Chapter 17. Toxicology

Clinical Summary

The incidence of pediatric poisoning follows a biphasic curve, with 85% to 90% in children age 1 to 6 years and a second smaller peak of 10% to 15% of cases in adolescents. Most cases in children are unintentional ingestions of a single agent (frequently nontoxic household products). The most often reported pharmaceutical exposures in children <6 years of age include analgesics, cough and cold preparations, cardiovascular agents, topical preparations, sedative hypnotic agents, and antidepressants. Adolescent toxic ingestions usually involve intentional ingestion of multiple pharmaceutical agents in attempted self-harm.

History

The most important factor in successfully treating a patient with a toxicologic exposure is to recognize a toxicologic etiology in the undifferentiated patient. Poisoning must be considered in the differential diagnosis of multiple conditions, especially when a patient presents with cyanosis, shock, vomiting, diarrhea, hypothermia or hyperthermia, abnormal behavior, or altered mental status. A thorough history must be obtained with a focus on the identification of the toxin, timing, dosage, route, intent of ingestion, and symptom development since ingestion.

The patient, or his or her caretakers, may be able to directly identify the involved toxin because of a known exposure (eg, medications taken, intentional overdose attempt, substance abuse, exposure to occupational chemicals). Determining whether the exposure was intentional or not may aid in assessing the reliability of the history given by the patient. Regardless of intention, patients may or may not report accurate amounts, and it may be necessary to search through medication containers and count the number of remaining pills or measure approximate quantities of liquid. Comparison with the reported amount by the patient may reveal a discrepancy.

Prehospital health care workers may aid in identification of the toxin and information about dosage/route at the time of arrival in the emergency department (ED) with findings of containers or other evidence of possible toxins and can also provide information on any treatment and attempts at decontamination before hospital arrival.

It is important to also consider and investigate possible occult coingestions (eg, acetaminophen) in adolescents and multiple routes of exposure in all children, including dermal, rectal, ocular, parenteral, or transplacental. The route of exposure often affects the severity and time course of toxicity.

Determination of symptoms since ingestion will aid in recognition of toxidromes (see below) as well as determination of degree of toxicity. Attention must be paid to past medical history and comorbidities with a focus on the patient’s medications, including herbal supplements, dietary supplements, over-the-counter medications, and alternative medical therapies.

Samples of the substance may be available (eg, plants, mushrooms). For potential carbon monoxide poisoning (CO), the local fire department may also be notified to quantify the amount of CO in a building. A poison control center or product manufacturer should be contacted if the ingredients of a product are unknown. Review of drug and chemical databases (eg, Poisindex®) is also useful.

Consider child abuse in children younger than age 1 year in the setting of repeated ingestions, or if the child’s developmental level and skills preclude performance of the described events (eg, a child too young to open childproof containers).

Physical Examination

Perform a thorough physical examination beginning with vital signs. Possible toxidromes (toxicologic syndromes that are characteristic signs and symptoms seen with certain poisons or classes of poisons) should be identified as these aid diagnosis and management of acutely ill patients, especially when a history of poisoning is lacking (see Table 17.2).

Laboratory studies should be performed, if clinically indicated, for diagnosis or to guide therapy (see specific chapters for agents and laboratory studies that may prove useful in management). These should include serum electrolytes, including glucose, blood urea nitrogen (BUN), and creatinine to determine renal function and calculate any anion gap. Obtaining serum osmolality will determine if substances causing an increased osmolal gap were ingested. These include ethanol, methanol, isopropyl alcohol, and ethylene glycol (osmolal gap = measured serum osmolality − calculated osmolality). Toxicology screens (either urine or serum) may occasionally help in determining occult coingestions; however, they are rarely helpful in the acute management of patients. These laboratory tests are generally used by consultants (eg, psychiatry) or admitting physicians to facilitate disposition and long-term management.

All patients with an intentional suicidal overdose should have serum acetaminophen and salicylate levels determined. All girls of childbearing age should have a pregnancy test performed.

If there is any gastric aspirate/vomitus, note appearance, pills, odor; test for occult blood in the stool.

Radiographic studies may be useful for management or confirmation of a diagnosis with a high index of suspicion, for example, iron. Chest radiographs may show pulmonary edema or aspiration pneumonitis consistent with hydrocarbon exposure. Abdominal radiographs may show radiopaque substances. However, it is important to note that absence of toxins generally considered to be radio-opaque does not exclude ingestion.

Emergency Department Treatment and Disposition

Proper external decontamination before entry into the ED is necessary to protect health care personnel and prevent contamination of the emergency department (ED). This may involve removal of all clothing and washing the skin.

All patients should have airway, breathing, and circulation (ABCs) stabilized based on abnormal vital signs before any diagnostic tests are performed. Focus on treating the patient, not the poison. Patients may have more than one type of exposure or ingestion, complicating the identification of distinct toxidromes. Consultations with the local medical toxicologist or regional poison control center may also be helpful.

Unresponsive patients may empirically be given intravenous (IV) thiamine 100 mg (in adolescents), followed by IV dextrose (1 g/kg) and IV naloxone (1–2 mg, may be repeated several times) and observed for a response. Patients with altered mental status should be evaluated for all causes of altered sensorium including nontoxicologic causes (see mnemonic COMATOSE PATIENT; Table 13-5).

Motor seizures are generally well-controlled by benzodiazepines. Anticonvulsants are rarely used in the treatment of toxin-induced seizures. If the toxic agent is known, seizures may be controlled with specific therapy (eg, pyridoxine for acute isoniazid toxicity).

GI decontamination should not routinely include syrup of ipecac or orogastric lavage. Orogastric lavage is indicated when there is a potentially life-threatening ingestion of a poison with no definitive antidote. The greatest benefit is most likely to be seen in a patient who presents within 60 minutes of ingestion. Patients presenting after 60 minutes could also benefit because of delayed gastric emptying. Contraindications include ingestion of caustics, hydrocarbons, and foreign bodies (FBs); bleeding diathesis; and an unprotected airway. Complications include aspiration pneumonia, GI perforation, laryngospasm, and emesis.

Decontamination with activated charcoal (AC) is indicated if a patient has ingested a potentially toxic amount of a poison that is known to be adsorbed by AC. AC does not adsorb acids, alkalis, lithium, iron (most metals), alcohols, or hydrocarbons. AC administration is likely to be most effective if begun within 60 minutes of ingestion, but may also be given after 60 minutes, especially if there is delayed gastric emptying, possible bezoar formation, and enterohepatic or enteroenteric circulation of the toxin. AC is given orally as a slurry in water or fruit juice (also by nasogastric or orogastric tube) and the usual single dose (children/adults) is 1 to 2 g/kg up to 50 g or 10:1 ratio of AC-drug is considered ideal. Multiple-dose AC (0.5–1 g/kg every 4–6 hours) should be considered if a patient has ingested a large quantity of agents that decreases gastric motility (eg, anticholinergics, enteric-coated preparations), theophylline, phenobarbital, carbamazepine, quinine, or dapsone. Patients should have good GI motility as evidenced by normal bowel sounds and passage of stool (ie, no evidence of GI obstruction). Contraindications include intestinal obstruction or perforation, altered sensorium (absent gag reflex/unprotected airway), and caustics (may obscure endoscopic visualization of gastroesophageal injury). Complications include pulmonary aspiration, intestinal obstruction, constipation, and development of charcoal bezoars. If desorption of ingestant from AC is a possibility, a single dose of cathartic may be given to an adolescent who has ingested a large amount of drugs. Administration of a cathartic alone has no role as a method of gut decontamination. Routine use of a cathartic with AC is not recommended. Complications include nausea, vomiting, diarrhea, abdominal pain, and dehydration with electrolyte disturbances (following multiple doses which should not be repeatedly given for >24 hours). Contraindications include absent bowel sounds, ingestion of caustics, or GI irritants.

Whole bowel irrigation (WBI) may be considered in patients who have ingested FBs, packets containing toxins, iron, and sustained-release or enteric-coated tablets. WBI should not be routinely used in the management of the poisoned patient. WBI is commonly performed by the continuous administration of a bowel-cleansing solution containing polyethylene glycol electrolyte solution (PEG ELS) via an oral or nasogastric tube. It is given at a rate of 0.5 L/h until the rectal effluent is clear. In older children and adolescents, it should be given at a rate of 1 to 2 L/h. No significant adverse effects of prolonged WBI with PEG ELS have been demonstrated.

Certain toxins can be managed with the administration of toxin-specific antidotes. Prophylactic use of antidotes is not recommended because of potentially serious side effects with inappropriate administration. Life-threatening poisonings such as opioids, cholinergics, CAs, methemoglobinemia, CO, and cyanide require simultaneous use of an antidote with the initial stabilization of vital signs.

Consider hospital admission if the patient manifests significant toxicity, suicidal intent, identification of poison is unclear, ingested substance has delayed toxicity, or patients that will require further management such as urinary alkalinization (eg, salicylates, phenobarbital), hemodialysis (eg, methanol, ethylene glycol, salicylates, lithium), or whole-bowel irrigation (eg, iron). Consider ICU admission for patients who manifest significant toxicity, or those in whom management will require rigorous nursing care.

Consider discharge to home all patients with unintentional ingestion if the patient (and/or guardians) has received appropriate counseling and social service intervention; the product or drug has been determined to be benign, the amount ingested is less than the smallest amount known to produce toxicity (note that the history is often unreliable), the patient has no signs of toxicity since the time of ingestion, the time elapsed since the ingestion is greater than the longest interval known between ingestion and peak toxicity and in cases where child abuse/neglect is not considered likely.

Pearls

1. The most important factor in successfully treating a patient with a toxicologic exposure is to recognize that there is a toxicologic etiology of the patient’s condition.

2. GI decontamination has not been shown to improve patient outcome; however removal of toxin by GI decontamination before adsorption may prevent or mitigate toxicity. It is critical to ask “Has the child ingested a potentially toxic dose?” and “What is the time since ingestion?”

3. Gastric lavage should not be considered unless the patient has ingested a potentially life-threatening amount of a poison and toxin is expected to be remaining in the stomach.

4. AC should only be considered if a patient has ingested a potentially toxic amount of a poison that is known to be adsorbed by AC. A nasogastric tube should not be placed for the sole purpose of AC administration.

5. WBI should be considered only in patients presenting with potentially toxic ingestion of iron, lead, packets of illicit drugs, sustained-release or enteric-coated tablets.

Clinical Summary

Acetaminophen (APAP) overdose can lead to hepatic necrosis, fulminant hepatic failure, and death. The therapeutic dose is 10 to 15 mg/kg with maximum dosage of 80 mg/kg/d. Acute toxicity usually occurs at doses above >150 mg/kg.

Clinical presentation is dependent on amount of time since ingestion and patients may be completely asymptomatic initially. After 24 hours, patients may also present with Gastrointestinal (GI) symptoms of nausea, vomiting, and malaise. After 24 to 72 hours, GI symptoms may lessen, during which time hepatic damage is occurring. Patients may have right upper quadrant pain or tenderness. After 72 to 96 hours, anorexia, nausea, and vomiting worsen. Progression to fulminant hepatic failure may occur by 4 to 5 days post ingestion.

The differential diagnosis of hepatotoxicity includes viral hepatitis, other drug- or toxin-induced hepatitis (eg, isoniazid, carbamazepine, Amanita phalloides mushroom, phenytoin), alcoholic hepatitis, hepatobiliary disease, Reye’s syndrome, ischemic hepatitis (usually following a prolonged period of hypotension).

Evaluation should include a careful history with particular attention to comorbidities that may predispose the patient to development of hepatotoxicity and formulations that decrease GI motility (eg, combination preparations containing anticholinergic agents such as diphenhydramine or opioids such as codeine). Laboratory tests should include serum acetaminophen concentration, complete blood count (CBC), glucose, electrolytes, BUN, creatinine, phosphate, prothrombin time, International Normalized Ratio (INR), serum transaminases (ALT, AST), and serum bilirubin. Serum lactate levels can be obtained and are believed to contribute to the elevated anion gap seen early in cases of severe APAP toxicity. It has been suggested that elevated serum phosphate values can be an early predictor of outcome in severe APAP-induced hepatotoxicity. Once a serum acetaminophen level has been obtained 4 hours post ingestion, the Rumack-Matthew nomogram should be applied to determine necessity for antidotal treatment.

