Chapter 13: Poisoning

Accidental and intentional exposures to toxic substances occur in children of all ages. Children younger than 6 years are primarily involved in accidental exposures, with the peak incidence in 2-year-olds. Of the more than 2 million exposures reported by the American Association of Poison Control Centers’ National Poison Data System in 2017, almost 60% of exposures occurred in those younger than 20 years: 45% in children aged 5 years and younger, 6% aged 6–12 years, and 8% aged 13–19 years. Fortunately, young children’s exposures are typically unintentional and of the low dose or volume type. They can be exposed to intentional poisoning through the actions of parents or caregivers and involvement of child abuse specialists is helpful in these cases (see Chapter 8). Substance abuse and intentional ingestions account for most exposures in the adolescent population. In some locales, small-scale industrial or manufacturing processes may be associated with homes and farms, and exposures to hazardous substances should be considered in the history.

Pediatric patients also have special considerations pertaining to nonpharmaceutical toxicologic exposures. Their shorter stature places them lower to the ground as well as the fact that many are crawling, and some gas and vapor exposures will gather closer to the ground. They may have a greater inhalational exposure due to their higher minute ventilation. They may not be physically mature enough to remove themselves from exposures. They also have a large body surface area to weight ratio making them vulnerable to topical exposures and hypothermia.

In the evaluation of the poisoned patient, it is important to compare the anticipated pharmacologic or toxic effects with the patient’s clinical presentation. If the history is that the patient ingested a sedative 30 minutes ago, but the clinical examination reveals dilated pupils, tachycardia, dry mouth, absent bowel sounds, and active hallucinations—clearly anticholinergic toxicity—diagnosis and therapy should proceed accordingly. In addition, standard pharmacokinetics (absorption, distribution, metabolism, and elimination) often cannot be applied in the setting of a large dose, since these parameters have been extrapolated from healthy volunteers receiving therapeutic doses.

Absorption

Depending on the route, absorption rates can vary in general, intravenous/intra-arterial > inhalation > sublingual > intramuscular > subcutaneous > intranasal > oral > rectal > dermal. Large overdoses, hypotension, and decreased gut mobility are the factors that can delay absorption.

Elimination Half-Life

The t_1/2 of an agent must be interpreted carefully. Most published t_1/2 values are for therapeutic dosages. The t_1/2 may increase as the quantity of the ingested substance increases for many common intoxicants such as salicylates. For example, one cannot rely on the published t_1/2 for salicylate (2 hours) to assume rapid elimination of the drug. In an acute salicylate overdose (150 mg/kg), the apparent t_1/2 is prolonged to 24–30 hours. Calculation formula for first-order drugs: T ½ = ln(2)/Ke and Ke = ln CP1-lnCP2/t2-t1.

Volume of Distribution

The volume of distribution (Vd) of a drug is determined by dividing the amount of drug absorbed by the blood level. With aspirin for example, the Vd is 150–170 mL/kg body weight, or 10 L in an average adult. In contrast, digoxin distributes well beyond total body water. Because the calculation produces a volume above body weight, this figure is referred to as an “apparent volume of distribution.”

Body Burden

Body burden represents the total amount of drug or toxin within the body and may be useful to determine the dose absorbed from an ingestion. For example, a 20-kg child with an acetaminophen blood level of 200 mcg/mL (200 mg/L) would have a body burden of 4000 mg of acetaminophen. This is ascertained by taking the volume of distribution of 1 L times the weight of the child times the blood level in milligram per liter. This would be consistent with an overdose history of having consumed eight extra strength 500-mg tablets but would not be consistent with a history of therapeutic administration of 15 mg/kg for four doses. Such a therapeutic administration would have a maximum administered dose of 1200 mg (20 kg times 15 mg/kg times four doses), which is well under the calculated body burden. Given metabolism of the drug with a normal half-life of 2 hours, it is apparent that much of the first doses would have been metabolized further showing that the dose was not a therapeutic dose. Formula for body burden by patient weight: Dose = Vd^*Cp^*W, where Vd is the volume of distribution, Cp is the plasma level, and W is the weight in kilograms.

Metabolism & Excretion

The route of excretion or detoxification is important for planning treatment, usually the liver and kidneys. Newborns and toddlers can have low Cytochrome P450 enzyme activity. Methanol, for example, is metabolized to the toxic product, formic acid. This metabolic step may be blocked by the antidote fomepizole or ethanol and patients with renal failure may not eliminate methanol as readily.

Blood Concentrations

Care of the poisoned patient should never be guided solely by laboratory measurements. Concentration results may not return in time to influence acute management. Initial treatment should be directed at symptomatic and supportive care, guided by the clinical presentation, followed by more specific therapy based on laboratory determinations. Clinical information may speed the identification of a toxic agent by the laboratory. CAUTION: Many laboratories report a normal range. When an overdose has occurred several hours earlier than peak times the lab may report a level that is within the normal range such as for aspirin and acetaminophen. It is important to look at the timing as well as signs and symptoms when an overdose is considered.

Inclusion of poison prevention as part of routine well-child care should begin at the 6-month well-baby visit. The poison prevention handout included as Table 13–1 may be copied and distributed to parents. It contains poison prevention information as well as first-aid actions that should be taken in the event of an exposure. All poison control centers in the United States can be reached by dialing 1-800-222-1222; the call will be automatically routed to the correct regional center.

INITIAL TELEPHONE CONTACT

Basic information obtained at the first telephone contact includes the patient’s demographics; the agent and amount of agent ingested; location; exposure; the patient’s present condition; and the time elapsed since the exposure. Other pertinent information includes the product ingredients, and potential maximum amounts of the drug or chemical involved. An emergency exists if the ingestant is high risk (caustic solutions, hydrogen fluoride, drugs of abuse, or medications such as a calcium channel blocker, opioid, hypoglycemic agent, or antidepressant, supratherapeutic dose) or if the self-poisoning was intentional. If immediate danger does not exist, obtain more details about the suspected toxic agent. If the specific substance is not identified it is important that the surroundings be searched for possible containers or other clues. Poison control centers (1-800-222-1222) are the source of expert telephone advice and have excellent follow-up programs to manage patients in the home as well as provide further poison prevention information.

Obtaining Information About Poisons

Current data on ingredients of commercial products and medications can be obtained from a certified regional poison center. It is important to have the actual container at hand when calling. Safety data sheets (SDSs) can be helpful in providing product ingredient and concentration information. Caution: Antidote information on labels of commercial products or in the Physicians’ Desk Reference may be incorrect or inappropriate. Many resources found on the Internet are inaccurate.

INITIAL EMERGENCY DEPARTMENT CONTACT

Address Initial Resuscitation Evaluation

As in all emergencies, the principles of treatment are attention to Pediatric Advance Life Support algorithms in resuscitation: circulation, airway, and breathing. The most important treatment in toxicological exposures is symptomatic and supportive care.

Treat Burns & Skin Exposures

Burns may occur following exposure to strongly acidic or strongly alkaline agents or petroleum distillates, and should be decontaminated by flooding with sterile saline solution or water. A burn unit should be consulted if more than minimal burn damage has been sustained. Skin decontamination should be performed in a patient with cutaneous exposure. Emergency department personnel in contact with a patient who has been contaminated (eg, with an organophosphate insecticide) should themselves be decontaminated if their skin or clothing becomes contaminated. Ocular exposures can initially be decontaminated at home by placing the child in the shower allowing the water to indirectly flow from the top of the head into the eyes. Otherwise, irrigation with assessment of pH should be performed in the emergency department.

Take a Pertinent History

The history should be taken from the parent/caregiver and all individuals present at the scene. It may be crucial to determine all of the kinds of poisons in the home. These may include drugs used by family members and their medical histories, dietary or herbal supplements, foreign medications, chemicals associated with the hobbies or occupations of family members, or the purity of the water supply.

DEFINITIVE THERAPY OF POISONING

Prevention of Absorption

A. Emesis and Lavage

These measures are rarely used in pediatric patients and have their own associated risk. They should not be used routinely in the management of poisonings and should be performed only in consultation with a poison center or medical toxicologist.

B. Charcoal

The routine use of charcoal has decreased substantially in recent years, especially in unintentional pediatric ingestions where lick, sip, taste ingestions are rarely dangerous. Charcoal can be considered in patients who are awake, alert, and able to drink it voluntarily, but it should not be routinely administered to all poisoned patients. It should never be given to patients with altered sensorium who are unable to protect their airway due to risk of aspiration. It is not recommended in ingestions of heavy metals, hydrocarbons, caustics, and solvent ingestions. The dose of charcoal is 1–2 g/kg (maximum, 100 g) per dose. Repeating the dose of activated charcoal may be useful for those agents that slow passage through the gastrointestinal (GI) tract, but repeated doses of sorbitol or saline cathartics must not be given. Repeated doses of cathartics may cause electrolyte imbalances and fluid loss. Charcoal dosing may be repeated every 4–6 hours until charcoal is passed through the rectum.

C. Catharsis

Cathartics do not improve outcome and should be avoided.

D. Whole Bowel Lavage (or Irrigation)

Whole bowel lavage uses an orally administered, nonabsorbable hypertonic solution such as CoLyte or GoLYTELY. The effectiveness of this procedure in poisoned patients remains controversial. Preliminary recommendations for use of whole bowel irrigation include poisoning with sustained-release preparations, mechanical movement of items through the bowel (eg, drug packets, iron tablets, lead foreign bodies), and poisoning with substances that are poorly absorbed by charcoal (eg, lithium, iron). Underlying bowel pathology and intestinal obstruction are relative contraindications to its use. Consultation with a certified regional poison center is recommended.

Enhancement of Excretion

Excretion of certain substances can be hastened by urinary alkalinization or dialysis and is reserved for special circumstances.

A. Urinary Alkalinization

1. Alkaline diuresis

Urinary alkalinization should be chosen on the basis of the substance’s pK_a, so that ionized drug will be trapped in the tubular lumen and not reabsorbed (see Table 13–1). Thus, if the pK_a is less than 7.5, urinary alkalinization is appropriate; if it is over 8.0, this technique is not usually beneficial. The pK_a is sometimes included along with general drug information. Alkaline diuresis is mainly used for salicylate toxicity. Urinary alkalinization is achieved with sodium bicarbonate. It is important to observe for hypokalemia, caused by the shift of potassium intracellularly. If complications such as renal failure or pulmonary edema are present, hemodialysis or hemoperfusion may be required.

B. Dialysis

Hemodialysis is useful in the treatment of some poisons and in the general management of a critically ill patient. Characteristics of drugs amendable to dialysis include low molecular weight, low protein binding, and low volume of distribution. Continuous hemofiltration techniques may be used when hypotensive patients may not tolerate traditional hemodialysis; however, clearance rates will be slower. Dialysis should be considered part of supportive care if the patient satisfies any of the following criteria:

1. Potentially life-threatening toxicity that is caused by a dialyzable drug and cannot be treated by conservative means.

2. Renal failure or insufficiency.

3. Marked hyperosmolality or severe acid–base or electrolyte disturbances not responding to therapy.

ACETAMINOPHEN (PARACETAMOL)

Overdosage of acetaminophen is common and can produce severe hepatotoxicity. Under than 0.1% of young children develop hepatotoxicity after acetaminophen overdose. In children, toxicity most commonly results from repeated overdosage arising from confusion about the age-appropriate dose, use of multiple products that contain acetaminophen or accidental large volume ingestion.

