Harrisons Manual of Medicine, 18th Ed.

CHAPTER 32. Poisoning and Drug Overdose

Poisoning refers to the development of dose-related harmful effects following exposure to chemicals, drugs, or other xenobiotics. Overdosage is exposure to excessive amounts of a substance normally intended for consumption (a pharmaceutical) or an illicit drug. Chemical exposures result in an estimated 5 million requests in the United States for medical advice or treatment each year, and about 5% of victims require hospitalization. Overall mortality is low (<1% of exposures); suicide attempts account for most serious or fatal poisonings (1–2% mortality). Up to 30% of psychiatric admissions are prompted by attempted suicide via overdosage.

Carbon monoxide is the leading cause of death from poisoning. Acetaminophen toxicity is the most common pharmaceutical agent causing fatalities. Other drug-related fatalities are commonly due to analgesics, antidepressants, sedative-hypnotics, neuroleptics, stimulants and street drugs, cardiovascular drugs, anticonvulsants, antihistamines, and asthma therapies. Nonpharmaceutical agents implicated in fatal poisoning include alcohols and glycols, gases and fumes, cleaning substances, pesticides, and automotive products. The diagnosis of poisoning or drug overdose must be considered in any pt who presents with coma, seizure, or acute renal, hepatic, or bone marrow failure.

DIAGNOSIS

The correct diagnosis can usually be reached by history, physical exam, and routine and toxicologic laboratory evaluation. All available sources should be used to determine the exact nature of the ingestion or exposure. The historyshould include the time, route, duration, and circumstances (location, surrounding events, and intent) of exposure; name of chemical(s) involved, time of onset, nature, and severity of symptoms; relevant past medical and psychiatric history. The Physicians Desk Reference, regional poison control centers, and local/hospital pharmacies may be useful for identification of ingredients and potential effects of toxins.

The diagnosis of poisoning in cases of unknown etiology primarily relies on pattern recognition. The first step is a physical exam with initial focus on the pulse, blood pressure, respiratory rate, temperature, and neurologic status and then characterization of the overall physiologic state as stimulated, depressed, discordant, or normal (Table 32-1).

TABLE 32-1 DIFFERENTIAL DIAGNOSIS OF POISONING BASED ON PHYSIOLOGIC STATE

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Examination of the eyes (for nystagmus, pupil size, and reactivity), neuromuscular status (for tremors, dyskinesia, rigidity, dystonia), abdomen (for bowel activity and bladder size), and skin (for burns, bullae, color, warmth, moisture, pressure sores, and puncture marks) may narrow the diagnosis to a particular disorder. The pt should also be examined for evidence of trauma and underlying illnesses. When the history is unclear, all orifices should be examined for the presence of chemical burns and drug packets. The odor of breath or vomitus and the color of nails, skin, or urine may provide diagnostic clues.

Initial laboratory studies should include glucose, serum electrolytes, serum osmolality, BUN/creatinine, LFTs, PT/PTT, and ABGs. An increased anion-gap metabolic acidosis is characteristic of advanced methanol, ethylene glycol, and salicylate intoxication, but can occur with other agents and in any poisoning that results in hepatic, renal, or respiratory failure; seizures; or shock. An increased osmolal gap—the difference between the measured serum osmolality (determined by freezing point depression) and that calculated from the serum sodium, glucose, and BUN of >10 mmol/L—suggests the presence of a low-molecular-weight solute such as an alcohol, glycol, ketone, unmeasured electrolyte, or sugar. Ketosis suggests acetone, isopropyl alcohol, or salicylate poisoning. Hypoglycemia may be due to poisoning with β-adrenergic blockers, ethanol, insulin, oral hypoglycemic agents, quinine, and salicylates, whereas hyperglycemia can occur in poisoning with acetone, β-adrenergic agonists, calcium channel blockers, iron, theophylline, or the rodenticide Vacor.

Radiologic studies should include a chest x-ray to exclude aspiration or ARDS. Radiopaque densities may be visible on abdominal x-rays. Head CT or MRI is indicated in stuporous or comatose pts to exclude structural lesions or subarachnoid hemorrhage, and LP should be performed when CNS infection is suspected. The ECG can be helpful in pointing to a poisoning agent: Bradycardia and A–V block may occur with poisoning by α-adrenergic agonists, antiarrhythmic agents, beta blockers, calcium channel blockers, cholinergic agents (carbamate and organophosphate insecticides), cardiac glycosides, lithium, or tricyclic antidepressants. QRS- and QT-interval prolongation may be seen with antidepressant and other membrane-active drug exposure. Ventricular tachyarrhythmias may be observed with exposure to cardiac glycosides, fluoride, methylxanthines, sympathomimetics, antidepressants, and agents that cause hyperkalemia or potentiate the effects of endogenous catecholamines (e.g., chloral hydrate, aliphatic and halogenated hydrocarbons). Toxicologic analysis of urine and blood (and occasionally of gastric contents and chemical samples) may be useful to confirm or rule out suspected poisoning. Although rapid screening tests for a limited number of drugs of abuse are available, comprehensive screening tests require 2–6 h for completion, and immediate management must be based on the history, circumstantial evidence, physical exam, and routine ancillary tests. Quantitative analysis is useful for poisoning with acetaminophen, acetone, alcohols (including ethylene glycol), antiarrhythmics, anticonvulsants, barbiturates, digoxin, heavy metals, lithium, salicylate, and theophylline, as well as for carboxyhemoglobin and methemoglobin. Results can often be available within an hour.

