39 POISONING AND DRUG OVERDOSE
Harrison’s Manual of Medicine
POISONING AND DRUG OVERDOSE
Poisoning refers to the development of harmful effects following exposure to chemicals. Overdosage is exposure to excessive amounts of a substance normally intended for consumption and does not necessarily imply poisoning. Chemical exposures result in an estimated 5 million requests in the U.S. for medical advice or treatment each year, and about 5% of victims of chemical exposure require hospitalization. Suicide attempts account for most serious or fatal poisonings. Up to 30% of psychiatric admissions are prompted by attempted suicide via overdosage.
Carbon monoxide (CO) poisoning is the leading cause of death. Drug-related fatalities are most 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, chemicals, 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.
The correct diagnosis can usually be reached by history, physical exam, and laboratory evaluation. Initial assessment of vital signs, cardiopulmonary status, and neurologic function determines the need for immediate supportive treatment. All available sources should be used to determine the exact nature of the ingestion or exposure. The Physicians Desk Reference, regional poison control centers, and local/hospital pharmacies may be useful for identification of ingredients and potential effects of toxins.
Examination of the eyes (for nystagmus, pupil size and reactivity), 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 blood tests should include glucose, serum electrolytes, serum osmolality, BUN/Cr, 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 serum osmolality (measured 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, or ketone or an unmeasured electrolyte or sugar. Ketosis suggests acetone, isopropyl alcohol, or salicylate poisoning. Hypoglycemia may be due to poisoning with b-adrenergic blockers, ethanol, insulin, oral hypoglycemic agents, quinine, and salicylates, whereas hyperglycemia can occur in poisoning with acetone, b-adrenergic agonists, calcium channel-blockers, iron, theophylline, or 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 useful to assist with the differential diagnosis and to guide treatment. 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 to 6 h for completion, and immediate management must be based on the history, physical exam, and routine ancillary tests. Quantitative analysis is useful for poisoning with acetaminophen, acetone, alcohol (including ethylene glycol), antiarrhythmics, anticonvulsants, barbiturates, digoxin, heavy metals, lithium, paraquat, 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 intravenous administration of dextrose, naloxone, or flumazenil is virtually diagnostic of hypoglycemia, narcotic poisoning, and benzodiazepine intoxication, respectively. The prompt reversal of acute dystonic (extrapyramidal) reactions following an intravenous 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 patients with CNS depression of any etiology.
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 39-1. 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 orogastric tube. Severity of poisoning determines the management. Suicidal pts require constant observation by qualified personnel.
Table 39-1 Fundamentals of Poisoning Management
Supportive Care Airway protection is mandatory. Gag reflex alone is not a reliable indicator of the need for intubation. 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.
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 hemodynamic instability, chest pain, or ischemia on ECG. Treatment with combined alpha and beta blockers or combinations of beta blocker and vasodilator is indicated in severe sympathetic hyperactivity. Physostigmine is useful for anticholinergic hyperactivity. 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. 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 g-aminobutyric acid agonists such as benzodiazepines or barbiturates. Barbiturates should only be given 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 or not 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, gastric lavage, and syrup of ipecac 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 ipecac or 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). Lavage is contraindicated with corrosives and petroleum distillate hydrocarbons because of risk of aspiration-induced pneumonia and gastroesophageal perforation.
Whole-bowel irrigation may be useful with ingestions of foreign-bodies, drug packets, and slow-release medications. Golytely is given orally or by gastric tube up to a rate of 0.5 L/h. Cathartic salts (magnesium citrate) and saccharides (sorbitol, mannitol) promote evacuation of the rectum. Dilution of corrosive acids and alkali is accomplished by having pt drink 5 mL water/ kg. Endoscopy or surgical intervention may be required in large foreign-body ingestion, heavy metal ingestion, and when ingested drug packets leak or rupture.
Syrup of ipecac is administered orally in doses of 30 mL for adults, 15 mL for children, and 10 mL for infants. Vomiting should occur within 20 min. Ipecac is contraindicated with marginal airway patency, CNS depression, recent GI surgery, seizures, corrosive (lye) ingestion, petroleum hydrocarbon ingestion, and rapidly acting CNS poisons (camphor, cyanide, tricyclic antidepressants, propoxyphene, strychnine). Ipecac is particularly useful in the field.
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 alkaline diuresis enhances the elimination of chlorphenoxyacetic acid herbicides, chlorpropamide, diflunisal, fluoride, methotrexate, phenobarbital, sulfonamides, and salicylates. Sodium bicarbonate, 1–2 ampules per liter of 0.45% NaCl, is given at a rate sufficient to maintain urine pH ³ 7.5 and urine output at 3–6 mL/kg per h. Acid diuresis is no longer recommended. Saline diuresis may enhance elimination of bromide, calcium, fluoride, lithium, meprobamate, potassium, and isoniazid; contraindications include CHF, renal failure, and cerebral edema.
Peritoneal dialysis or 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. Hemoperfusion may be indicated for chloramphenicol, disopyramide, and hypnotic sedative overdose. Exchange transfusion removes poisons affecting red blood cells.
ACETAMINOPHEN A dose of ³140 mg/kg of acetaminophen saturates metabolism to sulfate and glucuronide metabolites, resulting in increased metabolism of acetaminophen to mercapturic acid. Nonspecific toxic manifestations (and not predictive of hepatic toxicity) include nausea, vomiting, diaphoresis, and pallor 2–4 h after ingestion. Laboratory evidence of hepatotoxicity includes elevation of AST, ALT, and, in severe cases, PT and bilirubin, with ultimate hyperammonemia. A serum acetaminophen level drawn 4–24 h after ingestion is useful for purposes of predicting risk.
Initial therapy consists of activated charcoal, then N-acetylcysteine therapy, which is indicated up to 24 h after ingestion. Loading dose is 140 mg/kg PO, followed by 70 mg/kg PO q4h for 17 doses. Therapy should be started immediately and may be discontinued when serum level is below toxic range.