Acetaminophen is normally metabolized in the liver. A small percentage of the drug goes through a pathway leading to a toxic metabolite. Normally, this electrophilic reactant is removed harmlessly by conjugation with glutathione. In overdosage, the supply of glutathione becomes exhausted, and the metabolite may bind covalently to components of liver cells to produce necrosis.

Treatment

Treatment is to administer acetylcysteine. It may be administered either orally or intravenously. Consultation on difficult cases may be obtained from your regional poison control center. The blood acetaminophen concentration should be obtained 4 hours after a single acute ingestion or as soon as possible thereafter and plotted on Figure 13–1. The nomogram is used only for acute ingestion, not repeated or unknown ingestions. Acetylcysteine is administered to patients whose acetaminophen levels plot in the toxic range on the nomogram. Acetylcysteine is effective even when given more than 24 hours after ingestion, although it is most effective when given within 8 hours post ingestion.

For children weighing 40 kg or more, IV acetylcysteine should be administered as a loading dose of 150 mg/kg administered over 15–60 min; followed by a second infusion of 50 mg/kg over 4 hours, and then a third infusion of 100 mg/kg over 16 hours.

For patients weighing less than 40 kg, IV acetylcysteine must have less dilution to avoid hyponatremia (a dosage calculator is also available at http://www.acetadote.com) (Table 13–2). Patient-tailored therapy is critical when utilizing the IV “20-hour” protocol and those patients who still have acetaminophen measurable and/or elevated aspartate transaminase/alanine transaminase (AST/ALT) may need treatment beyond the 20 hours called for in the product insert. There is now evidence that a 2-bag infusion method of administering acetylcysteine may decrease associated adverse events, including flushing, vomiting and anaphylactoid reactions in addition to decreasing associated medication errors. This is administered as a 200 mg/kg IV bolus over 4 hours, followed by 100 mg/kg over 16 hours.

The oral form of acetylcysteine can also be given and is equally efficacious as intravenous. Consult your regional poison center for dosing recommendations.

AST–serum glutamic oxaloacetic transaminase (AST–SGOT), ALT–serum glutamic pyruvic transaminase (ALT–SGPT), serum bilirubin, and plasma prothrombin time should be followed daily. Significant abnormalities of liver function may not peak until 72–96 hours after ingestion.

ALCOHOL, ETHYL (ETHANOL)

Alcoholic beverages, tinctures, cosmetics, perfumes, mouthwashes, food extracts (vanilla, almond, etc), rubbing alcohol, and hand sanitizers are common sources of poisoning in children. Alcohol is even available in powdered form for mixing and consumption. In most states, alcohol levels of 50–80 mg/dL are considered compatible with impaired faculties, and levels of 80–100 mg/dL are considered evidence of intoxication. (Blood levels cited here are for adults; comparable figures for children are not available.)

Recent erroneous information regarding hand sanitizers has indicated that a “lick” following application on the hand could cause toxicity in children. In fact, this is not the case, but because these hand sanitizers contain 62% ethanol, toxicity following ingestion is possible. Potential blood ethanol concentration following consumption of a 62% solution in a 10-kg child is calculated as follows:

In a patient weighing 10 kg, the distribution into total body water (Vd) will be 6 L—this is the amount of the body water into which the ethanol will be distributed.

Based on these calculations, a 10-kg child consuming 0.5 oz would have a concentration of 122.5 mg/dL; a 20-kg child consuming 1 oz would have a concentration of 122.5 mg/dL; a 30-kg child consuming 1 oz would have a concentration of 81.7 mg/dL; and a 70-kg adult consuming 1 oz would have a concentration of 35 mg/dL.

One “pump” from a hand sanitizer bottle dispenses approximately 2.5 mL of the product. If ingested, this amount (containing 62% ethanol) would create a blood ethanol concentration as follows:

1. In a 10-kg child: 23.1 mg/dL.

2. In a 20-kg child: 11.6 mg/dL.

3. In a 30-kg child: 7.7 mg/dL.

Children show a change in sensorium with blood levels as low as 10–20 mg/dL, have higher risk for hypoglycemia than adults, and any child displaying such changes should be seen immediately. Complete absorption of alcohol requires 30 minutes to 6 hours, depending on the volume, the presence of food, and the time spent in consuming the alcohol. The rate of metabolic degradation is constant (about 20 mg/h in an adult). Absolute ethanol, 1 mL/kg, results in a peak blood level of about 100 mg/dL in 1 hour after ingestion.

Treatment

Management of sedation, hypoglycemia and acidosis is usually the only measure required. Start an IV drip of D₅W or D₁₀W if blood glucose is less than 60 mg/dL. Death is usually caused by respiratory failure. In severe cases, cerebral edema may occur and should be appropriately treated. Secondary evaluation for traumatic injury and coingestants should also be performed.

AMPHETAMINES & RELATED DRUGS (STIMULANTS, METHAMPHETAMINE, 3,4-METHYLENEDIOXY-N-METHYLAMPHETAMINE)

Clinical Presentation

A. Acute Poisoning

Amphetamine, 3,4-methylenedioxy-N-methylamphetamine (MDMA), and methamphetamine poisoning is common because of the widespread availability of “diet pills” and the use of “ecstasy,” “speed,” “crank,” “crystal,” and “ice” by adolescents. (Care must be taken in the interpretation of slang terms because they have multiple meanings.) A new cause of stimulant poisoning is drugs for treating attention-deficit/hyperactivity disorder, such as methylphenidate. There are also newer designer drugs, synthetic cannabinoids (“spice, K2”) and MPDV or mephedrone (“bath salts, plant food”), which cause effects similar to stimulants.

Symptoms include central nervous system (CNS) stimulation, anxiety, hyperactivity, hyperpyrexia, diaphoresis, hypertension, abdominal cramps, nausea and vomiting, and inability to void urine. MDMA has been associated with hyponatremia and seizures. Severe cases often include rhabdomyolysis and acidosis. A toxic psychosis indistinguishable from paranoid schizophrenia may occur. Methamphetamine laboratories in homes are a potential cause of childhood exposure to a variety of hazardous and toxic substances.

B. Chronic Poisoning

Chronic amphetamine users develop tolerance; more than 1500 mg of IV methamphetamine can be used daily. Hyperactivity, disorganization, and euphoria are followed by exhaustion, depression, and coma lasting 2–3 days. Heavy users, taking more than 100 mg/day, have restlessness, incoordination of thought, insomnia, nervousness, irritability, and visual hallucinations. Psychosis may be precipitated by the chronic administration of high doses. Chronic MDMA use can lead to serotonin depletion, which can manifest as depression, weakness, tremors, GI complaints, and suicidal thoughts.

Treatment

The treatment of choice are benzodiazepines, such as lorazepam, titrated in increments to effect. Very large total doses may be needed. In cases of extreme agitation or hallucinations, droperidol (0.1 mg/kg per dose) or haloperidol (up to 0.1 mg/kg) parenterally has been used. Hyperthermia should be aggressively controlled. Chronic users may be withdrawn rapidly from amphetamines.

ANESTHETICS, LOCAL

Intoxication from local anesthetics may be associated with CNS stimulation, acidosis, delirium, ataxia, shock, convulsions, and death. Methemoglobinemia has been reported following local mouth or dental analgesia, typically with benzocaine or prilocaine. It has also been reported with use of topical preparations in infants. The maximum recommended dose for subcutaneous (SQ) infiltration of lidocaine is 4.5 mg/kg (Table 13–3). The temptation to exceed this dose in procedures lasting a long time is great and may result in inadvertent overdosage. Oral application of viscous lidocaine may produce toxicity, and the US FDA has published warnings against its use for teething.

Local anesthetics used in obstetrics cross the placental barrier and are not efficiently metabolized by the fetal liver. Mepivacaine, lidocaine, and bupivacaine can cause fetal bradycardia, neonatal depression, and death. Accidental injection of mepivacaine into the head of the fetus during paracervical anesthesia has caused neonatal asphyxia, cyanosis, acidosis, bradycardia, convulsions, and death.

Treatment

If the anesthetic has been ingested, mucous membranes should be cleansed carefully, topical applications should be cleaned and irrigated. Oxygen administration is indicated, with assisted ventilation if necessary. Symptomatic methemoglobinemia is treated with methylene blue, 1%, 0.2 mL/kg (1–2 mg/kg per dose, IV) over 5–10 minutes; this should promptly relieve the cyanosis. Acidosis may be treated with sodium bicarbonate, hypotension with vasopressors, seizures with benzodiazepines, and bradycardia with atropine. In the event of cardiac arrest, 20% lipid (fat) emulsion therapy should be initiated. Initial 1.5 mL/kg bolus over 1 minute, followed by 0.25 mL/kg/min for up to 20–30 minutes until spontaneous circulation returns. Repeat bolus can be considered.

ANTIHISTAMINES & COUGH & COLD PREPARATIONS

The use of cough and cold preparations in young children has recently been called into question due to potential toxicity. Medications included in this area are antihistamine (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine), antitussive (dextromethorphan), expectorant (guaifenesin), and decongestant (pseudoephedrine, phenylephrine). In 2007, manufacturers voluntarily removed preparations intended for use in children younger than 4 years of age from the market. Most adverse events stem from unintentional ingestions of supratherapeutic doses of antihistamines or dextromethorphan. A high proportion of life threatening cases are associated with child abuse (sedating a child with medication). Considerable controversy remains as to the toxicity of these medications if they are used according to labeled directions and an evaluation of the cases on file at FDA stated, “In the cases judged to be therapeutic intent or unknown intent, several factors appeared to contribute to the administration of an overdosage: administration of two medicines containing the same ingredients, failure to use a measuring device, use of wrong units (mL vs teaspoon), use of an adult product, use of the wrong product because of product misidentification, and two or more caregivers administering the same medication. In the cases of nontherapeutic intent, circumstances involved attempts at sedation and several included apparent attempts of overt child abuse and were under investigation by law enforcement authorities.”

Although antihistamines typically cause CNS depression, children often react paradoxically with excitement, hallucinations, delirium, ataxia, tremors, and convulsions followed by CNS depression, respiratory failure, or cardiovascular collapse. A potentially toxic dose is 10–50 mg/kg of the most commonly used antihistamines, but toxic reactions have occurred at much lower doses. Anticholinergic effects such as dry mouth, fixed dilated pupils, flushed face, fever, and hallucinations may be prominent. Dextromethorphan can lead to altered mentation, hallucinations, nystagmus, and serotonin toxicity in large ingestions or when taken with other serotonergic agents. Death may occur with massive overdose.

Treatment

Benzodiazepines, such as lorazepam (0.1 mg/kg IV), can be used to control seizures or agitation. Physostigmine (0.5–2.0 mg IV, slowly administered) dramatically reverses the central and peripheral anticholinergic effects of antihistamines; however, the duration of effect is short. It can also be used only for diagnostic purposes in patients without cardiotoxicity or seizures. Cardiac dysrhythmias and hypotension should be treated with normal saline at a dose of 10–20 mg/kg and a vasopressor if necessary. Sodium bicarbonate may be useful if there is QRS widening at a dose of 1–2 mEq/kg, making certain that the arterial pH does not exceed 7.55. Forced diuresis is not helpful. Exchange transfusion was reported to be effective in one case.

