Substance	Hazard Factor
Rattlesnake envenomation	245
Methadone	75
Chloral hydrate	66
Cyclic antidepressant	57
Strychnine	50
Selenious acid (gun bluing)	48
Acid drain cleaner (toilet bowel cleaner)	47
Carbamazepine	33
Chloroquine (antimalarial)	32
Carbon monoxide	31
Paraquat	24

Litovitz TL, Manoguerra A: Comparison of pediatric poisoning hazards: an analysis of 3.8 million exposure incidents. A report from the American Association of Poison Control Centers. Pediatrics 89:999–1006, 1992.

12 Which medicinals are potentially life-threatening or fatal to a 10-kg toddler following ingestion of a single dose?

Benzocaine, camphor, chloroquine, clonidine, cyclic antidepressants, diphenoxylate/atropine (Lomotil), lindane, methadone (and other opioids), methyl salicylate (oil of wintergreen), oral hypoglycemics, quinidine, propranolol, theophylline, thioridazine, and verapamil.

Osterhoudt KC: The toxic toddler: Drugs that can kill in small doses. Contemp Pediatr 17:73–88, 2000.

KEY POINTS: POISONING EPIDEMIOLOGY

1 More than half of all poisoning exposures are reported among children younger than age 6 years.

2 Natural exploratory behaviors of young children put them at risk for poisoning.

3 Drug abuse, experimental risk taking, and depression put adolescents at risk for poisoning.

4 Poisoning can be prevented.

INITIAL MANAGEMENT

13 Which three antidotal drugs should be immediately considered in the resuscitation of the comatose child?

Two are often not thought of as drugs per se, but they are essential substrates for brain function: oxygen and glucose. Administration of the opioid antagonist naloxone may also be warranted.

14 What is a “toxidrome”?

The word toxidrome can be thought of as a combination of the words “toxic” and “syndrome.” Toxidromes are groupings of physical signs that may help to suggest the drug class responsible for a poisoning. These signs should be noted in the examination of every potentially poisoned patient: mental status, vital signs, pupil size and reactivity, skin color and moisture, and bowel sounds.

Osterhoudt KC: No sympathy for a boy with obtundation. Pediatr Emerg Care 20:403–406, 2004.

15 Describe the most common toxidromes

See Table 39-1.

Table 39-1 Common Toxidromes

16 How can the anticholinergic toxidrome be differentiated from the sympathomimetic toxidrome?

Anticholinergic agents and sympathomimetic agents may both produce altered mental status, tachycardia, hypertension, hyperthermia, and mydriatic pupils, so distinguishing between these drugs is not easy. Look to the skin, the bowels, and the eyes for help. Anticholinergic poisoning is likely to produce flushed skin that is surprisingly dry to the touch, diminished or absent bowel sounds, and less reactive pupils. Many people remember the characteristics of the anticholinergic toxidrome with the mnemonic: “Mad as a hatter, blind as a bat (pupils do not accommodate well), red as a beet, dry as a bone, and hot as Hades.”

17 What would be the significance of a bitter almond smell to your morning coffee?

Consider the possibility of cyanide in the coffee.

18 What other toxicants are associated with characteristic odors?

Odor	Agent
Acetone	Acetone, isopropyl alcohol, phenol
Almonds	Cyanide
Garlic	Arsenic, thallium, organophosphates, selenious acid
Pears	Chloral hydrate, paraldehyde
Rotten eggs	Hydrogen sulfide
Wintergreen	Methyl salicylate

19 List the most commonly considered methods of gastrointestinal decontamination of the poisoned patient

Gastric emptying: Induced emesis, gastric lavage

Prevention of drug absorption: Activated charcoal

Catharsis: Simple cathartics, whole-bowel irrigation

20 Elaborate the indications for ipecac-induced emesis

Induced emesis has little role in the emergency department setting. Indeed, its use as out-of-hospital first aid is now discouraged by the American Academy of Pediatrics.

American Academy of Pediatrics Committee on Injury, Violence, and Poison Prevention: Poison treatment in the home. Pediatrics 112:1182–1185, 2003.

21 What is the proper technique for gastric lavage?

Consider the need for airway protection with endotracheal intubation. Place the patient in left lateral decubitus position with the head slightly lower than feet if tolerated. Use a large-bore orogastric tube (24 Fr in toddlers and up to 36 Fr in adolescents). Lavage with saline aliquots until the effluent is clear of toxic materials.

22 Under what circumstances is gastric lavage indicated?

Gastric lavage, once the stalwart of emergency department management of poisonings, is falling from favor after recent investigation has questioned its efficacy. It may still have a role in the management of life-threatening overdoses presenting within the first hour. Gastric lavage may be considered more strongly for poisoning scenarios that lack dependable antidotes.

23 What is the gastrointestinal decontamination technique of choice for most poisonings?

In most cases, gastric emptying can be omitted in preference to administration of activated charcoal.

Osterhoudt KC, Durbin D, Alpern ER, et al: Activated charcoal administration in a pediatric emergency department. Pediatr Emerg Care 20:493–498, 2004.

24 What is activated charcoal?

Most would recognize charcoal as the byproduct of the pyrolysis of wood or other organic materials. “Activation” of charcoal refers to a process of further oxidizing the charcoal, either chemically or at high temperatures, to increase its surface area and adsorptive capacity.

25 List common drugs and toxicants that are poorly adsorbed by activated charcoal

Ineffective: Alcohols, iron, lithium

Poorly effective: Hydrocarbons, metals

26 What is whole-bowel irrigation?

Whole-bowel irrigation uses nonabsorbable polyethylene glycol solution (well-known as a surgical bowel prep) to wash intestinal contents through before absorption can take place. Typical administration is 500 mL/hour in a toddler and to 2 L/hour in an adolescent, continued until the rectal effluent is clear and clinical signs of continued drug absorption have subsided.

