L. Keith French
EPIDEMIOLOGY
Theophylline poisoning is waning as its use has become less common.
Life-threatening theophylline overdoses are more likely in elderly patients on chronic therapy than in younger patients following acute overdose.
Caffeine is the most commonly used psychoactive drug in the world.
In 2008, the American Association of Poison Control Centers (AAPC) received 4852 reports of caffeine exposures, including one death.
Approximately one-third of the US population uses nicotine in some form.
In 2008, the AAPC received 8356 reports of exposure.
PATHOPHYSIOLOGY
Methylxanthines (theophylline, aminophylline, caffeine, theobromine) have three distinct pathophysiologic features: adenosine antagonism, increased adrenergic stimulation, and phosphodiesterase inhibition.
Nicotine binds and, in low doses, agonizes nicotinic acetylcholine receptors within the central nervous, autonomic, and neuromuscular systems, thereby augmenting neurotransmitter release. At high doses, neurotransmitter release from the same neurons may become inhibited.
CLINICAL FEATURES
The main systems affected by methylxanthines are GI, neurologic, cardiovascular, and metabolic.
Nausea and vomiting are common with methylxanthines overdose and occur in >70% of patients following acute exposure.
Headache, agitation, tremor, and seizure are characteristic neurologic features.
The incidence of seizures is approximately 50% in patients with serum levels >40 micrograms/mL in chronic theophylline exposure or > 120 micrograms/mL following acute exposure.
Cardiovascular effects include tachycardia, atrial arrhythmias (multifocal atrial tachycardia, atrial fibrillation or flutter), ventricular arrhythmias, and hypotension.
Hypokalemia, hyperglycemia, and metabolic acidosis are common metabolic derangements with methylxanthine exposures.
In overdoses, nicotine mainly affects the GI, neurologic, cardiovascular, and respiratory systems.
Nausea and vomiting are the most common effects following significant nicotine exposure.
Tremor, dizziness, tachycardia, salivation, and bronchorrhea are early features following nicotine poisoning.
Delayed effects of nicotine, particularly in large overdoses, include bradycardia, arrhythmias, hypoventilation, seizures, weakness, and coma.
DIAGNOSIS AND DIFFERENTIAL
Therapeutic theophylline concentrations are 5 to 15 micrograms/mL, although serum concentrations do not always correlate with clinical findings.
The best predictor of major theophylline toxicity following acute overdose is peak serum concentration, while the best predictor of toxicity in chronic exposures is patient age.
Caffeine serum concentrations greater than 120 micrograms/mL are likely to cause life-threatening signs and symptoms; however, levels are not readily available in most institutions.
Nicotine and its major metabolite, cotinine, can be detected in the urine, but do not provide quantitative information and do not correlate with acute exposure.
Coingestants, such as acetaminophen or aspirin, should be considered in any patient who presents after an acute, intentional overdose.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Treatment for both methylxanthine and nicotine poisoning begins with IV access, cardiac monitoring, noninvasive blood pressure measurement, and fluid administration.
Activated charcoal is indicated for methylxanthine overdoses if conditions are appropriate (protected airway, no plan for endoscopy, no concomitant hydrocarbon ingestion, present bowel sounds). Consider whole-bowel irrigation following ingestions of sustained-release products.
Nausea and vomiting generally limit the utility of activated charcoal in nicotine ingestions, although it may theoretically reduce nicotine absorption.
Ondansetron is the antiemetic of choice. Avoid phenothiazines (which lower the seizure threshold) and cimetidine (which prolongs the half-life of methylxanthines).
Benzodiazepines are the first-line agents for seizures. Methylxanthines may generate refractory seizures, and in this instance, barbiturates or sedation/paralysis/intubation may be necessary.
Use cardioselective β-blockers, such as metoprolol or esmolol, for tachyarrhythmias associated with methylxanthine overdose.
Consider hemodialysis in theophylline poisonings associated with serum concentrations >90 micrograms/mL in acute exposures or >40 micrograms/mL in chronic exposures, or in any patient with life-threatening events such as seizures or tachyarrhythmias.
Intubation and mechanical ventilation may be necessary in the severely nicotine-poisoned patient who exhibits profound weakness or respiratory failure.
Asymptomatic patients may be safely discharged after 6 hours of observation following exposure to immediate release methylxanthines, 12 hours of observation following exposure to sustained release methylxanthines, and 3 hours of observation following nicotine exposures.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Guide, 7th ed., see Chapter 186, “Methylxanthines and Nicotine,” by Chip Gresham and Daniel E. Brooks.