Poisoning is a worldwide problem that consumes substantial health care resources and causes many premature deaths. The burden of serious poisoning is carried by the developing world^1,2; however, poisoning-related morbidity and mortality is also a significant public health concern in the developed world.^{3,4,5,6,7,8,9}

Unintentional poisoning deaths in the United States are increasing, especially as a result of prescription analgesics. This increase has been ascribed to increasing prescription rates and aging of the baby-boom population.^10,11,12 U.S. poison control centers documented 2.38 million human exposures in 2010, with 1146 associated deaths.¹³ Prevention is the key to reducing unintentional poisoning deaths. Pharmacists can that ensure medications are labeled correctly, anticipate potential drug interactions, and educate patients to use medications safely. To prevent pediatric deaths from poisoning, parents have the responsibility to ensure that poisons are placed in childproof, labeled containers stored in adult-only accessible nonfood storage areas. Teachers and healthcare providers can provide age-appropriate education to children about the dangers of poisons. After an exposure, poison control centers staffed by highly trained individuals can provide customized advice to healthcare providers and the public. Poison control centers also participate in prevention, education, and toxico-surveillance activities.

Exposures occur most commonly by ingestion; other routes include inhalation, insufflation, cutaneous and mucous membrane exposure, and injection. Some exposures have minimal risk. The criteria used to determine whether the exposure is nontoxic are: (1) an unintentional exposure to a clearly identified single substance, (2) where an estimate of dose is known, and (3) a recognized information source (e.g., a poison control center) confirms the substance as nontoxic in the reported dose. Asymptomatic patients with nontoxic exposures may be discharged after a short period of observation, providing they have access to further consultation and a safe discharge destination.

Serious clinical effects occur in <5% of acutely poisoned patients presenting to developed-world hospitals, and in-hospital mortality rates are <1%.^9,13

Resuscitation is the first priority in any poisoned patient. After resuscitation, a structured risk assessment is used to identify patients who may benefit from an antidote, decontamination, or enhanced elimination techniques. Most patients only require provision of good supportive care during a period of observation in an appropriate environment.

Treatment of cardiac arrest in poisoned patients follows Advanced Cardiac Life Support guidelines with the addition of interventions potentially beneficial in toxin-induced cardiac arrest (Table 176-1).¹⁴ Prolonged resuscitation is generally indicated, as patients are often young with minimal preexisting organ dysfunction. Utilization of extracorporeal cardiac and respiratory assist devices until organ toxicity resolves may be life-saving.

Stabilization of airway, breathing, and circulation represents initial priorities. Compromised airway patency or reduced respiratory drive may lead to inadequate ventilation; provision of a mechanical airway and assisted ventilation is vital in these circumstances. IV crystalloid bolus (10 to 20 mL/kg) is first-line treatment of hypotension. Since most patients without toxin-induced fluid loss are generally not fluid depleted, avoid administration of excess fluid. Persisting hypotension despite an adequate volume infusion may respond to a specific antidote. Otherwise, cautious administration of an inotropic agent is indicated. Inotrope choice is guided by knowledge of the toxin’s toxicodynamic properties and assessment of circulatory status (e.g., cardiac pump failure versus vasodilatory shock).

ANTIDOTES

Stabilization of airway, breathing, and circulation allows further assessment of blood glucose concentration, temperature, and conscious state. Although the proper use of antidotes (Table 176-2) is important, only a few are indicated before cardiopulmonary stabilization (e.g., naloxone for opiate toxicity, cyanide antidotes for cyanide toxicity, and atropine for organophosphate poisoning).

HYPOGLYCEMIA

Treat hypoglycemia with IV dextrose (glucose). Patients at risk of Wernicke’s encephalopathy also require thiamine, but do not require that it be administered before the dextrose.¹⁵ Altered mental status when hypoglycemia cannot be excluded is an indication for IV dextrose. Supplemental oxygen, thiamine, glucose, and naloxone are often administered empirically as a cocktail in cases of altered mental status. Although relatively safe and affordable in the developed world, this approach may not be cost-effective in developing countries. The decision to administer an antidote should be made after a rapid collateral history is obtained and targeted examination completed. Altered mental status not responding to an antidote or not consistent with exposure history requires further investigation. Metabolic, infective, and surgical (e.g., intracranial injury) causes of altered mental status should be considered.

CARDIAC ARRHYTHMIAS

In general, antiarrhythmic drugs are not first-line treatment for toxin-induced arrhythmias, as most antiarrhythmic drugs have proarrhythmic and negative inotropic properties. Most toxin-induced arrhythmias respond to correction of hypoxia, metabolic/acid–base abnormalities, and administration of an antidote (e.g., digoxin Fab). Sodium bicarbonate is administered for sodium-channel blocker toxicity with cardiovascular complications, such as wide QRS complex tachyarrhythmias. Ventricular tachyarrhythmias may respond to overdrive pacing.