27 List the possible indications for whole-bowel irrigation

Although not yet proven to improve patient outcomes, use of whole-bowel irrigation has been advocated for the following situations:

Body packers/stuffers

Ingestion of metals, lithium

Ingestion of sustained-release preparations

Ingestion of pharmaceutical patches

Massive overdoses

Concretions of pills

28 What is a body packer or a body stuffer?

Body packers are smugglers who attempt to evade customs officials by swallowing packages (typically tied condoms) of drugs. Body stuffers are drug sellers or users who hurriedly ingest illicit substances to hide evidence from authorities. Because of the planning involved, packers are less likely to become toxic than stuffers; however, packers typically ingest more dangerous quantities of drug.

Traub SJ, Hoffman RS, Nelson LS: Body packing: The internal concealment of illicit drugs. N Engl J Med 349:2519–2526, 2003.

29 How often do poisoned patients require special therapy, such as antidote administration, elimination enhancement, or extracorporeal elimination?

Antidotes and elimination enhancement, such as urinary alkalinization or multiple-dose activated charcoal, are performed in about 1% of all reported poisonings. Extracorporeal elimination (hemodialysis or hemoperfusion) is needed in less than 0.1%.

Watson WA, Litovitz TL, Rodgers GC, et al: 2004 annual report of the American Association of Poison Control Centers toxic exposure surveillance system. Am J Emerg Med 23:589–666, 2005.

30 What are the characteristics of the ideal toxic agent that would be amenable to multiple-dose activated charcoal?

The ideal toxicant has a small volume of distribution (< 1 L/kg), has low protein binding, binds to activated charcoal, and either has an enterohepatic circulation of an active metabolite in the bowel or undergoes enteroenteric dialysis with evidence of excretion of agent from the microvillous blood circulation into the gut, where it is bound by the charcoal. Multiple-dose activated charcoal may also be of benefit after ingestion of sustained-release compounds or after a toxic gastric concretion has formed.

31 Multiple doses of activated charcoal are believed to enhance clearance of what poison(s)?

Good evidence exists to support the use of multiple-dose activated charcoal to treat certain cases of poisoning from carbamazepine, dapsone, phenobarbital, quinine, and theophylline. Elimination of amitriptyline, dextropropoxyphene, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol increases with multiple-dose activated charcoal; however, improved outcomes for ingestion of these poisons with respect to morbidity and mortality have not been shown in controlled trials.

American Academy of Clinical Toxicology, European Association of Poisons Centers and Clinical Toxicologists. Position statement and practice guideline on the use of multi-dose activated charcoal in the treatment of acute poisoning. Clin Toxicol 37:731–751, 1999.

32 What is extracorporeal removal?

Extracorporeal removal refers to elimination of a poison from the blood after removing the blood or a portion of the blood from the body. The forms of extracorporeal elimination include hemodialysis, charcoal hemoperfusion, arteriovenous hemofiltration, venovenous hemofiltration, exchange transfusion, and plasmapheresis. Of these, hemodialysis is used most commonly.

33 What factors predict adequate removal of a poison by hemodialysis?

The substance should have the following characteristics: small volume of distribution, little protein binding, water solubility, low molecular weight, low endogenous clearance, and single-compartment kinetics.

34 For which toxic agents is hemodialysis most commonly considered?

Dargan PI, Jones AL: Acute poisoning: Understanding 90% of cases in a nutshell. Postgrad Med J 81:204–216, 2005.

35 When should hemodialysis be used?

The decision to perform hemodialysis should be based on physical findings as well as drug levels. Always repeat an elevated level and check units of measurement before instituting hemodialysis.

36 What is the rationale behind urinary alkalinization?

Urinary alkalinization refers to the administration of sodium bicarbonate to raise the urine pH to 8.0. This procedure converts renally excreted toxins, which are weak acids to their ionized form within the proximal renal tubules, and thereby prevents reabsorption in the distal tubules (ion trapping). This technique is most useful for enhancing the excretion of salicylates and phenobarbital (but not other barbiturates). Urinary alkalinization is also useful to protect the kidney during rhabdomyolysis.

Proudfoot AT, Krenzelok EP, Vale JA: Position paper on urine alkalinization. J Toxicol Clin Toxicol 42:1–26, 2004.

37 What are the pitfalls of urinary alkalinization?

Urine alkalinization is inhibited by the presence of hypokalemia. Urinary alkalinization has been associated with pulmonary and cerebral edema, and fluid administration must be monitored carefully. Electrolyte and acid-base disturbances can result from sodium bicarbonate administration and merit frequent monitoring.

Proudfoot AT, Krenzelok EP, Vale JA: Position paper on urine alkalinization. J Toxicol Clin Toxicol 42:1–26, 2004.

PHARMACEUTICALS

39 Describe the pathophysiology of acetaminophen poisoning

Acetaminophen is the drug most commonly administered to children. Toxicity may occur after acute overdose of 150–200 mg/kg or after repeated supratherapeutic ingestions. Overdose of acetaminophen saturates typical hepatic metabolism pathways, and expends glutathione, resulting in the production of an intermediate metabolite, N-acetyl-p-benzoquinoneimine via cytochrome oxidase (P450) metabolism. This metabolite binds to hepatocytes and causes centrilobular liver necrosis.

40 What are the three stages of acetaminophen overdose poisoning?

Stage I (1/2–24 hours after ingestion): Often asymptomatic; occasionally nausea, vomiting, diaphoresis, and pallor are seen.

Stage II (24–48 hours after ingestion): Nausea, vomiting, right-upper-quadrant abdominal pain, elevation of hepatic aminotransferase levels.

Stage III (72–96 hours after ingestion): Fulminant hepatic failure with jaundice, thrombocytopenia, prolonged prothrombin time, and hepatic encephalopathy. Renal failure and cardiomyopathy may occur. If the patient survives, complete resolution of liver abnormalities is possible.