BARBITURATES & BENZODIAZEPINES

Barbiturates are rarely used today, and have mostly been replaced with benzodiazepines for their use in seizures or for sedation. The toxic effects of barbiturates include confusion, poor coordination, coma, miotic or fixed dilated pupils, and respiratory depression. Respiratory acidosis is commonly associated with pulmonary atelectasis, and hypotension. Ingestion of more than 6 mg/kg of long-acting or 3 mg/kg of short-acting barbiturates is usually toxic. Benzodiazepines typically cause CNS depression and lethargy without hemodynamic compromise in unintentional oral ingestions. Large oral overdoses, co-ingestants with other sedative/hypnotics, or iatrogenic IV overdose can cause cardiovascular or respiratory depression.

Treatment

Careful, conservative management with emphasis on maintaining a clear airway, adequate ventilation, and control of hypotension is critical. Urinary alkalinization and the use of multiple-dose charcoal may decrease the elimination half-life of phenobarbital but have not been shown to alter the clinical course. Flumazenil can be considered if severe CNS depression or respiratory depression develops after benzodiazepine overdose using a dose of 0.01 mg/kg IV (maximum dose of 0.2 mg).

BELLADONNA ALKALOIDS (ATROPINE, JIMSONWEED, POTATO LEAVES, SCOPOLAMINE, STRAMONIUM)

The effects of anticholinergic (or antimuscarinic) compounds include dry mouth; thirst; decreased sweating with hot, dry, red skin; high fever; and tachycardia that may be preceded by bradycardia. The pupils are dilated, and vision is blurred. Speech and swallowing may be impaired. Hallucinations, delirium, and coma are common. Leukocytosis may occur, confusing the diagnosis.

Atropinism has been caused by normal doses of atropine or homatropine eye drops. Many common plants and over-the-counter medications (antihistamines and sleep aids) contain belladonna alkaloids or medications with anticholinergic effects.

Treatment

Gastric emptying is slowed by anticholinergics, so that gastric decontamination may be useful even if delayed. If the patient is awake and showing no signs or symptoms, administration of activated charcoal can be considered. Benzodiazepines should be administered to control agitation. Bolus dosing should be given in escalating doses, and high doses may be required. Physostigmine (0.5–2.0 mg IV, administered slowly) dramatically reverses the central and peripheral signs of atropinism but should be used only as a diagnostic agent, but clinical improvement is not sustained. Physostigmine infusions have been safely administered. It should not be given in patients with cardiotoxicity or seizures. Hyperthermia should be aggressively controlled. Catheterization may be needed if the patient cannot void.

β-BLOCKERS & CALCIUM CHANNEL BLOCKERS

β-Blockers and calcium channel blockers primarily cause cardiovascular toxicity; bradycardia, hypotension, and various degrees of heart block; cardiac dysrhythmias may develop. Severe toxicity can cause CNS depression (typically due to hemodynamic collapse). The β-blocker propranolol is associated with seizures and also QRS widening. Hyperglycemia can be seen with calcium channel blocker toxicity.

Treatment

Initial stabilization with IV fluid resuscitation with isotonic fluids should be initiated. Atropine can be given for symptomatic bradycardia. Calcium at doses of 20 mg/kg and repeated as needed should be administered. Infusions of calcium chloride 10%, 0.2–0.5 mL/kg/h, can be started after initial bolus dosing. Glucagon can be administered; 50–100 mcg/kg (5–10 mg) IV bolus followed by 2–5 mg/h infusion if patient improves. Vasopressors such as epinephrine or norepinephrine should be started if patient continues to be hypotensive and bradycardic. In patients who are severely poisoned and refractory to these initial measures, hyperinsulinemia euglycemic therapy should be started. Your regional poison control center or medical toxicologist should be contacted for further details on dosing of this therapy.

CARBON MONOXIDE

Carbon monoxide is a colorless, odorless gas produced from burning various fuels. The degree of toxicity correlates well with the carboxyhemoglobin concentration taken soon after acute exposure but not after oxygen has been given or when there has been some time since exposure. Onset of symptoms may be more rapid and more severe if the patient lives at a high altitude, has a high respiratory rate (ie, infants), is pregnant, or has myocardial insufficiency or lung disease. Normal blood may contain up to 5% carboxyhemoglobin (10% in smokers). Neonates may have elevated carboxyhemoglobin levels due to breakdown of bilirubin.

Presenting symptoms can include nonspecific symptoms such as headache or flu-like illness. Other effects include confusion, unsteadiness, and coma. Proteinuria, glycosuria, elevated serum aminotransferase levels, or ECG changes may be present in the acute phase. Other signs may include improvement of symptoms after leaving the exposed environment. Permanent cardiac, liver, renal, or CNS damage occurs occasionally. The outcome of severe poisoning may be complete recovery, vegetative state, or any degree of mental injury between these extremes. The primary delayed mental deficits are neuropsychiatric.

Treatment

The biologic half-life of carbon monoxide on room air is approximately 200–300 minutes; on 100% oxygen, it is 60–90 minutes. Thus, 100% oxygen should be administered immediately. Hyperbaric oxygen therapy at 2.0–2.5 atm of oxygen shortens the half-life to 30 minutes, but is practically difficult to deploy in a timely manner. The use of hyperbaric oxygen therapy for delayed neurologic sequelae can be considered, but remains controversial and the primary focus of care should be acute resuscitation and stabilization. After the level has been reduced to near zero, therapy is aimed at the nonspecific sequelae of anoxia. Evaluation of the source should be performed before the patient returns to the home.

CAUSTICS

Both acids and alkalis can burn the skin, mucous membranes, and eyes. Vomiting, dysphagia, airway emergencies, burns, and abdominal pain can occur after ingestion. Respiratory distress may be due to edema of the epiglottis, pulmonary edema resulting from inhalation of fumes, or pneumonia. In severe cases, mediastinitis, intercurrent infections, or shock can occur. Perforation of the esophagus or stomach is rare. Residual lesions include esophageal, gastric, and pyloric strictures as well as scars of the cornea, skin, and oropharynx.

1. Acids (Hydrochloric, Hydrofluoric, Nitric, & Sulfuric Acids; Sodium Bisulfate)

Strong acids are commonly found in metal and toilet bowl cleaners, batteries, and other products, and can lead to coagulative necrosis. Hydrofluoric acid is a particularly dangerous acid. Dermal exposure creates a penetrating burn that can progress for hours or days. Large dermal exposure or small ingestion may produce life-threatening hypocalcemia.

2. Bases (Clinitest Tablets, Clorox, Drano, Liquid-Plumr, Purex, Sani-Clor—Examine the Label or Call a Poison Center to Determine Contents)

Alkalis can produce more severe injuries than acids, resulting in liquefactive necrosis. Some substances, such as Clinitest tablets or Drano, are quite toxic, whereas the chlorinated bleaches (3%–6% solutions of sodium hypochlorite) are usually not toxic. When sodium hypochlorite comes in contact with acid in the stomach, hypochlorous acid, which is very irritating to the mucous membranes and skin, is formed. Chlorinated bleaches, when mixed with a strong acid (toilet bowl cleaners) or ammonia, may produce irritating chlorine or chloramine gas, which can cause serious lung injury if inhaled in a closed space (eg, bathroom).

Treatment

Emetics and lavage are contraindicated. Can be diluted with water, but take care not to induce emesis by excessive fluid administration. Neutralization should not be attempted. Burned areas of the skin, mucous membranes, or eyes should be washed with copious amounts of warm water. The eye should be irrigated for at least 20–30 minutes. Ophthalmologic consultation should be obtained for all alkaline eye burns. An endotracheal tube may be required to alleviate laryngeal edema. The absence of oral lesions does not rule out the possibility of laryngeal or esophageal burns following granular alkali ingestion. Esophagoscopy should be performed if the patient has significant burns or difficulty in swallowing, drooling, vomiting, or stridor. Evidence is not conclusive, but corticosteroids may be helpful in significant esophageal burns. Antibiotics may be needed if mediastinitis develops, but they should not be used prophylactically.

Hydrofluoric acid burns on skin are treated with 10% calcium gluconate gel or calcium gluconate infusion. Severe exposure may require large doses of IV calcium or cardiovascular monitoring. Therapy should be guided by calcium levels, the ECG, and clinical signs.

CENTRAL α₂-ADRENERGIC AGONIST

Central α₂-adrenergic agonists are common over-the-counter and prescribed medication. The imidazolines are found in nasal decongestants and eye drops to relieve redness. Clonidine and guanfacine are used most commonly to treat attention deficit hyperactivity disorder or hypertension. Dexmedetomidine is an IV central α₂-adrenergic agonist used for sedation. These medications exert their effects by stimulating presynaptic α₂-adrenergic receptors in the brain, resulting in decreased norepinephrine release and decreased sympathetic outflow.

Clinical Findings

Most common effects are related to CNS sedation. They can present similar to an opioid toxidrome with miosis, CNS depression, and respiratory depression. Other common effects include bradycardia and hypotension.

Treatment

If the patient becomes obtunded, or has inability to protect their airway, intubation may be indicated. Naloxone has been tried to reverse signs of toxicity with varying success. Symptomatic bradycardia can be treated with IV fluid resuscitation or atropine. Hypotension should be treated initially with IV fluid resuscitation, followed by vasopressors if needed.

COCAINE

Cocaine is absorbed intranasally, via inhalation or ingestion. Effects are noted almost immediately when the drug is taken intravenously or smoked and are delayed for about an hour when the drug is taken orally or nasally. Cocaine prevents the reuptake of endogenous catecholamines, thereby causing an initial sympathetic discharge, followed by catechol depletion after chronic abuse.

Clinical Findings

A local anesthetic and vasoconstrictor, cocaine is also a potent stimulant to both the CNS and the cardiovascular system. The initial tachycardia, hyperpnea, hypertension, and stimulation of the CNS are often followed by coma, seizures, hypotension, and respiratory depression. In severe cases of overdose, various dysrhythmias may be seen, including sinus tachycardia, atrial arrhythmias, premature ventricular contractions, bigeminy, and ventricular tachycardia and fibrillation. If large doses are taken intravenously, cardiac failure, dysrhythmias, rhabdomyolysis, or hyperthermia may result in death.

In addition to those poisoned through recreational use of cocaine, others are at risk of overdose. A “body stuffer” is one who quickly ingests the drug, usually poorly wrapped, to avoid discovery. A “body packer” wraps the drug carefully for prolonged transport. A stuffer typically manifests toxicity within hours of ingestion; a packer is asymptomatic unless the package ruptures, usually days later. Newborns of cocaine using mothers may continue to have seizures for months after birth. Cocaine can be contaminated with levamisole, which can lead to systemic vasculitis and agranulocytosis.

Treatment

Activated charcoal should be considered in body stuffers, and whole bowel irrigation may be useful in cases of body packers. Testing for cocaine in blood or plasma is generally not clinically useful, but a qualitative analysis of the urine may aid in confirming the diagnosis. Cocaine metabolites can be positive in urine for 3–5 days after exposure. For severe cases, an ECG is indicated. In suspected cases of body packing, radiographs of the GI tract may show multiple packets, but are usually not helpful for identifying stuffers. Seizures are treated with IV benzodiazepines such as lorazepam, titrated to response. Hypotension is treated with standard agents. Because cocaine abuse may deplete norepinephrine, an indirect agent such as dopamine may be less effective than a direct agent such as norepinephrine. Agitation is best treated with a benzodiazepine.

