CHAPTER 30: Toxicology

• Decreases absorption of some drugs in the stomach, however not routinely recommended unless a potentially toxic amount of poison has been ingested

• Should be used soon after ingestion, ideally within the first hour

• Technique: Activated charcoal given orally or by nasogastric (NG) tube at dose of 1g/kg (maximum, 100g); repeat dose 0.5–1g/kg every 4–6 hours, if necessary (see multiple-dose activated charcoal subsequently)

  • ✓ Ideally should achieve ratio of at least 10 g charcoal per gram of drug ingested

• Does not bind metals (iron, lithium, lead) or common electrolytes, mineral acids/bases, alcohols, cyanide, solvents, and water-insoluble compounds such as hydrocarbon

• Poses aspiration risk, especially among who vomit or receive charcoal via NG tube

• Contraindicated in caustic or hydrocarbon ingestion and in patients without protected airway (altered mental status or unconscious)

• Gastric lavage still performed, but exceedingly difficult in young children due to size of tube required

• Efficacy not proven, but most effective if done within 1 hour of ingestion

• Technique: Place patient on left side with head lower than body. Use large bore orogastric tube

  • ✓ Aspirate gastric contents prior to lavage

  • ✓ Lavage with normal saline until return of fluid is clear. Fifty to 100cc per cycle should be used, and up to 200cc in adolescents

• May delay administration of charcoal

• Contraindicated in patients with altered mental status (inability to protect airway), hydrocarbon or caustic ingestion, cardiac arrhythmia, or possibility of foreign body ingestion

• Syrup of ipecac no longer recommended

Includes methods such as hemodialysis, plasmapheresis, and exchange transfusion

• Reserved for life-threatening poisonings or renal failure; consult pediatric nephrologist

• Hemodialysis is most commonly used. Blood is pumped through dialysis machine and toxins diffuse passively from blood into dialysate solution

• Unstable patients may undergo continuous renal replacement therapy (CRRT, such as continuous veno-venous hemofiltration or CVVH) but the efficacy for poisoning is much less

• Plasmapheresis and exchange transfusion are seldom necessary but may be useful in the neonates or infants

• Urinary alkalinization enhances clearance of certain agents such as salicylates, phenobarbital, chlorpropamide via “ion trapping”

  • ✓ Alkaline environment favors generation of ionized drug species which cannot readily cross the renal tubular membrane, thus preventing reabsorption

  • ✓ Performed with sodium bicarbonate at 1–2 mEq per kg over 1–2 hours with careful monitoring for electrolyte abnormalities

• Whole bowel irrigation (WBI):

  • ✓ Uses: Iron ingestions, massive ingestions, ingestion of sustained-release or enteric-coated preparations, ingestion of packets of illicit drugs, late presentations when gastric emptying and charcoal will be unlikely to be effective, and when charcoal cannot be used, such as in lithium ingestion

  • ✓ Technique: Give preparation via NG tube until stool is clear

  • ✓ Use polyethylene glycol solution, such as GoLYTELY at 500cc/h in children and 2L/h in adolescents

  • ✓ Contraindicated in patients with ileus or intestinal obstruction, caustic ingestions, as well as in patients who are unable to protect airway (may require intubation)

  • ✓ Charcoal may be less effective when used together with WBI

• Multi-dose activated charcoal:

  • ✓ Multiple-dose activated charcoal (MDAC): Some recommend repeat doses after large ingestion (listed in management section for specific drugs)

  • ✓ May improve results by decreasing enterohepatic recirculation

  • ✓ Requires effective peristalsis

  • ✓ Use caution with sorbitol: May result in electrolyte abnormalities (sorbitol should not be administered more than every third dose)

Over-the-counter (OTC) analgesics (e.g., Tylenol), OTC cold remedies, prescription combination medications (e.g., Percocet)

TOXICOLOGY/PHARMACOLOGY

• Most common pharmaceutical poisoning exposure

• Hepatic metabolism, including cytochrome p450

• Toxicity via metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), which is normally detoxified by glutathione; in overdose, glutathione is depleted and metabolite causes direct hepatic cell injury and death

• Toxic dose is 150 mg/kg in children or 6–7g in adults

• Fulminant liver failure develops in 3–4% of children with hepatotoxicity

CLINICAL MANIFESTATIONS

• Early (first 24 hours): Asymptomatic or nausea, vomiting, malaise

• Initial symptoms may resolve 1–4 days after ingestion despite ongoing hepatotoxicity

  • ✓ Symptoms may include right upper quadrant abdominal pain and jaundice

• Three to 5 days after ingestion those with severe toxicity may develop symptoms or signs of fulminant hepatic failure with encephalopathy or coma; coagulopathy; renal failure; death from liver failure possible

DIAGNOSTICS

• Draw acetaminophen (APAP) level 4 hours after ingestion (also at 8 and 12 hours if extended release form or if co-ingestion with medications that delay gastric emptying) (Figure 30-1)

• Labs: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, PT, bilirubin, electrolytes, creatinine (elevated creatinine associated with higher mortality), arterial blood gas, urinalysis (proteinuria and hematuria suggest acute tubular necrosis)

• Single doses of less than 200 mg/kg are unlikely to cause serious harm, however accuracy of ingestion amount and timing may be unreliable in intentional overdose

MANAGEMENT

• Gastric lavage is controversial; give charcoal if within 4 hours

• For acute ingestions, base need for subsequent treatment on nomogram (see Figure 30-1)

• N-acetylcysteine (NAC, Mucomyst, Acetadote) has greatest benefit in preventing liver toxicity if given within 8 hours of ingestion, but is still beneficial even if initiated many hours to days later

  • ✓ If patient presents 6–8 hours following ingestion, administer N-acetylcysteine while obtaining a level

  • ✓ If patient presents 8 or more hours following ingestion, options include N-acetylcysteine administration while obtaining a level or administration if 4-hour level is above line on nomogram

• N-acetylcysteine dose

  • ✓ Oral dose: Loading dose, 140 mg/kg orally; maintenance dose, 70 mg/kg orally every 4 hours for 17 doses

  • ✓ IV dose: Loading dose, 150 mg/kg given over an hour; 2nd dose, 50 mg/kg given over 4 hours; 3rd dose, 100 mg/kg given over 16 hours

  • ✓ Amount of diluent is based on patient age; consider consultation with a pharmacist

  • ✓ Orally N-acetylcysteine can be difficult to tolerate which is avoided by giving the IV form; the greatest risk of IV N-acetylcysteine is anaphylactoid reactions

• Cannot use nomogram to determine need for treatment in chronic ingestions; decision to treat in these cases is based on amount ingested (150–200/kg in 24-hour period) or evidence of hepatotoxicity

• Criteria for admission: Admit all patients with 4 hour APAP level above line on nomogram (see Figure 30-1). All intentional ingestions warrant admission

Prescribed for narcolepsy, attention deficit hyperactivity disorder, fatigue, and weight loss; found in OTC diet pills and some nasal decongestants; includes illicit agents such as methamphetamine, which is the most commonly abused amphetamine, and hallucinogenic amphetamine derivatives such as MDMA (“Ecstasy”)

TOXICOLOGY/PHARMACOLOGY

Increase synaptic concentrations of catecholamines, thereby causing CNS stimulation

• Toxic effects are due to excess sympathetic stimulation as well as dopaminergic effects causing psychosis

• Toxicity through various routes: Ingestion, inhalation, or injection

• Tolerance develops with chronic use; low therapeutic index

CLINICAL MANIFESTATIONS

• Gastrointestinal: Nausea, vomiting, anorexia, diarrhea

• Central nervous system: Euphoria, agitation, pressured speech, seizures; stroke can occur from either hypertension or vasculitis

• Cardiac: Palpitations, chest pain, hypertensive crises, arrhythmias, myocardial infarction, and circulatory collapse

• Psychiatric: Psychotic state with hallucinations and paranoia which can be confused with schizophrenia. Hallucinations and altered perception may result with hallucinogenic amphetamine derivatives

• Other: Hyperthermia, sweating, tremor, difficulty urinating, dilated pupils, rhabdomyolysis

• With chronic use may see: Cardiomyopathy, cerebral vasculitis, weight loss; psychiatric disturbances may be permanent

DIAGNOSTICS

• Based on history of ingestion and clinical presentation

• Urine toxicologic screen (may not detect all compounds)

• Laboratory studies: Electrolytes, glucose, BUN, creatinine, creatine phosphokinase (CPK; to detect rhabdomyolysis), urinalysis (positive “blood” on dipstick in absence of red blood cells suggests rhabdomyolysis)

