammation and producing a swollen, cherry-red epiglottis. Since the advent of the HIB vaccine, the incidence of supraglottitis due to H influenzae type B has declined remarkably. Other infectious etiologic agents include Streptococcus, Staphylococcus, and Pseudomonas species.

Clinical Presentation

Supraglottitis most commonly affects children between 2 and 6 years of age, but can occur at any age. The classic presentation of supraglottitis is an anxious, toxic-appearing, febrile young child who quietly sits upright, leaning forward with his/her chin forward and neck extended, drooling, and with obvious inspiratory stridor and labored breathing. This position is known as the tripod position. In contrast to croup, cough and hoarseness are often not present. Unfortunately for the diagnostician, the tripod position and the other findings are often absent. Given the variable presentation and infrequent occurrence of supraglottitis, it is essential for the physician to maintain a high index of suspicion for this disease.

Diagnosis

Care should be taken as to not upset the child during the examination or perform painful procedures such as blood tests, as this can precipitate significant respiratory distress. During evaluating of the oropharynx, visualization of an edematous and erythematous epiglottis may be possible. Gentle external manipulation of the laryngotracheal area may produce pain. Any manipulation of the oropharynx of a child with supraglottitis can be unsafe, potentially leading to significant respiratory compromise from airway obstruction and possible respiratory failure. A lateral neck radiograph may reveal the classic “thumb sign,” depicting a swollen epiglottis (Fig. 118-3). An often present finding on lateral neck radiograph is the obliteration of the vallecula, which should otherwise be open and visible. If a radiograph is to be obtained, it should be performed in an unobtrusive manner, under direct observation by a healthcare provider.

Management

For children with supraglottitis, expedient care of the airway is the most important priority. Airway management in supraglottitis should involve experienced individuals under controlled conditions. While awaiting definitive airway management, preferably in the operating room by skilled anesthesiologists and otolaryngologists, it is imperative to handle the patient gently, and to administer oxygen in an unobtrusive manner. Blood collection and intravenous (IV) access should occur only after the airway is secured. Early intubation and intravenous parenteral antibiotics to eliminate the causative bacteria have reduced mortality significantly. Appropriate antibiotic choices include ampicillin/sulbactam, cefotaxime, ceftriaxone, or clindamycin. If methicillin-resistant Staphylococcus aureus is suspected, then addition of vancomycin is warranted.

Bacterial Tracheitis

Etiology

The incidence of bacterial tracheitis is far lower than that of uncomplicated viral croup. Bacterial tracheitis can occur as a primary bacterial infection or may follow viral croup as a secondary bacterial infection. This disease’s symptoms are similar to croup, but with copious purulent tracheal secretions and positive bacterial cultures. S aureus is the most commonly implicated bacteria. H influenzae and streptococcal species are less commonly isolated. Bacterial tracheitis can cause airway edema, purulent secretions, and development of a pseudomembrane, which may cause severe airway obstruction.

Clinical Presentation

Affected children may present with mild URI symptoms, followed by sore throat, fever, stridor, and a “brassy” cough. These symptoms may be present for up to a week prior to initial presentation. However, the progression of respiratory obstruction and distress can be more rapid and significant than in patients with croup. On initial presentation, patients with bacterial tracheitis are often highly febrile, appear ill, and have more severe symptoms than patients with croup. About 50% of children will also have a concomitant pneumonia. Of note, children with tracheostomy tubes are at higher risk for bacterial tracheitis.

Diagnosis

Although a peripheral white blood cell count might not be elevated, an obvious left shift with high band count is noted most often. Blood cultures are usually negative. Lateral neck radiographs may demonstrate subglottic edema, and chest radiographs may demonstrate focal infiltrates, although there are no pathognomonic radiographic signs of bacterial tracheitis. While the aforementioned studies may suggest bacterial tracheitis, airway endoscopy can confirm the diagnosis by visualization of an inflamed trachea and subglottis as well as a pseudomembrane.

Management

Children with bacterial tracheitis must be managed in an intensive care setting. The most important aspect of therapy is maintenance of a patent airway. Copious purulent secretions and subglottic space narrowing are common causes of airway obstruction and children may require an advanced airway. While the child is intubated, aggressive and frequent pulmonary and tracheal toilet should be performed, and endoscopy may be required for deeper suctioning. Broad spectrum antibiotics such as third-generation cephalosporins and vancomycin should be initiated until cultures results and sensitivities are available.

Retropharyngeal Abscess

Etiology

The retropharyngeal space is located on both sides of the pharyngeal midline, immediately posterior to the pharynx, larynx, and trachea, and extending from the base of the skull to the level of the seventh cervical and first thoracic vertebrae. Contained within this space are lymph nodes that drain the nose, paranasal sinuses, nasopharynx, and ears. The majority of these lymph nodes atrophy in later childhood, reducing the likelihood of abscess formation in older children. Retropharyngeal abscess (RPA) usually affects children between the ages of 6 months and 6 years, with the mean age being 3 to 5 years. Infections are often polymicrobial, but common isolated organisms include anaerobes, streptococcal species, and S aureus. Retropharyngeal abscess is rarely reported in infants younger than 3 months of age. In those instances, Escherichia coli and group B Streptococcus are often the identified pathogens.