ALKALI AND ACID Alkalis include industrial-strength bleach, drain cleaners (sodium hydroxide), surface cleaners (ammonia, phosphates), laundry and dishwashing detergents (phosphates, carbonates), disk batteries, denture cleaners (borates, phosphates, carbonates) and Clinitest tablets (sodium hydroxide). Common acids include toilet bowl cleaners (hydrofluoric, phosphoric, and sulfuric acids), soldering fluxes (hydrochloric acid), antirust compounds (hydrofluoric and oxalic acids), automobile battery fluid (sulfuric acid), and stone cleaners (hydrofluoric and nitric acids). Clinical signs include burns, pain, drooling, vomiting of blood or mucus, and ulceration. Lack of oral manifestations does not rule out esophageal involvement. The esophagus and stomach can perforate, and aspiration can cause fulminant tracheitis.
Endoscopy is safe within 48 h of ingestion to document site and severity of injury.
Immediate treatment consists of dilution with milk or water. Glucocorticoids should be given within 48 h to pts with alkali (not acid) burns of the esophagus and continued for at least 2 weeks. Antacids may be useful for stomach burns. Prophylactic broad-spectrum antibiotics are recommended.
ANTIARRHYTHMIC DRUGS Acute ingestion of >2× the usual daily dose is potentially toxic and causes symptoms within 1 h. Manifestations include nausea, vomiting, diarrhea, lethargy, confusion, ataxia, bradycardia, hypotension, and cardiovascular collapse. Anticholinergic effects are seen with disopyramide ingestion. Quinidine and class IB agents (lidocaine, mexiletine, phenytoin, tocainide) can cause agitation, dysphoria, and seizures. Ventricular fibrillation (including torsades de pointes) and QT prolongation are characteristic of class IA (disopyramide, procainamide, quinidine) and IC (encainide, moricizine, propafenone, flecainide) poisonings. Myocardial depression may precipitate pulmonary edema.
Activated charcoal is the treatment of choice for GI decontamination. Persistent hypotension and bradycardia may require monitoring of pulmonary artery pressure, cardiac pacing, intraaortic balloon pump counterpulsation, and cardiopulmonary bypass. Ventricular tachyarrhythmias are treated with lidocaine and bretylium. Sodium bicarbonate or lactate may be useful in class IA or IC overdoses. Torsades de pointes is treated with magnesium sulfate (4 g or 40 mL of 10% solution IV over 10–20 min) or overdrive pacing (with isoproterenol or pacemaker).
ANTICHOLINERGIC AGENTS Antimuscarinic agents inhibit acetylcholine in the CNS and parasympathetic postganglionic muscarinic neuroreceptors and include antihistamines (H1-receptor blockers and over-the-counter hypnotics), belladonna alkaloids (atropine, glycopyrrolate, homatropine, yoscine, ipatropium, scopolamine), Parkinsonian drugs (benztropine, biperiden, trihexyphenidyl), mydriatics (cyclopentolate, tropicamide), phenothizaines, skeletal muscle relaxants (cyclobenzaprine, orphenadrine), smooth muscle relaxants (clinidinium, dicyclomine, isometheptene, oxybutynin), tricyclic antidepressants, and a variety of plants (stramonium, jimsonweed) and mushrooms. Manifestations begin 1 h to 3 d after ingestion; agitation, ataxia, confusion, delirium, hallucinations, and choreoathetosis can lead to lethargy, respiratory depression, and coma.
Treatment involves GI decontamination with activated charcoal, supportive measures, and in severe cases the acetylcholinesterase inhibitor physostigmine; 1 to 2 mg is given IV over 2 min, and the dose may be repeated for incomplete response or recurrent toxicity. Physostigmine is contraindicated in the presence of cardiac conduction defects or ventricular arrhythmias.
ANTICONVULSANTS These drugs include carbamazepine, lamotrigine, phenytoin and other hydantoins, topiramate, valproate, barbiturates, ethosuximide, methsuximide, felbamate, gabapentin, and benzodiazepines (see below). Anticonvulsants are well absorbed after oral administration and primarily cause CNS depression. Cerebellar and vestibular function are affected first, with cerebral depression occurring later. Ataxia, blurred vision, diplopia, dizziness, nystagmus, slurred speech, tremors, and nausea and vomiting are common initial manifestations. Coma with respiratory depression usually occurs at serum carbamazepine concentrations >20 µg/mL, serum phenytoin levels >60 µg/mL, and serum valproate levels of >180 µg/mL. Anticholinergic effects (see above) may be present in carbamazepine poisoning and tricyclic antidepressant-like cardiotoxicity (see below) can occur at drug levels >30 µg/mL. Hypotension and arrhythmias (e.g., bradycardia, conduction disturbances, ventricular tachyarrhythmias) can occur during the rapid infusion of phenytoin. Cardiovascular toxicity after oral phenytoin overdose, however, is essentially nonexistent. Extravasation of phenytoin can result in local tissue necrosis due to the high pH of this formulation. Intravenous phenytoin may also cause the “purple glove syndrome” (limb edema, discoloration, and pain). Multiple metabolic abnormalites, including anion-gap metabolic acidosis, hyperosmolality, hypocalcemia, hypoglycemia, hypophosphatemia, hypernatremia, and hyperammonemia (with or without other evidence of hepatotoxicity) can occur in valproate poisoning. Three or more days may be required for resolution of toxicity in severe carbamazepine, phenytoin, and valproate poisoning.
The diagnosis of carbamazepine, phenytoin, and valproate poisoning can be confirmed by measuring serum drug concentrations. Serial drug levels should be obtained until a peak is observed following acute overdose. Quantitative serum levels of other agents are not generally available. Most anticonvulsants can be detected by comprehensive urine screening tests.
Activated charcoal is the method of choice for GI decontamination. Multiple-dose charcoal therapy can enhance the elimination of carbamezpine, phenytoin, valproate, and perhaps other agents. Airway protection and support of respirations with endotracheal intubation and mechanical ventilation, if necessary, are the mainstays of treatment. Seizures should be treated with benzodiazepines or barbiturates. Physostigmine (see anticholinergic agent section) should be considered for anticholinergic poisoning due to carbamazepine. Occasionally, CNS depression due to valproate will respond to naloxone (2 mg IV). Hemodialysis and hemoperfusion should be reserved for patients with persistently high drug levels (e.g., carbamazepine ³ 40 µg/mL and valproate ³1000 µg/mL) who do not respond to supportive care.