• ECG, CT of head if concern for cerebrovascular accident

MANAGEMENT

• Decontamination: Activated charcoal; do not induce emesis

• Symptomatic care: Hydration; treat seizures or agitation with benzodiazepines; treat hypertension with peripheral vasodilator (nitroprusside, phentolamine); treat hyperthermia

• Treat arrhythmias and rhabdomyolysis if they occur

• Criteria for hospitalization: Monitor for at least 6 hours; if symptomatic, admit for observation

Over-the-counter and prescription allergy medicines; cold and cough medicines; sleep aids; motion sickness medications

TOXICOLOGY/PHARMACOLOGY

• Antihistamines block H1 receptors

• Can cause CNS stimulation or depression

• In overdose can result in anticholinergic symptoms

• Elimination half-lives are variable, ranging from hours to days, depending on the specific drug

• Toxic dose is around three to five times the therapeutic dose

CLINICAL MANIFESTATIONS

• Lower doses: CNS depression-sedative effect

• Higher doses: CNS stimulation-agitation, confusion, hallucinations, excitement, tremors

• Neurologic: Seizures (diphenhydramine only)

• Cardiac: QRS widening with diphenhydramine (Benadryl)

• Anticholinergic toxidrome: Delirium, flushed skin, dry mouth, fever, tachycardia, hypertension, dilated pupils

DIAGNOSTICS

• Diagnosis based on history and presence of anticholinergic syndrome

• Can be detected on comprehensive urine toxicologic screen

• Laboratory studies: Electrolytes, glucose, blood gas; ECG

MANAGEMENT

• Charcoal and/or gastric emptying; WBI may be helpful when antihistamine is in sustained-release form

• Manage hyperthermia with external cooling

• Manage agitation or seizures with benzodiazepines

• If symptoms are severe and life-threatening, can use physostigmine to treat anticholinergic effects—not routinely recommended because of toxicity

  • ✓ Physostigmine dose: 0.02 mg/kg given over 1–2 minutes every 5 minutes to a maximum dose of 2 mg; can repeat if needed in 20 minutes

  • ✓ PERFORM ECG before physostigmine to rule out conduction delays

  • ✓ DO NOT use in tricyclic overdose

  • ✓ GIVE SLOWLY—Can precipitate seizures or asystole

  • ✓ Have atropine ready if needed for cholinergic cardiac effects (bradycardia and hypotension)

  • ✓ Atropine dose is half of the amount of physostigmine given

Most common use is for cardiac disorders, such as hypertension, angina, and arrhythmia; noncardiac uses include migraines, essential tremor, thyrotoxicosis, glaucoma, and anxiety.

TOXICOLOGY/PHARMACOLOGY

• In treatment doses, drugs are beta-receptor-specific; in overdose, this specificity is lost

• Sustained release preparations exist

• Can be fatal in doses of only two to three times the therapeutic dose

CLINICAL MANIFESTATIONS

• Cardiac: Bradycardia, hypotension, atrioventricular block; asystole can occur but is rare

• Central nervous system: Coma

• Bronchospasm: Mostly seen in patients who have asthma

• Labs may show hypoglycemia in young children; children require serial glucose checks to assess for fasting hypoglycemia

• ECG may show prolonged PR interval or wide QRS if severe; sotalol ingestion can result in a prolonged QT interval and torsades de pointes

DIAGNOSTICS

• Diagnosis based on history and vital signs

• Laboratory studies: Electrolytes, glucose, BUN, creatinine, blood gas

• ECG

MANAGEMENT

• Decontamination: Gastric lavage if large ingestion or immediate presentation; activated charcoal; can consider WBI for sustained-release preparations

• Hypotension: Treat with fluids; vasoactive pressor infusions may be needed

• Bradycardia: Atropine; isoproterenol can be used if no response to atropine

• Glucagon can also be used to treat hypotension and bradycardia that do not respond to previous measures

• Magnesium for torsades de pointes

• Bronchodilators for bronchospasm

• Cardiac pacing or extracorporeal membrane oxygenation (ECMO) is reserved for patients not responding to medical management

• Criteria for hospitalization: Must perform ECG monitoring for 6 hours after ingestion; all pediatric ingestions and ingestions with sustained-release preparation should be admitted

Medication for treatment of hypertension, atrial fibrillation, angina, migraines

TOXICOLOGY/PHARMACOLOGY

• Toxicity due to vasodilatory effects on both coronary and peripheral vessels, decreased myocardial contractility, slowing of the conduction system both at sinus node and through AV node

• Toxicity can occur from therapeutic use or in overdose

• Can be fatal in small doses

• Most severe toxicity seen with verapamil or diltiazem

• Sustained release preparations available

CLINICAL MANIFESTATIONS

• May be asymptomatic for hours after ingestion with sustained-release preparations

• Cardiac: Hypotension, bradycardia (verapamil, diltiazem), reflex tachycardia followed by bradycardia as poisoning worsens (amlodipine, nifedipine)

• Neurologic compromise (altered mental status, convulsions, coma) may result from impaired cerebral perfusion, but late in clinical picture. Mental status usually preserved at initial presentation

• Other symptoms: Hyperglycemia, metabolic acidosis; serum calcium may be normal

DIAGNOSTICS

• Based on history and clinical presentation

• Laboratory studies: Electrolytes, BUN, creatinine, glucose (risk for hyperglycemia, hypokalemia, metabolic acidosis), blood gas

• ECG shows prolonged PR interval with normal QRS

• Troponin or other cardiac biomarkers may help differentiate drug-induced from ischemic causes of bradycardia

• Urine toxicology screen (to detect co-ingested drugs)

MANAGEMENT

• Decontamination:

  • ✓ Gastric lavage: Only if within 1 hour and will not delay charcoal administration

  • ✓ Activated charcoal: Consider multiple-dose (MDAC) in large sustained-release ingestions

  • ✓ WBI for sustained-release preparations

• Treating hypotension:

  • ✓ IV fluids (normal saline bolus)

  • ✓ Calcium chloride (20 mg/kg IV) or calcium gluconate (50–75 mg/kg IV)

  • ✓ Dopamine, epinephrine, or norepinephrine for refractory hypotension

• High-dose insulin (Up to 1U/kg/h) and glucose (to maintain euglycemia) infusions

• Atropine for bradycardia

• Last-resort therapies: ECMO, cardiac pacing, intra-aortic balloon

• Some evidence exists in support of intravenous lipid emulsion

• Criteria for hospitalization: (1) Observe for 24 hours; (2) monitor for at least 24 hours if large ingestion or sustained release

Medication used for seizures (Tegretol, Carbatrol), neuropathic pain, some psychiatric disorders

TOXICOLOGY/PHARMACOLOGY

• Blocks sodium channels in the brain, preventing high-frequency firing; at high doses, also blocks cardiac sodium channels

• Mild anticholinergic activity

• Absorption can be erratic due to anticholinergic-induced delayed gastric emptying

• Peak level reached from 4 to 24 hours

• Metabolized via P450 to active compound, so drug level may not reflect magnitude of clinical toxicity

CLINICAL MANIFESTATIONS

• Central nervous system: Ataxia, mydriasis, nystagmus, altered mental status, nausea, vomiting, dystonic posturing, coma, seizures; status epilepticus indicates poor prognosis

• Cardiac: Sinus tachycardia, hypotension from myocardial depression, atrioventricular block, bradycardia, QRS or QT prolongation, ventricular dysrhythmias

• Chronic toxicity: Syndrome of inappropriate antidiuretic hormone secretion, leukopenia, thrombocytopenia

• Symptom onset may be delayed due to delayed absorption

DIAGNOSTICS

• Based on history and clinical signs

• Obtain immediate carbamazepine level; repeat levels every 4–6 hours; levels above 40 mg/L associated with severe toxicity in adults; toxic level is even lower in children

• Laboratory studies: CBC, electrolytes, glucose, ABG

• ECG

MANAGEMENT

• Treatment based on clinical status, not drug levels

• Supportive care

• Recognize that carbamazepine can significantly slow GI motility and that neurological status may warrant early airway management

• Activated charcoal

• Massive ingestion: Can consider MDAC or WBI

• Life-threatening toxicity: Hemodialysis

• Treat seizures with benzodiazepines and phenobarbital, NOT phenytoin (has same intracellular mechanism as carbamazepine)