Clinical Presentation

The clinical presentation can mimic epiglottitis; however, the onset of RPA is less abrupt. Typically, a several day–long prodrome (eg, URI symptoms, pharyngitis) precedes the onset of bacterial infection. Following extension of infection to the retropharyngeal space and lymph node suppuration, more serious signs and symptoms develop. Thus, the most common presenting complaints include fever, sore throat, and neck pain. The collection of purulent material can act as a mass lesion, extrinsically compressing or distorting upper airway structures and leading to stridor, drooling, and a toxic appearance. The abscess can also cause meningismus; thus, RPA should be considered in the child with nuchal rigidity but without cerebrospinal fluid (CSF) pleocytosis.

Diagnosis

Diagnosis is often made by clinical examination from the constellation of signs and symptoms, including ill appearance, neck swelling and pain with movement, torticollis, muffled “hot potato” voice, dysphonia, drooling, and trismus. If RPA is suspected, but physical findings are equivocal, radiographic studies can help confirm the diagnosis. Although sometimes interpreted as normal or nonconfirmatory, a lateral neck radiograph can be helpful. A positive film demonstrates an increase in the width of the soft tissues anterior to the upper cervical vertebrae. With proper neck extension, this space normally measures less than one-half the adjacent vertebral body width in a child older than 1 year, and less than the full adjacent vertebral body width in younger infants. Computed tomography (CT) of the neck with IV contrast can identify both abscess extension to neighboring spaces and its location relative to sensitive structures such as the internal jugular veins and carotid arteries. CT can also distinguish RPA from cellulitis and is often used when determining the course of treatment.

Management

A child with RPA should be managed in consultation with an otolaryngologist and hospitalized for intravenous antibiotic therapy. Initial antibiotic management can include ceftriaxone, ampicillin/sulbactam, or clindamycin. Intubation is indicated for airway compromise. Surgical intervention may be necessary in order to drain abscesses that are large, cause airway compromise, or are refractory to antibiotics.

Peritonsillar Abscess

Etiology

Peritonsillar abscesses are caused by an infection between the palatine tonsils and the capsule. It is the most common deep infection of the throat in adults and therefore is seen more commonly in adolescents. Depending on the size of the abscess, airway obstruction is a potential complication. Chronic tonsillitis can predispose patients to peritonsillar abscesses and this is often preceded by an acute streptococcal pharyngitis. Peritonsillar abscesses are often polymicrobial, consisting of both aerobic and anaerobic bacteria. The most common aerobic isolates include Streptococcus pyogenes, S aureus, H influenzae, and Neisseria species. There is no evidence of person-to-person transmission of infection, with the exception of those resulting from human bites.

Clinical Presentation

The adolescent often presents highly febrile and ill-appearing, complaining of worsening sore throat, and a “hot potato” or muffled voice. They may also complain of referred ear pain and odynophagia. On exam, patients will often exhibit trismus, along with palate edema on the same side as the abscess, with uvular deviation to the contralateral side.

Diagnosis

Peritonsillar abscess can be difficult to distinguish from cellulitis. While advanced radiographic imaging such as ultrasound or CT can be performed, the gold standard for diagnosis is needle aspiration by a trained physician. Due to the polymicrobial nature of this infection, aspirated fluid should be sent for both aerobic and anaerobic cultures.

Management

Initial antibiotic therapy should be broad spectrum to cover both aerobic and anaerobic species until the results of the culture from the needle aspiration become available. Broad-spectrum penicillins and clindamycin would cover the most common species; however, some resistance has been reported, particularly with anaerobes such as Bacteroides. Many otolaryngologists recommend 10 to 14 days of antibiotic therapy.

Foreign Bodies

Etiology

According to the National Safety Council, choking is one of the leading causes of unintentional deaths in infants and young children. Choking is also responsible for a high number of emergency department visits. The most common items include food (peanuts, seeds, popcorn, grapes) and nonfood items (coins, balloons, marbles). Round items are particularly dangerous, as they can become lodged and completely obstruct the airway.

Clinical Presentation

The initial presentation varies depending on the age of the child, the object aspirated, where the object is located in the airway, and how long the foreign body has been present. Patients with marked respiratory distress and cyanosis are true airway emergencies. More commonly, in the acute presentation, patients have sudden onset of choking or coughing, followed by wheezing, dyspnea, and/or stridor. Decreased air entry on auscultation, wheezing, and fever are more commonly observed with bronchial foreign bodies, while stridor and hoarseness are more often associated with laryngotracheal foreign bodies. It is important to understand that the symptoms associated with upper airway obstruction due to the presence of foreign bodies can be highly variable, and sometimes nearly absent. Thus, a continued high degree of suspicion should be maintained when a patient’s history suggests this possibility.

Diagnosis

In the absence of an observed acute choking episode, the diagnosis of foreign body aspiration can be delayed. In fact, as many as 15% to 20% of foreign body aspirations are diagnosed more than a month after aspiration. Patients with a chronic, unexplained cough, wheezing, or recurrent pneumonias should raise suspicion for a foreign body aspiration. Chest radiography may not be helpful as most aspirated foreign bodies are radiolucent. Some children with documented foreign body aspiration have completely normal chest radiographs, both upright and decubitus views. There can be secondary signs of obstructive emphysema with hyperinflation of one lobe of the lungs compared to the other. This is caused by a partial airway obstruction with subsequent air trapping, and is most apparent when images are captured during exhalation. CT imaging can also be useful to identify an otherwise radiolucent foreign body.