The response to antidotes may be useful for diagnostic purposes. Resolution of altered mental status and abnormal vital signs within minutes of IV administration of dextrose, naloxone, or flumazenil is virtually diagnostic of hypoglycemia, narcotic poisoning, and benzodiazepine intoxication, respectively. The prompt reversal of acute dystonic (extrapyramidal) symptoms following an IV dose of benztropine or diphenhydramine confirms a drug etiology. Although physostigmine reversal of both central and peripheral manifestations of anticholinergic poisoning is diagnostic, it may cause arousal in pts with CNS depression of any etiology.

TREATMENT Poisoning and Drug Overdose

Goals of therapy include support of vital signs, prevention of further absorption, enhancement of elimination, administration of specific antidotes, and prevention of reexposure. Fundamentals of poisoning management are listed in Table 32-2. When the type of poison is unknown or uncertain, blood and urine specimens for toxicologic studies should be obtained if possible before treatment is started. Treatment is usually initiated before routine and toxicologic data are known. All symptomatic pts need large-bore IV access, supplemental O2, cardiac monitoring, continuous observation, and, if mental status is altered, 100 mg thiamine (IM or IV), 1 ampule of 50% dextrose in water, and 4 mg of naloxone along with specific antidotes as indicated. Unconscious pts should be intubated. Activated charcoal may be given PO or via a large-bore gastric tube; gastric lavage requires an oro-gastric tube. Severity of poisoning determines the management. Admission to an ICU is indicated for pts with severe poisoning (coma, respiratory depression, hypotension, cardiac conduction abnormalities, arrhythmias, hypothermia or hyperthermia, seizures); those needing close monitoring, antidotes, or enhanced elimination therapy; and those with progressive clinical deterioration or significant underlying medical problems. Suicidal pts require constant observation by qualified personnel.

TABLE 32-2 FUNDAMENTALS OF POISONING MANAGEMENT

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SUPPORTIVE CARE Airway protection is mandatory. Gag reflex alone is not a reliable indicator of the need for intubation. Intubation is required in all pts with CNS depression or seizures to prevent aspiration of gastric contents. Need for O2 supplementation and ventilatory support can be assessed by measurement of ABGs. Drug-induced pulmonary edema is usually secondary to hypoxia, but myocardial depression may contribute. Measurement of pulmonary artery pressure may be necessary to establish etiology. Electrolyte imbalances should be corrected as soon as possible.

Adequate cardiovascular function and organ perfusion is necessary for elimination of toxin and pt recovery. If hypotension is unresponsive to volume expansion, pressors such as norepinephrine, epinephrine or dopamine may be required. In severe cases, intra-aortic balloon pump or other mechanical perfusion assists may be considered. Supraventricular tachycardia (SVT) with hypertension and CNS excitation is almost always due to sympathetic, anticholinergic, or hallucinogenic stimulation or to drug withdrawal. Treatment is indicated if associated with hemo-dynamic instability, chest pain, or ischemia on ECG. Treatment with combined α and β blockers or combinations of β blocker and vasodilator is indicated in severe sympathetic hyperactivity. Physostigmine is useful for hyperactivity due to an anticholinergic overdose. SVT without hypertension usually responds to fluid administration.

Ventricular tachycardia (VT) can be caused by sympathetic stimulation, myocardial membrane destabilization, or metabolic derangements. Lidocaine and phenytoin are generally safe. Sodium bicarbonate should be the agent given first for VT of toxicologic origin. Drugs that prolong the QT interval (quinidine, procainamide) should not be used in VT due to tricyclic antidepressant overdose. Magnesium sulfate and overdrive pacing (by isoproterenol or a pacemaker) may be useful for torsades de pointes. Arrhythmias may be resistant to therapy until underlying acid-base and electrolyte derangements, hypoxia, and hypothermia are corrected. It is acceptable to observe hemodynamically stable pts without pharmacologic intervention.