• Criteria for hospitalization: Observe asymptomatic patients for 6 hours; admit symptomatic patients to monitored bed if levels or clinical picture are concerning

Fire (indoor charcoal or house fire), automobile exhaust, gasoline engines operating in enclosed spaces (car or generator in garage), faulty furnaces or gas stoves, woodburning stoves, inhaled spray paint; also, the main ingredient in paint remover is metabolized to carbon monoxide

TOXICOLOGY/PHARMACOLOGY

• Children are at higher risk from CO because of their higher metabolic and respiratory rates

• Toxicity results from CO binding hemoglobin with higher affinity than oxygen, which results in decreased oxygen saturation tissue delivery

• CO also can bind myoglobin, resulting in cardiac toxicity by decreasing contractility

• Mild symptoms of toxicity can be seen at carboxyhemoglobin levels of 5% and death at levels of 50%

CLINICAL MANIFESTATIONS

• Most mild exposures present with flu-like symptoms, headache, visual changes, dizziness, nausea, and/or weakness

• More severe exposure can present with syncope, seizures, coma, cardiac ischemia or infarction, dysrhythmias, pulmonary edema, or death

• Physical exam findings can include tachycardia, hypotension or hypertension, tachypnea, and pallor; skin and soft tissue also more susceptible to trauma with pressure points most affected

• Classic description of cherry red skin is actually a late finding

• Delayed neurologic sequelae may develop days to weeks after exposure; symptoms include headache, disorientation, dementia, apraxia, peripheral neuropathy, ataxia, chorea, or Parkinson-like signs

  • ✓ 25% of patients with delayed neurologic sequelae may have permanent neurologic findings

DIAGNOSTICS

• Carbon monoxide hemoglobin (COHgb) levels: Remember, pulse-oximetry may be normal

• CBC, BUN, creatinine, cardiac enzymes, glucose, pregnancy test

• Chest x-ray

• ECG to look for ischemia or dysrhythmias

• Obtain history of risk factors for CO poisoning (e.g., fuel-burning space heaters, charcoal grills, portable generators)

MANAGEMENT

• Give 100% oxygen to reduce half-life of carboxyhemoglobin

• Consider hyperbaric oxygen in several situations: COHgb greater than 25%, pregnancy, or significant cardiac or neurologic symptoms

  • ✓ Hyperbaric oxygen may decrease the likelihood neurologic sequelae

• Continue therapy until COHgb less than 5–10%

• Monitor for metabolic acidosis, which may require therapy with sodium bicarbonate in extreme cases

• Criteria for hospitalization: (1) Adults with COHgb greater than 25%; (2) children with COHgb greater than 15%; (3) metabolic acidosis; (4) ECG changes; (5) neuropsychiatric symptoms; (6) abnormal thermoregulation; (7) PaO₂ less than 60 mm Hg

Acids or alkali; oven or drain cleaner; powdered laundry and dishwasher detergents; hair relaxers; industrial products

TOXICOLOGY/PHARMACOLOGY

• Causes burns when inhaled or ingested, but also with skin and eye contact

• Acids result in coagulation necrosis, and alkalis cause liquefaction necrosis

  • ✓ Although liquefaction necrosis is deeper, the clinical course is similar in both acid and alkali ingestions

CLINICAL MANIFESTATIONS

• Stridor, hoarseness, dyspnea, aphonia, vomiting, or drooling

• May initially be asymptomatic

• Symptoms do not reliably predict presence or absence of esophageal injury

• Usually present with burning of exposed areas

• Airway edema and obstruction can be delayed up to 48 hours in alkali exposures

• Acids and alkali both can cause esophageal injury

  • ✓ Acid ingestions usually also cause damage to stomach with risk for gastric perforation and peritonitis

  • ✓ Alkali ingestions are more likely to damage esophagus with possibility of perforation and resulting mediastinitis

• May present with acute GI bleed or acute gastric perforation

• Third-degree esophageal burns at risk for developing strictures

DIAGNOSTICS

• Based on history of exposure and symptoms

• Determine if substance was only irritant or if actually a corrosive

  • ✓ Determined by pH, concentration, and viscosity

  • ✓ Contact poison center for information

• Laboratory studies: CBC, type and screen, electrolytes, glucose, blood gas

• Chest x-ray and abdominal x-rays to look for free air

MANAGEMENT

• Stabilize airway: May need intubation under direct visualization (fiberoptic)

  • ✓ Blind intubation can worsen damage or cause perforation

• IV access; keep patient NPO, perform a CXR

• No GI decontamination, No ipecac, No lavage. Simple dilution may pose the risk of fluid leakage into surrounding tissues in the event of perforation, may worsen damage depending on the pH of administered fluids, and eliminates NPO status

• Perform endoscopy as soon as possible to determine extent of burn

• Surgery consult in all patients with significant burns

• Careful examination of the eyes with irrigation if indicated

• Corticosteroids may be beneficial in some esophageal burns to prevent strictures (controversial)

• Pain control

• Antibiotics: If evidence of perforation or if steroids are used

• Histamine-2 blocker to reduce gastric acid formation

• Criteria for hospitalization: All symptomatic patients with caustic ingestions

Imidazoline class, along with dexmedetomidine (Precedex^®), tetrahydrozoline (Visine^®), oxymetazoline (Afrin^®), guanfacine (Tenex^®, Intuniv^®)

Medication to treat hypertension and attention deficit hyperactivity disorder; has been used to treat withdrawal symptoms from opioids and nicotine

TOXICOLOGY/PHARMACOLOGY

• Agonist at central alpha-2 receptors resulting in decreased sympathetic outflow

• Binds to peripheral alpha-1 receptors resulting in vasoconstriction and hypertension early in the course

• Can cause significant toxicity in small doses

• Rapidly absorbed and distributed, so symptoms appear soon after ingestion

CLINICAL MANIFESTATIONS

• Neurologic: Altered mental status with irritability, lethargy, or coma

• Respiratory depression, occasionally necessitating endotracheal intubation, apnea

• Cardiac: Most commonly see hypotension and bradycardia, but can also see tachycardia, transient hypertension, or AV nodal blockade

• Other: Miosis, pallor, hypothermia

• Clinical effects typically last 8–24 hours

DIAGNOSTICS

• Based on history and physical finding

• Drug levels not available

• Laboratory studies: Electrolytes, glucose, blood gas

• ECG

MANAGEMENT

• Activated charcoal

• Treatment primarily supportive

• Hypotension: Give fluids; if refractory can also use dopamine or epinephrine

• Bradycardia: Treat with atropine

• Hypertension, when present, rarely needs treatment

• Naloxone is sometimes effective in reversing respiratory, cardiac, and neurologic effects. Initial dose is usually 1–2 mg though larger amounts may be necessary

• Criteria for hospitalization: Observe asymptomatic patients for 6 hours; admit all symptomatic patients

Used medically as local anesthetic; popular street drug

TOXICOLOGY/PHARMACOLOGY

• Toxic effects are via CNS stimulation and inhibited catecholamine uptake

• Toxicity develops though multiple routes (ingestion, inhalation, or injection)

• Toxic dose is highly variable, however toxicity usually decreased with ingestion given time for absorption

• “Body packers” swallow many tightly wrapped packets or condoms of cocaine in attempt to hide or smuggle drugs

  • ✓ Toxicity results when packets break open, releasing drugs into GI tract with potentially fatal effect

• “Body stuffers” hastily ingest smaller packets sold on the street to avoid detection by law enforcement

  • ✓ Body stuffing associated with a higher risk of rupture because drugs are not securely enclosed

  • ✓ Risk of mortality, however, is lower than with body packing because relatively small quantities are typically ingested

CLINICAL MANIFESTATIONS

• Central nervous system: Euphoria, agitation, psychosis, seizures, stroke

• Cardiac: Hypertension, tachycardia, arrhythmias including ventricular fibrillation, myocardial ischemia, and infarction

• Respiratory: Bronchospasm, pneumothorax, pneumomediastinum, hemoptysis

• Other: Dilated pupils, hyperthermia, rhabdomyolysis, renal failure, nasal septum perforation

• Cocaine adulterants may cause otherwise unexpected toxicity

  • ✓ For example, levamisole, a veterinary antihelminthic, has caused outbreaks of fever and agranulocytosis in cocaine users

DIAGNOSTICS

• Based on history of use and clinical presentation

• Urine toxicologic screen: Metabolites may be found up to 3 days after exposure

• Laboratory studies: Electrolytes, glucose, BUN, creatinine, CPK, urinalysis

• ECG

• Chest x-ray if respiratory symptoms present

• Head CT if suspect stroke

• Abdominal x-rays if suspect body packing; body stuffer packets not well visualized on radiographs