SEIZURES

Drug-induced seizures are treated with titrated doses of IV benzodiazepines, with the exception that isoniazid-induced seizures require pyridoxine. Metabolic disorders, such as hypoglycemia and hyponatremia, can also produce seizures and should be rapidly excluded. Barbiturates are second-line agents for benzodiazepine-resistant seizures (once isoniazid-induced seizures are excluded). There is no role for phenytoin in the treatment of toxin-induced seizures; it has neither theoretical nor proven efficacy, and may worsen toxicity.¹⁶

AGITATION

Agitation is treated with titrated doses of benzodiazepines. Large doses may be required and are appropriate in monitored settings where advanced airway interventions are available if required. Although antipsychotic agents are often used as second-line agents for toxin-induced agitation, they have theoretical disadvantages, including anticholinergic and extrapyramidal effects.¹⁷ Droperidol has been associated (rarely) with QT interval prolongation and cardiac arrhythmias.

HYPERTHERMIA AND HYPOTHERMIA

Patients with core temperatures of >39°C (>102.2°F) require aggressive active cooling measures to prevent complications such as rhabdomyolysis, organ failure, and disseminated intravascular coagulation. Sedation, neuromuscular paralysis, and intubation are required if active measures are ineffective. Several toxidromes associated with hyperthermia are treated with specific pharmaceutical agents: sympathomimetic (benzodiazepines), serotonin (cyproheptadine¹⁸), and neuromuscular malignant syndrome (bromocriptine¹⁹).

Drug-induced coma with subsequent immobility and environmental exposure or inherent drug toxicity (opioids, phenothiazines, ethanol) may produce hypothermia. A core temperature <32°C (<90°F) is an indication for active rewarming.

NALOXONE

Naloxone is a nontoxic, diagnostic, and therapeutic antidote. It is a competitive opioid antagonist administered IV, IM, or intranasally²⁰ to reverse opioid-induced deleterious hypoventilation. Naloxone can be used as a diagnostic agent when history and/or examination findings (respiratory rate of <12 breaths/min is a predictor of response to naloxone) suggest possible opioid exposure. Naloxone is titrated to clinical effect using bolus doses, typically 0.1 to 0.4 milligrams. Large initial bolus doses may precipitate vomiting and aspiration, acute opioid withdrawal, or an uncooperative, agitated patient. Miosis is an unreliable indicator of naloxone’s adequate clinical effect, as some opioids do not affect pupil size. Doses are titrated to achieve desirable ventilation and conscious state (adequate respiratory rate, normal arterial oxygen saturations on room air, and verbal or motor response to voice). Although naloxone may reverse the effects of opioids for 20 to 60 minutes, the effect of many opioids will outlast this time frame with possible return of respiratory depression. Patients should be observed for 2 to 3 hours after administration of IV naloxone.

INTRAVENOUS LIPID EMULSION

Animal studies demonstrate the potential for IV lipid emulsion to act as an antidote for lipophilic toxins. Provision of an intravascular “lipid sink” is postulated as the predominant mechanism, as sequestration of lipophilic toxins prevents target receptor interaction. Human case reports indicate that IV lipid emulsion may provide benefit in cases of potentially life-threatening toxicity from a local anesthetic agent, haloperidol, tricyclic antidepressant, lipophilic β-blocker, or calcium channel blocker.²¹ Currently, IV lipid emulsion can be considered in life-threatening cardiotoxicity caused by lipophilic cardiotoxins that is resistant to conventional therapies.

Following initial resuscitation and stabilization, a risk assessment is performed to predict course of clinical toxicity, interventions required, and patient disposition. Risk assessment is formulated using history, examination, and ancillary test results. Acute poisoning is a dynamic process; therefore, risk assessment may change with time and requires ongoing review.

HISTORY

Patients may not provide a clear history due to psychiatric illness, clinical effects of exposure, and fear of arrest or repercussions from family or friends. Information including identity of substances, doses, and route of exposure is crucial in formulating a risk assessment. Obtain collateral information from family, friends, previous medical records, and usual healthcare provider. Prehospital emergency services can provide information regarding empty medication containers or the scene environment (smells, particular materials or substances present). If possible, obtain knowledge of hobbies, occupation, presence of a suicide note, and recent changes in patient behavior.

EXAMINATION

A systematic physical examination can yield important clues to the nature and potential severity of an exposure (Table 176-3). Examine the skin folds, body cavities if appropriate, and clothing for retained tablets or substances.