ARSENIC Poisoning can occur from natural sources (contamination of deep-water wells); from occupational exposure (a byproduct of the smelting of ores and use in the microelectronic industry); commercial use of arsenic in wood preservatives, pesticides, herbicides, fungicides, and paints; and through foods and tobacco treated with arsenic-containing pesticides. Acute poisoning causes hemorrhagic gastroenteritis, fluid loss, and hypotension followed by delayed cardiomyopathy, delirium, coma, and seizures. Acute tubular necrosis and hemolysis may develop. Arsine gas causes severe hemolysis. Chronic exposure causes skin and nail changes (hyperkeratosis, hyperpigmentation, exfoliative dermatitis, and transverse white striae of the fingernails), sensory and motor polyneuritis that may lead to paralysis, and inflammation of the respiratory mucosa. Chronic exposure is associated with increased risk of skin cancer and possibly of systemic cancers and with vasospasm and peripheral vascular insufficiency.
Treatment of acute ingestion includes ipecac-induced vomiting, gastric lavage, activated charcoal with a cathartic, aggressive administration of IV fluids and electrolyte correction, and dimercaprol IM at an initial dose of 3–5 mg/kg every 4 h for 2 d, every 6 h on d 3, and every 12 h for 7 d. Succimer is an alternative agent if adverse reactions develop to dimercaprol. With renal failure doses should be adjusted carefully. Other than avoidance of additional exposure, specific therapy is not of proven benefit for chronic arsenic toxicity.
BARBITURATES Overdose may result in confusion, lethargy, coma, hypotension, hypothermia, pulmonary edema, and death.
Treatment consists of GI decontamination and repetitive charcoal administration for long-acting barbiturates. Renal excretion of phenobarbital is enhanced by alkalinization of urine to a pH of 8 and by saline diuresis. Hemoperfusion and hemodialysis can be used in severe poisoning with short-or long-acting barbiturates.
BENZODIAZEPINES Long-acting agents include chlordiazepoxide, clonazepam, clorazepate, diazepam, flurazepam, prazepam, and quazepam; short-acting drugs include alprazolam, flunitrazepam, lorazepam, and oxazepam; and ultrashort-acting agents include estazolam, midazolam, temazepam, and triazolam. Effects may begin within 30 min of overdosage and include weakness, ataxia, drowsiness, coma, and respiratory depression. Pupils are constricted and do not respond to naloxone.
Treatment includes GI decontamination and support of vital signs. Flumazenil, a competitive benzodiazepine-receptor antagonist, can reverse CNS and respiratory depression and is given IV in incremental doses of 0.2, 0.3, and 0.5 mg at 1-min intervals until the desired effect is achieved or a total dose of 3 to 5 mg is given; flumazenil must be used with caution in pts who have benzodiazepine dependency or have coingested stimulants and benzodiazepines.
BETA-ADRENERGIC BLOCKING AGENTS Some beta blockers are cardioselective (acebutolol, atenolol, betaxolol, bisoprolol, esmolol, metroprolol), some have sympathomimetic activity (acebutolol, cartelol, pindolol, timolol, possibly penbutolol), and some have quinidine-like effects (acebutolol, metoprolol, pindolol, propranolol, sotalol, possibly betaxolol). Toxicity is usually manifest within 30 min of ingestion. Symptoms include nausea, vomiting, diarrhea, bradycardia, hypotension, and CNS depression. Agents with intrinsic sympathomimetic activity can cause hypertension and tachycardia. Bronchospasm and pulmonary edema may occur. Hyperkalemia, hypoglycemia, metabolic acidosis, all degrees of AV block, bundle branch block, QRS prolongation, ventricular tachyarrhythmias, torsades de pointes, and asystole may occur.
Treatment includes GI decontamination, supportive measures, and administration of calcium (10% chloride or gluconate salt solution, IV 0.2 mL/kg, up to 10 mL) and glucagon (5–10 mg IV, then infusion of 1–5 mg/L). Bradycardia and hypotension sometimes respond to atropine, isoproterenol, and vasopressors. Cardiac pacing or an intraaortic balloon pump may be required. Bronchospasm is treated with inhaled b agonists.
CADMIUM Foods can be contaminated with cadmium from sewage, polluted ground water, or mining effluents. Airborne cadmium can be released from smelting or incineration of wastes containing plastics and batteries, and occupational exposure occurs in the metal-plating, pigment, battery, and plastics industries. Acute inhalation can cause pleuritic chest pain, dyspnea, cyanosis, fever, tachycardia, nausea, and pulmonary edema. Ingestion can cause severe nausea, vomiting, salivation, abdominal cramps, and diarrhea. Chronic exposure causes anosmia, microcytic hypochromic anemia, renal tubular dysfunction with proteinuria, and osteomalacia with pseudofractures.
Treatment involves avoidance of further exposure and supportive therapy. Chelation therapy is not useful, and dimercaprol may worsen nephrotoxicity and is contraindicated. Succimer is useful in cadmium toxicity in animals and may be useful for the disorder in humans.
CALCIUM CHANNEL BLOCKERS These agents include amlodipine, bepridil, diltiazem, felodipine, flunarizine, isradipine, lacidipine, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, and verapamil. Toxicity usually develops within 30–60 min following ingestion of 5–10 X usual dose. Manifestations include confusion, drowsiness, coma, seizure, hypotension, bradycardia, cyanosis, and pulmonary edema. ECG findings include all degrees of AV block, prolonged QRS and QT intervals, ischemia or infarction, and asystole. Metabolic acidosis and hyperglycemia may result.
Treatment consists of GI decontamination with activated charcoal, supportive care, calcium and glucagon (as above). Electrical pacing or intraaortic balloon pump may be required, and persistent hypotension may require vasopressors.