MANAGEMENT

• Decontamination: Give activated charcoal if cocaine taken orally; if suspect body packer give MDAC and consider WBI or surgical removal, given high mortality associated with cocaine packet rupture

• Supportive care: Benzodiazepines are used to decrease agitation, tachycardia, and hypertension, and treat seizures

• Severe hypertension: DO NOT use beta-blocker, which can cause unopposed alpha-adrenergic effect leading to increase in blood pressure and increased coronary vasospasm

• Treat hyperthermia

• Consider co-ingestions

• Treat arrhythmias and rhabdomyolysis

• Criteria for hospitalization: Admit patient with ECG changes, seizures, or neurologic deficits; “body packers”

Naturally occurring in some plants but also present in car exhaust and cigarette smoke in small amounts; toxic exposure usually from the burning of cyanide containing natural or synthetic products, and industrial exposure

TOXICOLOGY/PHARMACOLOGY

• Cyanide inhibits electron transport in mitochondria, impairing aerobic metabolism and causing metabolic acidosis

• Small amounts are metabolized under normal circumstances, symptoms occur when these systems are overwhelmed

CLINICAL MANIFESTATIONS

• Cardiac: Tachycardia, hypertension, myocardial toxicity, bradycardia, arrythmias, and cardiovascular collapse

• Respiratory: Tachypnea, dyspnea, no cyanosis (cherry-red skin is classically described but not reliably seen)

• Neurologic: Headaches, lightheadedness, ataxia, posturing, seizures

• Patients may have a “bitter almond” odor

DIAGNOSTICS

• Blood gas with lactate: Often reveals high mixed venous saturation and severe lactic acidosis

• Lactate

• Electrolytes

• CBC

• ECG

MANAGEMENT

• Decontamination by removal of wet clothes in the appropriate context (environmental exposure)

• Supportive care: 100% oxygen, support of circulation with fluids and pressors if needed, correction of acidosis with sodium bicarbonate, and treatment of seizures with benzodiazepines

• Antidotes:

  • ✓ Older therapy: Nitrites (amyl and sodium nitrite) and sodium thiosulfate. Nitrites can cause hypotension and affect oxygen-carrying capacity by inducing methemoglobinemia

    • ▪ In pediatric patients thiosulfate alone may be used; thiosulfate dose is 400 mg/kg for children <25kg with a maximum of 12.5g

  • ✓ Newer therapy: Involves use of hydroxocobalamin without attendant side effects of nitrites

    • ▪ Dose is 70 mg/kg IV given over 15 minutes; dose may need to be repeated

    • ▪ Side effects include hypertension and reddish discoloration of skin, mucous membranes, and urine

    • ▪ May be given with or without thiosulfate

Medication used to treat congestive heart failure and supraventricular tachycardias; digitoxin also found in plants (oleander, rhododendron, foxglove)

TOXICOLOGY/PHARMACOLOGY

• Inhibits sodium–potassium ATP pump, increases vagal tone, and slows AV conduction

• Toxicity can occur from chronic use or with overdose, symptoms may be more striking in patients with chronic toxicity

• Doses as small as 1 mg can be toxic in children

• Absorption and redistribution occur rapidly; therefore, digoxin levels can decrease rapidly after ingestion

• Elimination half-life is 30–50 hours, renal clearance is the major mode of elimination

CLINICAL MANIFESTATIONS

• Symptoms include nausea, vomiting, lethargy, visual changes (halos or changes in color vision)

• Higher levels of intoxication can cause lethargy, mental status changes, electrolyte abnormalities (the most prognostic of which is hyperkalemia), bradycardia, ventricular dysrhythmias, and cardiac arrest

DIAGNOSTICS

• Stat digoxin level; therapeutic level is 0.9–1.2ng/mL

• Laboratory findings include hyperkalemia or with chronic toxicity may see hypokalemia if concurrent diuretic use

• Other laboratory studies: Electrolytes, calcium, magnesium, BUN, creatinine

• ECG changes may vary; most common ECG abnormalities are sinus bradycardia and AV block

  • ✓ Ventricular dysrhythmias may occur precipitously so early treatment advised in the patient with ECG abnormalities and elevated serum digoxin concentration

MANAGEMENT

• Decontamination; activated charcoal may be of benefit

• Correction of hyperkalemia will not prevent dysrhythmias. Digoxin-specific Fab (Digibind) will correct hyperkalemia and rhythm disturbances: consider in any patient with ECG abnormalities, high serum digoxin concentration, and/or hyperkalemia (>5 mEq/L, depending on source)

• Calculating Digibind dosing:

  • ✓ If amount of digoxin ingested is known: 38 mg Digibind to bind 0.5 mg digoxin

  • ✓ If amount unknown: Number of vials = [(serum digoxin level in ng/mL) × (body weight in kg)]/100

  • ✓ Potential side effects include hypersensitivity reactions, decreased potassium, worsening of heart failure

  • ✓ Recognize that serum digoxin level may increase after administration, but this reflects inactive drug

• Additional treatment of hyperkalemia

  • ✓ Calcium salts are CONTRAINDICATED and may cause cardioplegia (“stone heart”)

  • ✓ Adjunctive therapies such as insulin/glucose and sodium bicarbonate may be useful

• Criteria for hospitalization: Admit patients with (1) symptoms of digoxin toxicity, (2) ECG abnormalities, (3) hypokalemia, (4) hyperkalemia, (5) elevated serum digoxin concentration, (6) any patient getting Digibind

  • ✓ Patients with normal digoxin levels, no electrolyte abnormalities, and a normal ECG can be discharged after 6 hours of observation

Beer, wine, liquors; used as solvent, topical antiseptic; ingredient in perfume, cologne, mouthwash; used as antidote in treatment of methanol and ethylene glycol overdoses

TOXICOLOGY/PHARMACOLOGY

• Acts as a direct CNS depressant by binding to GABA receptors

• Ethanol can also have effects on cardiac muscle, thyroid, and liver

• Ethanol is metabolized by the liver

• Dose-independent fasting hypoglycemia in children results from ethanol-inhibiting gluconeogenesis

• Levels at which symptoms appear are highly variable

CLINICAL MANIFESTATIONS

• Mild acute toxicity: Nausea, vomiting, euphoria, incoordination, ataxia, nystagmus, impaired judgment; hypoglycemia and seizures seen in younger age group

• More severe acute toxicity: Coma, respiratory depression, metabolic acidosis; can have death from apnea

• Presentation in infants and children includes hypothermia, hypoglycemia, metabolic acidosis, and coma

  • ✓ These occur at levels of 50–100 mg/dL

DIAGNOSTICS

• Blood glucose STAT

• Laboratory studies: Electrolytes, BUN, creatinine, liver enzymes, PT, blood gas

• Ethanol level

• Chest x-ray if suspicious for aspiration

MANAGEMENT

• Supportive care: Assess airway and establish access; treat hypoglycemia, seizures, hypothermia

• Decontamination: Gastric lavage if presenting within 2 hours of ingestion; activated charcoal should be given only if concern for co-ingestion

• Hemodialysis effective, but rarely needed (consider in patients with hepatic impairment or very high blood alcohol levels)

• Criteria for hospitalization: In acute ingestions, observe until mental status is at baseline

  • ✓ Admit those with ethanol level greater than 100 mg/dL (toddlers), or greater than 200 mg/dL (adolescents) and those with hypoglycemia

Main ingredient in antifreeze; occasionally used by alcoholics in place of ethanol

TOXICOLOGY/PHARMACOLOGY

• Metabolized by alcohol dehydrogenase to toxic glycoaldehyde, glycolic, glyoxylic, and oxalic acids, causing metabolic acidosis and acute renal failure

• Oxalic acid chelates serum calcium, causing hypocalcemia and calcium oxalate precipitation in renal tubules

CLINICAL MANIFESTATIONS

• Initially, patients will have CNS depression and coma from direct intoxicating effect

• As compound is metabolized, anion-gap metabolic acidosis ensues with tachycardia and hyperpnea, elevated WBC count, GI distress, and hypocalcemia

  • ✓ Cardiovascular compromise may result from metabolic derangements and dysrhythmias from hypocalcemia

• Acute kidney injury appears as calcium oxalate crystals precipitate in the kidney, causing direct tubular injury beginning approximately 24 hours after exposure