41 How is acetaminophen intoxication diagnosed?

The potential for acetaminophen poisoning must be thoughtfully considered since most patients are initially asymptomatic. The serum acetaminophen level should be measured in all patients with intentional drug overdose. Frequently, acetaminophen is overlooked as a coingestant with cough/cold preparations and combination analgesics such as Darvocet (propoxyphene and acetaminophen) and Percocet (oxycodone and acetaminophen). An acetaminophen level at 4–24 hours after ingestion can predict the potential for toxicity and determine the need for antidote administration based on the Rumack-Matthew nomogram.

42 What is the antidote for acetaminophen overdose? How does it work?

N-acetyl cysteine (NAC) replenishes, and substitutes for, depleted glutathione stores in the liver and detoxifies the toxic metabolite. NAC also seems to alleviate existing hepatotoxicity through antioxidant and procirculatory properties.

43 When is NAC given after acute acetaminophen overdose?

All patients with acute overdose whose acetaminophen levels fall within the potential toxicity area on the Rumack-Matthews nomogram merit administration of NAC. This therapy is most effective when initiated within 8 hours of ingestion, though it may provide benefit even if given later.

44 How is NAC administered?

Historically, within the United States, the inhalational form of NAC had been given enterally with a loading dose of 140 mg/kg, followed by 17 doses of 70 mg/kg given every 4 hours. Recently, an IV form of NAC has been approved; it is given as a continuous infusion over 21 hours. The IV route may be preferred in a pregnant patient to ensure adequate NAC delivery to the fetus via the placenta and in patients who present late with acetaminophen toxicity to augment the potential antioxidant effect.

45 Does IV NAC have any particular risks?

The IV administration of NAC may cause a life-threatening anaphylactoid reaction, which most commonly occurs during the first, higher-dose infusion. Patients with asthma may be at highest risk.

46 Can the oral NAC regimen be shortened?

Some poison centers will recommend “short-course” NAC therapy for patients who have received at least 24 hours of the antidote and have no evidence of liver toxicity by enzyme studies. Such a practice, if proven efficacious, may lead to favor of oral NAC over IV NAC in risk-benefit analysis.

Marzullo L: Update of N-acetylcysteine treatment for acute acetaminophen toxicity in children. Curr Opin Pediatr 17:239–245, 2005.

Rowken AK, Norvell J, Eldridge DL, Kirk MA: Updates on acetaminophen toxicity. Med Clin North Am 89:1145–1159, 2005.

47 Detail the pathophysiology of salicylate overdose

Salicylate overdose commonly causes gastritis and vomiting. Salicylates uncouple oxidative phosphorylation from the production of energy in the form of adenosine triphosphate. Metabolic consequences include hyperthermia, metabolic acidosis, increased glucose utilization, fatty acid catabolism, and increased free water loss. Salicylates also directly stimulate the medullary respiratory center, causing hyperpnea with respiratory alkalosis; impede platelet aggregation; and cause direct renal and hepatic impairment. Seizures and coma denote severe toxicity. Noncardiogenic pulmonary edema complicates treatment in severely affected patients.

48 Describe the treatment for acute salicylate poisoning

Activated charcoal may be considered early after overdose. Intravascular volume should be restored. Urinary alkalinization is appropriate for patients with symptoms and a peak salicylate level of > 35 mg/dL (350 mg/L). Mild alkalemia will reduce salicylate access to the brain. Patients with unremitting metabolic acidosis, pulmonary edema, severe renal impairment, coma or seizures, liver impairment, and salicylate level > 70 mg/dL meet criteria to receive hemodialysis.

Dargan P, Wallace CI, Jones AL: An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose. Emerg Med J 19:206–209, 2002.

49 What hazard is associated with endotracheal intubation of salicylate-poisoned patients?

Salicylate-poisoned patients typically have profound respiratory alkalosis. This process is abruptly reversed by paralytic and sedative medications, and resulting acidemia may increase salicylate entry to the brain.

50 How does iron produce toxicity?

Iron acts as a gastrointestinal mucosal irritant and as an inhibitor of oxidative phosphorylation in the mitochondria. The body has no mode of excretion of excess iron.

51 How much iron is toxic?

Expected toxicity can be estimated by the amount of elemental iron ingested (Table 39-2).

Table 39-2 Expected Toxicity of Elemental Iron

Dose Ingested (mg/kg Elemental Iron)	Toxicity
20–60	Mild gastrointestinal symptoms
60–100	Moderate toxicity
100–200	Serious toxicity
>200	Possibly lethal

52 How much elemental iron is present in commonly available preparations?

Product	Elemental Iron
Ferrous sulfate, 325 mg	65 mg (20% of tablet strength)
Ferrous gluconate, 325 mg	40 mg (12% of tablet strength)
Ferrous fumarate, 325 mg	105 mg (32% of tablet strength)
Feosol elixir (sulfate)	44 mg/5 mL
Children’s chewable vitamins	4–18 mg
Infant liquid vitamins	10 mg/mL

53 Has the epidemiology of childhood iron poisoning changed?

For more than a decade, iron poisoning was the leading cause of pediatric overdose death from pharmaceutical products, but this pattern abated with changes in iron formulations and packaging.

Tenenbein M: Unit-dose packaging of iron supplements and reduction of iron poisoning in young children. Arch Pediatr Adolesc Med 159:557–560, 2005.

54 What are the clinical manifestations of iron poisoning?

Gastrointestinal irritation leads to vomiting, diarrhea, abdominal pain, melena, and hematemesis. Coma and shock are the hallmarks of severe poisoning. Multiorgan system failure may ensue. Patients recovering from severe iron poisoning may develop gastric scarring with pyloric obstruction 4–6 weeks later.

