Approach Considerations
Some states have laws mandating the reporting of child abuse, suspicion of child abuse, and neglect. If the history of ingestion is suspicious, reporting may be necessary.
Paramedics should follow set protocols for gastric decontamination, hypotension, and seizures; symptomatic patients should be transported rapidly with intravenous access and cardiac monitoring. Benzodiazepines may be used for agitation or seizures.
In the emergency department (ED), basic tenets of emergency care should dictate therapy. Perform bedside determinations of glucose for patients with altered levels of conscious and treat with intravenous dextrose, if appropriate. For hypotensive patients, administer 0.9% sodium chloride solution or lactated Ringer solution as boluses. Dopamine, or other cardiac pressor, may be titrated to achieve an acceptable blood pressure.
Administer activated charcoal to patients who are cooperative, have a good gag reflex, and can take liquids by mouth safely. Perform endotracheal intubation before instillation of activated charcoal for patients with significant CNS depression and an unprotected airway. The clinician should be aware that a severely toxic patient can experience seizures and aspirate charcoal.
Gastric emptying has not proven beneficial if the patient presents more than 1 hour postingestion, although case reports involving anticholinergic agents have demonstrated erratic absorption and repeated worsening of anticholinergic symptoms over 9 days. Ipecac syrup is not recommended in the ED because it may delay the administration of activated charcoal and seizures may occur at any time, with the possibility of aspiration. Repeated doses of activated charcoal may prevent continued absorption, but the development of ileus generally limits its use.
Anticholinergic-induced delirium ranges from mild confusion to severe agitation with associated hyperthermia and rhabdomyolysis. The use of chemical and physical restraints often is necessary to prevent patients from harming themselves or others. Controlling muscular activity is crucial in severely agitated patients, because agitation may exacerbate muscle injury, acidosis, rhabdomyolysis, and hyperthermia.
Although benzodiazepines often are considered first-line agents, physostigmine is safe and effective for the treatment of antihistamine-induced agitated delirium, provided that the electrocardiogram (ECG) does not demonstrate conduction disturbances (ie, PR and QRS prolongation). One study suggests that physostigmine is more effective and just as safe as benzodiazepines for controlling antihistamine-induced agitated delirium. [73] Physostigmine also reverses peripheral anticholinergic signs and symptoms.
Considering that patients with anticholinergic symptoms usually fare well with supportive therapy alone, physostigmine is indicated only in the following limited circumstances [73] :
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Single-drug (anticholinergic) exposure
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Pronounced hallucinations, delirium, or agitation (suggesting a CNS effect) unresponsive to benzodiazepines
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Intractable seizures resistant to all other treatments
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Absence of QRS prolongation on ECG
Always have atropine at bedside when using physostigmine in order to reverse excessive cholinergic activity (eg, bradycardia, salivation).
Treat antihistamine-induced seizures with benzodiazepines and barbiturates. Reserve physostigmine for refractory seizures. Although case reports suggest that physostigmine ends seizures, clinical experience is limited and no proof of its efficacy for seizure control exists.
Neuroleptic agents, such as haloperidol, have been used but have anticholinergic effects and may exacerbate hyperthermia or provoke a dystonic reaction. Their use should be discouraged.
Manage hyperthermia, especially when severe agitation is present, with neuromuscular paralysis, evaporative cooling, and ice-bath immersion if temperature is higher than 105°F (40.6°C). Use of dantrolene or bromocriptine is controversial.
Sinus tachycardia usually does not require treatment. Sedation with a benzodiazepine may be helpful when agitation is also present. Intravenous (IV) sodium bicarbonate improves widening of QRS that may result from antihistamines with sodium channel blocking properties (eg, diphenhydramine, pyrilamine). Provide support for patients with profound cardiovascular toxicity. In rare cases of refractory shock, placement of an intra-aortic balloon pump for several hours may bridge the patient through a period of cardiovascular collapse.