CARBON MONOXIDE CO binds to hemoglobin (forming carboxyhemoglobin) with an affinity 200 times that of O2 and hence causes cellular anoxia. An elevated carboxyhemoglobin fraction confirms exposure but must be interpreted relative to the time elapsed from exposure. Once exposure is discontinued, CO is excreted via the lungs with a half-life of 4–6 h. The half-life decreases to 40–80 min with 100% O2 therapy and to 15–30 min with hyperbaric O2. Manifestations include shortness of breath, dyspnea, tachypnea, headache, nausea, vomiting, emotional lability, confusion, impaired judgment, and clumsiness. Pulmonary edema, aspiration pneumonia, arrhythmias, and hypotension may occur. The “cherry red” color of skin and mucous membranes is rare; cyanosis is usual.
Treatment consists of giving 100% O2 via a tightly fitting mask until CO levels are <10% and all symptoms have resolved. Hyperbaric O2 is recommended for comatose pts with CO levels ³ 40%, for pts with CO levels ³ 25% who also have seizures or intractable arrhythmias, and for pts with delayed onset of sequelae. Pts with loss of consciousness are at risk for neuropsychiatric sequelae 1 to 3 weeks later.
CARDIAC GLYCOSIDES, INCLUDING DIGOXIN Poisoning with digitalis occurs with therapeutic or suicidal use of digoxin and with plant (foxglove, oleander, squill) ingestion. Symptoms include vomiting, confusion, delirium, hallucinations, blurred vision, disturbed color perception (yellow vision), photophobia, all types of arrhythmias, and all degrees of AV block. The combination of SVT and AV block suggests digitalis toxicity. Hypokalemia is common with chronic intoxication, while hyperkalemia occurs with acute overdosage. Diagnosis is confirmed by measuring the serum digoxin level.
GI decontamination is done carefully to avoid vagal stimulation, repeated doses of activated charcoal are given, and hyperkalemia is treated with Kayexalate, insulin, and glucose. Atropine and electrical pacing may be required. In severe poisoning digoxin-specific Fab antibodies are given; dosage (in 40- mg vials) is calculated by dividing ingested dose of digoxin (mg) by 0.6 mg/ vial. If dose and serum levels are unknown, give 5–10 vials to an adult.
CYANIDE Cyanide blocks electron transport, resulting in decreased oxidative metabolism and oxidative utilization, decreased ATP production, and lactic acidosis. Lethal dose is 200–300 mg of sodium cyanide and 500 mg of hydrocyanic acid. Early effects include headache, vertigo, excitement, anxiety, burning of mouth and throat, dyspnea, tachycardia, hypertension, nausea, vomiting, and diaphoresis. Breath may have a bitter almond odor. Later effects include coma, seizures, opisthotonos, trismus, paralysis, respiratory depression, arrhythmias, hypotension, and death.
Treatment should begin immediately based on history. Supportive measures, 100% O2, and GI decontamination are begun concurrently with specific therapy. Amyl nitrite is inhaled for 30 s each min, and a new ampule is broken q3min. (Nitrite produces methemoglobinemia, which has a higher affinity for cyanide and promotes release from peripheral sites.) Sodium nitrite is then given as a 3% solution IV at a rate of 2.5–5.0 mL/min up to a total dose of 10–15 mL. Then, 50 ml of 25% sodium thiosulfate is given IV over 1–2 min, producing sodium thiocyanate, which is excreted in urine. (Children should be given 0.33 mL/kg sodium nitrite and 1.65 mL/kg sodium thiosulfate.) If symptoms persist, repeat half the dose of sodium nitrite and sodium thiosulfate.
CYCLIC ANTIDEPRESSANTS These agents include amitriptyline, imipramine, nortriptyline, desipramine, chlomipramine, doxepin, protriptyline, trimipramine, amoxapine, bupropion, maprotiline, mirtazepine, and trazadone. Depending on the agent, they block reuptake of synaptic transmitters (norepinephrine, dopamine) and have central and peripheral anticholinergic activity. Manifestations include anticholinergic symptoms (fever, mydriasis, flushing of skin, urinary retention, decreased bowel motility). CNS manifestations include excitation, restlessness, myoclonus, hyperreflexia, disorientation, confusion, hallucinations, coma, and seizures. Cardiac effects include prolongation of the QRS complex, other AV blocks, and arrhythmias. QRS duration ³ 0.10 ms is correlated with seizures and life-threatening cardiac arrhythmias. Serum levels ³ 3300 nmol/L (³1000 ng/mL) indicate serious poisoning.
Treatment with ipecac is contraindicated. Activated charcoal is the preferred method of GI decontamination and may require repeated treatments. Metabolic acidosis is treated with sodium bicarbonate; hypotension with volume expansion, norepinephrine, or high-dose dopamine; seizures with benzodiazepines and barbiturates; arrhythmias with sodium bicarbonate (0.5–1 mmol/kg), lidocaine, and bretyllium. b-Adrenergic blockers and class 1A antiarrhythmics should be avoided. The efficacy of phenytoin is not established. Physostigmine reverses anticholinergic signs and may be given in mild poisoning.
ETHYLENE GLYCOL Ethylene glycol is used as a solvent for paints, plastics, and pharmaceuticals and in the manufacture of explosives, fire extinguishers, foams, hydraulic fluids, windshield cleaners, radiator antifreeze, and de-icer preparations. As little as 120 mg or 0.1 mL/kg can be hazardous. Manifestations include nausea, vomiting, slurred speech, ataxia, nystagmus, lethargy, sweet breath odor, coma, seizures, cardiovascular collapse, and death. Hypocalcemia occurs in half of pts. Anion-gap metabolic acidosis, elevated serum osmolality, and oxalate crystalluria suggest the diagnosis. Renal failure may result from glycolic acid production.