55 What laboratory studies are helpful in the management of iron poisoning?

An abdominal radiograph can confirm iron ingestion and give an impression of the amount of unabsorbed iron. However, a negative radiograph does not rule out iron ingestion, particularly more than 2 hours after ingestion since dissolved or absorbed iron is not radio-opaque. A serum iron level 4–6 hours after ingestion confirms and helps categorize iron poisoning:

Serum Iron Level (μg/dL)	Toxicity
<350	Minimal
350–500	Mild
>500	Serious

The presence of metabolic acidosis may be the most telling indicator of cellular dysfunction from iron poisoning.

56 What special decontamination issues arise with iron poisoning?

Activated charcoal does not bind iron. Gastric emptying via large-bore lavage may be warranted after massive ingestion with evidence of retained gastric iron tablets. Gastric concretions of iron tablets frequently occur and sometimes require endoscopy or gastrotomy for removal and to prevent perforation. Whole-bowel irrigation has been recommended for iron poisoning.

Tenenbein M: Whole bowel irrigation in iron poisoning. J Pediatr 111:142–145, 1987.

57 What is the antidote for iron poisoning?

Deferoxamine is an iron chelator. The dose is 5–15 mg/kg/h, up to 6 gm/day intravenously. As use of deferoxamine has been associated with pulmonary fibrosis and the acute respiratory distress syndrome, children given deferoxamine infusion for longer than 24 hours should have the infusion stopped for 6 hours per each 24-hour period.

Yatscoff RW, Wayne EA, Tenenbein M: An objective criterion for the cessation of deferoxamine therapy in the acutely iron poisoned patient. J Toxicol Clin Toxicol 29:1–10, 1991.

58 List the major toxicities of cyclic antidepressants

Sodium-channel blockade in the cardiac conduction system (dysrhythmia)

Seizures

α₁-adrenergic blockade (hypotension)

Inhibition of norepinephrine reuptake

Anticholinergic toxicity

59 What electrocardiographic findings correlate with potential toxicity from cyclic antidepressants?

QRS > 0.1 second

Corrected QT interval prolonged for age

R height > 3 mm in aVR

Boehnert MT, Lovejoy FH: Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. N Engl J Med 313:474–479, 1985.

Liebelt E, Ulrich A, Francis PD, Woolf A: Serial electrocardiogram changes in acute tricyclic antidepressant overdoses. Crit Care Med 25:1721–1726, 1997.

Neimann JT, Bessen HA, Rothstein RJ, Laks MM: Electrocardiographic criteria for tricyclic antidepressant cardiotoxicity. Am J Cardiol 57:1154–1159, 1986.

60 Why is sodium bicarbonate helpful for drug-induced ventricular dysrhythmias associated with a prolonged QRS interval?

Many agents that cause ventricular tachycardia in overdose block fast sodium channels, which are essential to proper myocardial conduction. Sodium bicarbonate competitively inhibits this blockade by increasing available serum sodium. In addition, the modest serum alkalinization appears to promote, in a synergistic fashion, improved conduction that clinically appears as narrowing of the QRS interval and cessation of ventricular tachycardia.

Liebelt E: Targeted management strategies for cardiovascular toxicity from tricyclic antidepressant overdose: The pivotal role for alkalinization and sodium loading. Pediatr Emerg Care 14:293–298, 1998.

61 What are some special considerations for drug-induced bradydysrhythmias?

Bradydysrhythmias commonly follow ingestion of β-blockers, calcium-channel blockers, and digitalis-containing compounds. These rhythm disturbances may not be amenable to standard therapy with atropine, epinephrine, and pacing.

62 Name antidotes that may be useful for specific causes of drug-induced bradydysrhythmias

Overdose	Antidote
β-blocker	Glucagon
Calcium-channel blocker	Calcium, insulin/glucose
Digoxin	Digoxin-specific F_ab fragments (Digibind, Digifab)

Kenny J: Treating overdose with calcium channel blockers. BMJ 308:992–993, 1994.

Weinstein RS: Recognition and management of poisoning with beta-adrenergic blocking agents. Ann Emerg Med 13:1123–1131, 1984.

Woolf AD, Wenger T, Smith TW, et al: The use of digoxin-specific F_ab fragments for severe digitalis intoxication in children. N Engl J Med 326:1739–1744, 1992.

63 What signs and symptoms are expected after isolated benzodiazepine overdose in children?

Benzodiazepines usually do not cause severe symptoms when ingested alone. They typically cause sedation, ataxia, and, in rare cases, respiratory depression. Ataxia without lethargy may occur in up to 30% of children after benzodiazepine ingestion. Apnea, deep coma, or cardiovascular instability suggests co-ingestion of another agent (e.g., ethanol, barbiturates, other sedative-hypnotics). Benzodiazepines have frequently been implicated in child abuse by poisoning. Typically, the situation involves an elderly caretaker sedating a normally active toddler.

Wiley C, Wiley JF: Pediatric benzodiazepine ingestion resulting in hospitalization. J Toxicol Clin Toxicol 36:227–231, 1998.

64 What is flumazenil?

Flumazenil is a specific benzodiazepine receptor antagonist that reverses benzodiazepine-induced central nervous system depression.

65 List problems associated with flumazenil administration after drug overdose

May precipitate benzodiazepine withdrawal

May precipitate seizures and their complications

Has short duration of action compared with duration of benzodiazepine toxicity

Perry HE, Shannon MW: Diagnosis and management of opioid- and benzodiazepine-induced comatose overdose in children. Curr Opin Pediatr 8:243–247, 1996.

66 How are poison-induced seizures treated?

Benzodiazepines and barbiturates are the treatments of choice. Seizures may recur and be difficult to treat. The cardiovascular effects of IV phenytoin may complicate cyclic antidepressant overdose. Pyridoxine is a specific antidote for seizures caused by isoniazid overdose. Drug-induced status epilepticus requires advanced modalities, such as pentobarbital coma or general anesthesia, more frequently than does status epilepticus complicating other types of seizure disorders.

Wills B, Erickson T: Drug- and toxin-associated seizures. Med Clin North Am 89:1297–1321, 2005.