Emergency Department Treatment and Disposition

GI decontamination is primarily achieved through the administration of AC (1–2 g/kg orally). Antidotal therapy with N-acetylcysteine (NAC) can be empirically administered if >150 mg/kg of APAP has been ingested and the patient presents soon after ingestion via IV as three doses over 21 hours. The initial loading dose is 150 mg/kg diluted in 3 mL/kg of D5 ½ NS, infused over 60 minutes. The second dose is 50 mg/kg diluted in 7 mL of D5 ½ NS infused over then subsequent 4 hours. The third dose of 100 mg/kg diluted in 14 mL of D5 ½ NS, then infused over 16 hours. NAC dosing needs to be adjusted for young children < 20 kg because of hyperosmolarity.

All patients who have a toxic APAP level require a full course of NAC therapy and should be admitted. Patients with signs and/or symptoms of significant hepatotoxicity or other end organ toxicity, should be admitted to the ICU. Patients presenting after 24 hours following an overdose and with evidence of hepatotoxicity should be started on IV NAC immediately. Patients should be admitted for supportive care.

Contact the poison control center for all patients with APAP toxicity, patients who have developed signs and symptoms of hepatotoxicity, patients presenting with ingestion of extended-release preparations, or those presenting more than 24 hours post ingestion. Indications for transfer to a liver transplantation center in patients who develop hepatotoxicity include arterial pH <7.3 after fluid resuscitation, grade III or IV encephalopathy, creatinine >3.3 mg/dL, or INR >2 to 3. Psychiatry should be consulted for all cases of self-harm.

Pearls

1. Acetaminophen is the most widely used analgesic-antipyretic in the United States and accounts for more overdoses and overdose fatalities per year than any other pharmaceutical agent.

2. All patients presenting with an intentional overdose of medication should have a serum APAP concentration checked.

3. Severe acetaminophen toxicity may produce fulminant hepatic failure 3 to 5 days post ingestion.

4. A 10-kg infant can be poisoned by a 15-mL bottle of 80 mg/0.8 mL preparation (15 mL contains 1500 mg of APAP, or 150 mg/kg).

Clinical Summary

The most common salicylate therapeutically used is acetylsalicylic acid (ASA; aspirin). Many over-the-counter products contain salicylates, including Ben-Gay® and Pepto-Bismol®, as well as the highly concentrated salicylate product, oil of wintergreen. Toxicity generally occurs at doses of >150 mg/kg, with >300 mg/kg considered as potentially lethal. Ingested ASA tablets may occasionally form concretions (bezoars) or cause pylorospasm, resulting in delayed and prolonged absorption. Enteric-coated preparations may also result in delayed or prolonged absorption.

Clinical findings of salicylate toxicity include nausea, vomiting, epigastric pain, and possible hematemesis. Hyperpnea and tachypnea may lead to respiratory alkalosis and noncardiogenic pulmonary edema. Also known as acute lung injury (ALI). Patients may complain of tinnitus, deafness, delirium, seizures, or coma. Anion gap metabolic acidosis may develop. Increased sweating, vomiting, and tachypnea may lead to dehydration, hypernatremia, hypokalemia, or hypocalcemia. Hypoglycemia may also occur.

Differential diagnosis of other causes of increased anion gap metabolic acidosis should be considered (see Table 17.2). Other etiologies must also be considered for hypoglycemia, gastroenteritis, and acute respiratory distress syndrome (ARDS).

Take a careful history with attention to amount, time of ingestion, intent, possibility of coingestants, and type of preparation (ie, immediate-release vs enteric-coated). Laboratory tests should include CBC, serum electrolytes, glucose, BUN, creatinine, arterial blood gases (ABG), liver transaminases, coagulation studies, serum calcium, and ketone concentrations.

A serum salicylate level should be obtained on presentation and every 2 hours thereafter for the first 4 to 8 hours. If the salicylate level is >30 mg/dL, obtain serial concentrations hourly until a consistent decrease is noted. Determine urinary pH in all patients and obtain a urine pregnancy test in girls of reproductive age. Abdominal radiographs may demonstrate enteric-coated tablets, concretions, or bezoars. A chest radiograph may show acute lung injury.

Emergency Department Treatment and Disposition

All patients should be fluid resuscitated with IV crystalloid solution and electrolyte abnormalities corrected (eg, add potassium supplementation to IV fluids after urine output is established). In the case of GI bleeding, administer blood products such as packed red blood cells.

Treat patients with large ingestions, metabolic acidosis, symptoms of severe toxicity, or serum salicylate level >70 mg/dL with an initial sodium bicarbonate bolus of 1 to 2 mEq/kg followed by a continuous infusion made from 3 ampules (44–50 mEq each) of NaHCO3 in 1 L D5W and infused at 1.5 to 2 times maintenance fluid rate to alkalinize the urine (goal of urinary pH of 7.5–8.0) unless there is encephalopathy, cerebral edema, pulmonary edema, blood pH >7.55, renal failure, or serum sodium >150 mEq/L. Measure urinary pH hourly and titrate the NaHCO3 infusion accordingly. Serum potassium must be closely monitored and replaced as necessary.

Consider emergent hemodialysis for patients who are severely poisoned, that is, hemodynamically unstable, comatose, or seizing; have pulmonary edema, cerebral edema, or oliguric renal failure; or who have rising salicylate levels despite GI decontamination and proper urinary alkalinization.

Consider GI decontamination with AC after ingestion >150 mg/kg. Multiple-dose AC (0.5–1 g/kg) may be given for an additional 1 to 2 doses. Consider whole bowel irrigation if concretions are seen on abdominal x-ray or ingestion of enteric-coated preparations. Gastric endoscopy may rarely be required for bezoar removal.

Asymptomatic patients observed for 4 to 6 hours, with nontoxic serum salicylate levels, and no significant acid-base abnormalities may be medically cleared. Consult the local medical toxicologist, regional poison control center, nephrology (hemodialysis), psychiatry (suicidal intent), and rarely gastroenterology (possible endoscopic removal of aspirin bezoars) as indicated.

Admit symptomatic patients for repeat doses of AC, urinary alkalinization, observation, hemodialysis, and supportive care.

Pearls

1. Treat based on clinical and metabolic abnormalities not absolute serum salicylate concentration (unless very high [>100 mg/dL]).

2. Salicylate toxicity initially causes a respiratory alkalosis that progresses to a metabolic acidosis with increased anion gap.

3. Young children may initially present without apparent respiratory alkalosis. Adolescents and adults develop respiratory alkalosis early after an overdose.

4. Endotracheal intubation may be potentially harmful because of transient apnea and respiratory acidosis. Adjust ventilator settings to account for the patient’s increased minute ventilation prior to intubation as well. Failure to manage this aspect of a patient’s care may result in abrupt and rapid demise.

Clinical Summary

Iron is commonly available as ferrous fumarate, ferrous gluconate, and ferrous sulfate, each containing 33%, 12%, and 20% elemental iron, respectively. Children’s multivitamin tablets contain 10 to 18 mg elemental iron per tablet; adult multivitamins contain up to 65 mg elemental iron per tablet. To determine if the amount ingested is potentially toxic, determine the elemental iron ingested. Signs of toxicity usually begin with ingestions >20 mg/kg.

There are 5 stages of iron toxicity commonly described. In stage I, the first 12 hours after exposure, profuse GI symptoms occur including abdominal pain, nausea, vomiting, and diarrhea (occasionally bloody). In stage II, 6 to 24 hours after ingestion, GI symptoms improve, though patients may still be ill and develop metabolic acidosis and/or hypovolemia. In stage III, 1 to 3 days post ingestion, multiorgan failure develops. Patients may develop altered mental status, renal failure, respiratory failure, and cardiovascular collapse. During stage IV, 2 to 5 days post ingestion, hepatic failure is characterized by coagulopathy, and elevations in serum transaminases, ammonia and bilirubin, as well as hypoglycemia. In stage V, some patients develop gastric outlet and small bowel obstruction 1 to 2 weeks later after overdose.

Differential diagnosis includes acute GI injury (eg, poisoning by acetaminophen, salicylates, mushrooms, heavy metals, theophylline, and nonsteroidal anti-inflammatory drugs [NSAIDs]) and acute gastroenteritis (eg, Salmonella, Shigella, viral). Increased anion gap metabolic acidosis from other etiologies should be considered (see Table 17.2). Consider other causes of acute hepatitis or acute surgical abdomen.

Obtain a thorough history with careful attention to amount, time of ingestion, intent, possibility of coingestants, and specific type of preparation (eg, ferrous sulfate, fumarate). Laboratory analysis should include CBC (may show anemia or leukocytosis), ABG (metabolic acidosis), electrolytes (increased anion gap, hyperglycemia or hypoglycemia), prothrombin time (PT)/partial thromboplastin time (PTT) (coagulopathy), liver function tests, serum lactate, and a type and screen in the event of GI hemorrhage. Obtain serum iron levels. Use abdominal x-rays to check for presence of radio-opaque pills and GI perforation.

Emergency Department Treatment and Disposition

Consider gastric lavage if pill fragments are visualized on the kidney, ureters, and bladder (KUB) radiograph. AC does not adsorb iron and should not be used. If pills are seen on radiography, whole bowel irrigation with Go-Lytely® (25 mL/kg/h up to maximum 1–2 L/h) should be initiated. Consider endoscopic removal of adherent particles or bezoars.

For severely ill patients, initiate chelation therapy with deferoxamine mesylate as soon as possible. Indications for chelation therapy include severe GI symptoms, hypotension, shock, metabolic acidosis, or serum iron concentration >500 μg/dL. Deferoxamine should be slowly infused over 20 minutes at a dose of up to 15 mg/kg/h via continuous infusion. Infusion should be started at lower doses and titrated up if patient’s clinical course does not improve or titrated down if patient develops hypotension or ARDS. Monitor blood pressure; if hypotension occurs, decrease the infusion rate or temporarily stop the infusion.

Consult with the local medical toxicologist or regional poison control center, psychiatry and with gastroenterology as needed.

Asymptomatic patients may be discharged 6 hours postingestion provided there are no tablets seen on abdominal radiography, the serum iron level is <500 μg/mL, and psychiatry consultation has been provided, if indicated.

All other patients should be admitted to the hospital. Consider ICU admission for those with shock, lethargy, GI bleed, or metabolic acidosis.

Pearls

1. Do not induce emesis; iron toxicity-induced GI irritation may result.

2. Do not use declining serum iron concentrations as a sign of clinical improvement or response to therapy as this may reflect iron uptake into cells.

3. Serum iron concentration is unreliable in patients receiving deferoxamine.

4. Antidotal treatment should not be delayed while awaiting serum iron concentrations or other laboratory tests in patients who are severely ill.

Clinical Summary

Opioids are found in many forms including morphine, meperidine, codeine, oxycodone, methadone, hydromorphone, propoxyphene, and fentanyl as well as street drugs such as heroin. Opioid use is ubiquitous, thus, opioid toxicity is a common occurrence in the emergency department. Less common scenarios are “body packing” and “body stuffing.” “Body packing” is intentional transport of opioids inside a body cavity and is accomplished via ingestion of drug packets wrapped in condoms, latex, or tape. Generally, packets have multiple layers to prevent leakage. “Body stuffing” implies haphazard ingestion of contraband and is usually without layers or intent to prevent leakage.

Therapeutic and toxic doses vary, as does individual tolerance. Toxicity may be affected by coingestants, especially those that cause central nervous system (CNS) depression (eg, alcohol, benzodiazepines etc).

Opioid toxicity is characterized by CNS depression, miosis, and respiratory depression. Other CNS signs may include seizures and coma. GI involvement includes nausea, vomiting, and constipation. Patients may present with hypotension or bradycardia. In addition to respiratory depression, patients may develop pulmonary edema (acute lung injury).

Differential diagnosis includes altered mental status (see mnemonic COMATOSE PATIENT, Table 13.5) and miosis from other etiologies.

Obtain a thorough history with careful attention to amount, time of ingestion, intent, and possibility of coingestants. Laboratory analysis is not typically needed unless there is concern for other coingestants. ABG may be useful in patients with hypoxia or hypoventilation. Chest x-ray may be performed to evaluate for aspiration or acute lung injury.

Emergency Department Treatment and Disposition

AC adsorbs orally ingested opioids and can be used for GI decontamination. Consider multidose AC for body packers. Use whole bowel irrigation with Go-Lytely® (25 mL/kg/h up to maximum 1–2 L/h) for asymptomatic body packers.