DIAGNOSTICS

• Anion-gap metabolic acidosis, elevated osmolar gap

• Hypocalcemia

• Ethylene glycol levels are available, but may be low if already converted to toxic metabolite

• Other laboratory studies: Electrolytes, glucose, BUN, creatinine, liver enzymes, urinalysis (which may demonstrate oxalate crystals), blood gas

• ECG

• Urine: Some antifreeze contains fluorescein, so urine may fluoresce under Wood’s lamp; can see calcium oxalate crystals on microscopic urinalysis

MANAGEMENT

• Supportive: Cardiac monitoring; correct hypocalcemia with IV calcium salts; correct acidosis with sodium bicarbonate

• Decontamination: NO charcoal (ineffective); consider gastric lavage if presents within 1 hour

• Antidote: Fomepizole and ethanol bind ADH with higher affinity than ethylene glycol and thereby prevent formation of toxic metabolites

  • ✓ Treat with fomepizole (preferred) for ethylene glycol level greater than 20 mg/dL or patients with presumed ingestion and metabolic acidosis

  • ✓ IV ethanol infusion is a second-line option that is effective but difficult to administer

  • ✓ Other options include pyridoxine, folate, and thiamine prevent toxic metabolite formation

• Hemodialysis can be used to enhance elimination; indicated in renal failure or in cases of severe metabolic derangement

• Criteria for hospitalization: Any known ingestion of ethylene glycol; clinical or laboratory abnormalities suggestive of ethylene glycol toxicity

Solvents, degreasers, fuels, pesticides, gasoline, kerosene, lighter fluid, torch fuels

TOXICOLOGY/PHARMACOLOGY

• Three categories of hydrocarbons

  • ✓ Aliphatic (petroleum distillates, furniture polish, lamp oils, lighter fluid)

  • ✓ Aromatic (benzene, toluene, xylene, camphor found in glues, solvents, and nail polish)

  • ✓ Otherwise “toxic” (halogenated, hydrocarbons that serve as a vehicle for other substances)

• Toxicity can be due to inhalation, skin absorption, or ingestion with systemic toxicity (in aromatic, halogenated hydrocarbons or those with toxic additives)

• As little as 1 mL of fluid aspirated can lead to severe pneumonitis

CLINICAL MANIFESTATIONS

• Respiratory symptoms are the primary consequence of most aliphatic hydrocarbon ingestions, due to spillage into tracheobronchial tree: Tachypnea, dyspnea, cyanosis, grunting, cough

  • ✓ Severe pneumonitis and acute respiratory distress syndrome may develop

• Lower viscosity associated with higher aspiration risk

• Neurologic symptoms usually result from systemic toxicity: Seizures, lethargy, coma (usually with aromatic hydrocarbons)

• Gastrointestinal symptoms usually result from ingestion: Nausea, vomiting, liver failure (carbon tetrachloride)

• Hematologic: Hemolysis, hemoglobinuria

• Cardiac: Dysrhythmias (with halogenated hydrocarbons)

• Fever

• Skin or eye contact can result in burns or corneal injury

DIAGNOSTICS

• Based on history of exposure

• If respiratory symptoms, check ABG and chest x-ray

  • ✓ Repeat CXR may be needed in 4–6 hours if initially negative

• If concern over significant ingestion, check electrolytes, glucose, BUN, creatinine, liver enzymes, and an ECG

MANAGEMENT

• In general, No charcoal, No lavage, and No induction of emesis

  • ✓ Aspiration poses the greatest risk and prevention of aspiration is a mainstay of management

  • ✓ Exceptions to above “No” rules: (1) Consider charcoal if hydrocarbon contains a toxic substance (e.g., heavy metal, insecticide, camphor); (2) consider lavage (after intubating to protect airway) if massive amount is ingested

• Supportive respiratory care: Supplemental oxygen, continuous positive airway pressure, intubation as needed

• ECMO has been used successfully in some patients

• Antibiotics and steroids are not routinely indicated

• Epinephrine is contraindicated (increased risk of ventricular fibrillation)

• Criteria for hospitalization: All symptomatic patients and those with abnormal chest x-rays; monitor for at least 6 hours if asymptomatic

  • ✓ Symptoms can begin up to 24 hours after exposure therefore appropriate discharge instructions are needed

Ingredient in both pediatric and adult multivitamins; adult preparations have greater toxicity due to more elemental iron per tablet

TOXICOLOGY/PHARMACOLOGY

• In overdose, transferrin becomes saturated and unbound iron causes injury to cells

• Toxicity can be due to direct corrosive injury or to impaired cellular metabolism

• Toxic dose is 20–30 mg/kg of elemental iron

CLINICAL MANIFESTATIONS

• Four stages

  • ✓ Direct injury to GI mucosa results in vomiting and diarrhea, both of which can be bloody. Massive blood loss resulting in shock and death may result

  • ✓ Gastrointestinal symptoms are seen to resolve over the next 12–24 hours. In mild ingestions, this may indicate recovery. However, may represent a brief quiescence prior to phase III and patients should be monitored closely

  • ✓ Up to 48 hours after ingestion, systemic symptoms may begin with GI bleeding, metabolic acidosis, coagulopathy, liver failure, seizures, shock, and possibly death

  • ✓ Pyloric stenosis may occur from scarring 4–6 weeks after ingestion

DIAGNOSTICS

• Based on history of exposure and symptoms

• Laboratory studies: STAT iron level if possible, should be done 4–6 hours after ingestion and then repeated 8–12 hours after ingestion to evaluate possibility of delayed absorption

  • ✓ Level greater than 350μg/dL likely to have toxicity

  • ✓ Level greater than 500μg/dL suggests more severe toxicity

• CBC, electrolytes, glucose, BUN, creatinine, liver function tests, PT/PTT, type and cross-match

  • ✓ Elevated WBC (>15,000 mm³) and glucose (>150 mg/dL) are consistent with ingestion

  • ✓ Acidosis is most concerning for toxicity

• Abdominal radiograph at presentation and again after WBI, though a negative x-ray does not necessarily preclude a significant ingestion

MANAGEMENT

• Decontamination: If less than 30 minutes since ingestion, consider gastric lavage; WBI if iron tablets seen on abdominal films (DO NOT use phosphate-containing solutions); activated charcoal is NOT EFFECTIVE

• Supportive care: Treat hypotension with fluids; may need to give blood products to treat GI blood loss

• Chelation with continuous IV deferoxamine for severe toxicity

  • ✓ Dose is 10–15 mg/kg/h with maximum dose of 6g/day

  • ✓ Chelation treatment results in pink/orange appearance of urine (helpful to forewarn patient and family)

  • ✓ Discontinue when asymptomatic with normal laboratory studies and normal appearance of urine

  • ✓ Hypotension is a well-described side effect

• Criteria for hospitalization: Symptomatic patients; patients with iron level greater than 500 or if iron tablets seen on abdominal radiographs; asymptomatic patients should have iron levels repeated at 8–12 hours—if levels normal and still asymptomatic, can be discharged

Solvent, antiseptic, disinfectant; main ingredient in rubbing alcohol; often ingested by alcoholics as a substitute for liquor

TOXICOLOGY/PHARMACOLOGY

• Less toxic than other alcohols

• Toxicity can result from ingestion, inhalation, or via absorption through skin

• Causes CNS depression; large doses can also cause direct vasodilation resulting in hypotension

• Metabolized via alcohol dehydrogenase to acetone, which is also a CNS depressant

CLINICAL MANIFESTATIONS

• Gastrointestinal: Abdominal pain, vomiting, hemorrhagic gastritis

• Central nervous system: Slurred speech, ataxia, stupor, coma, respiratory arrest

• Cardiac: Myocardial depression

• Respiratory: Tracheobronchitis

DIAGNOSTICS

• Based on history of ingestion, presence of osmolar gap without metabolic acidosis (unlike other toxic alcohols)

• Odor of acetone may be detected

• Ketones (acetone) present in blood and urine

MANAGEMENT

• Supportive care

• Activated charcoal adsorbs alcohols poorly

• For large, recent ingestions, may consider gastric lavage

• Hemodialysis indicated for hemodynamic instability (very rare)

• Criteria for hospitalization: Any patient with symptomatic isopropanol ingestion; symptoms do not rely as heavily on toxic metabolites as other alcohols so symptoms emerge soon after ingestion

Most common source is chipping paint in homes built before the 1970s; also found in pipes, electric cable, munitions, batteries, glaze used for ceramics, imported toys, jewelry, cosmetics, and food