KEY POINTS: PHARMACEUTICALS

1 Dangerous acetaminophen poisoning may be asymptomatic initially but can be predicted with serum levels.

2 Prevention of acidemia, maintenance of intravascular volume, and urinary alkalinization are key goals in the treatment of moderate aspirin poisoning.

3 Prevention strategies are important in reducing the pediatric mortality of iron products.

4 Sodium bicarbonate therapy may be beneficial for toxic cardiac syndromes manifested by wide QRS tachycardia.

DRUGS OF ABUSE

67 How do opiates cause toxicity?

Opiates bind specific opiate receptors in the brain (μ, κ, σ, δ), causing global depression of the central and autonomic nervous systems. Meperidine (Demerol) and propoxyphene with acetaminophen (Darvocet) also have active metabolites that can cause seizures and cardiac dysrhythmias.

68 What is the mnemonic for the opiate toxidrome?

FAME: Flaccid coma, Apnea, Miosis, and Extraocular paralysis.

69 Which opioids may require high doses of naloxone to reverse toxicity?

Doses up to 10 mg of naloxone may be required to completely reverse the following opioids: methadone, LAAM (levo-α-acetyl-methadol), propoxyphene, dextromethorphan, pentazocine, and fentanyl and its derivatives. Also, anyone habituated to opioids that primarily bind μ receptors and are shorter acting (e.g., heroin, morphine) may need only small doses of naloxone to reverse respiratory depression. A dose of 1–2 mg of naloxone may induce opiate withdrawal in these patients.

70 What common pediatric drug toxicity closely mimics opiate intoxication but does not reliably respond to naloxone?

The α₂-adrenergic agonist clonidine acts centrally to reduce sympathetic outflow, and its toxidrome may mimic opiate poisoning. Naloxone reverses coma and respiratory depression in 10–15% or less of severely poisoned patients and cannot be considered a consistent antidote for clonidine poisoning. A trial of naloxone is reasonable in severely poisoned children. Yohimbine has been proposed as a specific α₂ antagonist but is available only in oral form and may cause clonidine withdrawal in patients receiving clonidine therapeutically.

Wiley JF: Clonidine poisoning: Is there any effective therapy? Clin Ped Emerg Med 1:207–212, 2000.

71 Describe the typical findings after clonidine ingestion

As little as 0.1 mg (one tablet) of clonidine has been associated with miosis, coma, apnea, bradycardia, and hypotension. Transient hypertension may also occur. More rare findings include modest hypothermia and pallor.

72 Are there any other distinguishing features between clonidine poisoning and opiate poisoning?

Children with clonidine poisoning often have transient arousal and improvement in respiratory and hemodynamic instability with stimulation. Patients comatose from opiate poisoning are usually not arousable despite painful stimulation.

73 Hallucinations or psychosis may be prominent from which drugs of abuse?

Anticholinergics (antihistamines, Jimson weed)

Dissociatives (phencyclidine, ketamine, dextromethorphan)

Hallucinogens (lysergic acid diethylamide, psilocybin, mescaline)

Sympathomimetics (amphetamines, cocaine, ecstasy)

Withdrawal from ethanol or sedative-hypnotics

74 Why should neuroleptics, such as haloperidol, be used cautiously in the treatment of drug-induced psychoses?

These agents may lower the seizure threshold of the overdose patient, may add to the cardiovascular toxicity of some drugs, and may limit the patient’s ability to dissipate heat.

75 What adverse effects are associated with cocaine intoxication?

Cocaine abusers seek a pleasurable “rush” of euphoria and increased energy. However, intoxicating doses may produce agitation, tachycardia, hypertension, hyperthermia, mydriasis, and tremor. Altered judgment may lead to an increased incidence of accidents and interpersonal violence, and abusers may neglect societal obligations while engaging in high-risk behaviors. Seizures, intracranial hemorrhage, myocardial ischemia, rhabdomyolysis, pneumothorax, psychosis, and death may occur from cocaine abuse.

76 What is the treatment for the tachycardia, hypertension, and hyperpyrexia associated with cocaine overdose?

High doses of benzodiazepines are the most effective and safest pharmacotherapy for cocaine intoxication. Extreme hyperthermia may also warrant aggressive environmental cooling methods. Rhabdomyolysis should be treated with mechanical ventilation, paralysis, and bicarbonate infusion to reduce the chance of renal failure. Sympatholytics should be reserved for the most extreme cases. β-adrenergic antagonist therapy may lead to detrimental unopposed α-adrenergic toxicity. Persistent hypertensive crisis may respond well to nitroprusside infusion or phentolamine.

77 Name seven hyperthermic syndromes in toxicology

1 Sympathomimetic poisoning

2 Anticholinergic poisoning

3 Neuroleptic malignant syndrome

4 Malignant hyperthermia

5 Serotonin syndrome

6 Uncoupling of oxidative phosphorylation

7 Acute withdrawal syndrome

78 Describe the serotonin syndrome

The serotonin syndrome is characterized by autonomic hyperactivity, increased neuromuscular tone (especially prominent in the lower extremities), hyperreflexia, and central nervous system depression after exposure to a drug or drugs with proserotonergic properties.

Boyer EW, Shannon M: The serotonin syndrome. N Engl J Med 352:1112–1120, 2005.

79 Name some of the methods by which inhalants are abused

Sniffing describes direct inhalation of vapors from an open container.

Huffing implies inhaling from a cloth soaked with the volatile substance.

Bagging involves holding a volatile-containing bag over the nose.

80 Describe the most widely proposed mechanism for “sudden sniffing death.”

Inhaled hydrocarbons are believed to potentiate the cardiovascular effects of catecholamines. Ventricular dysrhythmia may occur, especially if an inhalant abuser becomes surprised (perhaps by parents or police) or agitated.

81 What modification to advanced cardiac life support protocol might be beneficial in the treatment of tachydysrhythmia after inhalant abuse?