Airway and respiratory support are essential. Naloxone causes immediate reversal of CNS and cardiopulmonary depression and can be given IV, intramuscularly (IM), subcutaneously (SC), and sublingually. In children, the initial dose of naloxone is 0.01 mg/kg IV and may be repeated, up to a total of 10 mg. Failure to respond to 10 mg of naloxone excludes opioids as the sole cause of respiratory depression. Judicious use of naloxone is not associated with significant side effects except acute opioid withdrawal, which is generally not acutely life-threatening. However, in opioid-dependent neonates, acute opioid withdrawal may be associated with significant toxicity including seizures.

Patients with prolonged duration of symptoms or severe symptoms should be admitted. Consider admission to an ICU for continuous monitoring and additional doses of naloxone as indicated for patients with persistent altered mental status, recurrent respiratory depression, hypoxia, or hypotension. Consider admission for children under 12 years old. Older patients may be discharged from the ED if they are asymptomatic after 6 hours of observation and have been evaluated by psychiatry (if indicated).

Consult medical toxicology, poison control center, psychiatry (intentional ingestion), and, for body packers, gastroenterologist and/or surgery.

Pearls

1. Naloxone is generally effective for 30 to 60 minutes; most ingested opioids exert their effects for a longer time. Patients should be observed for more than 90 minutes; in case of relapse, naloxone may need to be readministered.

2. Children may have unusual sensitivity to opioids and can display signs of toxicity at therapeutic doses.

3. Maintain a high index of suspicion for aspirin and acetaminophen, which are often present in combination with opioids.

4. For chronic opioid users, start with small doses of naloxone for diagnostic and therapeutic purposes to decrease the likelihood of acute withdrawal. Excessive naloxone administration may result in withdrawal symptoms refractory to supportive care.

5. Body packers may place packets containing contraband in the ears, vagina, or rectum. Careful inspection of all body cavities is warranted.

6. Opioid toxicity due to synthetic opioids (eg, fentanyl) may require higher doses of naloxone.

Clinical Summary

Cocaine is most often used via nasal insufflation and intravenously or in its “freebase” or “crack” form smoked and inhaled through the lungs. Inhalational and IV routes have peak effect within 5 minutes, while insufflation produces a peak in 20 minutes. Although short-lived, rapid, intense euphoria is the usual impetus for recreational cocaine use.

Cocaine causes multisystem symptomats including tachycardia, hyperthermia, and hypertension. Head/neck examination may reveal mydriasis or nasal septal perforation. Cardiac effects include acute myocardial ischemia, aortic dissection, fatal dysrhythmias, or cardiac arrest. Chronic use may lead to congestive heart failure, myocarditis, or dilated cardiomyopathy. Pulmonary signs include wheezing pneumothorax, pneumomediastinum, or pulmonary edema. Bowel ischemia and infarction may be caused by splanchnic vasospasm. Patients may develop acute renal failure because of renal infarction or rhabdomyolysis. Neurologic effects include agitation, seizures, intracerebral hemorrhage, or infarction. Acute cocaine toxicity can be indistinguishable from acute psychiatric diseases because of the appearance of euphoria, agitation, or mania.

Cocaine washout syndrome refers to persistent lethargy and altered mental status following repeated use over a short period caused by depletion of CNS catecholamines. This may manifest as coma. The patient’s condition usually improves over several hours with supportive care.

Differential includes other stimulants including amphetamines, oral decongestants, thyroid hormone, β-adrenergic agents, ergot alkaloids, and monoamine oxidase (MAO) inhibitor toxicity. Neuroleptic malignant syndrome, malignant hyperthermia, and serotonin syndrome may present similarly with muscular rigidity, hyperthermia, and altered mental status. Nontoxicologic etiologies in the differential include hypoglycemia, pheochromocytoma, hyperthyroidism, alcohol or sedative-hypnotic withdrawal, or acute psychosis.

Obtain a thorough history with careful attention to amount, time of ingestion, intent, and possibility of coingestants. CBC may demonstrate a leukocytosis. Use serum chemistries, BUN, Cr, and glucose to evaluate for alternative causes of altered mental status or seizures and to assess for dehydration and renal function. Obtain an ECG and chest x-ray in any patient with chest pain. Abdominal radiographs may help evaluate for body packing/stuffing. Brain CT may demonstrate intracerebral hemorrhage or infarction. Exclude subarachnoid hemorrhage by lumbar puncture. Creatine kinase may be elevated with rhabdomyolysis. Serum transaminases may be elevated and patients may develop a coagulopathy in the setting of hyperthermia. Serum troponin may be elevated if patient develops myocardial ischemia or infarction. Obtain serum aspirin, acetaminophen, and urine drug screens to evaluate for coingestants.

Emergency Department Treatment and Disposition

Stabilize ABCs. GI decontamination is not recommended as ingestion is rare except in body packing/stuffing. Management is primarily supportive and includes control of hypertension, psychomotor agitation, hyperthermia, seizures, pneumothorax, cardiac dysrhythmias, cerebral infarction, intracerebral hemorrhage, pulmonary edema, and rhabdomyolysis. Aggressive IV hydration may help prevent renal impairment due to rhabdomyolysis. Treat myocardial ischemia or infarction with oxygen, nitrates, aspirin, but not beta-blockers. Use phentolamine or IV nitrates to manage acute hypertension and sodium bicarbonate and lidocaine for cardiac dysrhythmias. Admit patients with symptoms that do not resolve quickly, have severe toxicity, or serious sequelae of cocaine intoxication. All patients presenting with myocardial ischemia, hyperthermia, intracranial hemorrhage, or cocaine washout syndrome should be admitted to an ICU for monitoring and management. Patients with mild toxicity may be discharged on clinical improvement and referred for drug counseling.

Pearls

1. Never use beta-blockers to control heart rate or hypertension due to cocaine intoxication; these agents could exacerbate cocaine-induced coronary vasospasm.

2. Do not use haloperidol to control agitation of suspected cocaine intoxication as it may lower seizure threshold and impair the body’s ability to dissipate heat.

3. Benzodiazepines are the treatment of choice for psychomotor agitation, hyperthermia, seizures, tachycardia, hypertension, dysrhythmias, and ischemic chest pain.

4. Asymptomatic cocaine body packers may be treated with whole bowel irrigation. Symptomatic body packers may require immediate surgical intervention. Body stuffers usually do well with supportive care alone.

Clinical Summary

Methemoglobin (MetHb) is hemoglobin in which the normally reduced ferrous ion (Fe+) is oxidized to the ferric form (Fe+) preventing binding of oxygen (O2) to the abnormal hemoglobin (Hgb) and impairing O2 unloading by normal Hgb. Thus, symptoms of methemoglobinemia are related to decreased O2 delivery to the tissues. Serum MetHb concentration above 3% is termed methemoglobinemia and usually occurs in the setting of oxidative stress (eg, sepsis, toxins, or drugs like nitrates, topical anesthetics, aniline dyes, quinine, sulfonamides, hydrocarbons, and food additives containing nitrites or nitrates).

Clinically, patients present with signs of tissue hypoxia, including tachycardia, tachypnea, hypotension, cardiac dysrhythmias, cardiac arrest, dyspnea, nausea, vomiting, lethargy, confusion, coma, seizures, and persistent cyanosis despite supplemental oxygen therapy. Phlebotomy may show the pathognomonic sign of chocolate brown blood. Pulse oximetry readings are usually decreased with oxygen saturation readings characteristically between 80% and 90%.

Differential diagnosis includes CO poisoning (though patients are not typically cyanotic), sulfhemoglobinemia, and cardiac/pulmonary causes of cyanosis.

Obtain a thorough history with careful attention to amount, time of ingestion, intent, and possibility of coingestants. Consider underlying conditions that increase risk for methemoglobinemia. Obtain ABG with co-oximetry. ABG will give disparate O2 saturation compared to the pulse oximeter as the ABG O2 saturation is based on the amount of dissolved oxygen in blood whereas co-oximetry quantifies alternative hemoglobins such as MetHb and CoHb. Pulse oximetry assesses the ratio of oxyhemoglobin to deoxyhemoglobin only and will usually be decreased. The difference in oxygen saturation between ABG and pulse oximetry is referred to as the saturation gap. A CBC should be obtained to evaluate for anemia, especially if hemolysis is suspected. Serum electrolytes, BUN, and Cr aid in evaluating acid-base status. Patients may have an increased anion gap metabolic acidosis because of lactic acidosis.

Emergency Department Treatment and Disposition

Stabilize ABC and begin decontamination immediately. GI decontamination remains controversial. However, gastric lavage may be considered for massive ingestions in which ongoing toxicity is expected. Consider administering one dose of AC (dose: 1–2 g/kg).

Severity of symptoms correlates with serum MetHb concentrations. More than 50% is severe and more than 70% is potentially fatal. Treat all symptomatic patients and any with a MetHB concentration of >20% with an initial dose of methylene blue 1 to 2 mg/kg IV over 5 minutes. If clinical improvement is not seen within 1 hour, repeat serum MetHB measurement and repeat dose of methylene blue to a maximum of 7 mg/kg over 3 hours. In patients with G6PD deficiency or known NADPH-methemoglobin reductase deficiency methylene blue may not be effective or may precipitate hemolysis. Although it has been effectively used in these patients, it should be used with caution and awareness of possible adverse effects. Consider hyperbaric oxygen or exchange transfusion in these patients as well as any who do not respond to methylene blue or have MetHB concentration >70%. Use caution when administering repeated doses as methylene blue is a weak oxidant that may induce methemoglobinemia at higher concentrations.

All patients (especially infants and young children) who receive therapy with methylene blue should be admitted to an ICU for continuous monitoring and supportive care. Consult medical toxicology, poison control center and hematology for evaluation of underlying conditions that may predispose to development of methemoglobinemia.

Pearls

1. Methemoglobinemia may present with profound cyanosis with minimal symptoms.

2. Consider methemoglobinemia in all patients with cyanosis in spite of a normal Po2 determination from ABG or cyanosis unresponsive to supplemental O2 therapy.

3. Pulse oximetry and standard ABG analysis give disparate O2 saturation. ABG with co-oximetry must be obtained to determine the presence of MetHb.

4. Neonates are more at risk because of lower levels of NADH methemoglobin reductase and the presence of fetal Hgb, which is more readily oxidized than adult Hgb.

5. Methylene blue may cause hemolysis, methemoglobinemia, and a significant decrease in O2 saturation on pulse oximetry, especially in patients predisposed to methemoglobinemia (eg, G6PD deficiency, NADH methemoglobin reductase deficiency).

6. Sulfhemoglobin results in falsely elevated MetHb levels. Suspect sulfhemoglobinemia in cyanotic patients not responding to O2 therapy or failing to improve after treatment with methylene blue.

Clinical Summary

Organophosphate and carbamate exposures usually occur as accidental or intentional ingestion of pesticides, malathion (used to treat head lice) or pyridostigmine/neostigmine (used to treat myasthenia gravis). The highly toxic nerve agents sarin, soman, and tabun are organophosphates.

Organophosphates bind to the active site of acetylcholinesterase and inactivate it, leading to postsynaptic excitation. Carbamate toxicity is similar to that of organophosphates, but generally of shorter duration, reversible, and usually lacks CNS signs and symptoms, which are commonly present with organophosphate toxicity. Notable exceptions are medicinal carbamates like physostigmine (antidote for anticholinergic toxicity) and donepezil (treatment for Alzheimer disease). These agents readily cross the blood-brain barrier with a long half-life.

The severity and extent of toxicity is dependent on the specific agent, dose, and route of exposure. Inhalation leads to rapid symptomatology (within as little as 5 minutes), whereas effects after skin absorption may be prolonged or delayed. Agents with higher lipid solubility may produce delayed, prolonged, or cyclical toxicity.

The major clinical presentation of these agents occurs from hyperactivity of the parasympathetic nervous system leading to the classic DUMBELS symptoms (see mnemonic; Table 17.2). Nicotinic receptor activation will result in autonomic instability and neuromuscular junction hyperactivity manifested as twitching, weakness, ineffectual muscle contraction, and ultimately, paralysis. The CNS effects are confusion, coma, seizures, ataxia, and respiratory depression.

The intermediate syndrome may develop 1 to 4 days following acute organophosphate poisoning despite therapy with atropine and oximes (eg, pralidoxime). Signs and symptoms include cranial nerve palsies, nuchal weakness, acute respiratory paralysis, proximal limb weakness, and depressed reflexes. This occurs more commonly with organophosphates that are highly fat-soluble and may last up to 15 days; most patients have a full recovery. Delayed peripheral neuropathy may develop 1 to 3 weeks after organophosphate exposure and causes a distal flaccid paralysis with variable recovery (months to years) that may be permanent.