Management

Foreign body aspirations leading to airway compromise need emergent management to protect the airway, prior to determining the presence or absence of a foreign body. Blind finger sweeps should be avoided as the foreign body could be pushed back into the airway, causing further obstruction. In the young child who is unable to control his or her actions, this maneuver also puts the rescuer at risk for injury. In the unconscious, nonbreathing child, following failed chest or abdominal thrusts, a tongue-jaw lift should be performed by grasping both the tongue and lower jaw between the thumb and finger, and lifting. This draws the tongue away from the back of the throat and might partially relieve the obstruction. If the foreign body is visualized, it should be removed.

When there is a strong suspicion for a foreign body aspiration, rigid bronchoscopy can be both diagnostic and therapeutic. This method permits control of the airway and of any subsequent bleeding of the mucosa, as well as object visualization and removal. Flexible bronchoscopy can also be performed, but is less preferred as providers run the risk of dislodging the object, and there is less airway control.

Trauma

Blunt and Penetrating Injuries

Trauma to the airway causing obstruction can occur from both blunt and penetrating injuries. Given the aforementioned pediatric airway anatomy considerations, as well as less cartilaginous support, pediatric airways are more susceptible to obstruction from trauma. In addition to the traumatic injury, the airway can be obstructed by foreign bodies, loose teeth, secretions, bleeding, compression from external forces, or subcutaneous air (Fig. 118-4). According to Advanced Trauma Life Support guidelines, a trauma patient’s airway must be secured prior to proceeding with the primary and secondary surveys. This may require placement of an advanced airway or aggressively suctioning secretions to assist with the oxygenation and ventilation, thus preventing cardiopulmonary demise. Further evaluation with CT imaging may assist in determining the extent of injuries in a hemodynamically stable patient. Consultation with trauma surgery and/or otolaryngology may be necessary, especially for the unstable patient who requires operative management.

Thermal Injuries

The tissues of the upper airway are subject to injury when exposed to extremely high or low temperature substances, such as hot drinks or frozen foods. Case reports of thermal epiglottitis and uvulitis have been published sporadically. When such injuries occur, the management of the injured airway should follow usual guidelines. In the absence of secondary infection, antibiotics are not indicated for these injuries.

Anaphylaxis

Anaphylaxis is an acute, life-threatening immuonoglobulin E (IgE)-mediated systemic reaction to an allergen that requires immediate attention and effective management. Symptom onset occurs suddenly and involves 2 or more organ systems. Such symptoms include urticaria, angioedema, flushing, lip or tongue swelling, throat tightness/swelling, retropharyngeal or laryngeal edema, cough, wheezing, respiratory distress, abdominal pain, vomiting, syncope, or dizziness. Patients may also present in anaphylactic shock and be hypotensive, in addition to the above symptoms. The most common identified causes include insect bites or stings, ingested foods or medications, vaccinations, or contact with an offending agent. Often the etiologic agent is not determined. Intramuscular (IM) epinephrine is the initial treatment of choice and significantly decreases morbidity and mortality. Additional supportive therapies include corticosteroids, H₁ antihistamines, and H₂ antihistamines. Patients who have significant airway obstruction require multiple doses of IM epinephrine, and those who have refractory hypotension should be admitted for further management.

Patients and families should be counseled about potential exposures and when to administer IM epinephrine. Given the severity of anaphylaxis, it is prudent to refer patients to a pediatric allergist who can assist the family in identifying the allergen and initiating long-term therapies (anti-IgE therapy, desensitization) as indicated.

Ingestion of Caustic Substances

Over 200,000 exposures to cleaning substances are reported to the US Poison Control Center annually. Many of these are caustic agents, including acid, alkali, or oxidizing agents. These substances include laundry detergents, toilet bowel cleaners, floor cleaners, oven cleaners, ammonia, bleaches, and all-purpose cleaners. Approximately 80% of caustic ingestions occur in children younger than 5 years of age and are often unintentional. These products may appear attractive to a young child because of color, texture, scent, or packaging in alternate “safe” containers such as soft drink bottles.

Caustic agents can burn the skin, tongue, throat, esophagus, and stomach. Children may present with drooling, dysphagia, stridor, and/or wheezing. Upon presentation, it is imperative to determine the substance ingested and consult the Poison Control Center. If the patient has respiratory compromise, an advanced airway should be considered to prevent cardiopulmonary collapse. A chest radiograph should be obtained to rule out mediastinitis or aspiration pneumonitis. Occasionally, endoscopy is needed to assess the extent of injuries in a persistently symptomatic child. Treatment involves supportive care as the mucosa heals, as there is no antidote for caustic substances. Poison prevention and anticipatory guidance are necessary to prevent future ingestions and injuries.

Summary

Acute upper airway obstructions can be life-threatening and require quick recognition to prevent morbidity and mortality. Management depends on presenting symptoms and physical exam findings. Understanding and distinguishing among the various etiologies of acute upper airway obstruction are critical for instituting effective management to alleviate symptoms. Some cases may necessitate advanced airway placement, which should be performed by an experienced provider.