Theoretical and anecdotal evidence suggests that β-adrenergic antagonists may help reverse these catecholamine-driven cardiac disturbances. Epinephrine may be relatively contraindicated in this scenario.

Albertson TE, Dawson A, de Latorre F, et al: TOX-ACLS: Toxicologic-oriented advanced cardiac life support. Ann Emerg Med 37:S78–S90, 2001.

82 γ hydroxybutyrate and γ butyrolactone are drugs that have received considerable attention recently. What are they?

Both γ hydroxybutyrate (GHB) and γ butyrolactone (GBL) are central nervous system depressants similar to GABA (γ aminobutyrate). They produce mild euphoria in low doses but can produce rapid onset of coma in larger doses. They have been promoted as aids to sleeping or bodybuilding, and more recently have become popular as drugs of abuse. These tasteless, colorless chemicals are easily manufactured at home and have become notorious for alleged use as “date rape drugs.” Treatment is supportive.

KEY POINTS: DRUGS OF ABUSE

1 Naloxone dosing in patients overdosed on heroin requires careful consideration of habituation to avoid precipitation of withdrawal.

2 Overdoses with long-acting or synthetic opioids often require increased doses of naloxone to achieve adequate reversal of respiratory depression.

3 Benzodiazepines are the most appropriate initial treatment for agitation caused by sympathomimetic and hallucinogenic drugs of abuse.

4 Malignant hyperthermia from overdoses of cocaine, amphetamines, or serotonergic drugs requires rapid treatment, including cooling measures, benzodiazepine administration, and mechanical ventilation with paralysis and bicarbonate infusion in the setting of rhabdomyolysis.

5 γ hydroxybutyrate and γ butyrolactone (GBL) are popular club drugs that are easily manufactured at home and are widely promoted on the Internet.

ENVIRONMENTAL POISONS AND VENOMS

84 What is the differential diagnosis for lactic acidosis?

Lactic acidosis may be caused by sepsis, shock, seizures, anoxia, ischemia, or trauma. Toxic causes include poisoning from carbon monoxide, cyanide, sodium azide, hydrogen sulfide, ibuprofen, adrenergic agents, isoniazid, and others.

85 How is the osmolar gap calculated?

Osmolar gap = measured osmolality − calculated osmolarity

Calculated osmolarity = 2 ([sodium] mEq/L) + ([blood urea nitrogen] mg/dL)/2.8 + ([glucose] mg/dL)/18

86 What is a “normal” osmolar gap?

−7 to 10 mOsm

87 List the potential causes of a large osmolar gap

Acetone	Mannitol
Ethanol	Methanol
Glycols	Renal failure
Isopropanol	Severe ketoacidemia
Magnesium	Severe lactic acidemia

88 How do toxic alcohols produce an increased osmolar gap?

Once absorbed into the bloodstream, alcohols are osmotically active. This principle explains why people have to urinate so frequently at Happy Hour. It is also the principle behind administering mannitol to head-injured patients.

89 How can the osmolar gap be used to estimate the levels of toxic alcohols?

This calculation is based upon the molecular weight of the alcohols:

Methanol: molecular weight = 32 mg/mmol; conversion factor = 3.2

Ethanol: molecular weight = 46 mg/mmol; conversion factor = 4.6

Ethylene glycol: molecular weight = 62 mg/mmol; conversion factor = 6.2

Alcohol level (mg/dL) = [osmolar gap] × [conversion factor]

90 How does ethanol intoxication lead to life-threatening hypoglycemia in young children?

Ethanol is metabolized by the enzymes alcohol dehydrogenase and acetaldehyde dehydrogenase. This process involves the production of NADH (nicotinamide-adenine dinucleotide). An increased ratio of NADH to NAD inhibits gluconeogenesis, and may lead to hypoglycemia in patients with insufficient stores of glycogen.

Hoffman RS, Goldfrank LR: Ethanol-associated metabolic disorders. Emerg Med Clin North Am 7:943–961, 1989.

91 How fast does an inebriated 14-year-old metabolize an ethanol level of 150 mg/dL to zero?

Ethanol is metabolized at a constant rate according to zero order kinetics. The typical decrease is 15 mg/dL/h in the noninduced (nonalcoholic) patient. Therefore, the level should be zero in 10 hours.

Gershman H, Steper J: Rate of clearance of ethanol from the blood of intoxicated patients in the emergency department. J Emerg Med 9:307–311, 1991.

92 How do some toxic alcohols lead to metabolic acidosis?

Early after methanol or ethylene glycol ingestion, there will be increased serum osmolality but little acidosis. The body subsequently metabolizes methanol to formic acid, and ethylene glycol to glycolic and oxalic acids. The osmolar gap may drop while the anion gap increases. Isopropyl alcohol is somewhat distinctive as it is metabolized to acetone and typically does not lead to profound acidosis.

93 True or false: Ethylene glycol in the urine fluoresces when examined with a Wood’s lamp

False, but not entirely. The most common source of ethylene glycol exposure is automobile antifreeze. Some manufacturers put fluorescein in the antifreeze solution to allow detection of radiator leaks. Lack of fluorescent urine does not rule out ethylene glycol poisoning.

Casavant MJ, Shah MN, Battels R: Does fluorescent urine indicate antifreeze ingestion by children? Pediatrics 107:113–114, 2001.

94 What is the physiologic basis for the treatment of methanol or ethylene glycol poisoning?

Formic acid is toxic to the retina, and glycolic and oxalic acids are toxic to the kidneys. The treatment goal is to prevent metabolism to these toxic metabolites. Alcohol dehydrogenase is the enzyme responsible for this biotransformation, and inhibition of this enzyme will be protective.

95 What agents can be used to inhibit alcohol dehydrogenase in the setting of methanol or ethylene glycol poisoning?

Fomepizole

Ethanol

Barceloux DG, Krenzelok EP, Olson K, et al: American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning. J Toxicol Clin Toxicol 37:537–560, 1999.