Differential diagnosis includes other direct-acting cholinergic agents (eg, pilocarpine producing identical symptomatology), nicotine poisoning (symptoms of nicotinic receptor hyperactivity), opioid toxicity, muscarine-containing mushrooms, and bradycardia from other drugs (eg, digitalis). Nontoxicologic causes include Eaton-Lambert syndrome and myasthenia gravis.

History should focus on the agent, amount, time, and route of exposure. Physical examination should focus on vital signs, with careful attention to cardiovascular and neuromuscular status, respiratory effort, and motor strength. Note the amount of respiratory secretions, presence of garlic odor, fever, tenesmus, blurry vision, heart block, or cardiac dysrhythmias. CBC may show leukocytosis with a normal differential and hemoconcentration due to fluid loss. Serum electrolytes may show an increased anion gap acidosis (due to lactic acidosis), hyperglycemia, hypokalemia, hypomagnesemia, and prerenal azotemia. ABG may show metabolic acidosis. If the exposure is intentional, serum acetaminophen and salicylate levels should also be obtained on presentation.

Emergency Department Treatment and Disposition

Decontamination is of the utmost importance to prevent further toxicity and protect the health care providers. Remove the patient’s clothes and wash all exposed surfaces thoroughly. Universal protection to prevent transdermal absorption of toxins by health care providers is essential.

Stabilize ABCs and treat pulmonary edema, respiratory distress, altered mental status, and hypotension as indicated. If patient presents within 1 hour of ingestion without emesis, consider gastric lavage and administration of AC.

Atropine and pralidoxime are specific antidotes. For all patients with bronchorrhea, bronchospasm, or bradycardia, give atropine 0.05 mg/kg IV (adult dose is 2–5 mg; minimum dose of 0.1 mg in children), and repeat as needed every 5 to 15 minutes until pulmonary and oral secretions are controlled. After atropine administration, pralidoxime (treats both muscarinic and nicotine toxicity) may be given as an IV bolus of 25 mg/kg (up to 1 g) over 30 minutes. If fasciculations continue, repeat the dose of pralidoxime after 1 hour, and then every 6 to 12 hours over the subsequent 48 hours as needed. Alternatively, after initial bolus, pralidoxime may be given as a continuous IV infusion at 10 to 20 mg/kg/h. Effects are usually seen within the first 10 minutes of administration.

Admit all patients with significant symptoms or with evolving toxicity. It may be preferable to admit to the ICU for close observation and monitoring of CNS and cardiopulmonary status. Asymptomatic patients with unintentional exposures may be discharged home after a 6-hour observation period. However, some organophosphates may present with delayed toxicity, especially if the route of exposure was dermal.

Pearls

1. Paralytic agents often administered therapeutically for intubation may have an increased duration of action by organophosphates.

2. When death occurs, it is usually from respiratory failure; endotracheal intubation and mechanical ventilation may be necessary early in the course of treatment.

3. Atropine should be given until the drying of secretions is noted and should not be titrated to tachycardia or mydriasis.

4. Symptoms vary greatly; nerve agents may present with predominant nicotinic and CNS effects rather than muscarinic effects.

5. Atropine and pralidoxime given together have synergistic effects against signs and symptoms of cholinesterase inhibition, thus decreasing atropine requirements.

6. Although atropine alone is usually adequate for carbamate toxicity, pralidoxime also may be given when there is uncertainty about the agent involved (organophosphate and carbamate toxicity may be indistinguishable).

7. Give pralidoxime only after atropine (faster onset of action).

Clinical Summary

Castor beans are found in the fruit of Ricinus communis, a large, leafy plant that may be green or red, and are hard and shiny with grey and brown streaks. Rosary peas (also called Jequirty pea, crab’s eye, Buddhist’s rosary bead, and prayer bead) are found in the fruit of Abrus precatorius, a high-climbing, woody, green vine found in India, Florida, and the Caribbean. Rosary peas are hard and may be bright red with a black center, black with a white center, or white with a black center. Castor beans and rosary peas are used in jewelry and toys. R communis is also the source of castor oil, used as a purgative, and as a lubricant for engines. Ricin and abrin are extremely potent toxins within the seeds. Toxicity may occur when the seed casing is broken via chewing or digestion and subsequent GI absorption. Fortunately, toxicity is generally limited by poor GI absorption of the seed.

Although toxicity via ingestion is rare, if toxicity does occur, patients usually present 2 to 48 hours postingestion with tachycardia, hypotension, cardiac dysrhythmias, and may have abdominal pain with bloody vomiting and diarrhea. CNS depression, seizures, and cerebral edema may develop. Patients may develop a hemolytic anemia. Multiorgan injury typically occurs after 24 hours and hepatic failure, renal insufficiency, lethargy, stupor, and death can occur.

Differential diagnosis includes organophosphates and other cholinergic agents, and toxins that cause seizures (see CAMPHOR BALLS; Table 17.2) or CNS depression and infectious gastroenteritis.

Obtain a careful history, including identification and number of seeds ingested if observed and the timing of ingestion. Ask patients if they chewed the seed and analyze symptoms occurring after ingestion. Physical examination should focus on vital signs, mental status, and proper evaluation of the abdomen. Obtain CBC and type and screen in any patient with GI hemorrhage. Coagulation studies may demonstrate coagulopathy. Serum chemistries may show elevated BUN and Cr suggestive of dehydration or renal injury.

Emergency Department Treatment and Disposition

Stabilize ABC and treat hypovolemic shock, seizures, CNS depression, and cerebral edema. No antidote exists; treatment is supportive. Initiate aggressive fluid resuscitation in all hypovolemic patients. GI decontamination may be accomplished with AC; lavage or whole bowel irrigation may decrease GI transit time of seeds.

Admit all symptomatic patients for observation and supportive care. Asymptomatic patients may be safely discharged after a period of observation.

Pearls

1. Toxicity occurs when seeds are chewed rather than when ingested whole.

2. All patients who have ingested rosary peas or castor beans should have GI decontamination performed.

Clinical Summary

Phenothiazines (eg, prochlorperazine, chlorpromazine, thioridazine), historically called neuroleptics, are commonly prescribed as antiemetics, antipsychotics, and anxiolytics.

Extrapyramidal side effects like dystonia, akathisia, Parkinsonism, or tardive dyskinesia may result from these agents in both acute ingestions or chronic usage. Symptoms may be delayed up to 24 hours post ingestion, and patients are usually awake, alert, and aware of their symptoms. Dystonias include oculogyric crisis, torticollis, opisthotonos, trismus, difficulty speaking, facial grimacing, or chorea-like movements. In akathisia, typically seen 5 to 60 days after starting neuroleptic therapy, there is extreme restlessness or the feeling that the “body wants to jump out of its skin.” Parkinsonism, typically seen 2 to 3 months after starting neuroleptic therapy, includes resting tremor, bradykinesia, a shuffling gait, or mask-like facies. In tardive dyskinesia, developing months to years following initiation of antipsychotic therapy, there are involuntary buccolinguomasticatory movements and choreoathetoid movements. In neuroleptic malignant syndrome (NMS) seen within days to weeks of starting antipsychotic therapy, there is hyperthermia, muscular rigidity, autonomic instability, and altered mental status ranging from extreme confusion to catatonia. Rhabdomyolysis may occur. CNS depression is commonly seen. In large overdoses (especially thioridazine and mesoridazine), seizures and cardiac dysrhythmias may occur.

Phenothiazines also have anticholinergic properties, so tachycardia, hypertension, and, hyperthermia may occur (ie, the classic toxidrome is described as “Red as a Beet, Dry as a Bone, Mad as a Hatter, Hot as a Hare, and Blind as a Bat”). Cardiac conduction effects may occur including QT prolongation, QRS widening, atrioventricular (AV) block, or fatal dysrhythmias. GI symptoms include constipation, ileus, and cholestatic or hepatocellular jaundice. Urinary retention may also occur (anticholinergic effects). Rarely, hematologic effects of anemia or agranulocytosis are seen.

Differential diagnosis includes causes of CNS depression such as meningitis, intracranial hemorrhage, cerebral ischemia. Other causes of cardiac conduction abnormalities include electrolyte disturbances, myocardial ischemia, cyclic antidepressants, and type Ia antidysrhythmics.

Obtain a history focused on agent involved, dose, time of ingestion, chronicity of ingestion, and intent. Perform a physical examination focusing on vital signs, including orthostatic blood pressure and cardiovascular and neurologic status. Order serum chemistries, liver function tests (may show transaminitis or increased bilirubin), creatine kinase (elevated in rhabdomyolysis), and urinalysis (red, pink, purple, orange, or rust-coloring). Abdominal radiographs may show radio-opaque phenothiazine tablets.

Consult medical toxicology/regional poison control center as needed. Consult psychiatry in cases of intentional overdose or for patients taking phenothiazines for psychiatric disorders.

Emergency Department Treatment and Disposition

Treatment begins with stabilization of ABCs. Treat cardiac dysrhythmias such as QRS widening >100 ms with IV bolus of NaHCO3 (1–2 mEq/kg) until QRS interval narrows; this may be repeated once. NaHCO3 may exacerbate QT prolongation by causing hypokalemia. ABG analysis should be performed to monitor serum pH; it should not exceed 7.55. Continuous cardiac monitoring should be done. Control seizures with benzodiazepines. Accomplish GI decontamination with gastric lavage and AC for large or recent ingestions.

Treat acute dystonic reactions with diphenhydramine 1/mg/kg IV or IM or benztropine 0.5 to 2.0 mg IV or IM. Treat akathisia and parkinsonism with anticholinergic agents (diphenhydramine or benztropine) and benzodiazepines. Tardive dyskinesia is usually irreversible but may respond to changing the dose of the antipsychotic agent or to cholinergic agents (eg, physostigmine). Treatment of NMS includes rapid cooling, and pharmacologic agents such as benzodiazepines and dopamine agonists such as bromocriptine and amantadine.

Admit all patients presenting with acute overdose. Admit patients with cardiovascular instability or CNS depression to the ICU. Even though patients with acute dystonic reactions may respond to therapy (eg, diphenhydramine), extended-release products may require admission for extended observation. Patients may be discharged from the ED after appropriate GI decontamination if they do not develop seizures, hypotension, or ECG changes after a 6-hour observation period.

Pearls

1. Response to parenteral diphenhydramine or benztropine mesylate can be diagnostic as well as therapeutic in patients presenting with extrapyramidal signs.

2. Patients may develop signs of toxicity while receiving therapeutic doses or acute overdose of phenothiazines. Signs and symptoms may also develop unpredictably after chronic therapy.

3. A previous history of extrapyramidal signs is strongly associated with recurrence on repeat challenge of the drug.

4. Phenothiazines may cross-react with urine drug screens as tricyclic antidepressants, resulting in a false-positive test.

Clinical Summary

Many drugs (eg, antihistamines, cyclic antidepressants) and plants (eg, jimson weed, nutmeg, potatoes) possess anticholinergic properties, and exposure occurs through ingestion, intraophthalmic use, inhalation or even transdermally. The classic symptoms of anticholinergic toxicity are described by the mnemonic “Red as a Beet (flushing), Hot as a Hare (hyperthermia), Dry as a Bone (skin and mucus membrane dry), Blind as a Bat (mydriasis with blurry vision) and Mad as a Hatter (agitation and hallucinations).” Vital signs abnormalities include tachycardia and hyperthermia. GI examination shows decreased bowel sounds, constipation, or ileus. Patients may have urinary retention, psychomotor agitation, CNS agitation or depression, seizures, or coma. Patients are at risk of rhabdomyolysis from psychomotor agitation. Differential diagnosis includes ingestion of sympathomimetic agents.

Obtain a history focused on the agent involved, dose, and timing of exposure including both prescription and over-the-counter medications and possible plant ingestion. Physical examination should focus on vital signs, pupillary reactivity, skin characteristics, bowel and bladder function, and neurologic status. ECG may show sinus tachycardia, or cardiac dysrhythmias such as QRS widening or an R wave in aVR suggesting tricyclic antidepressants or other sodium channel blockers. Order serum electrolytes, salicylates, and acetaminophen levels if there is suspicion of coingestion. Serum BUN and Cr may be elevated because of dehydration or renal failure from rhabdomyolysis. Urine may be concentrated as suggested by an elevated urine specific gravity.