GI lavage should be followed by activated charcoal, and airway protection should be initiated immediately. Calcium salts should be given IV at a rate of 1 mL/min for a total dose of 7–14 mL (10% solution diluted 10:1). Metabolic acidosis should be treated with sodium bicarbonate. Phenytoin and benzodiazepines are given for seizures. Ethanol and fomepizole bind to alcohol dehydrogenase with higher affinity than ethylene glycol and block the production of toxic metabolites. Ethanol is administered when ethylene glycol level is >3 mmol/L (>20 mg/dL) and acidosis is present; ethanol is given as follows: the loading dose is 10 mL/kg of 10% ethanol IV or 1 mL/kg of 95% ethanol PO; the maintenance dose is 1.5 (mL/kg)/h of 10% ethanol IV and 3 (mL/kg)/h of 10% ethanol during dialysis. A serum ethanol level of ³20 mmol/L (³100 mg/ dL) is required to inhibit alcohol dehydrogenase, and levels must be monitored closely. Fomepizole is diluted in 100 mL of IV fluid and administered over 30 min in a loading dose of 15 mg/kg followed by 10 mg/kg every 12 h for four doses and 15 mg/kg thereafter until the ethylene glycol level falls below 1.5 mmol/L (10 mg/dL). Hemodialysis is indicated in cases not responding to above therapy, when serum levels are ³ 8 mmol/L (³50 mg/dL), and for renal failure. Give thiamine and pyridoxine supplements.
HALLUCINOGENS Mescaline, lysergic acid (LSD), and psilocybin cause disorders of mood, thought, and perception lasting 4–6 h. Psilocybin can cause fever, hypotension, and seizures. Symptoms include mydriasis, conjunctival injection, piloerection, hypertension, tachycardia, tachypnea, anorexia, tremors, and hyperreflexia.
Treatment is nonspecific: a calm environment, benzodiazepines for acute panic reactions, and haloperidol for psychotic reactions.
HYDROCARBONS Forms include aromatic hydrocarbons (xylene, toluene), halogenated hydrocarbons (carbon tetrachloride, trichlorethane), and petroleum distillate hydrocarbons (gasoline, lacquer thinner, mineral seal oil, kerosene, lighter fluid). All cause CNS excitation at low dose and depression at high doses. Other manifestations include nausea, vomiting, diarrhea, abdominal pain, renal tubular acidosis, bone marrow suppression, respiratory distress, rhabdomyolysis, psychosis and cerebral atrophy, and mucosal burns.
Prompt gastric lavage is required for aromatic hydrocarbons, but gastric lavage, ipecac, and activated charcoal are contraindicated for petroleum distillate hydrocarbons. Supportive care involves oxygen, respiratory support; monitoring of liver, renal, and myocardial function; and correction of metabolic abnormalities.
HYDROGEN SULFIDE Hydrogen sulfide is encountered in the petroleum and mining industries, tanning of leather, vulcanization of rubber, production of synthetic fabrics, refining of metal, production of heavy water for atomic reactors, and manufacture of glue and felt. The chemical is malodorous (rotten eggs) and irritative, producing rhinitis, conjunctivitis, and pharyngitis. Headache, vertigo, nausea, confusion, seizures, and coma may ensue. Respiratory depression causes hypoxia, cyanosis, and metabolic acidosis.
Treatment includes maintenance of airway, 100% O2 and the use of amyl and sodium nitrite (as for cyanide poisoning) when pts do not respond to oxygen. Hyperbaric O2 can be used in refractory cases.
IRON Ferrous iron injures mitochondria, causes lipid peroxidation, and results in renal, tubular, and hepatic necrosis and occasionally in myocardial and pulmonary injury. Ingestion of 20 mg/kg causes GI symptoms, and 60 mg/ kg causes fever, hyperglycemia, leukocytosis, lethargy, hypotension, metabolic acidosis, seizures, coma, vascular collapse, jaundice, elevated liver enzymes, prolongation of PT, and hyperammonemia. X-ray may identify iron tablets in stomach. Serum iron levels greater than iron-binding capacity indicate serious toxicity. A positive urine deferoxamine provocative test (50 mg/kg IV or IM up to 1 g) produces a vin rosé color that indicates presence of ferrioxamine.
Gastric lavage and whole-bowel irrigation should be administered, followed by x-ray to check adequacy of decontamination. Charcoal is ineffective. Endoscopic removal of tablets may be necessary. Volume depletion should be corrected, and sodium bicarbonate is used to correct metabolic acidosis. Deferoxamine is infused at 10–15 (mg/kg)/h (up to 1–2 g) if iron exceeds binding capacity. If iron level is >180 µmol/L (>1000 µg/dL), larger doses of deferoxamine can be given, followed by exchange transfusion or plasmapheresis to remove deferoxamine complex.
ISONIAZID Acute overdose decreases synthesis of g-aminobutyric acid and causes CNS stimulation. Symptoms begin within 30 min of ingestion and include nausea, vomiting, dizziness, slurred speech, coma, seizures, and metabolic acidosis.
Activated charcoal is the preferred method of GI decontamination. Pyridoxine (vitamin B6) should be given slowly IV in weight equivalency to ingested dose of isoniazid. If dose is not known, give 5 g pyridoxine IV over 30 min as a 5–10% solution.
ISOPROPYL ALCOHOL Isopropyl alcohol is present in rubbing alcohol, solvents, aftershave lotions, antifreeze, and window cleaners. Its metabolite, acetone, is found in cleaners, solvents, and nail polish removers. Manifestations begin promptly and include vomiting, abdominal pain, hematemesis, myopathy, headache, dizziness, confusion, coma, respiratory depression, hypothermia, and hypotension. Hypoglycemia, anion-gap (small) metabolic acidosis, elevated serum osmolality, false elevations of serum creatinine, and hemolytic anemia may be present.
Treatment consists of GI decontamination by gastric aspiration and supportive measures. Activated charcoal is not effective. Dialysis may be needed in severe cases.