COSMETICS & RELATED PRODUCTS

Cosmetics and personal care products are the most frequently involved substance in pediatric patients younger than 5 years (14% of all calls reported to NPDS) and second most common in all ages. Luckily, most of them do not cause significant toxicity. The relative toxicities of commonly ingested products in this group are listed in Table 13–4.

CYCLIC ANTIDEPRESSANTS

Cyclic antidepressants (eg, amitriptyline, imipramine) have a very low ratio of toxic to therapeutic doses, and even a moderate overdose can have serious effects. Diphenhydramine toxicity can have similarly symptoms as cyclic antidepressants and is more readily available.

Cyclic antidepressant overdosage can cause a progression of illness beginning with sudden onset coma within 1–2 hours of ingestion, followed by convulsions, hypotension, and dysrhythmias. Usually significant clinical effects occur within hours after the ingestion, may be life-threatening and require rapid intervention. One agent, amoxapine, differs in that it causes fewer cardiovascular complications, but it is associated with a higher incidence of seizures.

Treatment

After a significant ingestion, decontamination should include administration of activated charcoal unless the patient is already symptomatic. Benzodiazepines should be given for seizures.

An ECG should be obtained in all patients. A QRS interval greater than 100 milliseconds specifically identifies patients at risk to develop seizures and dysrhythmias. If dysrhythmias or tachycardia are demonstrated, the patient should be admitted and monitored until free of irregularity for 24 hours. The onset of dysrhythmias is rare beyond 24 hours after ingestion.

Alkalinization with sodium bicarbonate boluses (0.5–1.0 mEq/kg IV) may dramatically reverse ventricular dysrhythmias and narrow the QRS interval. If intubated, hyperventilation may be helpful. Lidocaine may be added for treatment of arrhythmias. Bolus administration of sodium bicarbonate (1–2 mEq/kg) is recommended for all patients with QRS widening to above 120 milliseconds and for those with significant dysrhythmias, to achieve a pH of 7.5–7.6. Lipid-emulsion therapy has been used in the setting of cardiotoxicity.

Cyclic antidepressants block the reuptake of catecholamines, thereby producing initial hypertension followed by hypotension. Vasopressors (such as norepinephrine, 0.1–1 mcg/kg/min, titrated to response) are generally effective. Diuresis and hemodialysis are not effective and physostigmine is contraindicated.

DIGITALIS & OTHER CARDIAC GLYCOSIDES

Acute toxicity with digitalis is typically the result of incorrect dosing, and chronic toxicity is due to unrecognized renal insufficiency. In acute overdosage, hyperkalemia is more common. Hypokalemia is common in chronic toxicity Clinical features include nausea, vomiting, diarrhea, headache, delirium, confusion, and, occasionally, coma. Cardiac dysrhythmias typically involve bradydysrhythmias, but every type of dysrhythmia has been reported in digitalis intoxication, including atrial fibrillation, paroxysmal atrial tachycardia, and atrial flutter. Transplacental intoxication by digitalis has been reported. Cardiac glycosides, such as yellow oleander and foxglove, can cause digitalis toxicity in large ingestions as well.

Treatment

If patient is awake and alert, consider administering activated charcoal. Potassium is contraindicated in acute overdosage unless there is laboratory evidence of hypokalemia. Adequate fluid resuscitation is essential to aid in renal elimination.

The patient must be monitored carefully for ECG changes. Bradycardias have been treated with atropine. Phenytoin, lidocaine, magnesium salts (but not in renal failure), amiodarone, and bretylium have been used to correct arrhythmias.

Definitive treatment is with digoxin immune Fab (ovine) (Digifab). Indications for its use include hypotension or any dysrhythmia, typically ventricular dysrhythmias and progressive bradydysrhythmias, or hyperkalemia (K > 5) in an acute overdose. Elevated T waves indicate high potassium and may be an indication for digoxin immune Fab (DigiFab) use. Techniques of determining dosage and indications related to levels, when available are described in product literature. High doses of digoxin immune Fab may be needed in cardiac glycoside overdose. Extracorporeal treatment is not indicated for digoxin poisoning.

DIPHENOXYLATE WITH ATROPINE (LOMOTIL) & LOPERAMIDE (IMODIUM)

Loperamide (Imodium) has largely replaced Lomotil and does not produce significant toxicity. Ingestions of up to 0.4 mg/kg can safely be managed at home. Both acute and chronic abuse of loperamide has been associated with cardiac dysrhythmias.

Lomotil is still widely available and contains diphenoxylate hydrochloride, a synthetic narcotic, and atropine sulfate. Small amounts are potentially lethal in children; it is contraindicated in children younger than 2 years. Early signs of intoxication with this preparation result from its anticholinergic effect and consist of fever, facial flushing, tachypnea, and lethargy. However, the miotic effect of the narcotic predominates. Later, hypothermia, increasing CNS depression, and loss of the facial flush occur. Seizures are probably secondary to hypoxia. Any ingestion of Lomotil must be observed for 8–12 hours as delayed respiratory arrest may be encountered.

Treatment

Prolonged monitoring (24 hours) with pulse oximetry and careful attention to airway is sufficient in most cases. Naloxone hydrochloride (0.4–2.0 mg IV in children and adults) should be given for signs of respiratory depression. Repeated doses may be required because the duration of action of diphenoxylate is considerably longer than that of naloxone.

DISINFECTANTS & DEODORIZERS

1. Naphthalene

Naphthalene is now less commonly found in mothballs, disinfectants, and deodorizers. It is absorbed not only when ingested but also through the skin and lungs. It is potentially hazardous to store baby clothes in naphthalene, because baby oil is an excellent solvent that may increase dermal absorption. Metabolic products of naphthalene may cause severe hemolytic anemia 2–7 days after ingestion. Other physical findings include vomiting, diarrhea, jaundice, oliguria, anuria, coma, and convulsions.

Treatment

If the patient is awake and alert, consideration can be given for administering activated charcoal. Methemoglobinemia and hemolysis may occur 24–48 hours after ingestion. Life-threatening hemolysis and anemia may require blood transfusions.

2. p-Dichlorobenzene, Phenolic Acids, & Others

Disinfectants and deodorizers containing p-dichlorobenzene or sodium sulfate are now more commonly found in mothballs and much less toxic than those containing naphthalene. They typically cause mucous membrane irritation and GI upset. Camphor can cause seizures after ingestion.

Disinfectants containing phenolic acids are highly toxic, especially if they contain a borate ion. Phenol precipitates tissue proteins and can also cause systemic toxicity resulting in respiratory alkalosis followed by metabolic acidosis. Some phenols cause methemoglobinemia. Phenol is readily absorbed topically and from the GI tract, causing local injury, diffuse capillary damage and, in some cases, methemoglobinemia. Pentachlorophenol, which has been used in terminal rinsing of diapers, has caused infant fatalities by causing metabolic acidosis.

The toxicity of alkalis, quaternary ammonium compounds, pine oil, and halogenated disinfectants varies with the concentration of active ingredients. Wick deodorizers are usually of moderate toxicity. Iodophor disinfectants are the safest. Spray deodorizers are not usually toxic, because a child is not likely to swallow a very large dose.

Signs and symptoms of acute quaternary ammonium compound ingestion include diaphoresis, strong irritation, thirst, vomiting, diarrhea, cyanosis, hyperactivity, coma, convulsions, hypotension, abdominal pain, and pulmonary edema. Acute liver or renal failure may develop later.

Treatment

Mainstay to phenol toxicity is symptomatic and supportive care. The metabolic acidosis must be managed carefully. Anticonvulsants or measures to treat shock may be needed.

Because phenols are absorbed through the skin, exposed areas should be irrigated copiously with water. Undiluted polyethylene glycol may be a useful solvent as well.

DISK-SHAPED “BUTTON” BATTERIES

Over 60% of batteries that are ingested by children are obtained from manufactured household products. These small, flat, smooth disk-shaped batteries measure between 10 and 25 millimeter in diameter. About 69% of them pass through the GI tract in 48 hours and 85% in 72 hours. Some may become entrapped and lead to caustic injury. Batteries impacted in the esophagus may cause symptoms of refusal to take food, increased salivation, vomiting with or without blood, and pain or discomfort. Fatalities have been reported in association with esophageal perforation or fistula formation.

When a history of disk battery ingestion is obtained, radiographs of the entire respiratory tract and GI tract should be taken immediately so that the battery can be located and the proper therapy determined.

Treatment

Any disk battery ingestion should be referred for evaluation and radiographs. If at home and the patient is greater than 1 year of age, 10 ml of honey every 10 minutes for up to 6 doses is recommended. Upon arrival to an emergency department, sucralfate suspension 10 mL every 10 minutes should be administered until sedation is given for endoscopy. If the disk battery is located in the esophagus, it must be removed immediately. Any prolonged time in the esophagus can cause injury, leading to esophageal perforation, or erosion/fistula formation into a blood vessel. Consultation with GI or surgical subspecialty is recommended.

Location of the disk battery below the esophagus has been rarely associated with tissue damage. Perforated Meckel diverticulum has been the major complication. It may take as long as 7 days for spontaneous passage to occur, and lack of movement in the GI tract may not require removal in an asymptomatic patient.

Batteries that have opened in the GI tract have been rarely associated with some toxicity due to mercury, but the patients have recovered.

Asymptomatic patients, with known time of ingestion, patients greater than 5 years old, and with disk batteries past the lower esophageal junction may simply be observed and stools examined for passage of the battery. If the battery has not passed within 7 days or if the patient becomes symptomatic, radiographs should be repeated. If the battery has come apart or appears not to be moving, a purgative, enema, or nonabsorbable intestinal lavage solution should be considered. If these methods are unsuccessful, surgical intervention may be required. Levels of heavy metals (mainly mercury) should be measured in patients in whom the battery has opened or symptoms have developed.

ETHYLENE GLYCOL & METHANOL

Ethylene glycol and methanol are the toxic alcohols. The primary source of ethylene glycol is antifreeze, whereas methanol is present in windshield wiper fluid and also as an ethanol denaturant. Ethylene glycol causes severe metabolic acidosis and renal failure. Methanol causes metabolic acidosis and blindness. Onset of symptoms with both agents occurs within several hours after ingestion, longer if ethanol was ingested simultaneously. Rarely, glycol ethers can cause acidosis, but only in the setting of large ingestions.

Treatment

The primary treatment is to block the enzyme alcohol dehydrogenase, which converts both agents to their toxic metabolites. This is accomplished with fomepizole (loading dose of 15 mg/kg). Ethanol could be used if fomepizole is unavailable, but can lead to CNS depression and hypoglycemia in children. Hemodialysis is indicated with high concentrations, persistent metabolic acidosis, or end-organ toxicity.

γ-HYDROXYBUTYRATE, γ-BUTYROLACTONE, BUTANEDIOL, FLUNITRAZEPAM, & KETAMINE

γ-Hydroxybutyrate (GHB), γ-butyrolactone (GBL), and butanediol have become popular drugs of abuse in adolescents and adults. GHB is a CNS depressant that is structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid. GBL and butanediol are converted in the body to GHB. These drugs cause deep but short-lived coma; the coma often lasts only 1–4 hours. Flunitrazepam (Rohypnol) is a benzodiazepine that can lead to somnolence and CNS depression. Ketamine is a dissociative anesthetic that can also cause rapid onset altered mental status and CNS depression. Although all of these drugs are often referred to as “date rape” drugs, ethanol is the most commonly used substance in drug-facilitated assault.