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PHYSIOLOGY OF TEMPERATURE REGULATION AND HEAT TRANSFER

Healthy humans are able to self-regulate their body temperature within a narrow range (37±0.4°C or 98.6±0.8°F), despite wide variations in ambient temperature. Temperature regulation is performed by the thermoregulatory center in the preoptic anterior hypothalamus, which integrates impulses transmitted by the peripheral warm and cold receptors of the skin and the central thermoreceptors located in the hypothalamus, spinal cord, viscera, and great veins. Normally, the body maintains a balance between the heat generated by the muscles and liver and the heat lost through the skin and lungs. During exercise, there may be as much as a 4-fold increase in heat production. In febrile states, homeostatic mechanisms such as vasoconstriction and shivering raise the body temperature by increasing heat production and decreasing heat dissipation until a new elevated set point is reached. When the illness abates, the set point returns to the original lower level. Lowering of the body temperature is heralded by the onset of sweating.

There are 4 methods of heat transfer to and from the body: conduction, radiation, convection, and evaporation. Conduction helps transfer heat from the body to a solid or liquid medium that is in contact with it, and is the primary mechanism of cooling during ice or water immersion, which, if prolonged, can lead to hypothermia, especially in cold climates. In the lungs, heat is lost by conduction to water vapor and air. Radiation transfers heat from a warmer body to a colder body via electromagnetic waves, and is a principal mechanism of heat elimination in temperate environments. The amount of heat transferred through conduction or radiation is dependent on the temperature gradient between the skin and surroundings, as well as skin blood flow and insulation characteristics (adiposity, hair, clothing). In convection, heat is transferred from the body to the surrounding air, according to the ambient air temperature and wind speed. Evaporation removes heat from the body when sweat (or water that is in contact with the body) vaporizes from its liquid state, and the rate of evaporation is dependent on the relative humidity, ambient air temperature, wind velocity, and degree of sweat production. The evaporation of sweat is a principal mechanism for heat elimination through body heat production or when the ambient temperature rises.

The adaptation to heat stress relies on both a greater rate of sweating at a lower degree of exercise and a lower electrolyte content of sweat. Sweating and subsequent evaporation are very effective mechanisms of temperature control, provided that the environmental humidity is low enough to permit evaporation. This does not occur when the air becomes saturated with water vapor at humidity levels of 90% to 95% and is reduced at humidity levels greater than 75%. In addition, sweating can cause a substantial water and electrolyte loss occurring at up to 1 L/hour/m² of body surface area.

When the ambient temperature drops, cold-sensitive neurons in the skin are stimulated, sending impulses to the hypothalamus to cause piloerection and heat generation by shivering. Piloerection traps an insulating layer of air around the body in order to minimize heat loss. Shivering is not a compensatory mechanism in neonates; instead, they generate heat independent of muscle contraction in their brown adipose tissue through the oxidation of fatty acids being mediated by the sympathetic nervous system. The role of brown adipose tissue beyond the neonatal period is unclear, though it has been suggested that an adaptive conversion from white to brown adipose tissue may occur as a response to cold stress beyond this age. In addition to the above metabolic responses, cold temperature leads to peripheral vasoconstriction and shunts blood away from the periphery to the core. Additionally, cold temperatures lead to antidiuretic hormone antagonism, resulting in increased urine output and hemoconcentration.

HEAT-RELATED ILLNESS

Hyperthermia is an uncontrolled elevation of the core body temperature that outpaces the body’s ability to lose heat. Fever is distinct from hyperthermia in that inflammation-induced cytokine activation leads to a reset of the hypothalamic thermostat set-point, resulting in an elevation of body temperature that exceeds the normal daily variation. Heat-related illnesses occur when an elevated body temperature caused by endogenous heat production and ambient heat exposure together exceed heat dissipation mechanisms in the body. The differential diagnoses of heat related illness are given in Table 119-1.

EPIDEMIOLOGY

There are 2 groups of children who are at risk for heat-related illness or heat stress. The first group includes infants who are left bundled in their cribs and young children who are left unattended in closed automobiles. Even with moderate ambient temperatures, the temperature inside closed vehicles can rise dangerously high causing significant morbidity or death. Studies show a greater than 14°C (40°F) temperature increase in the first hour inside the car for all ambient temperatures between 22°C (72°F) and 36°C (95.5°F). During the 13-year period from 1998 through the end of 2012, there were 556 child vehicular hyperthermia deaths in the United States, of which more than half resulted from the child being left unattended by the caregiver. In addition, there are approximately 1000 heat stroke injuries annually from vehicular hyperthermia.

The other at-risk group includes youth engaged in athletic activities and children exposed to excessive environmental heat (eg, during border crossings through the harsh desert environment in the southern United States). Heat-related illness is a common reason for missed athletic activities, and is highest among football players, with rates peaking in August. This is more prevalent in overweight or obese individuals.

Heat-related illnesses can exacerbate existing medical conditions, and death from heat exposure can be preceded by various symptoms, which makes the absolute rate or incidence of heat-related death difficult to determine. Additionally, the criteria used to determine heat-related causes of death vary across states in the United States. These factors can lead to underreporting heat-related deaths or to reporting heat as a factor contributing to death rather than the underlying cause.

PATHOPHYSIOLOGY

In hyperthermia, the body temperature is elevated above normal because the heat-dissipating homeostatic mechanisms activated at temperatures above the set point are overwhelmed. Contrary to earlier thinking, children do not have less effective thermoregulatory ability, insufficient cardiovascular capacity, or lower physical exertion tolerance compared to adults when they exercise in the heat and maintain adequate hydration. The main modifiable risk factors for exertional heat-illness risk related to sports and other physical activities in a hot environment include poor hydration status, undue physical exertion, lack of time to recover from repeated exercise bouts, closely scheduled same-day training or sports competition, and clothes, uniforms, and protective equipment that do not allow heat dissipation.