LEAD Exposure to lead occurs through paints, cans, plumbing fixtures, leaded gasolines, vegetables grown in lead-contaminated soils, improperly glazed ceramics, lead-containing glass, and industrial sources such as battery manufacturing, demolition of lead-contaminated buildings, and the ceramics industry. Manifestations in childhood include abdominal pain followed by lethargy, anorexia, anemia, ataxia, and slurred speech. Severe manifestations include convulsions, coma, generalized cerebral edema, and renal failure. Impairment of cognition is dose-dependent. In adults symptoms of chronic exposure include abdominal pain, headache, irritability, joint pain, fatigue, anemia, motor neuropathy, and deficits in memory. Encephalopathy is rare. A “lead line” may appear at the gingiva-tooth border. Chronic, low-level exposure can cause interstitial nephritis, tubular damage, hyperuricemia, and decreased glomerular filtration. Elevation of bone lead level is a risk for anemia and hypertension.
Treatment first involves prevention of further exposure and the use of chelating agents such as edetate calcium disodium, dimercaprol, penicillamine, and succimer. Chelation may not improve subclinical manifestations such as impaired cognition.
LITHIUM Manifestations begin within 2–4 h of ingestion and include nausea, vomiting, diarrhea, weakness, fasciculations, twitching, ataxia, tremor, myoclonus, choreoathetosis, seizures, confusion, coma, and cardiovascular collapse. Laboratory abnormalities include leukocytosis, hyperglycemia, albuminuria, glycosuria, nephrogenic diabetes insipidus, ECG changes (AV block, prolonged QT), and ventricular arrhythmias.
Within 2–4 h of ingestion, gastric lavage and bowel irrigation should be performed. Charcoal is not effective. Endoscopy should be considered if concretions are suspected. Experimentally, Kayexalate has been shown to bind lithium, but its clinical efficacy is unproven. Serial serum lithium levels should be measured until trend is downward. Supportive care includes saline diuresis and alkalinization of the urine for levels > 2–3 mmol/L. Hemodialysis is indicated for acute or chronic intoxication with symptoms and/or a serum level >3mmol/L.
MERCURY Mercury is used in thermometers, dental amalgams, and some batteries and is combined with other chemicals to form inorganic or organic mercury compounds. Fish can concentrate mercury at high levels, and occupational exposure continues in some chemical, metal-processing, electrical, and automotive manufacturing; building industries; and medical and dental services (e.g., ordinary dental amalgam). Inhalation of mercury vapor causes diffuse infiltrates or a pneumonitis, respiratory distress, pulmonary edema, fibrosis, and desquamation of the bronchiolar epithelium. Neurologic manifestations include tremors, emotional lability, and polyneuropathy. Chronic exposure to metallic mercury produces intention tremor and erethism (excitability, memory loss, insomnia, timidity, and sometimes delirium); acute high-dose ingestion of metallic mercury may lead to hematemesis and abdominal pain, acute renal failure, and cardiovascular collapse. Organic mercury compounds can cause a neurotoxicity characterized by paresthesia; impaired vision, hearing, taste, and smell; unsteadiness of gait; weakness; memory loss; and depression. Exposed mothers give birth to infants with mental retardation and multiple neurologic derangements.
Treatment acutely involves emesis or gastric lavage followed by the oral administration of polythiol resins to bind mercury in the GI tract. Chelating agents include dimercaprol, succimer, and penicillamine. Acute poisoning is treated with dimercaprol in divided doses IM, not exceeding 24 mg/kg per day; 5-day courses are usually separated by rest periods. N-acetyl penicillamine is also useful at a dose of 30 mg/kg per day in divided doses. Peritoneal dialysis, hemodialysis, and extracorporeal hemodialysis with succimer have been used for renal failure. Chronic inorganic mercury poisoning is best treated with acetyl penicillamine.
METHANOL Methanol is a component of shellacs, varnishes, paint removers, Sterno, windshield-washer solutions, copy machine fluid, and denaturants for ethanol. It is metabolized to formic acid, which causes metabolic acidosis. Manifestations begin within 1–2 h of ingestion and include nausea, vomiting, abdominal pain, headache, vertigo, confusion, obtundation, and ethanol-like intoxication. Late manifestations are due to formic acid and include an anion-gap metabolic acidosis, coma, seizures, and death. Ophthalmic manifestations 15–19 h after ingestion include clouding, diminished acuity, dancing and flashing spots, dilated or fixed pupils, hyperemia of the disc, retinal edema, and blindness. An osmol gap is often present.
Gastric aspiration should be undertaken. Activated charcoal is not effective. Acidosis is corrected with sodium bicarbonate. Seizures respond to diazepam and phenytoin. Ethanol or fomepizole therapy (as described for ethylene glycol) is indicated in pts with visual symptoms or a methanol level >6 mmol/L (>20 mg/dL). Therapy with ethanol is continued until the methanol level falls <6 mmol/L. Hemodialysis is indicated when visual signs are present or when metabolic acidosis is unresponsive to sodium bicarbonate.
METHEMOGLOBINEMIA Chemicals that oxidize ferrous hemoglobin (Fe2+) to its ferric (Fe3+) state include aniline, aminophenols, aminophenones, chlorates, dapsone, local anesthetics, nitrates, nitrites, nitroglycerine, naphthalene, nitrobenzene, nitrogen oxides, phenazopyridine, primiquine, and sulfonamides. Cyanosis occurs with methemoglobin levels >15%. When levels exceed 20–30%, symptoms include fatigue, headache, dizziness, tachycardia, and weakness. At levels >45%, dyspnea, bradycardia, hypoxia, acidosis, seizures, coma, and arrhythmias occur. Death usually occurs with levels >70%. Hemolytic anemia may lead to hyperkalemia and renal failure 1–3 days after exposure. Cyanosis in conjunction with a normal O2 and decreased O2 saturation (measured by oximeter) and “chocolate brown” blood suggest the diagnosis. The chocolate color does not redden with exposure to O2 but fades when exposed to 10% potassium cyanide.
Ingested toxins should be removed by treatment with activated charcoal. Methylene blue is indicated for methemoglobin level >30 g/L or methemoglobinemia with hypoxia. Dosage is 1–2 mg/kg as a 1% solution over 5 min. Additional doses may be needed. Methylene blue is contraindicated in G6PD deficiency. Administration of 100% O2 and packed red blood cell transfusion to a hemoglobin level of 150 g/L can enhance O2 carrying capacity of the blood. Exchange transfusions may be indicated in G6PD-deficient pts.