Treatment consists of supportive care with close attention to airway and endotracheal intubation if respiratory depression or decreased gag reflex complicates the poisoning. Atropine has been used successfully for symptomatic bradycardia.

Withdrawal from GHB, GBL, or butanediol can cause several days of extreme agitation, hallucination, or tachycardia. Treatment with high doses of sedatives such as benzodiazepines or with butyrophenones (eg, haloperidol or droperidol) or secobarbital may be needed for several days.

HYDROCARBONS (BENZENE, CHARCOAL LIGHTER FLUID, GASOLINE, KEROSENE, PETROLEUM DISTILLATES, TURPENTINE)

Ingestion of hydrocarbons may cause irritation of mucous membranes, CNS depression, or aspiration pneumonitis. Hydrocarbons with high volatility, low viscosity, and low surface tension have more risk or aspiration pneumonitis. Benzene, kerosene, red seal oil furniture polish, and some of the essential oils are very dangerous. A dose exceeding 1 mL/kg is likely to cause CNS depression. A history of coughing or choking, as well as vomiting, suggests aspiration with resulting hydrocarbon pneumonia. Several weeks may be required for full resolution of hydrocarbon pneumonia. Pulmonary edema and hemorrhage, blebs, cardiac dilation and dysrhythmias, hepatosplenomegaly, proteinuria, and hematuria can occur following large overdoses.

Treatment

Both emetics and lavage should be avoided. Initial supportive care, observing for CNS depression or respiratory distress. Patients who are asymptomatic with a normal chest x-ray (CXR) after 8 hours are unlikely to develop significant illness; however, patients who develop respiratory symptoms, hypoxia, or CXR changes should be observed.

Epinephrine should be avoided with halogenated hydrocarbons because it may affect an already sensitized myocardium. The usefulness of corticosteroids is debated, and antibiotics should be reserved for patients with infections (pneumonitis can cause fevers and infiltrates). Surfactant therapy for severe hydrocarbon-induced lung injury has been used successfully. Extracorporeal membrane oxygenation has been successful in at least two cases of failure with standard therapy.

IBUPROFEN

Most exposures in children do not produce symptoms. In one study, for example, children ingesting up to 2.4 g remained asymptomatic. When symptoms occur, the most common are abdominal pain, vomiting, drowsiness, and lethargy. In rare cases, apnea (especially in young children), seizures, metabolic acidosis, and CNS depression leading to coma have occurred.

Treatment

If a child has ingested less than 100 mg/kg, supportive care for GI upset is typically all that is needed. When the ingested amount is more than 400 mg/kg, seizures or CNS depression may occur. There is no specific antidote. Neither alkalization of the urine nor hemodialysis is helpful in elimination of ibuprofen. However, hemodialysis may be needed to correct acid–base abnormalities.

INSECT STINGS (BEE, WASP, & HORNET)

Insect stings are painful but not usually dangerous; however, death from anaphylaxis may occur. Bee venom has hemolytic, neurotoxic, and histamine-like activities that can on rare occasion cause hemoglobinuria and severe anaphylactoid reactions. Massive envenomation from numerous stings may cause hemolysis, rhabdomyolysis, and shock leading to multiple-organ failure.

Treatment

The physician should remove the stinger, taking care not to squeeze the attached venom sac. For allergic reactions, epinephrine 1:1000 solution, 0.01 mL/kg, should be administered IV or SQ above the site of the sting. Albuterol, corticosteroids, and diphenhydramine are useful ancillary drugs but have no immediate effect. Ephedrine or antihistamines may be used for 2 or 3 days to prevent recurrence of symptoms.

For the more usual stings, cold compresses, aspirin, and diphenhydramine (1 mg/kg PO) are sufficient.

INSECTICIDES

The petroleum distillates or other organic solvents used in these products are often as toxic as the insecticide itself.

1. Chlorinated Hydrocarbons (eg, Aldrin, Carbinol, Chlordane, DDT, Dieldrin, Endrin, Heptachlor, Lindane, Toxaphene)

Signs of intoxication include salivation, GI irritability, abdominal pain, vomiting, diarrhea, CNS depression, and convulsions. Inhalation exposure causes irritation of the eyes, nose, and throat; blurred vision; cough; and pulmonary edema.

Chlorinated hydrocarbons are absorbed through the skin, respiratory tract, and GI tract. Decontamination of skin with soap and evacuation of the stomach contents should be considered in significant ingestions. All contaminated clothing should be removed. Convulsions should be treated with diazepam (0.1–0.3 mg/kg IV). Epinephrine should cautiously be used as it may precipitate cardiac arrhythmias.

2. Organophosphate (Cholinesterase-Inhibiting) Insecticides (eg, Chlorothion, Co-Ral, DFP, Diazinon, Malathion, Paraoxon, Parathion, Phosdrin, TEPP, Thio-TEPP)

Dizziness, headache, blurred vision, miosis, tearing, salivation, nausea, vomiting, diarrhea, hyperglycemia, cyanosis, sense of constriction of the chest, dyspnea, sweating, weakness, muscular twitching, convulsions, loss of reflexes and sphincter control, and coma can occur.

The clinical findings are the result of cholinesterase inhibition, which causes an accumulation of acetylcholine. The onset of symptoms occurs within 12 hours of the exposure. Red cell cholinesterase levels should be measured as soon as possible. (Some normal individuals have a low serum cholinesterase level.) Normal values vary in different laboratories. In general, a decrease of red cell cholinesterase to below 25% of normal indicates significant exposure.

Repeated low-grade exposure may result in sudden, acute toxic reactions. This syndrome usually occurs after repeated household spraying rather than agricultural exposure.

Although all organophosphates act by inhibiting cholinesterase activity, they vary greatly in their toxicity. Parathion, for example, is 100 times more toxic than malathion. Toxicity is influenced by the specific compound, type of formulation (liquid or solid), vehicle, and route of absorption (lungs, skin, or GI tract).

Treatment

Decontamination of skin, nails, hair, and clothing with soapy water is extremely important. Atropine plus a cholinesterase reactivator, pralidoxime, is an antidote for organophosphate insecticide poisoning. After assessment and management of the ABCs, atropine should be given and repeated every few minutes until airway secretions diminish. An appropriate starting dose of atropine is 2–4 mg IV in an adult and 0.05 mg/kg in a child. Severe poisoning may require gram quantities of atropine administered over 24 hours. Glycopyrrolate can also be used if delirium occurs.

Because atropine antagonizes the muscarinic parasympathetic effects of the organophosphates but does not affect the nicotinic receptor, it does not improve muscular weakness. Although the benefits remain controversial, pralidoxime should also be given immediately in more severe cases and repeated every 6–12 hours as needed (25–50 mg/kg diluted to 5% and infused over 5–30 minutes at a rate of no > 500 mg/min). Pralidoxime should be used in addition to—not in place of—atropine if red cell cholinesterase is less than 25% of normal. Pralidoxime is most useful within 48 hours after the exposure but has shown some effects 2–6 days later. Morphine, theophylline, aminophylline, succinylcholine, and tranquilizers of the reserpine and phenothiazine types are contraindicated. Hyperglycemia is common in severe poisonings.

3. Carbamates (eg, Carbaryl, Sevin, Zectran)

Carbamate insecticides are reversible inhibitors of cholinesterase. The signs and symptoms of intoxication are similar to those associated with organophosphate poisoning but are generally less severe. Atropine titrated to effect is sufficient treatment. In combined exposures to organophosphates, give atropine but reserve pralidoxime for cases in which the red cell cholinesterase is depressed below 25% of normal or marked effects of nicotinic receptor stimulation are present.

4. Botanical Insecticides (eg, Black Flag Bug Killer, Black Leaf CPR Insect Killer, Flit Aerosol House & Garden Insect Killer, French’s Flea Powder, Raid)

Allergic reactions, asthma-like symptoms, coma, and convulsions have been reported. Pyrethrins, allethrin, and rotenone do not commonly cause significant toxicity. Antihistamines, short-acting benzodiazepines, and atropine are helpful as symptomatic treatment.

IRON

Iron has many different formulations with varying amounts of elemental iron. Three common formulations include ferrous fumarate (33%), ferrous sulfate (20%), and ferrous gluconate (12%). Typically, doses of more than 20 mg/kg of elemental iron will cause symptoms. Five stages of intoxication may occur in iron poisoning: (1) Hemorrhagic gastroenteritis, which occurs 30–60 minutes after ingestion and may be associated with shock, acidosis, coagulation defects, and coma; this phase usually lasts 4–6 hours; (2) phase of improvement, lasting 2–12 hours, during which patient looks better; (3) delayed shock, which may occur 12–48 hours after ingestion; metabolic acidosis, fever, leukocytosis, and coma may also be present; (4) liver damage with hepatic failure; and (5) residual pyloric stenosis, which may develop about 4 weeks after the ingestion.

Treatment

GI decontamination is based on clinical assessment. The patient should be referred to a health care facility if symptomatic or if the history indicates toxic amounts (typically > 20 mg/kg of elemental iron). Gastric lavage and whole bowel irrigation should be considered in potentially life-threatening overdoses.

Shock is treated in the usual manner. Deferoxamine, a specific chelating agent for iron, is a useful adjunct in the treatment of severe iron poisoning. It forms a soluble complex that is excreted in the urine. It is contraindicated in patients with renal failure unless dialysis can be used. IV deferoxamine chelation therapy should be instituted if the patient has a metabolic acidosis, persistent symptoms, and a serum iron determination cannot be obtained readily, or if the peak serum iron exceeds 500 mcg/dL at 4–5 hours after ingestion.

Deferoxamine should not be delayed until serum iron levels are available in serious cases of poisoning. Intravenous administration is indicated if the patient is in shock, in which case it should be given at a dosage of 10–15 mg/kg/h. Infusion rates up to 35 mg/kg/h have been used in life-threatening poisonings. Rapid IV administration can cause hypotension, facial flushing, urticaria, tachycardia, and shock. Deferoxamine, 90 mg/kg IM every 8 hours (maximum, 1 g), may be given if IV access cannot be established, but the procedure is painful. The indications for discontinuation of deferoxamine have not been clearly delineated. Generally, it can be stopped after 12–24 hours if the acidosis has resolved and the patient is improving. Use of deferoxamine for greater than 24 hours has been associated with acute respiratory distress syndrome (ARDS).

Hemodialysis, peritoneal dialysis, or exchange transfusion can be used to increase the excretion of the dialyzable complex. Urine output should be monitored and urine sediment examined for evidence of renal tubular damage. Initial laboratory studies should include blood typing and cross-matching; total protein; serum iron, sodium, potassium, and chloride; PCO₂; pH; and liver function tests. Serum iron levels fall rapidly even if deferoxamine is not given.

After the acute episode, liver function studies and an upper GI series are indicated to rule out residual damage.

LEAD

Lead poisoning (plumbism) causes vague symptoms, including weakness, irritability, weight loss, vomiting, personality changes, ataxia, constipation, headache, and colicky abdominal pain. Late manifestations consist of developmental delays, convulsions, and coma associated with increased intracranial pressure, which is a medical emergency.