TOXICOLOGY/PHARMACOLOGY

• Majority of toxicity results from chronic exposure

• Toxicity from enzyme inhibition, resulting in blocked heme synthesis

• Can also effect neurotransmitter functioning

CLINICAL MANIFESTATIONS

• Most children are actually asymptomatic

• Gastrointestinal: Can be nonspecific; abdominal pain, vomiting, constipation, anorexia

• Neurologic: Seen at higher lead levels (>70μg/dL); irritability, lethargy, ataxia, seizures, encephalopathy or death; may have increased intracranial pressure

• Renal: Clinical picture similar to Fanconi; aminoaciduria and glycosuria

DIAGNOSTICS

• Venous whole blood lead level

• CBC will show microcytic anemia with basophilic stippling

• Elevated free erythrocyte protoporphyrin

• Long bone radiograph: May see metaphyseal “lead lines”

• Abdominal radiographs: May see opacities

• Avoid lumbar puncture if possible due to potential of increased ICP

MANAGEMENT

Symptomatic patients and asymptomatic patients with elevated BLL are at increased risk of CNS involvement

• Prevention: Screening should start at 9–12 months of age at well-child visit

• Decontamination: For acute ingestion, consider inducing vomiting or doing gastric lavage

  • ✓ Activated charcoal does not bind lead

  • ✓ Perform WBI if there are findings (paint chips) on abdominal radiographs

• Identify and remove the source

• Need for subsequent treatment based on blood lead levels: Should be less than 5μg/dL

  • ✓ Level >20μg/dL: Consider chelation

  • ✓ Level >45μg/dL: start oral chelation with succimer or with IV CaEDTA

  • ✓ Level >69μg/dL or signs of encephalopathy: Hospitalize for two-drug chelation therapy with BAL and CaEDTA (give BAL first and then both together 4 hours later) or BAL and succimer

• Chelation dosing

  • ✓ Succimer (DMSA): Dose is 1050 mg/m²/day (or 30 mg/kg/day) divided every 8 hours for 5 days, then 700 mg/m²/day (or 20 mg/kg/day) divided every 12 hours for 14 days

  • ✓ Edetate Calcium Disodium (CaNa₂ EDTA): 1000 mg/m²/day IV divided every 12 hours for 3–5 days; for lead level greater than 69μg/dL or signs of encephalopathy, use 1500 mg/m²/day as a continuous infusion for first 48 hours; maintain adequate hydration

  • ✓ Dimercaprol or British anti-Lewisite (BAL): Used if lead level greater than 69μg/dL or signs of encephalopathy; dose is 75 mg/m² per dose IM every 4 hours for 3–5 days; give first dose alone, then give BAL with CaEDTA; at 48 hours get lead level to decide whether to continue chelation

    • ▪ DO NOT use BAL in patients with hepatic insufficiency, peanut allergy, or glucose-6-phosphate dehydrogenase deficiency

    • ▪ Use cautiously in patients with hypertension or renal insufficiency

• Criteria for hospitalization: Lead level greater than 69μg/dL or signs of encephalopathy; if only option for removing child from source of lead exposure

• Supportive care (in lead encephalopathy): Anticonvulsants; manage increased ICP, adequate hydration to maintain urine output

Windshield washer fluid; sterno fuel; solvents, paint remover, antifreeze; used by alcoholics as substitute for ethanol

TOXICOLOGY/PHARMACOLOGY

• Metabolized by alcohol dehydrogenase to formaldehyde and formic acid, which are responsible for the toxicity

• Metabolism is slow and symptoms may be delayed for hours. though in large ingestions CNS depression and acidosis may manifest more acutely

• In children, small ingestions (5 mL of 100% methanol) can result in death

CLINICAL MANIFESTATIONS

• Ophthalmologic: “Snowfield vision,” retinal toxicity, papilledema, ophthalmoplegia, loss of pupillary light reflex, blindness

• Central nervous system: Inebriation, CNS depression, seizures, coma, death

• Cardiovascular: Hypotension, reflex tachycardia

• These findings may not appear for up to 24–30 hours

DIAGNOSTICS

• Based on history and symptoms

• Fundus exam may show optic disc hyperemia, venous engorgement, or papilledema

• Anion-gap metabolic acidosis may be preceded by an elevated osmolar gap

• Other laboratory studies: Electrolytes, glucose, BUN, creatinine, serum osmolality, blood gas, methanol level, lactate level

MANAGEMENT

• Decontamination: Do not induce emesis; activated charcoal is NOT effective

  • ✓ May perform gastric lavage

  • ✓ Treat metabolic acidosis with IV sodium bicarbonate

• Antidote: Fomepizole and ethanol bind alcohol dehydrogenase with higher affinity than ethylene glycol and thereby prevent formation of toxic metabolites

  • ✓ Treat with fomepizole (preferred) for methanol level greater than 25 mg/dL or patients with presumed ingestion and metabolic acidosis

  • ✓ If not available, IV ethanol infusion is also effective but difficult to administer

• Folic acid helps conversion of formic acid to carbon dioxide and water

• Hemodialysis is indicated in cases of severe metabolic acidosis or blood methanol concentrations greater than 50 mg/dL

• Criteria for hospitalization: Any known methanol ingestion or clinical and lab findings suggestive of methanol ingestion

Can be natural or synthetic; most commonly used to treat severe pain, can also be used as antitussive; opioid abuse can result from use of prescription medication or illegal street drugs.

TOXICOLOGY/PHARMACOLOGY

• Opioid effects result from binding directly to opioid receptors in CNS

• Tolerance develops with chronic use, except for miosis, constipation

• Buprenorphine is an opioid partial agonist with low potential for abuse, which can also block the effect of full opioid agonists at high doses; prescribed for opioid addiction

• Rising common accidental pediatric ingestion with increased toxicity in children

CLINICAL MANIFESTATIONS

• Classic triad of pinpoint pupils, coma, and respiratory depression

• Gastrointestinal: Decreased motility and increased sphincter tone can result in constipation; effects on biliary sphincter may cause RUQ pain that mimics other biliary conditions

• Cardiac: Hypotension; propoxyphene may cause arrhythmias

• Central nervous system: Lethargy, respiratory depression, coma, seizures (primarily with meperidine)

• Pulmonary: Pulmonary edema

• Diphenoxylate results in delayed onset of symptoms secondary to formulation that includes atropine

DIAGNOSTICS

• Can be based on clinical findings

• Can perform urine or blood toxicologic screen, though methadone, fentanyl, and oxycodone may not be detected on routine drug screens

• Laboratory studies: Electrolytes, glucose, BUN, creatinine, blood gas

• Chest x-ray

MANAGEMENT

• Decontamination: Activated charcoal for oral ingestion; consider MDAC or WBI for “body stuffers”

• Supportive care: May need to intubate to maintain airway; treat hypotension, seizures, pulmonary edema if they occur

• Naloxone is an opioid antagonist; dose is 0.4–2 mg IV; may repeat if no response after 2–3 minutes

  • ✓ May need to use repeat doses or an infusion to maintain response

  • ✓ May precipitate withdrawal in addicted patients; therefore, detoxification of an addicted patient is usually done with methadone

• Criteria for hospitalization: In general, patients should be admitted for observation; length of observation is based on half-life of specific drug

Insecticides; ingredient in chemical warfare agents

TOXICOLOGY/PHARMACOLOGY

• Toxicity is a result of inhibition of acetylcholinesterase; clinical findings are result of accumulation of acetylcholine at muscarinic, nicotinic, and CNS receptors

  • ✓ Enzyme inhibition can become irreversible with increasing time of exposure, a process known as “aging”

• Can be from inhalation, ingestion, or absorption from skin

• Rapid onset of symptoms after exposure

• Children and pregnant women are at increased risk of toxicity due to lower baseline cholinesterase levels

• Note that carbamate insecticides act similarly on acetylcholinesterase but do not cause irreversible inhibition (“aging”)

CLINICAL MANIFESTATIONS

• Central nervous system: Headache, agitation, seizures, coma

• Nicotinic: Weakness, fasciculations, increased heart rate and blood pressure; can result in death from respiratory muscle paralysis

• Muscarinic: Abdominal pain, vomiting, diarrhea, urinary and fecal incontinence, bronchospasm, decreased heart rate and blood pressure (opposite from nicotinic effects), salivation, diaphoresis, miosis