Seizures are best treated with γ-aminobutyric acid agonists such as benzodiazepines or barbiturates. Barbiturates should be given only after intubation. Seizures caused by isoniazid overdose may respond only to large doses of pyridoxine IV. Seizures from beta blockers or tricyclic antidepressants may require phenytoin and benzodiazepines.

PREVENTION OF POISON ABSORPTION Whether to perform GI decontamination, and which procedure to use, depends on the time since ingestion; the existing and predicted toxicity of the ingestant; the availability, efficacy, and contraindications of the procedure; and the nature, severity, and risk of complications. The efficacy of activated charcoal and gastric lavage decreases with time, and there are insufficient data to support or exclude a beneficial effect when they are used >1 h after ingestion. Activated charcoal has comparable or greater efficacy, fewer contraindications and complications, and is less invasive than gastric lavage and is the preferred method of GI decontamination in most situations.

Activated charcoal is prepared as a suspension in water, either alone or with a cathartic. It is given orally via a nippled bottle (for infants), or via a cup, straw, or small-bore nasogastric tube. The recommended dose is 1 g/kg body weight, using 8 mL of diluent per gram of charcoal if a premixed formulation is not available. Charcoal may inhibit absorption of other orally administered agents and is contraindicated in pts with corrosive ingestion.

When indicated, gastric lavage is performed using a 28F orogastric tube in children and a 40F orogastric tube in adults. Saline or tap water may be used in adults or children. (Use saline in infants.) Place pt in Trendelenburg and left lateral decubitus position to minimize aspiration (occurs in 10% of pts). Repeated administration of fluid (5 mL/kg) followed by aspiration results in progressive removal of gastric content. Lavage is contraindicated in pts resisting the procedure, and with ingested corrosives and petroleum distillate hydrocarbons because of risk of aspiration-induced pneumonia and gastroesophageal perforation.

Syrup of ipecac, once the most commonly used decontamination procedure, has no role in the hospital setting and is no longer recommended for the management of poisoning.

Whole-bowel irrigation may be useful with ingestions of foreign bodies, drug packets, slow-release medications, and heavy metals. Electrolyte/polyethylene glycol solution (e.g., Golytely, Colyte) is given orally or by gastric tube up to a rate of 2 L/h. Cathartic salts (magnesium citrate) and saccharides (sorbitol, mannitol) promote evacuation of the rectum but have not been shown to of benefit in poison decontamination. Dilution of corrosive acids and alkali is accomplished by having the pt drink 5 mL water per kg body weight. Endoscopy or surgical intervention may be required in large foreign-body ingestion, concretions of ingested material (heavy metals, lithium, salicylate, or sustained-release tablets), and when ingested drug packets leak or rupture.

Skin and eyes are decontaminated by washing with copious amounts of water or saline.

ENHANCEMENT OF ELIMINATION Activated charcoal in repeated doses of 1 g/kg q2–4h is useful for ingestions of drugs with enteral circulation such as carbamazepine, dapsone, diazepam, digoxin, glutethimide, meprobamate, methotrexate, phenobarbital, phenytoin, salicylate, theophylline, and valproic acid.

Forced urinary alkalinization enhances the elimination of chlorophenoxyacetic acid herbicides, chlorpropamide, diflunisal, fluoride, methotrexate, phenobarbital, sulfonamides, and salicylates through ionization and inhibition of tubular reabsorption. Sodium bicarbonate, 1–2 ampules per liter of 0.45% NaCl, is given at a rate sufficient to maintain urine pH ≥7.5 and urine output at 3–6 mL/kg per h. Acid diuresis is no longer recommended.

Hemodialysis may be useful in severe poisoning due to barbiturates, bromide, chloral hydrate, ethanol, ethylene glycol, isopropyl alcohol, lithium, heavy metals, methanol, procainamide, and salicylate. Peritoneal dialysis is less effective. Hemoperfusion may be indicated for chloramphenicol, disopyramide, and hypnotic-sedative overdose, but is no longer widely available. Exchange transfusion removes poisons affecting red blood cells (arsine, sodium chlorate causing hemolysis, methemoglobinemia, sulfhemoglobinemia).

The features of specific toxic syndromes and approaches to treatment are summarized in Table 32-3. The features of selected heavy metal toxicity and approaches to treatment are summarized in Table 32-4. Readers are encouraged to contact poison control centers for additional information (www.aapcc.org/DNN/).

TABLE 32-3 PATHOPHYSIOLOGIC FEATURES AND TREATMENT OF SPECIFIC TOXIC SYNDROMES AND POISONINGS

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TABLE 32-4 HEAVY METALS

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For a more detailed discussion, see Hu H: Heavy Metal Poisoning, Chap. e49 and Mycyk MB: Poisoning and Drug Overdosage, Chap. e50; in HPIM-18.