CLASSIFICATION

The spectrum of heat-illness spans minor conditions such as heat cramps, heat edema, and heat syncope to the more serious heat exhaustion and life-threatening heatstroke. In heat cramps, there are painful, involuntary muscle contractions during or immediately after exercise. This resolves after rest, cooling off, and drinking an electrolyte-carbohydrate mixture. Heat edema, caused by interstitial fluid pooling in the dependent extremities, is treated by elevation of the extremities and use of compression stockings. Heat syncope is characterized by a brief loss of consciousness in relation to heat exposure with rapid recovery to baseline. It is usually precipitated by peripheral vasodilation, orthostatic pooling of blood in the dependent areas, prolonged standing, and dehydration. The victim usually recovers after a period of rest and rehydration and after being moved to a cooler area.

Heat exhaustion is a moderately severe heat illness characterized by muscle cramps, fatigue, headache, nausea, vomiting, dizziness, or fainting. The skin is often cool and moist, indicating that body sweating is still intact. The pulse rate is typically fast and weak, and breathing is rapid and shallow. The core temperature may be normal or slightly elevated but less than 40°C (104°F). If untreated, heat exhaustion can progress to heatstroke.

Heatstroke is a life-threatening condition that occurs in patients who are exposed to excessive environmental heat when the core body temperature reaches or exceeds 40°C. It is accompanied by tachycardia, headache, and central nervous system dysfunction such as dizziness, headache, confusion, seizures, or coma. This can progress to rhabdomyolysis, encephalopathy, liver and kidney failure, coagulopathy, and multiple organ system failure. Sweating is usually absent in heatstroke, though its absence is not essential to make a diagnosis.

Heatstroke is classified as classical (nonexertional) or exertional. Nonexertional heatstroke is most commonly seen during heat waves and affects people who are least able to tolerate heat, such as the chronically ill, the very young, and the aged. The exertional form is seen in people who are actively exercising or those with convulsive status epilepticus or prolonged agitation. The prodrome may consist of nonspecific complaints such as lethargy, vomiting, nausea, weakness, or headache, and may go unrecognized. Risk factors include poor conditioning, recent illness, lack of rest or sleep, poor acclimatization, or dehydration.

CLINICAL EFFECTS

Hyperthermia initially causes an increase in cellular metabolism with an increase in heat production. There is cutaneous vasodilatation, tachypnea, and increased cardiac output. At further elevations in body temperature, as in heatstroke, cardiac output and oxygen delivery cannot keep pace with the accelerated metabolic rate. Heat stress induces an acute inflammatory reaction mediated by interleukins, cytokines, and proteins that cause an increase in mucosal permeability. Together with endotoxemia, alterations in the microcirculation occur, with resultant endothelial and tissue injury. Common complications of hyperthermia include acute respiratory distress syndrome, disseminated intravascular coagulation, acute renal injury, hepatic injury, and rhabdomyolysis. Rhabdomyolysis, which is the uncontrolled breakdown of skeletal muscle, is an important and life-threatening consequence of heatstroke.

LABORATORY FINDINGS

Early in the disease, hypokalemia, hypophosphatemia, and respiratory alkalosis (due to stimulation of the respiratory center) occur. Serum lactate dehydrogenase will be elevated as a consequence of cellular injury, and elevated transaminases, usually peaking at 48 hours, indicate hepatic damage. As the disease advances, patients will have metabolic acidosis with elevation in the serum lactate. If significant skeletal muscle injury has occurred, rhabdomyolysis ensues and can be diagnosed by elevated creatine kinase levels and myoglobinuria, hyperkalemia, and acidosis with derangements of renal function. Rhabdomyolysis requires aggressive proactive management with hydration, maintenance of normal to alkaline blood pH, and, potentially, dialysis. Myocardial injury may occur during heatstroke, resulting in an increase in cardiac enzymes and ST-segment changes on the electrocardiogram (ECG).

MANAGEMENT

The principles of management include cooling, airway protection, supporting cardiorespiratory function, repleting intravascular volume, and pre-emptive management and early intervention to minimize complications. For milder forms of heat injury, reducing the level of physical activity, transport to a cooler environment, and oral rehydration are usually sufficient, and when heat cramps are present, salt as well as water may be replaced using a simple 0.1% to 0.2% salt solution (~ 1/4 teaspoon of table salt per 8 oz of water).

Heatstroke, however, is a medical emergency, and rapid temperature reduction is of paramount importance. First aid should involve removing the patient’s clothes and cooling the body by applying wet towels, drenching the victim with water, and maintaining a cool environment during transport. Victims will need basic or advanced life support measures, based on the severity of the heatstroke. On arrival in the emergency department, the patient’s airway, breathing, and circulation should be assessed and supported as necessary. Patients will need intravenous or intraosseous access and resuscitation using isotonic fluids at room temperature. Most will need at least 20 to 40 mL/kg of normal saline, and those with exertional heat stroke require more fluids. After initial fluid resuscitation, fluid administration should be guided by central venous pressure monitoring to avoid circulatory overload. Since cardiac function may be reduced in victims of heatstroke, vasopressors may be required. To ensure rapid cooling, ice should be placed in the neck, axillae, and groin, and water-soaked sheets and cooling fans utilized; in severe cases, the patient should be placed on a cooling blanket, targeting normothermia. Additional measures for active cooling include the administration of cold intravenous fluids or nasogastric fluids, as well as instillation of cooled fluids to the peritoneum. The use of cardiopulmonary bypass and extracorporeal membrane oxygenation have both been used in the most refractory cases and to support those with multiorgan failure. Benzodiazepines and potentially neuromuscular blockade may be administered for agitation and shivering during active cooling in order to minimize oxygen consumption in intubated patients. Patients with heatstroke, and those with any organ system dysfunction or failure, and those requiring continued active cooling should be monitored in an intensive care unit (ICU).