96 Do any vitamins or nutritional supplements have a role in the treatment of methanol or ethylene glycol poisoning?

Folic acid may promote the metabolic degradation of formic acid. Pyridoxine and thiamine may speed transformation of glycolic acids to nontoxic metabolites.

97 When should an ingested button battery be emergently removed?

Disc batteries may contain potentially toxic components, such as mercury or lithium, but are most dangerous as mucosal corrosives. Disc batteries lodged in the nares, ear canal, or esophagus should be removed immediately. Once in the stomach they will almost always pass uneventfully.

98 List some of the dangerous caustic agents frequently found in U.S. households

Many cleaning products, especially phosphate dishwashing detergents, are mildly corrosive. Hair-relaxing products typically have basic pH. Oven cleaners, toilet bowl cleaners, and drain products often contain hydrochloric acid or sodium hydroxide.

99 What characteristics of a caustic agent are most predictive of injury?

Therefore, thick hair-relaxer creams licked by an explorative child rarely lead to severe esophageal injury, but suicidal ingestions of liquid acids can be expected to lead to significant morbidity.

Friedman EM, Lovejoy FH Jr: The emergency management of caustic ingestions. Emerg Med Clin North Am 2:77–86, 1984.

101 Which patients should be examined endoscopically after caustic ingestion?

Ingestion involving a concentrated, strong acid or base

Suicidal ingestions

Large-volume ingestions

Patients with vomiting, or two or more signs or symptoms of injury

Note: The absence of oral burns is not a sensitive sign for excluding esophageal injury.

103 When should steroids be used to palliate caustic esophageal burns?

Esophageal burns should be graded at endoscopy. First-degree burns do not lead to stricture formation, so steroids are not warranted. Third-degree burns will probably lead to stricture regardless of treatment, and the benefit is not likely worth the risk. Controversy surrounds the value of using steroids together with antibiotics to treat circumferential second-degree burns of the esophagus. Many clinicians believe that corticosteroids may modestly reduce stricture formation in this situation. Note that a less controversial indication for steroid therapy is the palliation of glottic edema and airway obstruction.

104 What are the indications for surgical exploration after caustic ingestion?

Evidence of perforation

Abdominal tenderness after acid ingestion

Inability to evaluate injuries endoscopically

Significant central nervous system depression

Progressive metabolic acidosis

Hypotension with tachycardia

105 What is the major long-term concern for patients recovered from caustic burns of the esophagus?

These patients are at a 1000-fold increased risk for esophageal carcinoma. The mean latency period is over 40 years.

Appelqvist SM: Lye corrosion carcinoma of the esophagus: A review of 63 cases. Cancer 45:2655–2658, 1980.

106 Which characteristics of certain hydrocarbon products make them prone to aspiration?

Low viscosity

Low surface tension

High volatility

107 Describe the time course of aspiration injury after hydrocarbon ingestion

Children may cough, gag, or sputter at the time of ingestion. A gradual evolution of radiographic findings occurs, but most children who will develop pneumonitis will have visible abnormality by 6 hours. More than 98% of children who will develop clinical pneumonitis will do so by 24 hours.

108 Do any hydrocarbons have serious systemic toxicity?

Central nervous system depression, seizures, hepatotoxicity, nephrotoxicity, and bone marrow toxicity are among the injuries that can occur after specific hydrocarbon ingestions. The hydrocarbons most noted for systemic toxicity can be remembered with this CHAMPion of mnemonics:

C= Camphor

H= Halogenated hydrocarbons (e.g., carbon tetrachloride, trichloroethane)

A= Aromatic hydrocarbons (e.g., Benzene, toluene)

M = Metal-containing hydrocarbons

P= Pesticide-containing hydrocarbons

111 What antidotes are used to treat organophosphate poisoning?

Atropine may be needed in large doses to reverse muscarinic toxicity. Pralidoxime regenerates active acetylcholinesterase, the enzymatic site of action of organophosphate insecticides.

112 What is the appropriate response to an exploratory anticoagulant rodenticide ingestion by a toddler?

Suicidal ingestions of anticoagulant rodenticides have led to catastrophic consequences. Single exploratory ingestions by curious children have not been reported to produce dangerous bleeding diatheses. Some poison centers recommend decontamination with activated charcoal at the time of the event, and evaluation of a prothrombin time 2 to 3 days afterward. Other poison centers recommend no treatment other than expectant observation at home.

113 How should coagulopathy from the warfarin-like rodenticides be treated?

These rodenticides inhibit hepatic production of the vitamin K–dependent coagulation factors II, VII, IX, and X. Acute bleeding can be palliated with transfusion of fresh-frozen plasma. Administration of vitamin K₁ will restore production of clotting factors with a lag time of approximately 6 hours. Prophylactic use of vitamin K₁ often complicates evaluation of the anticoagulant-poisoned patient. As the “superwarfarins” have a very long duration of effect, any patient treated with vitamin K₁ warrants monitoring for at least 5 days after the last dose.

114 Describe the typical symptoms of carbon monoxide poisoning

Typical symptoms are nonspecific and include malaise, nausea, lightheadedness, and headache, leading many children to be misdiagnosed with a viral illness. More severe poisoning may manifest as confusion, coma, syncope, seizure, or death. Survivors of acute intoxication are at risk of delayed neurologic sequelae, including cognitive deficits, personality changes, and movement disorders.

115 Which member of the family is most likely to suffer the most from equivalent carbon monoxide (CO) exposure?

Infants and small children have higher oxygen consumption and a higher basal metabolic rate than adults. Therefore, they may be most susceptible to the effects of CO. This is the basic concept behind the “canary in a coal mine.”

116 Describe the pathophysiology of toxicity from CO exposure

1 CO displaces oxygen from the hemoglobin molecule, leading to decreased oxygen-carrying capacity. CO has an affinity for hemoglobin approximately 250 times that for O₂.