Emergency Department Treatment and Disposition

Stabilize ABCs, treat altered mental status, agitation, CNS depression, cardiac dysrhythmias, or seizures. Treat intraocular exposure by irrigation with normal saline. Accomplish GI decontamination with gastric lavage if patient presents within 1 hour of ingestion, or with AC. Decreased GI motility seen with anticholinergics may allow both gastric lavage and AC to have an increased efficacy despite delay in implementation.

Physostigmine is a specific antidote and should be used if there is severe agitation, extrapyramidal movement disorders, recurrent or refractory seizures, severe hallucinations, or refractory dysrhythmias. Physostigmine can be diagnostic to determine if altered mental status is due to anticholinergic toxicity. Care must be taken during administration as excessive physostigmine can cause cholinergic side effects. Continuous cardiac monitoring, atropine, and an airway tray must be available at the bedside. Give physostigmine slowly as an IV push (over 2–5 minutes) at a dose of 0.02 mg/kg (up to 2 mg) and repeat every 5 to 10 minutes until anticholinergic symptoms improve. If cholinergic toxicity develops, administer atropine (dose is typically half of total amount of physostigmine given).

Admit all patients with signs of toxicity. Admit those with significant tachycardia, altered mental status, seizures, or hyperthermia to an ICU. Discharge patients if they are asymptomatic following a 6- to 12-hour observation period (or 4–6 hours after their last dose of benzodiazepine), and if they have received appropriate GI decontamination and psychiatric evaluation.

Pearls

1. A careful history is of utmost importance as many diverse agents and plants contain anticholinergic substances.

2. Refer patients attempting “to get high” to substance abuse counseling to help prevent future repetition of events.

3. Physostigmine is contraindicated in patients with suspected tricyclic antidepressant ingestion.

Clinical Summary

Isoniazid (INH) is an antimicrobial used to treat tuberculosis, and is also found in Rifamate. Ingestion of 80 to 150 mg/kg INH typically produces seizures though seizures may occur with ingestion of 40 mg/kg. Acute ingestion of 2 to 3 g causes acute toxicity in most, and 10 to 15 g frequently causes death if untreated. The classic triad of symptoms is refractory seizures, coma, and increased anion gap metabolic acidosis. Seizures, typically occur 1 to 2 hours post ingestion, and may be associated with altered mental status, slurred speech, hyper- or areflexia, psychosis, hallucinations, and peripheral neuropathy (chronic overdose). Patients with severe toxicity present with hyperthermia, tachycardia, and hypotension. Optic neuritis, nystagmus, mydriasis, photophobia, and blurred vision may be present. Patients may present with Kussmaul respirations due to metabolic acidosis, or respiratory depression due to seizures. Patients may complain of nausea, vomiting, and dizziness. Patients may also develop anuric or oliguric renal failure.

Differential diagnosis includes other causes of increased anion gap metabolic acidosis and other causes of seizures with anion gap acidosis (primarily because of lactic acidosis; see CAMPHOR BALL mnemonic; Table 17.2).

Obtain a history focused on preparation involved, dose, timing, and symptoms. Physical examination should focus on vital signs, cardiopulmonary assessment, abdominal pain, and neurologic status. Consider chest radiographs, head CT, and lumbar puncture to evaluate for other causes of altered mental status and seizures.

Order serum chemistries (increased anion gap metabolic acidosis, hyperglycemia), serum ketones (elevated), serum lactate (increased), urinalysis (glycosuria, ketonuria, myoglobinuria), transaminases (increased), creatine kinase (elevated from rhabdomyolysis), serum creatinine (elevated from rhabdomyolysis).

Emergency Department Treatment and Disposition

Stabilize ABCs and treat seizures, hypotension, and altered mental status. Accomplish GI decontamination with gastric lavage in the case of a large ingestion if within an hour of ingestion. AC may be given.

Pyridoxine (vitamin B6 ) is the antidote and is indicated for treatment of INH-induced seizures or for use in patients presenting with seizures of unknown origin who are refractory to conventional anticonvulsants. If the INH dose is known, give pyridoxine on a gram-for-gram basis. If the INH amount ingested is unknown, give 70 mg/kg to a maximum of 5 g and repeat once if there is no improvement in patient’s status. If active seizures persist, question diagnosis of INH toxicity. If IV pyridoxine is not available, give a slurry of crushed vitamin B6 tablets orally, at the same dose. Adverse effects of excess pyridoxine include peripheral neuropathy, ataxia, seizures, paralysis or death (very high doses) but this should not be a concern in treating most INH overdoses. Admit patients with altered mental status, seizures, or other signs of serious INH toxicity to an ICU for continuous monitoring and supportive care. Consult medical toxicology, the regional poison control center, and psychiatry as needed.

Pearls

1. Classic clinical presentation is the triad of refractory seizures, coma, and increased anion gap metabolic acidosis.

2. Consider acute INH toxicity in any patient with status epilepticus.

3. The dose of pyridoxine is 1 g for every 1 g of INH ingested and deplete hospital stores. A 5 g empiric dose may require up to 100 vials of medication.

Clinical Summary

Camphor is an ingredient in many over-the-counter liniments (eg, Ben-Gay, Children’s Vaporizing Rub, Vicks VapoRub, Deep Down Rub), antipruritics, cold remedies, antiseptics, topical anesthetics, and aphrodisiacs. Camphor is also found in moth repellents, lacquers, varnishes, explosives, embalming fluid, and cosmetics. Camphor toxicity can occur through inhalation, ingestion, or dermal absorption. Although significant toxicity is rare, death has been reported.

Clinical symptoms include tachycardia, burning sensation in oropharynx, visual disturbances (veiling, darkening, or flickering), and an aromatic odor on the breath. Patients often present with nausea and vomiting; clinically, patients may have headache, fasciculations, confusion, delirium, coma, tremors, and seizures (typically seen as early as 5 minutes and as late as 2 hours post ingestion). Severe toxicity can result in cardiovascular collapse.

Obtain a careful history with attention to dosage, time, route, intent of exposure, and symptoms since exposure, and assess neurologic status. Serum camphor levels are not readily available nor clinically useful. Serum chemistries with liver function tests may reveal a transaminitis.

Emergency Department Treatment and Disposition

Treatment is primarily supportive and there is no specific antidote. Decontamination must be performed to prevent further exposure. Gastric lavage may be beneficial if the patient presents shortly after exposure to a large amount of liquid product.

Patients who are asymptomatic 6 hours post exposure may be discharged home after appropriate decontamination and psychiatric evaluation (if indicated). Admit any patient who presents with significant signs of toxicity (eg, seizures, altered mental status, hepatotoxicity) from camphor exposure for continued monitoring and supportive care.

Pearls

1. In liquid form, camphor has potential morbidity with ingestion of as little as 50 mg/kg, and a potentially fatal dose of 100 mg/kg.

2. Consider camphor toxicity in all cases of toxin-induced seizures (especially in patients who have access to over-the-counter preparations containing camphor).

3. Patients with camphor toxicity may seize abruptly without antecedent signs or symptoms. Seizures are rare following dermal contact or inhalation exposure. Seizures may be recurrent or develop into status epilepticus with respiratory depression, a common cause of morbidity and mortality in camphor toxicity.

Clinical Summary

Many common household products contain hydrocarbons (HCs) including solvents, polishes, felt-tipped markers, glues, paints, car waxes, stain removers, and paint thinners. Exposure to HCs commonly occurs through inhalation, ingestion, or dermal routes. Several terms are used to describe intentional inhalation including “sniffing,” “bagging,” and “huffing,” and each technique differs in its exact method of inhalation. HCs may be intentionally inhaled to achieve a euphoric state.

The hydrocarbons naphthalene and paradichlorobenzene (PDB) are commonly found in moth repellent products. However, unlike camphor-containing mothballs, PDB ingestions are usually nontoxic. Naphthalene ingestion may precipitate methemoglobinemia, especially in patients with decreased ability to handle oxidative stress (eg, patients with G6PD deficiency).

Pulmonary aspiration is the most common serious side effect of ingesting liquid hydrocarbons and risk increases with decreased viscosity and increased volatility of the HC. Patients who aspirate HCs present with dyspnea, cough, chest tightness, or hypoxia and may develop bronchitis, interstitial pneumonitis, pulmonary edema or aspiration pneumonia. Lower-molecular-weight HCs are more readily absorbed systemically, and rapid CNS distribution to the brain occurs with some agents, leading to CNS depression or excitation. Myocardial irritation and depression from halogenated HCs predisposes cardiac dysrhythmias and sudden death from ventricular fibrillation has been reported. Significant hepatic toxicity may result from exposure to halogenated HCs. Patients may complain of nausea, vomiting, or abdominal pain. Hematologic effects include disseminated intravascular coagulation. Certain hydrocarbons lead to the development of renal tubular acidosis (eg, toluene). Ocular complaints include eye irritation, pain, lacrimation, and blurring of vision. Vital sign abnormalities include tachycardia, bradycardia, tachypnea, bradypnea, hypoxia, or fever.

Differential diagnosis includes other causes of CNS depression such as ethanol, opiates, benzodiazepines, and hypoglycemic agents and other causes of altered mental status such as infection, trauma, and cerebral ischemia. Other causes of methemoglobinemia include nitrites, benzocaine, dapsone, topical anesthetics, and exposure to well water in neonates.

Obtain a thorough history focused on the agent involved, route of exposure, timing, intent, dose, and symptoms. Physical examination should focus on vital signs and neurologic and cardiopulmonary assessment. A chest radiograph may show pulmonary edema, aspiration pneumonia, or pneumonitis. In chronic exposure, CBC may demonstrate aplastic anemia or leukemia. Serum electrolytes may demonstrate acute renal failure. Elevated serum transaminases are evidence of hepatic injury. ABG analysis confirms hypoxia, hypercarbia, and assessment of pulmonary status.

Emergency Department Treatment and Disposition

Management is primarily supportive and external decontamination and adequate skin and respiratory protection of health care professionals are essential. Stabilize ABCs and treat respiratory distress, seizures, coma, and cardiac dysrhythmias. Reserve gastric lavage only for those with large, recent ingestions or coingestions as it may result in increased risk of aspiration. AC should not be used; it does not adsorb HC and may increase risk of emesis and aspiration. Prophylactic antibiotics and steroids are not recommended.

Patients believed to have ingested small amounts and asymptomatic require only observation with no intervention. Discharge patients who remain asymptomatic over a 6-hour observation period. Order labs for symptomatic patients to evaluate and monitor respiratory status. Admit anyone with altered mental status, cardiac dysrhythmias, or respiratory insufficiency to the ICU for continuous monitoring and supportive care.

Admit patients exposed to naphthalene mothballs if signs of acute hemolytic anemia or methemoglobinemia are present. Perform packed red blood cell transfusion in hemodynamically unstable or symptomatic patients with hemoglobin value of ≤6 g/dL or hemoglobin of 6 to 9 g/dL with ongoing hemolysis. Use parenteral hydration to maintain adequate urine output, and urinary alkalinization to prevent renal damage from precipitation of hemoglobin in renal tubules. Follow asymptomatic patients with G6PD deficiency closely as outpatients. Hemolysis and methemoglobinemia usually occur 1 to 2 days after exposure; patients should be monitored with serial CBCs, and parents should be told to bring the child to the ED immediately if there is dark urine, pallor, jaundice, or any symptoms of anemia. Asymptomatic patients who are not G6PD deficient can be sent home with close outpatient follow-up.

Pearls

1. Less than one naphthalene mothball in a patient with G6PD deficiency can cause significant toxicity.

2. Neonates without G6PD deficiency may develop hemolytic anemia or methemoglobinemia on exposure to naphthalene mothballs as fetal hemoglobin is more susceptible to oxidant stress.

3. Parents should be advised not to use naphthalene or camphor mothballs; cedar mothballs are a safe alternative.

4. Perform GI decontamination with great care as it may result in increased risk of aspiration pneumonitis.

5. Chest radiography may be unreliable as radiographic findings often lag physical examination findings by 4 to 6 hours.

6. Maintain a high index of suspicion for substance abuse in adolescents.

Clinical Summary

3,4-Methylenedioxymethamphetamine (MDMA) or “Ecstasy” is an entactogen known for its euphoric and stimulant effects. Commonly used street slang names for MDMA include “E,” “X,” or “Adam.” Popular in the club and rave scene, users describe feelings of inner peace, empathy, self-confidence, and a heightened sense of awareness. Once ingested, the user can experience these effects within 60 seconds, yet the duration of action can last hours or even days. Although not fully elucidated, the effects of MDMA appear to be mediated by the enhanced secretion of serotonin, inhibition of its reuptake mechanism in the synapse, and release of dopamine.