PROGNOSIS

The prognosis of pediatric victims of heatstroke is not well described, most likely because there is a broad spectrum of manifestations and degrees of severity. However, factors associated with a poor prognosis include the magnitude of temperature elevation, refractoriness to initial measures, and the number of organ systems involved. Survivors may manifest neurocognitive deficits of varying degrees.

PREVENTION

Acclimatization of athletes and educating participants and coaches involved in sporting activities are primary methods of prevention of heat-related illness. Current National Athletic Trainers’ Association (NATA) recommendations suggest a 14-day acclimatization period for all warm weather conditioning. Additionally, the education of participants and caregivers on the dangers of heat-related illness and the importance of proper hydration before, during, and after strenuous activity are key factors in prevention. Fluid replacement should approximate sweat and urine losses so that athletes lose no more than 2% body weight per day on average. This equates to an older child consuming 200 to 300 mL fluid every 10 to 20 minutes during exercise.

To prevent hyperthermia related to automobiles, caregivers should never leave a child unattended in a vehicle, even if the windows are partially open or the engine is running and the air conditioning is turned on. Absentee child-care policies requiring parent and caregiver notification if a child does not arrive to daycare, as well as physical reminders (written, electronic, or visual) that their child is in the vehicle, may also help avoid a caregiver inadvertently leaving a child in the vehicle. Finally, parents should teach children that a vehicle is not a play area, ensure all vehicles remain locked when not in use, and store keys out of a child’s reach.

Secondary prevention is crucial to prevent progression. A child exhibiting nausea, vomiting, headache, dizziness, or mental status change after heat exposure should be removed from the activity, rehydrated, and immediately evaluated for potential heat exhaustion or heatstroke by a healthcare professional trained in the assessment of this condition, so that active measures can be instituted to prevent further complications of heat exhaustion and heatstroke.

NONENVIRONMENTAL HYPERTHERMIA

Malignant Hyperthermia

Malignant hyperthermia (MH) is an autosomal-dominant disorder with an estimated prevalence of 1:3000. The principal defect is a mutation in the gene for the skeletal muscle ryanodine receptor (RyR1), which is a calcium channel found in the sarcoplasmic reticulum. Malignant hyperthermia is a rare event and is most commonly triggered by the use of volatile inhalation anesthetic agents or the muscle-depolarizing agent succinylcholine.

In the appropriate setting, the early signs of MH include an inappropriately elevated CO₂ production and O₂ consumption, a mixed metabolic and respiratory acidosis, profuse sweating, and mottling of the skin. Other clinical features include tachycardia, cardiac arrhythmias and blood pressure instability, masseter spasm (if succinylcholine is used), and generalized muscle rigidity. Later in the illness, hyperkalemia, a rapid increase in body temperature, very elevated serum creatine kinase and myoglobin levels, myoglobinuria, and disseminated intravascular coagulation occur, terminating in cardiac arrest.

The important management goals are to avoid the use of triggering agents in at-risk individuals (by using total intravenous anesthesia), and to have a high index of suspicion if clinical signs could indicate the onset of this.

The treatment of MH begins with stopping the trigger agent, hyperventilating the patient, using nontrigger anesthesia, and terminating the surgery. Intravenous (IV) dantrolene 2.5 mg/kg should be administered. Additional doses or an infusion of dantrolene should be administered until cardiac and respiratory systems stabilize. Immediate additional supportive care involves the treatment of hyperthermia with IV fluids and cooling measures; anticipatory management; early intervention for hyperkalemia, metabolic acidosis, and arrhythmias; and maintaining a urine output of > 2 mL/kg/hour.

Drug-Induced Hyperthermia

Patients who are intoxicated from using illicit drugs such as cocaine, amphetamines, synthetic cathinone (“bath salt”), and MDMA (3,4-methylenedioxymethamphetamine) present with signs of sympathetic overactivity, such as hypertension, tachycardia, and hyperthermia. Hyperthermia results from the direct drug effects on the central nervous system, prolonged physical exertion, and hot environmental conditions. Patients are diaphoretic and agitated, and may have delirium. This condition is differentiated from anticholinergic toxicity in that patients with anticholinergic toxicity generally present with reduced or absent sweating, whereas patients with MDMA toxicity are usually diaphoretic. The pattern of speech is clear but pressured for MDMA and resembles a “mouthful of marbles” with anticholinergic toxicity.

The management consists of cardiorespiratory support, fluid resuscitation, management of hyperthermia and hypertension, and the use of sedatives for psychomotor agitation.

HYPOTHERMIA

Hypothermia, which is defined as a core body temperature less than 35°C (95°F), is caused by exposure to cold but can also occur in warm climates when the victim is exposed to wet and windy conditions. Every year, there are about 1300 hypothermia deaths in the United States, with rates being highest among those with advanced age, male sex, drug intoxication, homelessness, and mental illness. In the United States, the highest death rates are observed in areas with mild climates that experience rapid temperature changes or at higher elevations where a significant drop in nighttime temperature can occur.