• Can occasionally see a delayed, permanent, peripheral neuropathy

DIAGNOSTICS

• Diagnosis based on history of exposure and classic clinical presentation

• Not detected on urine toxicologic screens

• Can measure plasma pseudocholinesterase levels or red blood cell cholinesterase activity, but this is not very helpful unless baseline levels have been obtained

• Laboratory studies: Electrolytes, glucose, BUN, creatinine, liver function tests, blood gas

• ECG

MANAGEMENT

• Avoid contact with contaminated clothing, skin, or gastric aspirates

• Decontamination: Contaminated clothing must be removed and discarded as toxic waste, skin should be cleaned with soap and water

  • ✓ No ipecac, gastric lavage for recent ingestions, activated charcoal

• Antidote: Atropine in doses of 0.05–0.1 mg/kg should be repeated until asymptomatic; administer either IV or IM

  • ✓ Pralidoxime (used in conjunction with atropine) is used specifically to treat muscle weakness and prevent “aging”—dose is 20–40 mg/kg either IV or IM; doses can be repeated every hour as needed until muscle weakness and other cholinergic signs and symptoms resolve

• Avoid any concurrent therapy with drugs that affect acetylcholine uptake (i.e., phenothiazines)

• Criteria for hospitalization: Any patient requiring treatment

Used for depression, psychosis, aggression, emotional instability, sleep disturbance, and acute management of agitation and delirium

TOXICOLOGY/PHARMACOLOGY

• Typical antipsychotics: Phenothiazines/butyrophenones—chlorpromazine, thioridazine, haloperidol, droperidol

  • ✓ Toxicity is due to effects on CNS, anticholinergic effects, alpha-adrenergic blocking effects

  • ✓ Have variable antagonism at the D2 dopamine receptor but cause nonspecific blockade throughout the brain leading to side effects

  • ✓ Toxicity can be seen with therapeutic doses

• Atypical antipsychotics (risperidone, clozapine, olanzapine, quetiapine)

  • ✓ Serotonin receptor antagonists or partial agonists in addition to dopamine receptor blockade

  • ✓ Lower risk of extrapyramidal side effects

  • ✓ Can bind with high affinity leading to long lasting adverse effects

CLINICAL MANIFESTATIONS

Typical antipsychotics:

• Toxicity

  • ✓ Mild toxicity: CNS: sedation, ataxia, slurred speech; anticholinergic symptoms include constipation, urinary retention, dry mouth (except clozapine causes hypersalivation); orthostatic hypotension, tachycardia

  • ✓ Severe toxicity: CNS: hypothermia or hyperthermia, coma, seizures, respiratory arrest; cardiac: QRS or QT prolongation, dysrhythmias, hypotension; extrapyramidal effects: torticollis, rigidity, tremor, cogwheel rigidity

• Dystonic reactions: Can be seen regardless of amount ingested

• Neuroleptic malignant syndrome: Rigidity, hyperthermia, rhabdomyolysis, lactic acidosis

Atypical antipsychotics:

• Mild toxicity: Sialorrhea (clozapine), orthostasis, sedation, metabolic and endocrinologic abnormalities, nausea and vomiting, urinary retention, sleep abnormalities, blurred vision

• Severe toxicity: Coma, respiratory depression, seizures, movement disorders, hypotension, myocardial depression, QT prolongation, hepatic toxicity, severe allergic reactions, delirium, agranulocytosis, neuroleptic malignant syndrome

DIAGNOSTICS

• Based on history of ingestion and symptoms

• Drug levels not generally available: Some cause a false positive tricyclic screen

• Laboratory studies: Electrolytes, BUN, creatinine, glucose, CPK, blood gas, liver function tests

• Abdominal x-ray: Pills can be radio-opaque

• ECG to look for conduction delays

MANAGEMENT

• Decontamination: Activated charcoal, WBI for some sustained-release formulations. In specific cases a lipid emulsion may be helpful in consultation with local poison control

• Supportive care: Treat dystonic reactions with either diphenhydramine (0.5–1.0 mg/kg IV or IM) or benztropine (0.02 mg/kg IV or IM for children over 3 years)

  • ✓ Be alert for other sequelae such as arrhythmias (requires cardiac monitoring), seizures, and hypotension

• Neuroleptic malignant syndrome

  • ✓ Cooling blankets for hyperthermia

  • ✓ Benzodiazepines for muscular rigidity

  • ✓ Intubation and paralysis if needed

  • ✓ Dantrolene or bromocriptine for severe cases

• Criteria for hospitalization: Admit patients with signs of toxicity; observe asymptomatic ingestions for 6 hours

TOXICOLOGY/PHARMACOLOGY

• Phenytoin increases brain concentrations of GABA, reduces high-frequency neuronal firing, and affects cardiac conduction through Class Ib antidysryhthmic effect (sodium channel blockade)

• Toxicity can be seen at doses of 20 mg/kg

• Erratic oral absorption

• Drug is highly protein bound and toxicity can develop from decreased protein binding or displacement of drug by other drugs

• With IV preparations, toxicity may be due to diluent, propylene glycol

CLINICAL MANIFESTATIONS

• Cardiac: Can see tachycardia or bradycardia; hypotension (ventricular fibrillation and asystole can be seen with IV overdose)

• Neurologic: Ataxia, encephalopathy, tremor, agitation, nystagmus, confusion, hallucinations; seizures are rare (must rule out co-ingestion)

• Gastrointestinal: Nausea, vomiting, hepatitis

• Can also see hypersensitivity reactions

• Rapid intravenous administration can result in hypotension (due to propylene glycol) and arrhythmias

DIAGNOSTICS

• Diagnosis based on history of ingestion

• STAT phenytoin concentration (10–20 mg/L considered therapeutic); need to recheck due to possibility of delayed absorption

• Laboratory studies: Electrolytes, BUN, creatinine, glucose, albumin

• ECG if drug was given IV

MANAGEMENT

• Decontamination: Activated charcoal, may consider MDAC

• Supportive care: Treat hypotension, manage dysrhythmias (ACLS/PALS guidelines)

• Criteria for hospitalization: Cardiac or neurologic symptoms; unable to tolerate fluids due to severity of nausea and vomiting, fall risk due to ataxia

Over-the-counter analgesics and cold medications; Pepto-Bismol (bismuth subsalicylate); liniments, oil of wintergreen (methyl salicylate)

TOXICOLOGY/PHARMACOLOGY

• Direct CNS stimulation of respiration resulting in respiratory alkalosis

• Uncouples oxidative phosphorylation and inhibits Krebs cycle, causing elevated anion-gap metabolic acidosis

• A unique mixed acid–base disorder ensues: Concomitant respiratory alkalosis and metabolic acidosis

  • ✓ Young children are more likely to present with acidosis

• 60% of cases of salicylism are from acute ingestion

• Start to see toxicity at doses of 150 mg/kg

• Elimination half-life can be as high as 36 hours in cases of overdose because of loss of first-order kinetics as drug concentrations increase

CLINICAL MANIFESTATIONS

• Acute toxicity

  • ✓ Mild symptoms include vomiting, tinnitus, lethargy, tachypnea

  • ✓ Moderate symptoms include agitation, diaphoresis, fever

  • ✓ Severe symptoms include seizures, coma, pulmonary edema, death results from CNS toxicity and inhibition of cardiorespiratory centers in the brain

• Chronic toxicity: Symptoms can appear at much lower serum concentrations

• Can be nonspecific with only confusion or dehydration

• Can see metabolic acidosis and pulmonary and cerebral edema

DIAGNOSTICS

• Salicylate level: Therapeutic level is 15–30 mg/dL

  • ✓ Mild toxicity (tinnitus) at levels of 30–40 mg/dL

  • ✓ CNS depression at levels greater than 80 mg/dL

  • ✓ Severe toxicity at levels greater than 100 mg/dL

• Chronic toxicity may manifest at lower levels

• Obtain serial salicylate levels (every 2–4 hours) and blood gases until level falling into nontoxic range

• Other

  • ✓ Electrolytes (repeat every 2 hours during alkalinization and then every 12 hours until acid–base disturbances resolve; early hyperglycemia followed by hypoglycemia and hypokalemia)

  • ✓ Arterial blood gas (combined respiratory alkalosis and anion gap metabolic acidosis)

  • ✓ Liver function tests

  • ✓ CBC, PT, and PTT (coagulopathy may occur)

  • ✓ Urinalysis (every 2 hours; for pH and specific gravity; maintain urine pH of 7.5–8)