MDMA is available as a tablet and is frequently adulterated with other drugs such as ketamine or caffeine. As a recreational drug, it is associated with a wide range of effects, including mydriasis, tachycardia, hypertension, bruxism, hyperthermia, psychosis, seizures, and coma.

Individuals abusing MDMA will oftentimes present to the ED agitated or exhibiting signs of psychosis. It is important to control agitation with the use of benzodiazepines and assess for other untoward effects (eg, rhabdomyolysis, renal failure, hepatotoxicity, hyperthermia).

Emergency Department Evaluation and Management

Treatment is supportive care; there is no specific antidote. Monitor vital signs, mental status, and oxygen saturation, continually. Hyponatremia may develop as a result of inappropriate secretion of antidiuretic hormone. Increased free water intake from exertion may exacerbate and contribute to hyponatremia. Laboratory evaluation should include measurement of electrolytes, serum transaminases, renal function, and creatine phosphokinase. Assess for cerebral edema with a head CT if altered mental status is present and obtain an ECG to look for other potential coingestants and potential dysrhythmias. Consider endotracheal intubation to protect the airway. Treat hyperthermia with active cooling.

Observe individuals with mild toxicity for 6 to 8 hours. Admit moderate to severe cases with persistent CNS involvement to the ICU. Consult psychiatry in self-harm attempts.

Pearls

1. Always assess for other causes for altered mental status (eg, infection, intracranial hemorrhage).

2. Control agitation and seizure activity with benzodiazepines.

3. Treat significant hyponatremia with hypertonic saline (3% NaCl) in patients with altered mental status and/or seizures.

4. In young children with ecstasy ingestion, notify child protective services and social work.

Clinical Summary

Ketamine is a nonopioid anesthetic known for its dissociative effects. Ketamine usage as a recreational drug is associated with a wide range of effects, including inebriation, anxiety, slurred speech, sedation, hallucinations, nystagmus, mydriasis, chest pain, complete dissociation, and coma. It is available as a clear liquid or white/off-white powder, which can be injected IM or IV, insufflated (snorted), or ingested. Individuals may also exhibit an emergence reaction, during the recovery phase, which is characterized by confusion, delirium, hallucinations, irrational behavior, and vivid dreams. This reaction is more commonly seen in adults. Monikers commonly used include “Special K” or simply “K.”

Emergency Department Treatment and Disposition

Treatment is supportive care; there is no specific antidote. Monitor vital signs, mental status, and oxygen saturation continually. If there is altered mental status, obtain blood glucose and electrolyte measurements, ECG, and cardiac monitoring. Endotracheal intubation should be considered in cases of prolonged CNS or respiratory depression. Patients should be observed until they are asymptomatic or admitted to the hospital depending on the severity of symptoms.

Pearls

1. GI decontamination with AC is not indicated, especially in the obtunded patient without a protected airway.

2. Control agitation and seizure activity with benzodiazepines.

3. Always consider the possibility of a coingestion.

4. Consider other causes of altered mental status, despite drug history.

5. Supportive care is the mainstay of treatment, with supplemental oxygen, symptomatic therapy, and IV hydration.

Clinical Summary

Dextromethorphan (DXM) is an antitussive medication commonly found in formulations containing antihistamines, analgesics, cough suppressants, decongestants, and expectorants. Its availability without a prescription makes it susceptible to abuse, especially in the adolescent population. Its allure as a drug of abuse is associated with a heightened sense of perceptual awareness, euphoria, and visual hallucinations. Dextromethorphan exhibits effects similar to other well-known NMDA antagonists (eg, phencyclidine [PCP] and ketamine), and is also known to cross react with urine drug screens for PCP, resulting in a false-positive test.

Use as a recreational drug is associated with a wide range of effects including, nausea, vomiting, tachycardia, respiratory depression, seizure activity, stupor, ataxia, hyperexcitability, dystonia, psychosis, and coma. When taking in combination with other serotonergic agents, individuals can develop the serotonin syndrome (altered mental status, autonomic hyperactivity, and neuromuscular abnormalities). Street names include “Robo,” “Skittles,” or “Triple c.”

Emergency Department Treatment and Disposition

Treatment is supportive care; there is no specific antidote. Use caution when considering GI decontamination with AC; seizures and CNS depression have been observed within 30 minutes of ingestion. Continually monitor vital signs, mental status, and oxygen saturation. Observe patients for 3 to 6 hours until they are asymptomatic. Admit patients with persistent respiratory and CNS depression. Consult social services in cases involving young children, and psychiatry in self-harm attempts.

Pearls

1. Always consider the possibility of toxicity from coingestions (eg, acetaminophen).

2. Use AC only in the awake and alert patient with a protected airway.

3. Control agitation and seizures with benzodiazepines.

4. Supportive care is the mainstay of treatment, with supplemental oxygen, symptomatic therapy, and IV hydration.

Clinical Summary

Derived from the Cannabis plant, the use of “medicinal” marijuana in history dates back to 400 BC. The active ingredient of marijuana is Δ-tetrahydrocannabinol (THC). THC binds to the cannabinoid receptor (CB1), which results in inhibition of neurotransmitter release through various intracellular mechanisms. Marijuana use is associated with alteration of perception and euphoria. Monikers commonly used include “Dope,” “Ganja,” “Mary Jane,” and “Hashish.”

With recreational usage of marijuana, individuals can experience euphoria, short-term memory impairment, disinhibition, impaired motor coordination, lethargy, slurred speech, and ataxia. In cases involving young children, the agent is commonly ingested; these patients can present with drowsiness, mydriasis, hypotonia, or with particulate matter in the mouth.

Recently, newer designer drugs have appeared on the scene marketed as “legal marijuana,” substances known as “JWH-018,” “Spice,” or “K2.” These variations of marijuana are modified chemical structures of THC that bind to the cannabinoid receptors (CB1 and CB2). Although it can be easily acquired in the United States, many countries in Europe have since made it illegal to possess it. Originally synthesized for laboratory animal research, short- and long-term effects in humans have yet to be determined from these synthetic agents. Acute symptoms are variable and can resemble that of THC but with greater efficacy. JWH-018 is available in a white crystalline powder or can be sprayed on dried vegetable matter to resemble its counterpart.

Emergency Department Treatment and Disposition

Treatment for these patients is focused on supportive care; there is no specific antidote. AC can be utilized to decrease absorption from ingestion, but may be difficult to administer in the young child. While in the ED, continuously monitor patient’s vital signs, mental status, and oxygen saturation. Patients presenting with altered mental status will need a blood glucose and electrolyte measurement, ECG, and cardiac monitoring. These individuals can often be observed in the ED for 4 to 6 hours until asymptomatic. Incorporate social services in cases involving young children, or psychiatry in self-harm attempts.

Pearls

1. AC is indicated for use in patients who have ingested marijuana products, except in the obtunded patient without a protected airway.

2. Place agitated or hallucinating individuals in a quiet room.

3. Extreme agitation and seizure activity should be controlled with benzodiazepines.

4. Always consider the possibility of a coingestion.

5. Consider other causes of altered mental status.

6. Supportive care is the mainstay of treatment.

Clinical Summary

Ethylene glycol is a highly toxic alcohol. Antifreeze is the major source for exposure. It has a sweet taste, which makes it appealing to young children and animals. Some antifreeze formulations introduce bitter agents in an attempt to counteract this appeal and mitigate potential toxicity.

Ethylene glycol is rapidly absorbed following ingestion. It undergoes metabolism by alcohol dehydrogenase to glycoaldehyde, which is then metabolized by aldehyde dehydrogenase to glycolic acid. Ethylene glycol has a half-life of about 4 hours when metabolized by alcohol dehydrogenase. Ethylene glycol, itself, is eliminated by the kidneys, with a half-life of 11 to 18 hours.

Signs and symptoms of toxicity include tachycardia, tachypnea, nausea/vomiting, CNS depression, and seizures. Hypocalcemia, high anion gap metabolic acidosis, renal failure, increased osmolar gap and urinary calcium oxalate crystals are all findings of ethylene glycol toxicity. Differential diagnosis includes other types of alcohols or sedative-hypnotic ingestion; other causes of increased anion gap acidosis (see Table 17.2) and seizures are also considerations.

Emergency Department Treatment and Disposition

Obtain serum electrolytes with calcium, measured serum osmolality, BUN, creatinine, lactate, and blood gas. Calculate the anion gap and osmolar gap (ie, the difference between measured osmolality and calculated osmolality). Check urine for calcium oxalate crystals. Order serum ethylene glycol and methanol levels; however, because of their turnaround times, these results might not be obtained in a clinically relevant manner. If the child is believed to have ingested a trivial amount of ethylene glycol, he can be observed for 12 hours in the ED with serial laboratory testing to assess for acidosis. Consult regional poison control center or medical toxicologist. Psychiatry should be notified for intentional suicidal ingestions. Prior to ED discharge, consider social work consult. If the child becomes symptomatic during observation or develops any laboratory abnormalities (eg, anion gap metabolic acidosis, lethargy), he or she should be treated and admitted to the ICU.

As this is a liquid toxin that is rapidly absorbed and distributed, no gastric decontamination is advised. Antidotal therapy for ethylene glycol toxicity first consists of pharmacologic blockade of ethylene glycol metabolism by inhibition of alcohol dehydrogenase. Although IV ethanol may be used, it is complicated to administer and is associated with complications such as hypoglycemia. The current treatment of choice is fomepizole. Thiamine and pyridoxine are also recommended to enhance formation of nontoxic metabolites.

If the patient has altered mental status, renal failure and worsening acidosis or electrolyte abnormalities that are not responding to conventional medical treatment, emergent hemodialysis should be performed. Occasionally, more than one course of hemodialysis will be necessary for large ingestions.

Pearls

1. Osmolar gap = measured Osm − (2Na + BUN/2.8 + glucose/18 + ethanol/4.6). Normal osmolar gap range is between −14 and +10. A normal osmolar gap does not exclude toxicity.

2. If ethanol has also been ingested, it will be preferentially metabolized by alcohol dehydrogenase, delaying metabolism and onset of toxicity of ethylene glycol.

3. Consult the renal service early to ensure timely hemodialysis when indicated.

Clinical Summary

Methanol is a toxic alcohol that can be found in windshield wiper fluid, antifreeze, solvents, and in homemade ethanol (eg, moonshine).

Signs and symptoms of toxicity include tachycardia, tachypnea, nausea/vomiting, occasional hepatitis or pancreatitis, visual impairment (from blurry vision to blindness), ataxia, CNS depression, and seizures. Methanol is osmotically active, creating an osmolal gap. As it is metabolized to formic acid, it causes a high anion gap metabolic acidosis. Differential diagnosis includes ingestion of other types of alcohols and other causes of elevated anion gap metabolic acidosis (see Table 17.2).

Methanol is rapidly absorbed and distributed following ingestion. Like ethanol, it undergoes metabolism by alcohol dehydrogenase to formaldehyde, which is then metabolized by aldehyde dehydrogenase to formic acid. Methanol has a half-life of up to 28 hours when metabolized by alcohol dehydrogenase. The parent compound appears to be slowly eliminated by the lungs, with a half-life of 30 to 54 hours.

Emergency Department Treatment and Disposition

Obtain serum electrolytes, measured serum osmolality, BUN, creatinine, liver enzymes, amylase, lipase, and serum pH. Calculate the anion gap. Calculate the osmolal gap (ie, the difference between measured osmolality and calculated osmolality). Order serum ethylene glycol and methanol levels; however, because of turnaround time, these results might not be obtained in a clinically relevant manner.

If methanol ingestion is suspected, the child will need a minimum period of 12 hours of observation and serial blood work in the ED. Consult regional poison center or medical toxicologist and psychiatry for intentional suicidal ingestions. Consider social work consult prior to discharge. If the child becomes symptomatic during observation or develops any laboratory abnormalities (eg, anion gap metabolic acidosis, lethargy), he or she should be treated and admitted.

As this is a liquid toxin that is rapidly absorbed and distributed, no gastric decontamination is advised. Antidotal therapy for methanol toxicity first consists of pharmacologic blockade of alcohol dehydrogenase. Although IV ethanol may be used, it is complicated to administer and is associated with complications such as hypoglycemia. The current treatment of choice is fomepizole. Folic acid may also provide benefit in the detoxification of formic acid.