Other conditions associated with hypothermia include major trauma with blood loss and/or exposure, sepsis, extensive burns, hypothalamic dysfunction such as in traumatic brain injury, drug overdose from sedatives, hypnotics or opiates, adrenal insufficiency, anorexia nervosa, and malnutrition. Rarely, it may be a manifestation of child maltreatment due to cold bathing or submersion.

PATHOPHYSIOLOGY

Children, especially young infants, are at increased risk for hypothermia because of their larger body surface area relative to mass and their inability to recognize low ambient temperature as a danger. Very young children also have limited glycogen stores to augment heat production and are unable to shiver. Though children are more likely to experience hypothermia than adults, severely hypothermic children can have better neurological outcomes, especially if severe cooling rapidly occurs before circulatory arrest.

CLASSIFICATION

Hypothermia is classified as mild, with a core temperature of 32°C to 35°C (90°F–95°F); moderate, with a core temperature of 28°C to 32°C (82°F–90°F); or severe, with a core temperature below 28°C (82°F). Mild hypothermia causes shivering, cutaneous vasoconstriction, and increased metabolic rate. Behavioral responses include seeking a warm environment and putting on protective clothing. As hypothermia progresses, these compensatory mechanisms begin to fail and victims are unable to generate enough heat. Circulatory insufficiency and manifestations of inadequate cerebral oxygen delivery with altered mental status occur, with apathy, ataxia, slurred speech, confusion, lethargy, and odd behavior such as “paradoxical undressing,” which occurs due to perceived warmth caused by changes in peripheral blood flow. In severe hypothermia, all body systems begin to fail. Bradycardia, ventricular arrhythmias, fixed and dilated pupils, cardiorespiratory arrest, coma, and muscle rigidity ensue. Victims of severe hypothermia may lack detectable vital signs, thus all patients with hypothermia should be rewarmed and vital signs and brain stem activity should be reassessed before being declared dead.

CLINICAL EFFECTS

For every 1°C (1.8°F) drop in body temperature, metabolic activity decreases by 7%. Hypothermia has membrane depressant effects with resultant ionic and electrical conduction disturbances of the brain, heart, peripheral nerves, and other organs and systems. The most important changes include decreased cerebral metabolism and cardiorespiratory depression and failure. The initial exposure to cold induces a release of catecholamines, which results in increased cardiac output, peripheral vasoconstriction, and respiratory drive. As hypothermia progresses, there is a decrease in myocardial depolarization, resulting in bradycardia and decreased cardiac output. Circulatory collapse may occur due to hypovolemia, depression of myocardial function, sludging of blood, bradycardia, or malignant arrhythmias such as ventricular fibrillation. Altered respiratory drive is first manifested by shallow, slow, irregular respirations and, eventually, apnea. Specific neurological signs range from altered mental status to coma and include lack of pupillary and corneal reflexes and global areflexia. Clinically, the skin is mottled, and there may be concurrent frostbite. Cold-induced diuresis, failure of the renal concentrating mechanism and vascular-leak–induced interstitial extravasation of fluids contribute to hypovolemia. Hypothermia can cause reduced gastrointestinal motility, which results in gastric dilatation and ileus. Cardiac arrest may occur in patients with severe hypothermia during their extrication and transport. This is termed rescue collapse and is attributed to a combination of factors including circulatory collapse caused by hypovolemia, malignant arrhythmias associated with moving the patient, or further cooling. Afterdrop, defined as a continued drop in body temperature after rescue, has been described in experimental models. However, with the use of active external and minimally invasive rewarming and concurrent esophageal temperature measurement, afterdrop has not been reported in hypothermia victims.

LABORATORY FINDINGS

Hypoglycemia should be ruled out in all victims of hypothermia. Hypokalemia may occur in mild hypothermia, although in severe cases, hyperkalemia occurs due to cell death and renal dysfunction. Coagulopathy, thrombocytopenia, leukopenia, and deranged liver and renal function are often present; creatine kinase may be elevated due to rhabdomyolysis. The hematocrit increases 2% for every 1°C drop in body temperature. A chest radiograph may reveal pulmonary aspiration or pulmonary edema, the latter often seen during rewarming, likely due to reperfusion injury.

The effect of cold on arterial pH and blood gases may lead to confusion in the interpretation of arterial blood gas results. Blood pH increases with cooling due to the inhibition of dissociation of water molecules, and the partial pressures of CO₂ and O₂ decrease with cooling, although the blood content of these gases remain unchanged. Since blood is warmed to 37°C (98.6°F) in blood gas analyzers, the measured values (uncorrected) represent what the blood gas parameters would have been if the patient were normothermic. Actual in vivo values in the hypothermic patient (corrected) are derived mathematically. If the clinician acts on the corrected values, there is a risk of inducing hypoventilation and alveolar collapse. Therefore, pH and the partial pressure of carbon dioxide (PCO₂) should be left uncorrected after the sample has been warmed in the machine, and the test should be interpreted just as in a normothermic patient.

Electrocardiogram

Hypothermia first results in prolongation of PR, QRS, and QT intervals, with sinoatrial node depression and bradycardia. As core body temperature decreases, sinus bradycardia progresses to atrial fibrillation, then ventricular fibrillation, and finally cardiac asystole. Artifacts in the ECG may occur due to shivering. The Osborn wave (J point deflection at the junction of the QRS and ST segment) may be present when the body temperature drops below 30°C (86°F), though it is of no prognostic value.