Plumbism usually occurs insidiously in children younger than age 5 years. The most likely sources of lead include flaking leaded paint, artist’s paints, fruit tree sprays, solder, brass alloys, home-glazed pottery, fumes from burning batteries, and foreign country remedies. Only paint containing less than 1% lead is safe for interior use (eg, furniture, toys). Repetitive ingestions of small amounts of lead are far more serious than a single massive exposure. Toxic effects are likely to occur if more than 0.5 mg of lead per day is absorbed. In the United States, lead levels continue to decline and are more common abroad, so particular attention should be paid to immigrant and refugee populations or use of foreign remedies.

Blood lead levels are used to assess the severity of exposure. A complete blood count and serum ferritin concentration should be obtained; iron deficiency increases absorption of lead. Glycosuria, proteinuria, hematuria, and aminoaciduria occur frequently. Abnormal capillary blood lead levels should be repeated with venous sample in asymptomatic patients to rule out laboratory error. Specimens must be meticulously obtained in acid-washed metal-free containers. A normocytic, slightly hypochromic anemia with basophilic stippling of the red cells and reticulocytosis may be present in plumbism. Stippling of red blood cells is absent in cases involving only recent ingestion.

The cerebrospinal fluid (CSF) protein is elevated, and the white cell count usually is less than 100 cells/mL. CSF pressure may be elevated in patients with encephalopathy; lumbar punctures must be performed cautiously to prevent herniation.

Treatment

Refer to the CDC guidelines for the most up-to-date recommendations on lead treatment and evaluation. There is no “safe” concentration of lead. Removing the source of exposure is the most important initial treatment to toxicity. Succimer is an orally administered chelator approved for use in children and reported to be as efficacious as calcium edetate. Succimer should be initiated in asymptomatic children at blood lead levels over 45 mcg/dL. The initial dose is 10 mg/kg (350 mg/m²) every 8 hours for 5 days. The same dose is then given every 12 hours for 14 days. At least 2 weeks should elapse between courses. Blood lead levels increase somewhat (ie, rebound) after discontinuation of therapy. Courses of dimercaprol/BAL (300–450 mg/m²/day) and calcium sodium edetate/CaNa2EDTA (1000–1500 mg/m²/day) should be considered in symptomatic children or levels over 70 mcg/dL.

Encephalopathy associated with cerebral edema needs to be treated with standard measures. Anticonvulsants may be needed. A high-calcium, high-phosphorus diet and large doses of vitamin D may remove lead from the blood by depositing it in the bones. A public health team should evaluate the source of the lead. Necessary corrections should be completed before the child is returned home.

MAGNETS

Although not strictly toxic, small magnets have been found to cause bowel obstructions in children. Recent cases have resulted in warnings and a recall by the Consumer Product Safety Commission following intestinal perforation and death in a 20-month-old child. Obstruction may occur following ingestion of as few as two magnets. Radiographs should be obtained and surgical consultation may be indicated.

MARIJUANA

Marijuana is becoming more readily available as over half of US states have allowed medical marijuana, and several more allowing recreational marijuana. It is also available for use in multiple forms, including high concentrated products (dabs, butters, waxes), vaporizers, and infused edible products that all can have high concentrations of THC (tetrahydrocannabinol), the most psychoactive component.

Young children who ingest edible products can have a range of symptoms. These symptoms can be mild such as sleepiness and ataxia. However, more severe symptoms can develop, including CNS depression, coma, and respiratory depression requiring mechanical ventilation. Symptoms in young children can sometimes last over 24 hours. Inhalational use/abuse of high concentrated products can lead to tachycardia, hypertension, agitation, and acute psychosis. Habitual use has led to significant nausea, vomiting, and abdominal pain relieved by hot showers, often labeled “Cannabinoid Hyperemesis Syndrome (CHS).” Symptomatic and supportive care is mainstay for treatment: supporting cardiorespiratory adverse effects, and treating psychosis and agitation with benzodiazepines or antipsychotics. Capsaicin cream has reported to improve CHS symptoms.

MUSHROOMS

Toxic mushrooms are often difficult to distinguish from edible varieties. Contact a poison control center to obtain identification assistance. Symptoms vary with the species ingested, time of year, stage of maturity, quantity eaten, method of preparation, and interval since ingestion. Most mushrooms lead to early GI symptoms and do not lead to significant toxicity; however, some can be fatal and so it is critical to determine from poison center experts what mushroom may have been involved. A mushroom that is toxic to one individual may not be toxic to another. Drinking alcohol and eating certain mushrooms may cause a reaction similar to that seen with disulfiram and alcohol. Cooking destroys some toxins but not the deadly one produced by Amanita phalloides, which is responsible for 90% of deaths due to mushroom poisoning. Mushroom toxins are absorbed relatively slowly. Onset of symptoms within 2 hours of ingestion suggests muscarinic toxin, whereas a delay of symptoms for 6–48 hours after ingestion strongly suggests Amanita (amanitin) poisoning. Patients who have ingested A phalloides may relapse and die of hepatic or renal failure following initial improvement.

Treatment

Treatment of mushroom poisoning is highly specialized and consultation with a poison center is highly recommended. Supportive care with IV fluid resuscitation may be needed due to emesis and diarrhea. If the patient has muscarinic signs, give atropine, 0.05 mg/kg IM (0.02 mg/kg in toddlers), and repeat as needed (usually every 30 minutes) Atropine, however, is used only when cholinergic effects are present and not for all mushrooms. Hypoglycemia is most likely to occur in patients with delayed onset of symptoms. Try to identify the mushroom if the patient is symptomatic. Local botanical gardens, university departments of botany, and societies of mycologists may be able to help. Supportive care is usually all that is needed; however, in the case of A phalloides, silibinin, biliary drainage, and aggressive management of fluids including hemodialysis may be indicated. Currently, there is clinical trial using intravenous silibinin for amatoxin-induced hepatic failure, protocol available on http://www.clinicaltrials.gov.

NITRITES, NITRATES, ANILINE, PENTACHLOROPHENOL, & DINITROPHENOL

Nausea, vertigo, vomiting, cyanosis (methemoglobinemia), cramping, abdominal pain, tachycardia, cardiovascular collapse, tachypnea, coma, shock, convulsions, and death are possible manifestations of nitrite or nitrate poisoning.

Nitrite and nitrate compounds found in the home include amyl nitrite, butyl nitrates, isobutyl nitrates, nitroglycerin, pentaerythritol tetranitrate, sodium nitrite, nitrobenzene, and phenazopyridine. Pentachlorophenol and dinitrophenol, which are found in wood preservatives, produce methemoglobinemia and acidosis because of uncoupling of oxidative phosphorylation. Headache, dizziness, and bradycardia have been reported. High concentrations of nitrites in well water or spinach have been the most common cause of nitrite-induced methemoglobinemia. Other common causes of methemoglobinemia include local anesthetics. Symptoms do not usually occur until 15%–50% of the hemoglobin has been converted to methemoglobin. A rapid test is to compare a drop of normal blood with the patient’s blood on a dry filter paper. Brown discoloration of the patient’s blood indicates a methemoglobin level of more than 15%.

Treatment

In the setting of a recent ingestion, consider administering activated charcoal if the patient is awake and alert. Decontaminate affected skin with soap and water. Oxygen and artificial respiration may be needed. If the blood methemoglobin level exceeds 30%, or if levels cannot be obtained and the patient is symptomatic, give a 1% solution of methylene blue (0.2 mL/kg IV) over 5–10 minutes. Avoid perivascular infiltration, because it causes necrosis of the skin and subcutaneous tissues. A dramatic change in the degree of cyanosis should occur. Transfusion is occasionally necessary. If reflex bradycardia occurs, atropine should be used.

OPIOIDS & OPIATES

Opioid and opiate-related medical problems may include drug addiction, withdrawal in a newborn infant, and accidental overdoses. They can vary in onset of action and duration of action. Many opioids are detected in common urine drug assays, but the substances detected vary by facility. Check with your hospital laboratory to determine which opioids are detected. Use of fentanyl analogs (carfentanyl) and fentanyl contamination in heroin and other drugs of abuse have increased, contributing to local outbreaks and mortality rates.

Opioid-addicted adolescents often have other medical problems, including cellulitis, abscesses, thrombophlebitis, tetanus, infective endocarditis, human immunodeficiency virus (HIV) infection, tuberculosis, hepatitis, malaria, foreign body emboli, thrombosis of pulmonary arterioles, diabetes mellitus, obstetric complications, nephropathy, and peptic ulcer.

Treatment

A. Overdose

Opioids and opiates can cause respiratory depression, stridor, coma, increased oropharyngeal secretions, sinus bradycardia, and urinary retention. Pulmonary edema rarely occurs in children but has been reported; deaths usually result from aspiration of gastric contents, respiratory arrest, and cerebral edema.

The indication for the administration of naloxone is respiratory depression. Although suggested doses for naloxone hydrochloride range from 0.01 to 0.1 mg/kg, it is generally unnecessary to calculate the dosage on this basis. This extremely safe antidote should be given in sufficient quantity to reverse opioid-binding sites. Doses as low as 0.04 mg have been affective for reversal. For children younger than 1 year, one ampoule (0.4 mg) should be given initially; if there is no response, five more ampoules (2 mg) should be given rapidly. Older children should be given 0.4–0.8 mg, followed by 2–4 mg if there is no response. An improvement in respiratory status may be followed by respiratory depression, because the antagonist’s duration of action is less than 1 hour. Neonates poisoned in utero may require 10–30 mg/kg to reverse the effect. Naloxone infusion can be used for persistent symptoms. Depending on the formulation, some exposures (such as buprenorphine and methadone) may need to be observed for 24 hours due to the duration of effect.

B. Withdrawal in the Addicted Patient

Benzodiazepines such as diazepam (10 mg every 6 hours PO) and antiemetics have been recommended for the treatment of mild narcotic withdrawal in ambulatory adolescents. Management of withdrawal may be accomplished with the administration of clonidine, by substitution with methadone or buprenorphine, or with reintroduction of the original addicting agent, if available through a supervised drug withdrawal program. A tapered course over 3 weeks will accomplish this goal. Death rarely, if ever, occurs. The abrupt discontinuation of narcotics (cold turkey method) is not recommended and may cause severe physical withdrawal signs.

C. Withdrawal in the In-utero Exposed Newborn

A newborn infant in opioid withdrawal is usually small for gestational age and demonstrates yawning, sneezing, decreased Moro reflex, hunger but uncoordinated sucking action, jitteriness, tremor, constant movement, a shrill protracted cry, increased tendon reflexes, convulsions, vomiting, fever, watery diarrhea, cyanosis, dehydration, vasomotor instability, seizure, and collapse.

The onset of symptoms commonly begins in the first 48 hours but may be delayed as long as 8 days, depending on the timing of the mother’s last use and her predelivery medication. Several treatment methods, both pharmacologic and nonpharmacologic, have been suggested for narcotic withdrawal in the newborn, including phenobarbital, morphine, methadone, and buprenorphine. The mortality rate of untreated narcotic withdrawal in the newborn may be as high as 45%.

