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CHAPTER 124: Toxicology in Adults 1197

Seizures may occur in the setting of cyclic antidepressant coingestion; TABLE 124-4 Common Drugs and Toxins Causing Seizures
however, prospective data demonstrate that cautious administration of
flumazenil is safe in this setting. Flumazenil is effective in improving Amphetamines
23
mental status in patients with suspected drug overdose and depressed Antihistamines/decongestants
mental status; however, it does not decrease the cost or number of major
diagnostic and therapeutic interventions. 24 Antipsychotics
Flumazenil is generally not recommended as a routine diagnostic Caffeine/theophylline
or therapeutic agent in patients with depressed mental status. Still, Carbamates
2
flumazenil can be useful to distinguish benzodiazepine overdose from
mixed-drug intoxication or non–drug-induced coma, and it may Carbon monoxide
improve clinical status. The recommended initial dose of flumazenil is Cocaine
0.2 mg (2 mL) IV over 30 seconds. A further 0.3-mg (3-mL) dose can Cyclic antidepressants
be given over 30 seconds if the desired clinical effect is not seen within Ethylene glycol
30 seconds. Additional 0.5-mg doses can be administered over 30 seconds
at 1-minute intervals as needed to a total dose of 3 mg. Flumazenil dosed Isoniazid
beyond 3 mg generally does not provide additional benefit. Patients Lead
should be monitored for resedation, particularly in cases involving high- Lidocaine
dose or long-acting preparations or when there has been long-term use
of benzodiazepines. Lithium
■ THE AGITATED OR SEIZING PATIENT Methanol
Organophosphates
Agitated, violent, or acutely psychotic patients unresponsive to verbal Phencyclidine (PCP)
counseling and a calm environment require pharmacologic treatment Salicylates
and/or physical restraints to establish adequate control and enhance
patient and staff safety. A common error in the management of the agi- Withdrawal from alcohol or sedative-hypnotics
tated patient is to delay treatment, allowing patients to harm themselves
and others.
Haloperidol (1-5 mg IM or IV) may be repeated every 30 to 60 minutes when drugs alter hypothalamic activity or a patient is exposed to a hot
to a total dose not exceeding 100 mg/d. Debilitated and elderly patients environment.
should receive lower doses, and care must be taken in patients with car- The differential diagnosis for hypothermia includes infection, hypo-
diovascular disease to avoid hypotension and arrhythmias. Haloperidol glycemia, CNS injury, and hypothyroidism. For hyperthermic patients,
prolongs the QT interval and therefore must be used cautiously (and with consider infection, thyrotoxicosis, environmental heat stroke, and drug
continuous monitoring) in the presence of other QT-prolonging drugs. withdrawal.
Haloperidol lowers the seizure threshold and can cause neuroleptic Extreme temperatures must be treated aggressively to minimize
malignant syndrome, tardive dyskinesia, and extrapyramidal symptoms life-threatening complications. Specifics regarding complications and
25
(which may be treated with benztropine 1-2 mg IV). Haloperidol also has treatment of hypo- and hyperthermia are included in chapters 131
anticholinergic effects that are undesirable in anticholinergic overdose. and 63. Two of the more notable life-threatening hyperthermic disor-
Adding a benzodiazepine (eg, lorazepam 1 mg IV) to each dose of halo- ders are neuroleptic malignant syndrome and malignant hyperthermia.
peridol may accelerate control of the difficult patient. Neuroleptic malignant syndrome occurs in patients taking antipsychotic
Seizures are a cause of drug-related morbidity and mortality. Multiple medications or withdrawing from levodopa. Clinical features include
drugs and toxins (Table 124-4) cause them, but other etiologies such as hyperthermia, muscle rigidity, mental status changes, rhabdomyoly-
CNS infection, stroke, head trauma, and severe metabolic disturbance sis, and metabolic acidosis. Routine treatment consists of withdrawal
must be considered in the differential diagnosis. A brief seizure that
is temporally related to drug ingestion (eg, cocaine) may be observed
without further evaluation provided the patient is alert and has a nor- TABLE 124-5 Selected Drugs Affecting Temperature
mal neurologic examination. Recurrent seizures from cocaine should
raise suspicion of body packing (which may be evaluated by abdominal Hypothermia Hyperthermia
imaging and digital and visual search of body cavities). Status epilepticus Alcohols Amphetamines
should be treated with a benzodiazepine IV followed by a barbiturate Barbiturates Anticholinergics
(amobarbital or phenobarbital) if necessary. Phenytoin is less likely to
be of benefit in cocaine or caffeine/theophylline overdose. Patients who Cyclic antidepressants Antihistamines
continue to seize despite adequate treatment with a benzodiazepine Hypoglycemic agents Cocaine
and barbiturate should be considered for isoniazid toxicity (requir- Opioids Cyclic antidepressants
ing treatment with pyridoxine). Patients with seizures refractory to
all above therapy should be considered for paralysis with continuous Phenothiazines Drug withdrawal
electroencephalographic (EEG) monitoring to prevent hyperthermia Lysergic acid diethylamide (LSD)
and rhabdomyolysis. Monoamine oxidase inhibitors
■ ALTERATIONS IN TEMPERATURE Malignant hyperthermia

Drugs and toxins have the potential to alter body temperature through Neuroleptic malignant syndrome
a number of mechanisms (Table 124-5). Hypothermia is caused by Phencyclidine (PCP)
peripheral vasodilation, inhibition of shivering, depression of metabolic Phenothiazines
activity, and environmental exposure. Hyperthermia occurs when there Salicylates
is excessive heat generation from seizures, muscle rigidity, increased
metabolic rate, or decreased sweating. Hyperthermia also occurs Serotonin syndrome

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