MANAGEMENT

The principles of management include support of the airway, breathing, and circulation; institution of effective rewarming techniques; and assessment for and treatment of comorbidities such as trauma, medical illness, and intoxication. When assessing patients with hypothermia, it is important to use a low-reading thermometer to measure accurate core body temperature, as standard clinical thermometers do not read under 34°C (93°F). Temperature should be monitored centrally.

The intensity of treatment depends on the length of cold exposure and the victim’s body temperature, but rewarming should commence immediately. Victims should be moved to a warm environment, wet clothing removed, and all exposed body surfaces covered with anything at hand, including blankets, clothing, newspapers, etc. This method of passive external rewarming protects the patient from further heat loss and uses the patient’s own endogenous heat for rewarming. Additionally, these patients will benefit from active external rewarming, such as forced-air heating blanket, radiant heat lamp, or a water heating pad. The administration of warm oral fluids is beneficial. Most patients with mild hypothermia can be treated in the nearest emergency department.

Patients with moderate and severe hypothermia should be transported to a medical center for advanced rewarming measures and critical care. Supplemental oxygen administration with warm, humidified 100% oxygen via a nonrebreather mask is essential, as the oxygen–dissociation curve shifts leftward with hypothermia. Aggressive fluid resuscitation with warm intravenous fluids at 38°C to 42°C is recommended, and concurrent hypoglycemia should be treated with intravenous dextrose. Severe hypothermia leads to hypoventilation or respiratory arrest, so these patients will require bag-valve mask ventilation and endotracheal intubation. Rarely, cold-induced trismus may preclude orotracheal intubation and necessitate fiberoptic intubation or placement of a surgical airway. A severely hypothermic patient may have a very weak and irregular pulse, making the assessment for a pulse difficult. Cardiopulmonary resuscitation (CPR) should be initiated if no vital signs or cardiac activity are detected. Defibrillation and pharmacologic therapy based on advanced pediatric life support protocols will be necessary for the treatment of ventricular fibrillation or pulseless ventricular tachycardia. Unfortunately, these patients may be refractory to conventional therapy until they are rewarmed. Toxic accumulation of drugs may occur due to altered metabolism at very low temperatures. It is reasonable to administer 1 to 3 doses of vasopressors during CPR while actively rewarming to 30°C. Patients should be placed in a horizontal position and all maneuvers should be performed gently to avoid inducing malignant arrhythmias such as ventricular fibrillation.

In the hospital, more aggressive or “active” rewarming should be instituted, ideally through the use of forced-air rewarming and warmed intravenous fluids. A rate of rewarming of 1°C to 1.5°C pr hour can be achieved in patients with a perfusing rhythm. More invasive rewarming techniques may be necessary for severe hypothermic patients with limited or absent circulation. These include gastric, peritoneal, pleural, or bladder lavage with warmed fluids at 40°C and extracorporeal rewarming. Extracorporeal support is reserved for patients with severe hypothermia with cardiac arrest or absent circulation or who are refractory to other methods of increasing body temperature. If the patient does not regain mental status when the temperature reaches 32°C, a search for metabolic, toxic, or CNS causes should be undertaken. Termination of CPR should be considered if there is no return of cardiac activity once a core temperature of 32°C has been achieved. Additionally, potassium levels greater than 12 mmol/L, a marker of cell death and possible prehypothermia hypoxia, should prompt a consideration of termination of resuscitation.

FROSTBITE

Victims of hypothermia may also suffer from frostbite, typically affecting exposed body parts such as the ears, nose, cheeks, chin, fingers, and toes. In the early stages, the affected areas become very painful and the skin becomes cold and numb. Later in the illness, blisters develop, and in severe frostbite, the skin may turn black. Patients should be moved to a warm environment and wet clothing removed. The affected extremity should be placed in a basin of warm water (38°C–42°C or 100°F–108°F) for 30 minutes. The temperature of the water should be continually adjusted. Affected areas should not be rubbed, and analgesics may be required. Patients’ tetanus immunization status should be assessed and prophylaxis administered accordingly.

PROGNOSIS

Hypothermia decreases cerebral oxygen requirements, so survival without neurologic impairment is possible, even when these patients may require prolonged CPR. It is very difficult to accurately prognosticate outcome at the initial presentation in the setting of severe hypothermia. The lowest initial temperature in a surviving child and adult with hypothermia were 14.2°C (57.6°F) and 13.7°C (56.7°F), respectively, and survival without neurologic impairment in patients with severe hypothermia treated with cardiac bypass or extracorporeal membrane oxygenation can range from 47% to 63%.

DIFFERENTIAL DIAGNOSIS

The diagnosis is straightforward in exposure-related hypothermia. However, one should consider other conditions as a cause or contributing factor in mild hypothermia. Increased heat loss may occur from iatrogenic causes, such as administration of cold fluids; overdose from sedatives, hypnotics, or opiates; dermatologic conditions with skin desquamation; or burns. Decreased heat production can occur in very young or old patients, hypoglycemic states, malnutrition, endocrinopathies such as adrenal insufficiency or profound hypothyroidism, diabetic or alcoholic ketoacidosis, or stress or trauma states. Impaired thermoregulation can result from other etiologies, such as traumatic brain or spine injury, stroke, or cerebral hemorrhage.