  • ✓ ECG

MANAGEMENT

• Activated charcoal where appropriate

• Treat fluid deficits (often profound) and electrolyte abnormalities

• Alkalinize to enhance salicylate excretion and maintain serum pH greater than 7.4: Give 100–150 mEq sodium bicarbonate/L of D5W at two times maintenance; goal urine pH is 7.5–8.0

• Maintain normal serum potassium (>4.0 mEq/L)

• If intubation needed, attempt to mimic the patient’s own respiratory rate as depression of their spontaneous rate may worsen neurological outcomes

• Hemodialysis should be considered for metabolic acidosis not easily reversed with alkalinization, CNS dysfunction impairing patient’s ability to maintain hyperpnea, salicylate levels >100 mg/dL, renal failure, pulmonary edema, or deterioration despite therapy

• Criteria for hospitalization: Admit all symptomatic patients; observe asymptomatic patients for at least 6 hours

Used to treat depression and obsessive compulsive disorder and other behavioral disorders; examples include fluoxetine, paroxetine, and sertraline (SSRIs) and venlafaxine, duloxetine (SNRIs)

TOXICOLOGY/PHARMACOLOGY

• Caused by CNS depression

• Safer than tricyclic or monoamine oxidase inhibitor (MAOI) antidepressants; death from overdose is uncommon

• Trazadone is an SARI (serotonin antagonist/reuptake inhibitor) and can cause SIADH and priapism

CLINICAL MANIFESTATIONS

• Neurologic: Confusion, sedation, coma

• Respiratory depression can occur, more likely after co-ingestion with other sedatives

• Cardiac: Usually mild, can get tachycardia and hypotension or hypertension, arrhythmias due to QT prolongation

• GI: Nausea, vomiting, and anorexia

• Serotonin syndrome: Can be seen after starting drug, switching drugs, increasing dose, or overdose; presents with rigidity, hyperreflexia, autonomic instability, alteration in mental status, restlessness, hyperthermia; may resemble neuroleptic malignant syndrome

DIAGNOSTICS

• Drug levels are not useful

• Laboratory studies: Electrolytes, glucose, CPK, UA, blood gas; ECG

MANAGEMENT

• Decontamination

• Supportive care: Hydration; alkalinize urine if signs of rhabdomyolysis; manage seizures with benzodiazepine, manage hyperthermia with external cooling, neuromuscular paralysis, and intubation

• In some reports, serotonin syndrome has been successfully treated with cyproheptadine, a serotonin receptor antagonist

Used to treat depression, enuresis, neuropathic pain

TOXICOLOGY/PHARMACOLOGY

• Due to anticholinergic effects, peripheral alpha blocking effects, sodium channel blockade causing ventricular conduction delay and myocardial depression, and inhibition of norepinephrine and serotonin reuptake

• Large volumes of distribution

CLINICAL MANIFESTATIONS

• Anticholinergic syndrome: Urinary retention, delayed gastric emptying, flushed and dry skin, delirium, dilated pupils, hyperthermia

• Extreme hyperthermia can result in rhabdomyolysis

• Cardiac: Hypotension from peripheral vasodilation; sinus tachycardia; conduction abnormalities (prolongation of PR, QRS, or QT intervals); QRS interval greater than 0.1 seconds is predictive of significant morbidity; various arrhythmias including PVCs, ventricular tachycardia, ventricular fibrillation

• Neurologic: Can range from lethargy to seizures to coma

DIAGNOSTICS

• Drug levels are usually not helpful

• Most can be detected on urine screening

• Laboratory studies: Electrolytes, BUN, creatinine, glucose, blood gas, CPK, urinalysis

• ECG: Width of QRS interval >100 milliseconds is predictive of ventricular dysrhythmias and seizures

MANAGEMENT

• Decontamination: Consider lavage, activated charcoal

• Sodium bicarbonate reverses cardiac sodium channel blockade and narrows QRS complex, by alkalinizing the blood (thereby trapping the drug in the circulation and not the myocardium) and overcoming channel blockade with sodium loading. 1 mEq/kg bolus dosing to narrow QRS, repeat PRN for wide complex. Consider infusion if repeated doses needed

• Supportive care: Treat seizures with benzodiazepines. Norepinephrine can be used for persistent hypotension. Lidocaine can be used for persistent arrhythmias. Prevent hyperthermia

• Physostigmine SHOULD NOT be given and will worsen cardiac toxicity

• Criteria for hospitalization: Observe all ingestions at least 6 hours. If any signs of toxicity, admit for 24 hours of observation

Can refer to any synthetic form of a controlled substance

TOXICOLOGY/PHARMACOLOGY

Synthetic cannabinoids

• Similar to THC in function by binding to cannabinoid receptors

• Common names: “Spice,” “yucatan fire,” “aroma,” “incense,” “potpourri,” “K2”

• Attractive to users because they are not typically detected by drug screens and are advertised as “safe and legal”

• Limited data on human toxicity and high variability in preparations contribute to danger

• Common effects include nausea, vomiting, tachycardia, and hypertension; chest pain and ischemia occur in more severe cases, psychiatric effects include anxiety, depression, and psychosis; seizures reported

Synthetic stimulants

• Can be marketed as “bath salts” or “plant food”

• Derivatives of a stimulant called cathinone, a controlled substance

• Can be taken orally, intranasally, or intravenously

• Inhibit dopamine and norepinephrine reuptake

• Common effects include tachycardia and hypertension, agitation, diaphoresis, psychosis, and hallucinations. Dysphoric reactions causing panic and anxiety have also been described

DIAGNOSTICS

• Chemistry (synthetic cannabinoids have been reported to cause hypokalemia), ECG

• Drug screens may identify co-ingestions and high performance liquid chromatography/tandem mass spectroscopy might identify more rare drugs but is rarely useful in the immediate setting

MANAGEMENT

• Recognize that even designer drugs of the same name can have unreliable chemical compositions and can cause variable reactions

• Management consists largely of supportive care and close cardiorespiratory monitoring. Patients may benefit from benzodiazepines for psychiatric symptoms

Includes button batteries, detergent pods, magnet toys, and expanding toys

TOXICOLOGY/PHARMACOLOGY

• Button batteries:

  • ✓ Increased number of objects powered by button batteries (toys, remote controls, children’s books with musical push buttons) with a resultant increase in ingestions

  • ✓ Injury occurs primarily from direct electrical current and caustic alkaline injury with liquefactive necrosis, heavy metal leaching, and direct pressure can also be a factor

  • ✓ Increasing number of fatal cases in recent years, most of which are associated with 20 mm 3V lithium disc battery

• Detergent pods:

  • ✓ Agents thought to contribute to symptomatology include propylene glycol, ethoxylated alcohols, and highly concentrated detergents

• Magnet toys:

  • ✓ Increasing incidence as magnets are more common in toys and household objects

• Expanding toys:

  • ✓ Commonly balls made of superabsorbent polymers that expand when exposed to water

  • ✓ Generally attractive to toddlers because of their size and color, easy to swallow

  • ✓ Superabsorbent polymer technology more common now in household products and gardening supplies in addition to toys

CLINICAL MANIFESTATIONS

• Button battery ingestions may be asymptomatic or might cause respiratory symptoms, pain, drooling, or dysphagia

• Detergent pods:

  • ✓ Detergent pods may cause drooling, coughing or gagging, respiratory distress, vomiting, and mental status changes which may be profound

• Magnet toys:

  • ✓ Number of magnets is important as more than one may attract and cause intestinal obstruction, necrosis, and perforation

  • ✓ Magnet ingestions are often asymptomatic but may cause abdominal obstruction or fistulas

• Expanding toys:

  • ✓ Ingestion of expanding toys may also be initially asymptomatic but can rapidly cause symptoms of GI obstruction including nausea/vomiting, abdominal distension, and pain

DIAGNOSTICS

• Plain film of the chest and abdomen (does not rule out foreign body as many are radiolucent)

• For detergent pods, a blood gas, metabolic panel, glucose, ECG, and CBC might be helpful in the differential diagnosis of the mental status changes

MANAGEMENT

• Supportive care including close airway monitoring, in patients with worsening respiratory distress or mental status changes securing the airway early might be indicated

• For proximal foreign bodies (esophageal and pre-pyloric) involve GI/ENT to discuss removal (always indicated for button batteries and multiple magnets, highly recommended for expanding toys)

• Admission criteria: Any symptomatic patient should be admitted for serial exams and monitoring, patients requiring intervention, unknown type, or quantity of ingested object