If the patient has altered mental status, vision changes, renal failure, and worsening acidosis or electrolyte abnormalities that are not responding to conventional medical treatment, consult the renal service for emergent hemodialysis.

Pearls

1. As methanol is metabolized, the osmolar gap will get smaller while the anion gap will grow larger.

2. Osmolar gap = measured Osm − (2Na + BUN/2.8 + glucose/18 + ethanol/4.6). Normal osmolar gap is −14 to +10. A normal osmolar gap does not exclude toxicity.

3. Visual testing and funduscopy are important components of the physical exam.

Clinical Features

Ethanol, commonly referred to as alcohol, is one of the most frequently and socially accepted drugs in the world. Ethanol abuse is a significant social disease afflicting many adults. Ethanol is responsible for the most number of yearly deaths in the 15- to 45-year-old age group. In young children, ethanol exposures are usually unintentional and significant toxicity occasionally occurs. Common household products containing ethanol include mouthwashes, antitussive medications, and perfumes and colognes.

In adolescents, intentional abuse of ethanol-containing beverages is extremely common and much more likely to be dangerous. Ethanol concentration is expressed usually as proof or percent. In the United States, percent refers to ½ of the proof. To the general public, “proof ” is commonly used but in science, percent (or mg/dL) is used as the unit of concentration.

Important considerations in the history include amount, time of ingestion, intent, possibility of coingestants, and awareness of possible factors delaying absorption. In general, increasing concentrations of ethanol will result in CNS depression and, occasionally, respiratory depression. Depending on the age of the patient, the quantity ingested, and the individual, the clinical manifestations can be markedly different. Occasionally, paradoxical CNS stimulation may occur from CNS disinhibition. In cases of massive ingestions, respiratory depression, loss of protective reflexes, coma, and death may occur.

Ethanol metabolism interferes with gluconeogenesis, and significant hypoglycemia may occur especially in young children with low glycogen stores. The acute neuroglycopenia is known to cause generalized tonic-clonic seizures. Symptomatic hypoglycemia in adolescents and healthy adults is less frequent. Other effects include myocardial depression, vasodilatation, dysrhythmias (eg, atrial fibrillation), hypotension and tachycardia, gastritis, pancreatitis, skin flushing, urticaria, and hypothermia.

Differential diagnosis includes overdose of other sedative-hypnotic agents (eg, benzodiazepines), hypoglycemia from other etiology (eg, oral hypoglycemia agents): (1) infection (eg, meningitis), (2) head trauma, and (3) toxic alcohols (eg, methanol, ethylene glycol).

Emergency Department Treatment and Disposition

History should focus on determining the agent involved, amount, time of ingestion, and intent. The patient’s mental status may impede obtaining a thorough history. Initial stabilization of ABCs is necessary especially in patients with a depressed mental status. Hypotension and reflex tachycardia may be prominent. Obtain ECG to detect any cardiac dysrhythmias and electrolyte disturbances and a bedside fingerstick glucose test on all patients with altered mental status. If unavailable, give empiric treatment with IV dextrose.

GI decontamination will rarely be necessary for isolated ethanol ingestions but should be considered in patients presenting with a recent massive ingestion or serious coingestants. In patients with persistent altered mental status, consider other etiologies besides ethanol intoxication (see COMATOSE; Table 13.5).

Obtain serum chemistry (including calcium, magnesium, and phosphate), ketones, CBC, and ethanol concentration. Coingestants (eg, acetaminophen) and subsequent toxidromes should be sought in patients who present with intentional ingestion. Although individual variation exists, ethanol intoxication in non–alcohol-dependent individuals is usually apparent at a blood ethanol concentration of 50 mg/dL.

Supportive care (ie, IV fluids, warm blankets, etc) is the mainstay of therapy. In cases of massive overdose with respiratory depression, hemodialysis is effective at removing ethanol from the body. Patients with simple intoxication may be discharged home after a period of observation. Admit patients with hemodynamic instability, persistent altered mental status, hypoglycemia, and coingestants. Consult medical toxicologist, regional poison control center, psychiatry (if intentional) or and social services (for suspected abuse) as necessary.

Pearls

1. Consider ethanol intoxication in the differential diagnosis of altered mental status and/or hypoglycemia.

2. Significant head or neck trauma may be overlooked in trauma patients who are intoxicated. Have a low threshold to perform a head CT to look for intracranial hemorrhage.

3. No measures of enhanced elimination of ethanol aside from hemodialysis are effective at removing ethanol from the body.

4. Parents should be educated on proper storage of ethanol-containing beverages. Older children may need to be referred for substance abuse counseling.

5. Toxic alcohols (ie, methanol and ethylene glycol) may present in a similar manner to ethanol intoxication, but these patients can develop a persistent nonlactate, nonketotic, anion gap, and metabolic acidosis. Suspicion of these agents must be high to prevent missing the diagnosis.

Clinical Summary

Opioids: Opioids (eg, OxyContin, Percocet, Vicodin, Fentanyl) are a class of medications known for their analgesic effects. They are derived from naturally occurring opiates, such as morphine. Although indicated for moderate to severe pain, prescription opioids have become an increasing source of drug abuse. Users not only experience a euphoric effect but also develop tolerance and physical dependence, therefore resulting in fortified behavior. There are a number of opioid receptors in the CNS; however, opioids primarily exert their analgesic effects through the μ (mu) opioid receptor. The mu receptors are present in the peripheral and central nervous systems and modulate pain perception by inhibiting the presynaptic release of neurotransmitters, hyperpolarization of the postsynaptic membrane, and via activation of a descending inhibitory system.

Benzodiazepines: Benzodiazepines (eg, Xanax, Valium, Ativan, Klonopin) are members of a family known as sedative hypnotics. They are commonly prescribed to treat anxiety, agitation, sleep disturbances, and seizure disorders. In a controlled setting, benzodiazepines are frequently administered for sedation. Benzodiazepines exert their effect by binding to GABAA receptors, resulting in GABAergic neurotransmission potentiation. These drugs are frequently abused in combination with other drugs, and are sought after for their calming and relaxing effects. Like opioids, individuals can develop tolerance and physical dependence.

Emergency Department Treatment and Disposition

For Opioid Toxicity: Treatment for these patients is focused on supportive care and airway maintenance. Individuals that present to the ED with respiratory or CNS depression, secondary to opioid overdose, can be given naloxone, an opioid receptor antagonist. When administering the antidote, always begin with a low dose and titrate to arousal or improvement of respiration; rapid reversal may result in withdrawal symptoms in opioid-tolerant patients. Individuals should be closely monitored as naloxone is relatively short-acting compared to some opioids, and patients can have recurrence of opioid toxicity.

Some oral opioid preparations are available in combination with acetaminophen or aspirin. Acetaminophen or salicylate toxicity may result from these combination preparations. Serum levels for these agents should be obtained in conjunction with renal and hepatic function tests, especially in overdose cases, and toxicity must be treated appropriately (see Acetaminophen and Salicylate Poisoning).

For Benzodiazepine Toxicity: Flumazenil is a benzodiazepine receptor antagonist; however, its use is rarely indicated except in iatrogenic oversedation. Extreme caution should be used when giving this antidote to patients on long-standing benzodiazepine use because patients can develop withdrawal seizures that may be difficult to treat. While in the ED, patients should have their vital signs (including cardiac monitor), mental status, and oxygen saturation continually checked. An ECG should be performed to look for other potential coingestants. Laboratory evaluation should include measurement of electrolytes, renal function, hepatic function, acetaminophen, and salicylate concentrations. If the patient presents agitated or actively seizing, treat with benzodiazepines and consider endotracheal intubation in order to protect the airway.

For Opioid and Benzodiazepine Toxicity: With mild toxicity, these individuals can often be observed in the ED for 6 to 8 hours. In moderate to severe cases, designated by persistent CNS involvement, admit these patients to the ICU. Consult social services in cases involving young children, or psychiatry in self-harm attempts.

Pearls

1. In acute overdoses, impending respiratory depression should be taken into consideration before entertaining the utility of AC; risk of aspiration is high.

2. Naloxone is a short-acting antidote; a continuous infusion may be necessary in patients with ingestion of long-acting opioids.

3. Agitation and seizure activity should be controlled with the use of benzodiazepines.

4. Always consider the possibility of a coingestion.

5. Consider other causes of altered mental status, despite drug history.

Clinical Summary

Beta-blockers (BBs) and calcium channel blockers (CCBs) are antihypertensive medications that can be toxic in young children after ingesting as little as one tablet. Beta-blockade of β1 receptors in the heart slow cardiac conduction at the sinoatrial (SA) and AV nodes and decrease inotropy, thereby decreasing blood pressure. Blockade of β2 receptors causes constriction of the peripheral vasculature, bronchospasm, hyperkalemia, and hypoglycemia.

Diltiazem and verapamil are CCBs that exert their primary effect on the heart, slowing cardiac conduction at the SA and AV nodes, decreasing inotropy, and thus lowering blood pressure. The dihydropyridine CCBs act more peripherally causing dilatation of the vasculature to lower blood pressure; which may result in a reflex tachycardia. Calcium channel blockade of pancreatic beta islet cells inhibits insulin release, resulting in hyperglycemia.

The differential diagnosis for toxicity from these agents includes digoxin, imidazoline, opiate, and sedative hypnotic and cholinergic toxicity.

The pharmacokinetics are widely varied based on the drug and formulation taken. Most of the immediate-release preparations usually have an effect within 1 to 2 hours and not later than 6 hours. The extended/controlled/sustained-release products have later onset and peak effects and are more likely to be associated with delayed toxicity.

Emergency Department Treatment and Disposition

As there are a wide variety of BBs and CCBs, it is important to determine the name of the drug, the strength, formulation, and the maximum number of tablets that may have been ingested and the time of ingestion. Consider social work and psychiatry consults as needed.

Obtain vital signs, including blood pressure. Obtain an ECG and place child on cardiac monitor. Send serum electrolytes, BUN, creatinine. and check a bedside glucose.

Gastric decontamination may be indicated, depending on the timing of the ingestion and specific preparation (ie, immediate vs sustained release), with orogastric lavage, AC, and whole bowel irrigation, all potential options. The choice of decontamination technique will vary depending on the severity of the overdose; orogastric lavage and whole bowel irrigation are generally reserved for patients with large overdoses.

The ability to observe the asymptomatic patient in the ED and discharge home will vary based on the drug/formulation. For some immediate-release preparations, if the child is completely asymptomatic and with normal vital signs at 6 to 8 hours, it may be safe to discharge home.

For any child with signs or symptoms of toxicity or overdose of a sustained-release preparation, admission to an ICU is advised.

Treatment is similar for both BBs and CCBs. IV fluids and atropine can be given initially. There is no true order in which to administer treatment, but glucagon and calcium are often the next step. Vasopressors, such as norepinephrine, may be necessary in severe cases of hemodynamic instability. High-dose insulin-euglycemia therapy has been shown to improve cardiac function. When these treatments are insufficient, an intra-aortic balloon pump or extracorporeal membrane oxygenation may be required. Extracorporeal removal (eg, hemodialysis) is generally ineffective for most BBs and CCBs.

Pearls

1. BBs and CCBs can be highly toxic in young children, with significant toxicity occurring from only a single pill. Early consultation with the poison control center or medical toxicologist is advised.

2. Aggressive early decontamination and treatment are important.

3. High-dose insulin is given as a 1 unit/kg bolus with a dextrose bolus of 0.5 g/kg, followed by an insulin drip of 0.5 unit/kg/h, titrated to effect, with dextrose infusion of 0.5 g/kg/h.

4. In the event of cardiac arrest, there are case reports of successful resuscitation with IV fat emulsion rescue (20% intralipid).

Clinical Summary

Clonidine is an imidazole derivative that acts via central α2 agonism to produce its antihypertensive effect. In addition to being used to treat hypertension, it may be used therapeutically for attention deficit hyperactivity disorder, Tourette syndrome, neuropathic pain, and opioid withdrawal.

Following overdose, vital sign abnormalities may include an initial period of hypertension and tachycardia, followed by hypotension and bradycardia, respiratory depression, hypoxia and hypothermia. Lethargy, coma, miosis, and decreased deep tendon reflexes can be seen. A clonidine withdrawal syndrome has also been described that is manifested by hypertension, anxiety, agitation, headache, and confusion.

