Page 1741 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1210 PART 11: Special Problems in Critical Care

inhibition and consideration of hemodialysis in any intoxicated patient doses, barbiturates cause hypothermia, hypotension, bradycardia, flac-
with an unexplained elevation of the plasma osmol gap, especially if cidity, hyporeflexia, coma, and apnea. Patients with severe overdose may
serum levels are not immediately available. Furthermore, diethylene appear dead, including absence of EEG activity.
glycol intoxication, which is undetected by assessment for serum Cardiovascular depression is caused by a combination of decreased
ethylene glycol but is associated with elevation of the osmol gap and arterial tone and myocardial depression, leading to variable filling pres-
development of metabolic acidosis and acute renal failure, also responds sures, low cardiac output, and hypotension. Respiratory depression with
to inhibition of ADH and dialytic therapy. It is thus conceivable that an hypercarbia and hypoxemia are common. In deep coma, the usual acid-
inebriated patient presenting with an elevated osmol gap but negative base disturbance is a mixed respiratory and metabolic acidosis. Patients
serum levels for ethanol, methanol, and ethylene glycol might benefit completely unresponsive to painful stimuli tend to be significantly more
from empiric inhibition of ADH and hemodialysis. 139 acidemic and hypoxemic than those who show some response, a finding
Isopropanol is metabolized by ADH to acetone, which is excreted that is not explained by differences in alveolar ventilation. Hypoxemia
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through the kidneys and breath, creating a sweet smell. Clinical features may be aggravated by ventilation/perfusion mismatch and/or increased
of poisoning include ketonemia, ketonuria, lack of an elevated anion capillary permeability with development of the acute respiratory distress
gap or metabolic acidosis, an elevated osmolal gap, and hemorrhagic syndrome, possibly related to aspiration. Local tissue hypoxia resulting
gastritis. A serum isopropanol level confirms the diagnosis. Supportive from vascular stasis and arterial hypoxemia may contribute to the devel-
140
measures are usually sufficient in the treatment of these patients. opment of barbiturate-related skin blisters, which commonly develop
Hemodialysis is indicated when lethal doses have been ingested (150- over areas of increased pressure. 147
240 mL of 40%-70% solution), or when lethal serum levels are detected The diagnosis of barbiturate overdose is generally made on clinical
(400 mg/dL). Refractory shock and prolonged coma are other indica- grounds. Routine urine toxicology screening can aid in the diagnosis
tions for dialysis. Fomepizole is not indicated. of barbiturate intoxication. Blood levels are generally available and cor-
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■ AMPHETAMINES relate with the severity of clinical findings; however, they rarely affect
management.
Common amphetamine and amphetamine-like prescription drugs As in all toxic ingestions, treatment of barbiturate overdose starts
include methylphenidate, dextroamphetamine, and pemoline, used with supportive measures. There is no antidote. Gastric lavage may be
primarily for narcolepsy and attention-deficit disorder, and various useful in acute massive overdose. Activated charcoal (AC) decreases
anorectic medications used for weight loss, including diethylpropion further drug absorption and increases drug elimination, 148-150 but may
and phentermine. not alter clinical course. Multidose AC may be useful in life-threatening
Illicit drugs include methamphetamine, an addictive stimulant that overdoses. 68,151
is made in small laboratories. Street methamphetamine is referred Alkalinization of the urine (pH >7.5) increases the elimination of
to by many names, such as “speed” and “meth.” When methamphet- phenobarbital, but not other barbiturates, and may aggravate pulmonary
amine is inhaled in powder form or by smoking, it is referred to as edema. Forced alkaline diuresis may be sustained by dopamine hydro-
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“crank,” “crystal,” or “ice.” Ecstasy or “XTC” is the street name for 3, chloride, but this is generally not required or recommended. Although
4-methylenedioxymethamphetamine (MDMA). Ecstasy use has become charcoal hemoperfusion has often been used for extracorporeal removal
common among teenagers and young adults, particularly at “rave” of barbiturates (specifically phenobarbital) in severe life-threatening
parties. Although amphetamine use as a class has been decreasing in the cases, hemodialysis is likely as effective. 153,154
recreational use of prescription amphetamines) continues to increase. ■ BENZODIAZEPINES
last 2 to 3 years in the United States, use of certain forms (specifically
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Amphetamines exert their toxicity via central nervous system stimu- Benzodiazepines enhance the inhibitory effects of the neurotransmitter
lation, peripheral release of catecholamines, inhibition of reuptake of γ-aminobutyric acid (GABA), causing generalized depression of the
catecholamines, or inhibition of monoamine oxidase. They generally central nervous system. Symptoms in overdose range from slurred
have a low therapeutic index. In overdose, they cause confusion, tremor, speech and lethargy to respiratory arrest and coma, depending on the
anxiety, agitation, and irritability. Additional features include mydriasis, dose and compound ingested. In general, patients in coma from benzo-
tachyarrhythmias, myocardial ischemia, stroke, hypertension, hyper- diazepine poisoning are hyporeflexic with small to midposition pupils.