2 Allosteric inhibition of oxygen release to tissues occurs (displacement of the oxyhemoglobin dissociation curve to the left).

3 Cellular oxidative metabolism is reduced through inhibition of cytochrome oxidase enzyme systems.

4 Oxidative injury to the brain endothelium begins a cascade of leukocyte activation, lipid peroxidation, and impaired cerebral metabolism.

Martin JD, Osterhoudt KC, Thom SR: Recognition and management of carbon monoxide intoxication in children. Clin Pediatr Emerg Med 1:244–250, 2000.

117 How long does it take the body to eliminate carboxyhemoglobin?

Carboxyhemoglobin elimination depends on inspired oxygen concentration.

Room air: 4–6 hours

100% O₂: 40–90 minutes

Hyperbaric O₂ (3 atm): 15–30 minutes

118 When is hyperbaric oxygen therapy indicated for CO intoxication?

Oxygen, in the highest concentration possible, should be administered to all symptomatic patients until CO levels are below 5% and symptoms subside. Hyperbaric oxygen therapy may prevent oxidative cerebral vasculitis, and prevent delayed neurologic injury. Proposed criteria for considering hyperbaric oxygen include syncope, confusion, central nervous system depression, or very high carboxyhemoglobin levels.

Weaver LK, Hopkins RO, Chan KJ: Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 347:1057–1067, 2002.

119 Describe the characteristic brain abnormalities after significant CO poisoning on magnetic resonance imaging of the brain

Approximately half of patients with neurologic dysfunction will have bilateral lucencies in the basal ganglia. They are most prominent in the globus pallidus, an area of high metabolic demand. Less frequently, subcortical white matter lesions may also be noted.

120 Cyanosis, unreponsive to supplemental oxygen therapy and in the face of a normal partial pressure of oxygen in arterial blood, is characteristic of what physiologic abnormality?

Poor response to oxygen makes a pulmonary disorder unlikely. Normal partial pressure of oxygen rules out intracardiac shunting. This is the characteristic clinical scenario of an abnormal hemoglobin, most commonly methemoglobinemia.

121 What is methemoglobin?

Hemoglobin is a heme (iron-containing) protein. Methemoglobin exists when the iron moiety is ferric (3⁺) rather than ferrous (2⁺). Methemoglobin is incapable of transporting oxygen.

123 Describe the transient, illness-associated methemoglobinemia of infancy

Young infants have been found to be cyanotic with methemoglobinemia in conjunction with a number of illnesses, including diarrheal dehydration, metabolic acidosis, urinary tract infection, and others. Babies are uniquely susceptible to oxidant stress, and this condition should be considered in the evaluation of septic-appearing infants.

124 What are some of the more common toxicants associated with the production of excessive methemoglobin?

Many chemicals and pharmaceuticals can produce methemoglobinemia in susceptible people. Among the most commonly noted exposures are benzocaine, dapsone, environmental (i.e., well water) nitrates, nitrites (i.e., amyl nitrite), and phenazopyridine.

125 What is the appropriate therapy for methemoglobinemia?

Provide supplemental oxygen. Eliminate or treat the oxidative stress responsible for methemoglobin formation. Antidotal therapy with methylene blue (1–2 mg/kg of a 1% solution) is indicated in the presence of tissue hypoxia. Methylene blue is unlikely to be effective, and may worsen illness, when administered to patients with severe forms of glucose-6-phosphate dehydrogenase deficiency.

Wright RO, Lewander WJ, Woolf AD: Methemoglobinemia: Etiology, pharmacology, and clinical management. Ann Emerg Med 34:646–656, 1999.

126 What are the clinical classifications syndromes for toxic mushrooms syndromes, typical clinical findings, and poisoning treatment syndromes?

See Table 39-3.

Table 39-3 Description of Toxic Mushroom Syndromes

127 What are the most common toxic plant poisonings?

Of the 20 most common plant exposures, the most commonly encountered toxic plants are:

The Arum family (Dieffenbachia, Philodendron), which may cause severe pharyngeal edema and possible airway obstruction through the elaboration of calcium oxalate crystals and proteolytic enzymes and direct mucosal irritation

The Taxus species (yew), which cause gastrointestinal irritation, cardiac dysrhythmias, coma, and seizures if large amounts of leaves or seeds are ingested

Solanum family (Jerusalem cherry, black nightshade, climbing nightshade), which cause gastrointestinal effects, lethargy, or delirium

Rhododendron and Azalea spp., which cause gastrointestinal effects, bradycardia, lethargy, and paresthesias through elaboration of grayanotoxins

128 What other plants have potential for severe toxicity? Describe the treatment

See Table 39-4.

Table 39-4 Categories of Toxic Plants

Symptom Class	Plants	Potential Treatment
GI irritants	Pokeweed Horse chestnut English ivy	Supportive care
Toxalbumin	Castor bean Rosary pea Autumn crocus (colchicine-containing)	Multisystem organ failure Supportive care
Digitalis-like toxin	Foxglove Oleander Lily of the valley	Digoxin F_ab fragments
Other cardiac effects	Mistletoe Monkshood False hellebore Mountain laurel	Supportive care, standard treatment for dysrhythmias
Nicotinic effects	Wild tobacco Tobacco Poison hemlock	Atropine, supportive care for weakness, paralysis
Anticholinergic effects	Jimsonweed Angel’s trumpet Matrimony vine Henbane Belladonna	Physostigmine for seizures, malignant hyperthermia Benzodiazepines for delirium
Seizures	Water hemlock	Anticonvulsants
Hallucinations	Morning glory Nutmeg Peyote	Sedation
Cyanogenic	Chokecherry Cherry (pit) Plum (pit) Peach (pit) Apple (seeds) Pear (seeds) Cassava Elderberry (leaves and shoots) Black locust	Cyanide antidote (rarely needed)