ORAL ANTI-DIABETICS (SULFONYLUREAS, METFORMIN)

Noninsulin hypoglycemic and antidiabetic medications include α-glucosidase inhibitors, biguanides (metformin), dipeptidyl peptidase-4 inhibitors (-gliptins), glucagon-like peptides (-glutide), meglitinides (-glinide), sodium glucose transporter inhibitors (-flovzin), sulfonylureas, and thiazolidinediones (-glitazone). They are all used to treat hyperglycemia in diabetics. Sulfonylureas (acetohexamide, glipizide, glyburide) are the only oral hypoglycemic that actively secretes endogenous insulin and can cause hypoglycemia. The meglitinides (nateglinide, repaglinide) have scarce reports of hypoglycemia. Biguanides can rarely cause lactic acidosis in acute large overdose or in renal failure. Hypoglycemic symptoms are variable but can include altered mental status, diaphoresis, seizures, or coma.

Treatment

Children with possible exposures to sulfonylureas should be admitted for 12–24 hours. Mainstay of treatment is treating hypoglycemia. If patient is awake and alert, with minimal symptoms, PO glucose can be given. With more severe hypoglycemia or symptomatic, immediate treatment with 0.5–1 g/kg IV dextrose bolus should be administered. With repeated episodes of hypoglycemia, once euglycemia is achieved, octreotide should be considered at 1 mcg/kg SC/IV every 6–8 hours as needed for hypoglycemia. Metformin toxicity should be treated supportively, lactate can be a measure for toxicity, and hemodialysis may be needed for severe acid-base abnormalities or patients with renal failure.

ANTIPSYCHOTICS (TYPICAL & ATYPICAL)

Typical antipsychotics include butyrophenones (droperidol, haloperidol), and the phenothiazines (promethazine, chlorpromazine, thioridazine). Atypical antipsychotics include benzapines (clozapine, olanzapine, quetiapine) and indoles (risperidone, ziprasidone).

Clinical Findings

A. Extrapyramidal Crisis

Episodes characterized by torticollis, stiffening of the body, spasticity, poor speech, catatonia, and inability to communicate although conscious are typical manifestations. Extrapyramidal crises may represent idiosyncratic reactions and are aggravated by dehydration. The signs and symptoms occur most often in children who have received prochlorperazine. They are commonly mistaken for psychotic episodes. These extrapyramidal symptoms are more common with typical antipsychotics (butyrophenones, phenothiazines).

B. Overdose

Lethargy and deep prolonged coma are the most common symptoms seen in toxicity. Of the typical antipsychotics, promazine, chlorpromazine, and prochlorperazine are the drugs most likely to cause respiratory depression and precipitous drops in blood pressure. Risperidone and quetiapine are atypical antipsychotics that can cause CNS depression. Clozapine, olanzapine, and quetiapine most commonly cause hypotension and also antimuscarinic symptoms. QTc prolongation can occur, most commonly with thioridazine and ziprasidone, however dysrhythmias are rare. Occasionally, paradoxical hyperactivity and extrapyramidal signs as well as hyperglycemia and acetonemia are present. Seizures are uncommon.

C. Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome is a rare idiosyncratic complication that may be lethal. It is a syndrome involving mental status change (confusion, coma), motor abnormalities (lead pipe rigidity, clonus), and autonomic dysfunction (tachycardia, hyperpyrexia). Typically, it occurs 1–2 weeks after starting therapy, can occur at therapeutic doses, and may last for several days.

Treatment

Extrapyramidal signs are alleviated within minutes by the slow IV administration of diphenhydramine, 1–2 mg/kg (maximum, 50 mg), or benztropine mesylate, 1–2 mg IV (1 mg/min). No other treatment is usually indicated. Further doses may be needed.

Patients with overdoses should receive conservative supportive care. Hypotension may be treated with standard agents, starting with isotonic saline administration. Agitation is best treated with benzodiazepines. Neuroleptic malignant syndrome is treated by discontinuing the drug, and treating hyperthermia and agitation aggressively with benzodiazepines and sedation. In refractory cases, bromocriptine can be considered, although the evidence for its use is not clear.

PLANTS

Many common ornamental, garden, and wild plants are potentially toxic. Only in a few cases will small amounts of a plant cause severe illness or death. Table 13–5 lists the most toxic plants, symptoms and signs of poisoning, and treatment. Contact your poison control center for assistance with identification.

PSYCHOTROPIC DRUGS

Psychotropic drugs consist of four general classes: stimulants (amphetamines, cocaine, nicotine), depressants (eg, narcotics, barbiturates), antidepressants and tranquilizers, and psychoactive drugs (hallucinogens such as lysergic acid diethylamide [LSD], phencyclidine [PCP]).

Clinical Findings

The following clinical findings are commonly seen in patients abusing drugs. See also other entries discussed in alphabetic order in this chapter.

A. Stimulants

Agitation, euphoria, grandiose feelings, tachycardia, fever, abdominal cramps, visual and auditory hallucinations, mydriasis, coma, convulsions, and respiratory depression. Nicotine is associated with vomiting, hypertension and tachycardia, followed by symptoms of cholinergic excess, seizures and weakness.

B. Depressants

Emotional lability, ataxia, diplopia, nystagmus, vertigo, poor accommodation, respiratory depression, coma, apnea, and convulsions. Narcotics cause miotic pupils and, occasionally, pulmonary edema.

C. Antidepressants and Tranquilizers

Hypotension, lethargy, respiratory depression, coma, and extrapyramidal reactions.

D. Hallucinogens and Psychoactive Drugs

Belladonna alkaloids cause anticholinergic toxicity: mydriasis, dry mouth, nausea, vomiting, urinary retention, delirium, agitation, hallucinations, fever, hypotension, convulsions, and coma. Psychoactive drugs such as LSD cause mydriasis, unexplained bizarre behavior, hallucinations, and generalized undifferentiated psychotic behavior. Marijuana can cause tachycardia, anxiety, dysphoria, and vomiting.

Treatment

Only a small percentage of the persons using drugs come to the attention of physicians; those who do are usually experiencing adverse reactions such as panic states, drug psychoses, homicidal or suicidal thoughts, or respiratory depression.

Even with cooperative patients, an accurate history is difficult to obtain. A drug history is most easily obtained in a quiet spot by a gentle, nonthreatening, honest examiner, and without the parents present. Street drugs are often adulterated with one or more other compounds and the exact dose is unknown. Multiple drugs are often taken together. Friends may be a useful source of information.

Hallucinogens are not life-threatening unless the patient is frankly homicidal or suicidal. A specific diagnosis is usually not necessary for management; instead, the presenting signs and symptoms are treated. Does the patient appear intoxicated? In withdrawal? “Flashing back?” Is some illness or injury (eg, head trauma) being masked by a drug effect? (Remember that a known drug user may still have hallucinations from meningoencephalitis.)

The signs and symptoms in a given patient are a function not only of the drug and the dose but also of the level of acquired tolerance, the “setting,” the patient’s physical condition and personality traits, the potentiating effects of other drugs, and many other factors.

A common drug problem is the “bad trip,” which is usually a panic reaction. This is best managed by speaking calmly with the patient and minimizing auditory and visual stimuli. Allowing the patient to sit with a friend while the drug effect dissipates may be the best treatment. This may take several hours.

Drug therapy is often unnecessary and may complicate the clinical course of a drug-related panic reaction. Although phenothiazines have been commonly used to treat bad trips, they should be avoided if the specific drug is unknown, because they may enhance toxicity or produce unwanted side effects. Benzodiazepines are the drug of choice if a sedative effect is required. Physical restraints are rarely indicated and usually increase the patient’s panic reaction. After the acute episode, the physician must decide whether psychiatric referral is indicated.

SALICYLATES

The use of childproof containers and publicity regarding accidental poisoning have reduced the incidence of acute salicylate poisoning. Oil of wintergreen ingestion can also lead to salicylate toxicity. Nevertheless, serious intoxication still occurs and must be regarded as an emergency.

Salicylates uncouple oxidative phosphorylation, leading to increased heat production, excessive sweating, and dehydration. They also interfere with glucose metabolism and may cause hypo- or hyperglycemia. Respiratory center stimulation occurs early. The severity of acute intoxication can, in some measure, be judged by serum salicylate levels. High levels are always dangerous irrespective of clinical signs, and low levels may be misleading in chronic cases.

In mild and moderate poisoning, stimulation of the respiratory center produces respiratory alkalosis and may complain of tinnitus or hearing loss. Vomiting is also a common presenting symptom. In severe intoxication (occurring in severe acute ingestion with high salicylate levels and in chronic toxicity with lower levels), respiratory response is unable to overcome the metabolic overdose which may lead to fever, diaphoresis, pulmonary edema, seizures, and death.

Once the urine becomes acidic, less salicylate is excreted. Until this process is reversed, the half-life will remain prolonged, because metabolism contributes little to the removal of salicylate. Chronic severe poisoning may occur as early as 3 days after a regimen of salicylate is begun. Findings usually include vomiting, diarrhea, and dehydration.

Treatment

Charcoal binds salicylates well and should be given for acute ingestions in patients now vomiting with normal mentation. Mild poisoning may require only the administration of oral fluids and confirmation that the salicylate level is falling (< 30 mg/dL). Moderate poisoning involves moderate dehydration and depletion of potassium. Fluids must be administered at a rate of 2–3 mL/kg/h to correct dehydration and produce urine with a pH of greater than 7.0. Initial IV solutions should be isotonic (D5W with 150 mEq sodium bicarbonate). Once the patient is rehydrated, the solution can contain more free water and approximately 40 mEq/L of K⁺.

Severe toxicity is marked by major dehydration. Symptoms may be confused with those of Reye syndrome, encephalopathy, and metabolic acidosis. Salicylate levels may even be in the therapeutic range. Major fluid correction of dehydration is required. Once this has been accomplished, hypokalemia must be corrected and sodium bicarbonate given. Usual requirements are sodium bicarbonate, 1–2 mEq/kg/h over the first 6–8 hours, and K⁺, 20–40 mEq/L. A urine flow of 2–3 mL/kg/h should be established. Despite this treatment, some patients will develop the paradoxical aciduria of salicylism. This is due to hypokalemia and the saving of K⁺ and excretion of H⁺ in the renal tubule. Correction of K⁺ will allow the urine to become alkaline and ionize the salicylate, resulting in excretion rather than reabsorption of nonionized salicylate in acid urine.

Patients with renal failure, pulmonary edema, mental status changes, seizures, or concentrations of greater than 100 mg/dL should be considered for hemodialysis.

SCORPION STINGS

Scorpion stings are common in the southwestern United States. Although neurologic manifestations may last a week, most clinical signs subside within 24–48 hours.

The most common scorpions in the United States are Vejovis, Hadrurus, Androctonus, and Centruroides species. Stings by the first three produce edema and pain. Stings by Centruroides (the Bark scorpion) are most clinically significant and can cause tingling or burning paresthesias that begin at the site of the sting. In small children, hypersalivation, restlessness, muscular fasciculation, abdominal cramps, opisthotonos, convulsions, urinary incontinence, and respiratory failure may occur.

Treatment

Sedation with benzodiazepines is the primary therapy. Antivenom is reserved for severe poisoning, recommended dosing of 1–3 vials. In severe cases, the airway may become compromised by secretions and weakness of respiratory muscles. Endotracheal intubation may be required. Patients may require treatment for seizures, hypertension, or tachycardia. The prognosis is good as long as the patient’s airway is managed appropriately and sedation is achieved.