reflexia, hyperthermia, rhabdomyolysis, renal failure, coagulopathy, and The diagnosis of benzodiazepine overdose depends on a history of
seizures. Hepatotoxicity requiring liver transplantation has been reported ingestion or a high index of suspicion for overdose, combined with
with ecstasy abuse. Certain amphetamines referred to as the “designer” compatible clinical features. Urine toxicology screens test for metabo-
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amphetamines (MDMA, methylone, and MDEA) also have serotoner- lites of certain benzodiazepines. However, these tests have high false-
gic activity and can cause hyperthermia and serotonin syndrome when positive (with ingestion of sertraline or oxaprozin) and false-negative
combined with other serotonergic medications. Death may result from rates and vary dramatically based on the individual assay being used.
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arrhythmias, seizures, intracranial hemorrhage, or aspiration pneumonitis. Some benzodiazepines, such as clonazepam, are not metabolized to
Treatment is supportive, including maintenance of the airway and frequently tested metabolites and will therefore not be detected by urine
mechanical ventilation if necessary. Hypertension generally responds to drug screens. Others, such as alprazolam, will undergo insufficient
systemic vasodilation with phentolamine or nitroprusside. Tachyarrhythmias metabolism to reach the testing threshold for a positive urine drug test,
may respond to esmolol or propranolol. Benzodiazepines or a phenothi- so therapy should be based more on clinical information. 155-157
azine are indicated for agitation. Treatment of benzodiazepine overdose consists of initial supportive
Gastric lavage is helpful if performed within 1 hour of ingestion measures, gastric emptying in acute ingestions, AC, and flumazenil.
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and AC should be administered promptly to adsorb remaining drug. There is no role for forced diuresis, dialysis, or hemoperfusion.
Historically, the use of forced-acid diuresis had been used to enhance Flumazenil, a specific benzodiazepine antagonist, is useful in reversing
elimination of amphetamines; however, this is not effective and carries sedation or coma in patients undergoing procedures and in patients
with it increased risk of renal injury and metabolic acidosis. Dialysis and who have taken an intentional benzodiazepine overdose. Its effect on
hemoperfusion are not effective. In hyperthermic patients, dantrolene reversal of respiratory depression is less clear. 159-161 In the past, judicious
can be safely used and recent studies suggest improved survival. 143-145 use of flumazenil was used to provide diagnostic information, because
■ BARBITURATES flumazenil does not antagonize the CNS effects of alcohol, barbiturates,
cyclic antidepressants, or narcotics.
Clinical manifestations of mild to moderate barbiturate overdose Flumazenil should be considered if benzodiazepine overdose is highly
include reduced consciousness, slurred speech, and ataxia. In higher suspected or confirmed, and benzodiazepines have not been prescribed

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