MONOAMINE OXIDASE (MAO) INHIBITORS MAO inhibitors include furzolidone, isocarboxazid, nialamide, pargyline, phenelizine, procarbazine, and tranylcypromine. Manifestations are apparent within 6–12 h of ingestion and include CNS stimulation, fever, tachycardia, tachypnea, hypertension, nausea, vomiting, dilated pupils with nystagmus, and papilledema. Fasciculations, twitching, tremor, and rigidity may be present.
Activated charcoal is the preferred method of GI decontamination. Dantrolene (2.5 mg/kg PO or IV q6h) may be effective for hyperthermia. Control of hypertension may require nitroprusside, and tachycardia may require propranolol. Hypotension should be treated with fluids and cautious use of pressors. Seizures are treated with benzodiazepines and phenytoin. In severe cases hyperthermia may require external cooling, and neuromuscular paralysis may be necessary for agitation.
MUSCLE RELAXANTS Manifestations of poisoning by carisoprodol, chlorphenesin, chlorzoxazone, and methocarbamol include nausea, vomiting, dizziness, headache, nystagmus, hypotonia, and CNS depression. Cyclobenzaprine and orphenadrine cause agitation, hallucinations, seizures, stupor, coma, and hypotension. Orphenadrine can also cause ventricular tachyarrhythmias. Baclofen causes CNS depression, hypothermia, excitability, delirium, myoclonus, seizures, conduction abnormalities, arrhythmias, and hypotension.
Prompt GI decontamination, single-dose activated charcoal (repeated for baclofen overdose), and cathartics are indicated. Physostigmine (1–2 mg IV over 2–5 min) is useful for anticholinergic effects.
NEUROLEPTICS The phenothiazines chlorpromazine, fluphenazine, mesoridazine, perphenazine, prochlorperazine, promazine, promethazine, and thioridazine and pharmacologically similar agents such as haloperidol, loxapine, pimozide, and thiothixene are CNS depressants and can cause lethargy, obtundation, respiratory depression, and coma. Pupils are often constricted. Hypothermia, hypotension, SVT, AV block, arrhythmias (including torsades de pointes), prolongation of PR, QRS, and QT intervals, and T-wave abnormalities are seen. Malignant neuroleptic syndrome occurs rarely. Acute dystonic reaction symptoms include rigidity, opisthotonos, stiff neck, hyperreflexia, irritability, dystonia, fixed speech, torticollis, tremors, trismus, and oculogyric crisis.
Treatment of overdose includes GI decontamination with activated charcoal. Seizures should be treated with benzodiazepines; hypotension responds to volume expansion and a agonists. Sodium bicarbonate is given for metabolic acidosis. Avoid the use of procainamide, quinidine, or any agent that prolongs cardiac repolarization. Acute dystonic reactions respond to diphenhydramine (1–2 mg/kg IV) or benztropine (1–2 mg). Doses may be repeated in 20 min if necessary.
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) All NSAIDs may cause gastroenteritis, drowsiness, headache, glycosuria, hematuria, and proteinuria. Ibuprofen toxicity is usually mild but can cause metabolic acidosis, coma, and seizures. Diflunisal produces, in addition, hyperventilation, tachycardia, and diaphoresis; fenoprofen is nephrotoxic. Seizures occur with mefenamic acid and phenylbutazone and rarely with ketoprofen and naproxen. Coma, respiratory depression, and cardiovascular collapse can occur with mefenamic acid and phenylbutazone.
Activated charcoal and cathartics are indicated. Charcoal treatment should be repeated with indomethacin, phenylbutazone, and piroxicam ingestions. Hemodialysis is not efficient because of protein binding but may be useful with severe toxicity.
ORGANOPHOSPHATE AND CARBAMATE INSECTICIDES Organophosphates (chlorpyrifos, phosphorothioic acid, dichlorvos, fenthion, malathion, parathion, sarin, and numerous others) irreversibly inhibit acetylcholinesterase and cause accumulation of acetylcholine at muscarinic and nicotinic synapses. Carbamates (carbaryl, aldicarb, propoxur, and bendicarb) reversibly inhibit acetylcholinesterase; therapeutic carbonates include ambenonium, neostigmine, physostigmine, and pyridostigmine. Both types are absorbed through the skin, lungs, and GI tract and produce nausea, vomiting, abdominal cramps, urinary and fecal incontinence, increased bronchial secretions, coughing, sweating, salivation, lacrimation, and miosis; carbamates are shorter acting. Bradycardia, conduction blocks, hypotension, twitching, fasciculations, weakness, respiratory depression, seizures, confusion, and coma may result. A decrease in cholinesterase activity ³50% in plasma or red cells is diagnostic.
Treatment begins with washing exposed surfaces with soap and water and, in cases of ingestion, GI decontamination, then activated charcoal. Atropine, 0.5–2 mg is given IV q15 min until complete atropinization is achieved (dry mouth). Pralidoxime (2-PAM), 1–2 g IV over several minutes, can be repeated q8h until nicotinic symptoms resolve. Use of 2-PAM in carbamate poisoning is controversial. Seizures should be treated with benzodiazepines.
SALICYLATES Poisoning with salicylates causes vomiting, tachycardia, hyperpnea, fever, tinnitus, lethargy, and confusion. Severe poisoning can result in seizures, coma, respiratory and cardiovascular failure, cerebral edema, and renal failure. Respiratory alkalosis is commonly coupled with metabolic acidosis (40–50%), but respiratory alkalosis (20%) and metabolic acidosis (20%) can occur separately. Lactic and other organic acids are responsible for the increased anion gap. PT may be prolonged. Salicylates in blood or urine can be detected by ferric chloride test. Levels >2.2 mmol/L (30 mg/dL) are associated with toxicity.