The toxicologic differential diagnosis of clonidine overdose includes beta blocker, calcium channel blocker, digoxin, and opioid toxicity.

Clonidine is available as tablets and patches. Ingestion of a single 0.1-mg tablet or a patch may cause toxicity in a small child. The onset of action for tablets is 30 to 90 minutes, with a half-life of 12 to 16 hours. Toxicokinetics are delayed for patch ingestion and symptom onset may be delayed. The drug is mainly eliminated by the kidneys but a considerable portion is also excreted in the bile.

Emergency Department Treatment and Disposition

GI decontamination with AC is advised if the airway is protected. There may be a role for whole bowel irrigation in the case of an ingested patch.

All patients should have an ECG and cardiac monitoring. Send serum electrolytes, BUN, and creatinine.

If the child ingests the tablet form of clonidine and is asymptomatic after 4 hours of observation, the child can be discharged home from the ED. If the child ingests a patch, or if the child is symptomatic, admission to the ICU is advised.

There is no antidote for clonidine; treatment is supportive. Perform endotracheal intubation if airway protection is necessary. Naloxone may reverse some of the CNS and respiratory depression in some patients but the therapeutic response is inconsistent. Atropine, pacing, and vasopressors can be used as needed for bradycardia and hypotension.

Consultation with the regional poison control center or medical toxicologist is advised. Consult social services in cases involving young children or psychiatry in self-harm attempts.

Pearls

1. As little as one dose of clonidine can be toxic in a child.

2. AC should be given if the airway is protected.

3. Supportive care is the mainstay of therapy for most symptomatic patients.

4. Naloxone may be attempted to reverse CNS depression. The dose of naloxone for infants and children up to age 5 years or weighing 20 kg is 0.1 mg/kg. Children >5 years or weighing >20 kg should be given 2 mg.

Clinical Summary

Cyclic antidepressants (CAs) (eg, imipramine, amitriptyline, desipramine, nortriptyline) are commonly used medications for the treatment of various disorders including depression, nocturnal enuresis, anxiety disorders, attention deficit hyperactivity disorder (ADHD), and migraine headaches. They are one of the most common causes of reported deaths from pharmaceutical products in the United States.

CAs inhibit CNS reuptake of norepinephrine, serotonin, and dopamine. Not all cyclic antidepressants have three rings; hence the term cyclic antidepressants is a better classification than the more often used term tricyclic antidepressants.

Toxicity from CA may be mostly attributed to cardiovascular and CNS effects. Toxicity may occur with therapeutic doses as well but are usually less clinically significant. Anticholinergic effects (central and peripheral) may be prominent. Central effects include lethargy, delirium, hallucinations, seizures, and coma. Peripheral effects include dry skin, tachycardia, mydriasis, decreased bowel sounds, and urinary retention. Neurologic effects include depressed or altered mental status; seizures secondary to anticholinergic toxicity and GABA antagonism. Cardiovascular effects include type Ia sodium channel blockade (“quinidine-like”) leading to conduction delays and myocardial depression. On the ECG, this manifests as a prolonged QRS interval and possibly wide complex ventricular dysrhythmias; negative inotropy; hypotension occurs secondary to vasodilation from α-adrenergic blockade. Tachycardia usually occurs secondary to anticholinergic effect and the normal reflexive physiologic response to hypotension.

The differential diagnosis includes agents causing CNS depression, especially those that impair cardiac conduction (eg, type Ia antidysrhythmics, phenothiazines) and other medical etiologies of CNS depression (eg, meningitis, intracranial hemorrhage, cerebral ischemia). Electrolyte imbalances leading to cardiac conduction abnormalities are also a consideration.

Emergency Department Treatment and Disposition

History should focus on determining agent involved, dose, time of ingestion, and intent. Patient’s mental status may impede obtaining a thorough history. Physical examination should focus on vital signs, including evaluation for anticholinergic effects and observation of mental status. Obtain a 12-lead ECG as soon as possible. The QRS interval is highly predictive of toxicity. This is based on a previous landmark study where approximately 30% of patients with a QRS duration >100 ms had seizures; there was a 50% incidence of ventricular dysrhythmias in patients with a QRS duration >160 ms. Also, in the setting of an acute overdose, the terminal 40 ms right axis changes (S waves in leads I and aVL and R in aVR) had positive predictive value of 66% and a negative predictive value of 99%. Obtain serum acetaminophen levels to evaluate for occult ingestion. Consult medical toxicologist, regional poison control center, psychiatry, and social services as needed.

Consider GI decontamination with AC if no contraindications; perform gastric lavage if patients have life-threatening toxicity or a history of a large ingestion. AC should be administered with caution because patients may have a rapid deterioration in mental status.

Sodium bicarbonate should be administered to patients with signs of significant cardiac toxicity (ie, prolonged QRS duration on the 12-lead ECG). Hypotension is managed initially with IV fluids and/or NaHCO3 and then vasopressors if hypotension persists. Patients may be discharged from ED if they do not develop seizures, hypotension, or ECG changes after a 6-hour observation period, and evaluation by a psychiatrist (if indicated) is completed. Admit patients with seizures, cardiac dysrhythmias, or CNS depression to an ICU for monitoring.

Pearls

1. CA toxicity presents with cardiovascular and CNS effects.

2. A 12-lead ECG is the best diagnostic test to determine if a patient has significant CA toxicity.

3. A QRS duration >100 ms is suggestive of CA toxicity.

4. CAs have a low toxicity threshold and ingestion of small amounts may be toxic in young children.

5. Physostigmine should not be given to reverse anticholinergic toxicity from CAs because of potential deleterious cardiovascular consequences.

Clinical Summary

Lead is a heavy metal that can be found in paint, food/liquids cooked or stored in ceramic vessels, fishing weights, bullets, and many other items. Pediatric lead screening is based on risk of exposure generally at 12 and 24 months of age. Symptoms are usually seen once blood lead levels are above 50 μg/dL. Levels of >70 μg/dL are associated with severe toxicity.

GI symptoms (abdominal pain, vomiting, anorexia) are common in acute lead toxicity but these are nonspecific. CNS findings correlate with lead levels. As levels exceed 70 μg/dL, children are at risk for encephalopathy and may exhibit change in mental status, incoordination, seizures, and coma. Early symptoms can be misdiagnosed as gastroenteritis or a behavioral disorder.

Lead is absorbed most when ingested or inhaled and is transported by red blood cells throughout the body. The majority of lead is stored in bone. Other areas of deposition are the liver, kidney, and brain. The kidneys are the primary site of excretion, followed by the liver. The half-life of lead in children is approximately 10 months in the blood, 40 days in soft tissue, and up to 20 years in bone.

Important information that should be obtained regarding lead exposures include: take a medical history, determine age of the patient’s home, recent remodeling, family history including pica, and patient’s country of origin. Perform a full neurologic exam, including funduscopy.

Emergency Department Treatment and Disposition

Discharge asymptomatic patients with serum lead level of less than <45 μg/dL home if return to safe lead-free environment is possible. Arrange follow-up with primary care and notify local health department (or lead bureau). Asymptomatic children with BLL between 45 and 70 μg/dL may undergo outpatient chelation, but admission may be necessary especially if adequate follow-up cannot be arranged.

Check CBC with peripheral smear for basophilic stippling, the whole blood lead level, basic chemistry panel with renal function and urinalysis. Obtain an abdominal radiograph to look for ingested FBs and radiographs of long bones to look for lead lines. Perform whole bowel irrigation if radiographs show lead FBs in the GI tract and there is no contraindication. Hospitalize for chelation therapy any child with severe symptoms or BLL greater than 70 μg/dL. Admit patients with lead encephalopathy to the pediatric ICU. Consult local medical toxicologist or regional poison control center, if required.

Depending on the case, chelation may be performed with oral succimer, intramuscular dimercaprol (BAL), and IV edetate calcium disodium (CaNa2EDTA). For children with acute encephalopathy, administer both BAL and CaNa2EDTA. Benzodiazepines are first-line therapy for seizures.

Pearls

1. With mild symptoms, lead toxicity may be overlooked.

2. Most asymptomatic children with mildly elevated blood lead levels do not require inpatient management.

3. For acute lead encephalopathy, start BAL 75 mg/m IM (every 4 hours × 5 days) as soon as possible. If the patient is still in the ED 4 hours later, give the second IM dose and then start the CaNa2EDTA 1500 mg/m/d (can be divided or given continuously).

4. Check siblings of affected children for lead poisoning.

5. Patients who are discharged home from the ED must be sent to a safe, lead-free environment.

Clinical Summary

Caustics are agents that cause both functional and histologic damage on contact with body surfaces. Caustic substances are commonly associated with agents with extremes of pH such as acids and alkalis (bases). However, they are a diverse group of agents and other factors besides pH (eg, concentration, amount and intrinsic characteristics of a particular substance) in determining the potential for tissue injury. Examples of various caustic agents includes hydrochloric acid, sodium hydroxide, hydrofluoric acid, mercuric chloride, and phenol. A significant number of cases occur in the pediatric population, especially in children <5 years old.

Direct contact of any external or internal tissue surface by a caustic agent can result in injury.

Pain is usually the first symptom. Because most caustic agents are ingested, localization of pain is most common to the oropharynx, chest, and abdomen. GI effects such as nausea, vomiting, drooling, and inability to swallow are often present. Upper airway injury may result in the development of stridor, and rapid deterioration of respiratory status may occur.

Although signs of physical injury around the mouth and oropharynx may be visualized, significant esophageal injury may still be present in the absence of physical examination findings. Burns on the face and upper chest (ie, “dribble burns”) may be apparent. Ocular injury may occur and examination of the eyes for pH, abrasions, and ulcers is very important. Examination of the chest may reveal subcutaneous emphysema, abnormal breath sounds, pericardial friction rub (Hamman’s crunch). Examination of the abdomen may reveal tenderness and peritoneal signs; however, peritoneal signs may be absent even with significant intestinal perforation.

For some patients, long-term or delayed complications of caustic ingestion may be particularly troublesome, especially when GI strictures develop. The patient may suffer from repeated hospitalizations, nutritional deficiencies, and multiple esophageal dilatations. Other laryngotracheal and pharyngeal injuries such as stenosis or reflux, can further contribute to morbidity and patient discomfort. Pyloric obstruction and impaired gastric function may also occur.

History should focus on determining agent involved, amount, time of ingestion, and intent. The patient’s mental status may impede obtaining a thorough history.

Emergency Department Treatment and Disposition

Initial stabilization of ABCs is crucial because injury occurs so rapidly. Establish two large-bore IVs to administer fluids. Order serum chemistry, CBC, PT/PTT (INR), and ABG with serum lactate concentration. Coingestants (eg, acetaminophen) and subsequent toxidromes should be sought for in patients who present with intentional ingestion. Order type and screen for blood products. Plain radiographs of the chest and abdomen may be useful to assess for perforation. As clinically indicated, consult with medical toxicologist, regional poison control center, gastroenterology, surgery, otolaryngology, and psychiatry (if intentional).

Emesis should never be induced because tissue injury may be exacerbated by reexposing potentially damaged areas. AC should NOT be given. If a solid substance has been ingested, a small quantity of water may be given to dissolve the agent. This will also be effective if the caustic material becomes lodged at an area of anatomic narrowing.

Imaging studies such as contrast studies with gastrograffin or barium and CT are not useful in the acute setting. Emergent endoscopy should be performed in patients with intentional suicidal ingestions, and in children with unintentional ingestions if they have two of three of the following signs: vomiting (inability to drink), drooling, or stridor. The optimal time to perform endoscopy is controversial, but ideally should be performed within 24 to 48 hours of injury. Critically ill patients may benefit from surgical intervention to remove necrotic tissue. Indications for surgical intervention include obvious perforation, presence of peritoneal signs, or persistent hypotension. Coagulopathy and acidosis are also poor prognostic findings. Treatment with either corticosteroids or antibiotics does not appear to improve outcome or prevent stricture formation.

Various endoscopic grading systems of GI burns exist. In general, burns can be classified as follows:

Pearls

1. Most tissue injury from caustic agents occurs immediately on contact with tissue.

2. Dilution or neutralization is NOT recommended in the ED.

3. Absence of obvious burns on physical examination does not exclude significant GI tract injury.

4. Suspect child abuse with exposures in very small infants and children.

5. Endoscopic evaluation should be performed within 24 to 48 hours.

6. Patients with significant caustic injuries to the GI tract require long-term follow-up for many years to monitor for development of complications, including malignancy.