SEROTONIN REUPTAKE INHIBITORS

Fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and many other agents comprise this class of drugs. Adverse effects in therapeutic dosing include sedation, suicidal thoughts, aggressive behavior, and extrapyramidal effects. In overdose may include vomiting, lethargy, hypertension, tachycardia, hyperthermia, and abdominal pain, but rarely seizures and cardiac dysrhythmias. The findings in overdose are included in the serotonin syndrome due to the action of these drugs, which results in an increase of serotonin (5-hydroxytryptamine [5-HT]). Despite the degree of toxicity these agents generally are not life-threatening and intervention usually is not necessary.

Laboratory measurements of the drugs are not of benefit other than to establish their presence.

Treatment of agitation, hyperthermia with benzodiazepines is most beneficial. Hypotension may be treated with fluids or norepinephrine. Cyproheptadine is an antagonist of serotonin, but evidence for its use is limited. A dose of 0.25 mg/kg/day divided every 6 hours to a maximum of 12 mg/day may be useful in treating the serotonin syndrome. Adults and older adolescents have been treated with 12 mg initially followed by 2 mg every 2 hours to a maximum of 32 mg/day.

SNAKEBITE

Nearly all poisonous snakebites in the United States are caused by pit vipers (rattlesnakes, water moccasins, and copperheads). A few are caused by elapids (coral snakes), and occasional bites occur from cobras and other nonindigenous exotic snakes kept as pets. Snake venom is a complex mixture of enzymes, peptides, and proteins that may have predominantly cytotoxic, neurotoxic, hemotoxic, or cardiotoxic effects but other effects as well. Up to 25% of bites by pit vipers do not result in venom injection. US pit viper venom causes predominantly local injury with pain, discoloration, edema, and thrombocytopenia.

The outcome depends on the size of the child, the site of the bite, the degree of envenomation, the type of snake, and the effectiveness of treatment. Swelling and pain occur soon after rattlesnake bite and are a certain indication that envenomation has occurred. During the first few hours, swelling and ecchymosis extend proximally from the bite. The bite is often obvious as a double puncture mark surrounded by ecchymosis. Hematemesis, melena, hemoptysis, and other manifestations of coagulopathy rarely develop in severe cases. Rarely, respiratory difficulty and shock are the ultimate causes of death.

Coral snake envenomation causes little local pain, swelling, or necrosis, and systemic reactions are often delayed. The signs of coral snake envenomation include bulbar paralysis, dysphagia, and dysphoria; these signs may appear in 5–10 hours and may be followed by total peripheral paralysis and death in 24 hours.

Treatment

A. Emergency (First-Aid) Treatment

The most important first-aid measure is transportation to a medical facility. Splint the affected extremity and minimize the patient’s motion. Tourniquets and ice packs are contraindicated. Incision and suction are not useful for either crotalid or elapid snake bite.

B. Definitive Medical Management

Blood should be drawn for hematocrit, clotting time and platelet function, and serum electrolyte determinations. Establish two secure IV sites for the administration of antivenom and other medications.

Specific antivenom is indicated when signs of progressive envenomation are present. For coral snake bites, an eastern coral snake antivenom (Wyeth Laboratories) is sparingly available. Patients with pit viper bites should receive polyvalent crotaline antivenom IV (Fab or Fab₂) if progressive local injury, coagulopathy, or systemic signs (eg, hypotension, confusion) are present. See package labeling or call your poison center for details of use. Antivenom will halt progression of symptoms and improve hemorrhage, pain, and shock. For any history of coral snake bites, give three to five vials of antivenom in 250–500 mL of isotonic saline solution if available and observation for at least 24 hours. An additional three to five vials may be required. While generally considered best if administered within the first 6 hours, recent evidence demonstrates that delayed use may be therapeutic.

Administer an opioid or opiate to control pain. Cryotherapy is contraindicated because it commonly causes additional tissue damage. Early physiotherapy minimizes contractures. In rare cases, fasciotomy to relieve pressure within muscular compartments is required; recommend measurements of pressures before fasciotomy. Antihistamines and corticosteroids (hydrocortisone, 1 mg/kg, given PO for a week) are useful in the treatment of serum sickness or anaphylactic shock. Antibiotics are not needed unless clinical signs of infection occur. Tetanus status should be evaluated and the patient immunized, if needed. Recurrent coagulopathy and thrombocytopenia may occur after discharge, and patients should have follow up examinations and repeat laboratory values within 1 week after hospital discharge.

SOAPS & DETERGENTS

1. Soaps

Soap is made from salts of fatty acids. Ingestion of soap bars may cause vomiting and diarrhea, but they have a low toxicity.

2. Detergents

Detergents are nonsoap synthetic products used for cleaning purposes because of their surfactant properties. Commercial products include granules, powders, and liquids. Dishwasher detergents are very alkaline and can cause caustic burns. Low concentrations of bleaching and antibacterial agents as well as enzymes are found in many preparations. The pure compounds are moderately toxic, but the concentration used is too small to alter the product’s toxicity significantly, although occasional primary or allergic irritative phenomena have been noted in persons who frequently use such products and in employees manufacturing these products. Unit dose detergents, or packets, have become popular and have packaging attractive to young children. They are usually a mix of glycol ethers, ethyl alcohol and surfactant. They typically cause local irritation but can lead to more severe symptoms including corneal injuries, CNS depression and respiratory distress if ingested.

A. Cationic Detergents (Ceepryn, Diaparene Cream, Phemerol, Zephiran)

Cationic detergents in dilute solutions (0.5%) cause mucosal irritation, but higher concentrations (10%–15%) may cause caustic burns to mucosa. Clinical effects include nausea, vomiting, collapse, coma, and convulsions. As little as 2.25 g of some cationic agents have caused death in an adult. In four cases, 100–400 mg/kg of benzalkonium chloride caused death. Cationic detergents are rapidly inactivated by tissues and ordinary soap. Because of the caustic potential and rapid onset of seizures, emesis is not recommended. Anticonvulsants may be needed.

B. Anionic Detergents

Most common household detergents are anionic. Laundry compounds have water softener (sodium phosphate) added, which is a strong irritant and may reduce ionized calcium. Anionic detergents irritate the skin by removing natural oils. Although ingestion causes diarrhea, intestinal distention, and vomiting, no fatalities have been reported. The only treatment usually required is to discontinue use if skin irritation occurs and replace fluids and electrolytes. Induced vomiting is not indicated following ingestion of automatic dishwasher detergent, because of its alkalinity.

C. Nonionic Detergents (Brij Products; Tritons X-45, X-100, X-102, and X-144)

These compounds include lauryl, stearyl, and oleyl alcohols and octyl phenol. They have a minimal irritating effect on the skin and are almost always nontoxic when swallowed.

SPIDER BITES

Most medically important bites in the United States are caused by the black widow spider (Latrodectus mactans) and the North American brown recluse (violin) spider (Loxosceles reclusa). Positive identification of the spider is helpful, because many spider bites may mimic those of the brown recluse spider.

1. Black Widow Spider

The black widow spider is endemic to nearly all areas of the United States. The initial bite causes sharp fleeting pain that spreads centripetally. Local and systemic muscular cramping, abdominal pain, periorbital edema, nausea and vomiting, tachycardia, and hypertension are common. Systemic signs of black widow spider bite may be confused with other causes of acute abdomen. Although paresthesias, nervousness, and transient muscle spasms may persist for weeks in survivors, recovery from the acute phase is generally complete within 2–3 days. In contrast to popular opinion, death is extremely rare.

Initial pain control should be achieved with use of benzodiazepines and opioids or opiates. Antivenom is effective and is recommended in severe cases in which the previously mentioned therapies have failed.

2. Brown Recluse Spider (Violin Spider)

The North American brown recluse spider is most commonly seen in the central and Midwestern areas of the United States. Its bite characteristically produces a localized reaction with progressively severe pain within 24 hours. The initial bleb on an erythematous ischemic base is replaced by a black eschar within 1 week. This eschar separates in 2–5 weeks, leaving an ulcer that heals slowly. Systemic signs (loxoscelism) include cyanosis, morbilliform rash, fever, chills, malaise, weakness, nausea and vomiting, joint pains, hemolytic reactions with hemoglobinuria, jaundice, and delirium and are more common in children. Fatalities are rare. Fatal disseminated intravascular coagulation has been reported.

Although of unproved efficacy, the following therapies have been used: dexamethasone, 4 mg IV four times a day, during the acute phase; polymorphonuclear leukocyte inhibitors, such as dapsone or colchicine. Supportive wound care is recommended, with possible reconstruction/debridement. Plasma exchange has been described for severe hemolysis.

VITAMINS

Accidental ingestion of excessive amounts of vitamins rarely causes significant problems. Rare cases of hypervitaminosis A do occur, however, particularly in patients with poor hepatic or renal function. Hypervitaminosis A can result in increased intracranial pressure, ocular toxicity, and hepatotoxicity. However, chronic doses more than 50,000–100,000 IU are required for toxicity. The fluoride contained in many multivitamin preparations is not a realistic hazard, because a 2- or 3-year-old child could eat 100 tablets, containing 1 mg of sodium fluoride per tablet, without experiencing serious symptoms. Iron poisoning has been reported with multivitamin tablets containing iron; most gummy vitamins do not contain iron. Pyridoxine abuse has caused neuropathies; nicotinic acid can result in flushing, and rarely hypotension and hepatotoxicity.

WARFARIN (COUMADIN) & NEWER ORAL ANTICOAGULANTS (NOAC)

Warfarin is used as an anticoagulant and rodenticide. It causes hypoprothrombinemia and capillary injury. A dose of 0.5 mg/kg of warfarin may be toxic in a child. Long-acting anticoagulant rodenticides (brodifacoum, difenacoum, bromadiolone, diphacinone, pinene, valone, and coumatetralyl) can cause a more serious toxicologic problem than warfarin as the anticoagulant activity may persist for periods ranging from 6 weeks to several months. However, most unintentional ingestions can be watched at home without further evaluation. If there are concerns for large ingestions, a prothrombin time at 48 hours can determine extent of toxicity. Treatment with vitamin K₁ at high doses may be needed for weeks for long-acting anticoagulant toxicity.

Refer to published American College of Chest Physicians guidelines on management of bleeding in patient receiving vitamin K antagonists. With evidence for bleeding, give fresh frozen plasma, prothrombin complex concentrated, or activated factor. Without significant bleeding, oral vitamin K is recommended.

Newer oral anticoagulants have been developed that have direct inhibition to specific clotting factors. Examples include direct Xa inhibitors (apixaban, edoxaban, rivaroxaban), and direct thrombin (IIa) inhibitors (dabigatran). Toxic doses have not been established, but accidental ingestions do not typically lead to significant toxicity. If available, chromogenic antifactor Xa assay can quantitate direct Xa inhibition, and ecarin clotting time (ECT) or dilute thrombin time (dTT) is the most the most sensitive coagulation parameter for direct thrombin inhibitors. Activated four-factor prothrombin complex concentrates, activated Factor VII, or fresh frozen plasma should be used to treat potentially life-threatening bleeding. Idaracizumab and andexanet alfa are now available for the reversal of dabigatran and factor Xa inhibitors, respectively. Their availability and clinical experience in overdose is limited.