Treatment includes repeated administration of activated charcoal for up to 24 h. Forced alkaline diuresis (urine pH > 8.0) increases excretion and decreases serum half-life. Seizures can be controlled with diazepam or phenobarbital. Hemodialysis should be considered in pts who fail conventional therapy or have cerebral edema or hepatic or renal failure.
SEROTONIN SYNDROME This syndrome is due to excessive CNS and peripheral serotonergic (5HT-1a and possibly 5HT-2) activity and results from the concomitant use of agents that promote the release of serotonin from presynaptic neurons (e.g., amphetamines, cocaine, codeine, methylenedioxy-methamphetamine, or MDMA (Ecstasy), reserpine, some MAO inhibitors), inhibit its reuptake (e.g., cyclic antidepressants, particularly the SSRIs, ergot derivatives, dextromethorphan, meperidine, pentacozine, sumatriptan and related agents, tramadol, some MAO inhibitors) or metabolism (e.g., cocaine, MAO inhibitors), or stimulate postsynaptic serotonin receptors (e.g., bromocryptine, bupropion, buspirone, levodopa, lithium, L-tryptophan, LSD, mescaline, trazodone). Less often, it results from the use or overdose of a single serotonergic agent or when one agent is taken soon after another has been discontinued (up to 2 weeks for some agents).
Manifestations include altered mental status (agitation, confusion, delirium, mutism, coma, and seizures), neuromuscular hyperactivity (restlessness, incoordination, hyperreflexia, myoclonus, rigidity, and tremors), and autonomic dysfunction (abdominal pain, diarrhea, diaphoresis, fever, elevated and fluctuating blood pressure, flushed skin, mydriasis, tearing, salivation, shivering, and tachycardia). Complications include hyperthermia, lactic acidosis, rhabdomyolysis, kidney and liver failure, ARDS, and DIC.
Gastrointestinal decontamination may be indicated for acute overdose. Supportive measures include hydration with intravenous fluids, airway protection and mechanical ventilation, benzodiazepines (and paralytics, if necessary) for neuromuscular hyperactivity, and mechanical cooling measures for hyperthermia. Cyproheptadine (Periactin), an antihistamine with 5HT-1a and 5HT-2 receptor blocking activity, and chlorpromazine (Thorazine), a nonspecific serotonin receptor antagonist, have been used with success. Cyproheptadine is given orally or by gastric tube in an initial dose of 4 to 8 mg and repeated as necessary every 2 to 4 h up to a maximum of 32 mg in 24 h. Chlorpromazine can be given parenterally (intramuscularly or by slow IV injection in doses of 50 to 100 mg).
SYMPATHOMIMETICS Amphetamines; bronchodilators such as albuterol and metaproterenol; decongestants such as ephedrine, pseudoephedrine, phenylephrine, and phenylpropanolamines; and cocaine can cause nausea, vomiting, diarrhea, abdominal cramps, irritability, confusion, delirium, euphoria, auditory and visual hallucinations, tremors, hyperreflexia, seizures, palpitations, tachycardia, hypertension, arrhythmias, and cardiovascular collapse. Sympathomimetic symptoms include dilated pupils, dry mouth, pallor, flushing of skin, and tachypnea. Severe manifestations include hyperpyrexia, seizures, rhabdomyolysis, hypertensive crisis, intracranial hemorrhage, cardiac arrhythmias, and cardiovascular collapse. Rhabdomyolysis and intracranial hemorrhage can occur.
Activated charcoal is preferred for GI decontamination. Seizures are treated with benzodiazepines; hypertension with a nonselective beta blocker or the a- adrenergic antagonist phentolamine (1 to 5 mg IV q5min); fever with salicylates; and agitation with sedatives and, if necessary, paralyzing agents. Lidocaine and propranolol are useful for cardiac arrhythmias.
THALLIUM Thallium is used as insecticide, in fireworks, in manufacturing, as an alloy, and in cardiac imaging, and epidemic poisoning has occurred with ingestion of grain contaminated with thallium. Acute manifestations include nausea and vomiting, abdominal pain, bloody diarrhea, and hematemesis. Subsequent manifestations include confusion, psychosis, choreoathetosis, organic brain syndrome, convulsions, coma, and sensory and motor neuropathy; autonomic nervous system effects include tachycardia, hypertension, and salivation. Optic neuritis, ophthalmoplegia, ptosis, strabismus, and cranial nerve palsies may occur. Late effects include diffuse hair loss, memory defects, ataxia, tremor, and foot drop.
Treatment includes GI decontamination by lavage or ipecac syrup and cathartics, forced diuresis with furosemide and KCl supplements, and either peritoneal dialysis, hemodialysis, or charcoal hemoperfusion.
THEOPHYLLINE Theophylline, caffeine, and other methylxanthines are phosphodiesterase inhibitors that reduce the degradation of cyclic AMP, thereby enhancing the actions of endogenous catecholamines. Vomiting, restlessness, irritability, agitation, tachypnea, tachycardia, and tremors are common. Coma and respiratory depression, generalized tonic-clonic and partial seizures, atrial arrhythmias, ventricular arrhythmias, and fibrillation can occur. Rhabdomyolysis with acute renal failure develops occasionally. Laboratory abnormalities include ketosis, metabolic acidosis, elevated amylase, hyperglycemia, and decreased potassium, calcium, and phosphorus.
Treatment requires prompt administration of activated charcoal every 2–4 h for 12–24 h after ingestion. Metoclopramide and ondansetron may be given to control vomiting. Tachyarrhythmias are treated with propranolol and standard antiarrhythmics; hypotension requires volume expansion. Seizures are treated with benzodiazepines and barbiturates; phenytoin is ineffective. Indications for hemodialysis and hemoperfusion with acute ingestion include a serum level >500 µmol/L (>100 mg/L) and with chronic ingestion a serum level >200– 300 µmol/L (>40–60 mg/L). Dialysis is also indicated in pts with lower serum levels who have refractory seizures or arrhythmias.
For a more detailed discussion, see Linden CH, Burns MJ: Poisoning and Drug Overdosage, Chap. 396, p. 2595; and Hu H: Heavy Metal Poisoning, Chap. 395, p. 2590, in HPIM-15.