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 United States

for medical advice or treatment eachyear, 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. 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, chemicals, cleaning substances, pesticides, and automotive products.

The diagnosis of poisoning or drug overdose must be considered in any pt who

presents withcoma, 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 history

should include the time, route, duration, and circumstances (location, surrounding

events, and intent) of exposure; 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 physical exam should focus initially on the vital signs, cardiopulmonary

system, and neurologic status including assessment of mental status and documentation of neuromuscular abnormalities. Focal neurologic signs are uncommon in poisoning.

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 laboratory studies 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

suchas 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 _-adrenergic blockers, ethanol, insulin, oral hypoglycemic agents, quinine, and salicylates, whereas hyperglycemia can

occur in poisoning withacetone, _-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 withth e differential diagnosis and

to guide treatment. 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 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 withCNS depression of any etiology.

TREATMENT

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 23-1. 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 withspecific 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. 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; enhanced elimination therapy; progressive clinical deterioration; significant underlying medical problems. Suicidal pts require constant observation by qualified personnel.

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. Druginduced

pulmonary edema is usually secondary to hypoxia, but myocardial

depression may contribute. Measurement of pulmonary artery pressure may

be necessary to establishetiology. 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 _-aminobutyric acid agonists suchas 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 withtime, and there are insufficient data to support

or exclude a beneficial effect when they are used _1 hafter 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 witha 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 withcorrosives 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 2 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 withmarginal 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 q2–4his 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 _ 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.

SPECIFIC POISONS

ACETAMINOPHEN A dose of _140 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 hafter 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 (particularly within 30 min of

ingestion), 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 q4hfor

17 doses. Therapy should be started immediately and may be discontinued when

serum level is below toxic range.

ALKALI AND ACID Alkalis include industrial-strengthbleach , 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), anti-rust 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 withmilk 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 stomachburns.

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.

Sodium bicarbonate or lactate may be useful in class IA or IC overdoses.

Torsades de pointes is treated withmagnesium sulfate (4 g or 40 mL of 10%

solution IV over 10–20 min) or overdrive pacing (withisoproterenol 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, homatropine, scopolamine),

Parkinsonian drugs (benztropine, biperiden, trihexyphenidyl), mydriatics (cyclopentolate, tropicamide), phenothizaines, skeletal muscle relaxants (cyclobenzaprine, orphenadrine), smooth-muscle relaxants (clinidinium, dicyclomine), 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; dry skin and mucous membranes.

Treatment involves GI decontamination withactivated 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 withrespiratory depression usually occurs at serum carbamazepine concentrations _20 _g/mL, serum phenytoin levels _60 _g/mL,

and serum valproate levels of _180 _g/mL. Anticholinergic effects (see above)

may be present in carbamazepine poisoning, and tricyclic antidepressant–like

cardiotoxicity (see below) can occur at drug levels _30 _g/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. Flumazenil can be used for benzodiazepine or zolpidem poisoning. Physostigmine (see “Anticholinergic Agents,” above) 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 _ 40 _g/mL and valproate _ 1000 _g/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 witharsenic-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 withvasospasm 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 q4hfor 2 days, q6hon day 3, and q12hfor 7 days. Succimer is an

alternative agent if adverse reactions develop to dimercaprol. Withrenal 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 branchblock, 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 _ agonists.

CADMIUM Foods can be contaminated withcadmium 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 withpseudofractures.

Treatment involves avoidance of further exposure and supportive therapy.

Chelation therapy is not useful, and dimercaprol may worsen nephrotoxicity

and is contraindicated.

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 _ 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 withactivated 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)

withan 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 with100% 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 withCO levels _ 40%, for pts withCO levels _ 25%

who also have seizures or intractable arrhythmias, and for pts with delayed onset

of sequelae. Pts withloss of consciousness are at risk for neuropsychiatric sequelae

1 to 3 weeks later.

CARDIAC GLYCOSIDES, INCLUDING DIGOXIN Poisoning with

digitalis occurs withth erapeutic 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 withspecific 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 _ 0.10 ms is

correlated with seizures and life-threatening cardiac arrhythmias. Serum levels

_ 3300 nmol/L (_1000 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 withsodium bicarbonate; hypotension with volume expansion,

norepinephrine, or high-dose dopamine; seizures with benzodiazepines

and barbiturates; arrhythmias with sodium bicarbonate (0.5–1 mmol/kg) and

lidocaine. _-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 breathodor, 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 _ 20 mmol/L (_100 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 hfor 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 _ 8 mmol/L (_50 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.

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 rose´ 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 _ 180 _mol/L (_1000 _g/dL), larger doses of deferoxamine

can be given, followed by exchange transfusion or plasmapheresis to

remove deferoxamine complex.

ISONIAZID Acute overdose decreases synthesis of _-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 polishremovers. 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 suchas 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 suchas oral succimer or IM edetate calcium disodium. Chelation

may not improve subclinical manifestations suchas 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. 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 _ 3 mmol/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. Fishcan 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 birthto infants withmental 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 withdimercaprol in divided doses IM, not exceeding 24 mg/kg per day;

5-day courses are usually separated by rest periods. 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 hafter 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 withsodium bicarbonate. Seizures respond to diazepam

and phenytoin. Ethanol or fomepizole therapy (as described for ethylene glycol)

is indicated in pts withvisual symptoms or a methanol level _ 6 mmol/L (_20

mg/dL). Therapy with ethanol is continued until the methanol level falls to _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 withmeth emoglobin 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 witha 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 methemoglobinemi withh ypoxia. 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.

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 withactivated charcoal.

Seizures should be treated with benzodiazepines; hypotension responds to volume

expansion and _ 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.

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 _50% in plasma or red cells is diagnostic.

Treatment begins withwash ing exposed surfaces with soap and water and,

in cases of ingestion, GI decontamination, then activated charcoal. Atropine,

0.5–2 mg is given IV q15min until complete atropinization is achieved (dry

mouth). Pralidoxime (2-PAM), 1–2 g IV over several minutes, can be repeated

q8huntil nicotinic symptoms resolve. Use of 2-PAM in carbamate poisoning is

controversial. Seizures should be treated with benzodiazepines.

SALICYLATES Poisoning withsalicylates 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 withmetabolic 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

withtoxicity.

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 _-

adrenergic antagonist phentolamine (1 to 5 mg IV q5min); fever with salicylates;

and agitation withsedatives and, if necessary, paralyzing agents. Propranolol is

useful for tachycardia.

THALLIUM Thallium is used as insecticide, in fireworks, in manufacturing,

as an alloy, and in cardiac imaging, and epidemic poisoning has occurred

withingestion 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. Prussian blue (250 g/

kg) prevents absorption.

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 withacute 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. Tachyarrhythmias are treated with propranolol;

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 _mol/L

(_100 mg/L) and withch ronic ingestion a serum level _ 200–300 _mol/L

(_40–60 mg/L). Dialysis is also indicated in pts withlower serum levels who

have refractory seizures or arrhythmias.