The American Association of Poison Control Centers has issued evidence-based consensus guidelines on the out-of-hospital management of diphenhydramine and dimenhydrinate poisoning. [71]
Emergency Department Management
Ensure the patient has adequate airway, breathing, and circulation. Place the patient on a cardiorespiratory monitor and obtain intravenous (IV) access if the patient appears ill or is symptomatic. Administer oxygen, naloxone, and glucose if an unexplained decreased level of consciousness is observed.
Obtain the patient's history through a relative or emergency medical services (EMS) personnel. Examine the patient, looking for an anticholinergic toxidrome. Obtain appropriate lab tests and an ECG. Perform cardiac monitoring on all symptomatic patients or as long as tachycardia, conduction delays, or prolonged QT intervals persist.
Consider decontamination with activated charcoal, if ingestion was recent and airway control is assured. Treat acute dystonic reactions with benzodiazepines.
Provide other supportive measures. Consider hospital admission if ingestion is significant or if the patient continues to be symptomatic. Contact the regional poison control center.
Gastrointestinal Decontamination
Activated charcoal is the first-line defense in GI decontamination and should be given to the patient if a significant ingestion has occurred within recent hours before presentation. Activated charcoal is most effective if administered within 1 hour of ingestion.
Complications of activated charcoal administration include emesis and aspiration; consequently, patients should be cooperative, have a good gag reflex, and be able to take liquids by mouth safely. Patients with significant CNS depression require endotracheal intubation to secure the airway before administration of activated charcoal.
The optimal dose of charcoal is not well established. Usual doses are as follows:
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Adults and adolescents: 25-100 g in adults and adolescents
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Children aged 1-12 years: 25-50 g
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Infants younger than 1 year: 1 g/kg
Multiple doses of activated charcoal are not recommended because charcoal concretions may form leading to intestinal obstruction or ileus. Antihistamines may induce intestinal ileus causing delayed absorption of drug and delayed toxicity.
Other methods of decontamination
Controversial methods of decontamination include gastric lavage and ipecac syrup. Use of these agents should be on the advice of a poison center or toxicologist.
Ipecac and gastric lavage have fallen into disfavor, and cathartic therapy is not recommended, especially in children. Emesis is not usually recommended and is specifically contraindicated if a depressed gag reflex, CNS depression, ingestion of a corrosive substance, or high aspiration potential is noted.
Treatment of Dystonic Reactions
Dystonic reactions are treated with diphenhydramine in doses of 1 mg/kg IV every 2 minutes, with a maximum of 5 mg/kg/d, unless the dystonic reaction is thought to be caused by or involve antihistamine intoxication. Acute dystonic reactions to antihistamines may be treated with oral (PO) or IV diazepam. The dose is 0.1-0.3 mg/kg (slowly if IV) and as much as 10 mg in adults.
Treatment of Seizures
Seizures can be treated with lorazepam. The pediatric dose is 0.05-0.1 mg/kg, not to exceed 4 mg/dose; doses may be repeated every 10-15 minutes as needed. The adult dose is 4 mg, given by slow IV at 2 mg/min; if seizures persist after 10-15 minutes, administer 4 mg IV again. Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Case reports suggest that physostigmine may be effective for seizures refractory to benzodiazepines.
Treatment of Serotonin Syndrome
Serotonin syndrome must be managed by addressing each symptom individually. Hyperthermia should be managed by undressing the patient and enhancing evaporative heat loss by keeping the skin damp and using cooling fans. Muscle activity and agitation may be diminished with the use of diazepam.
Cyproheptadine is a nonspecific 5-hydroxytryptamine (5HT, serotonin) antagonist that has been shown to block development of serotonin syndrome in animals and is suggested as an antidote for serotonin syndrome in humans. It is available only as an oral preparation. Propranolol also has been used to some benefit as a 5HT1A receptor antagonist.
Treatment of Other Conditions
Cardiac arrhythmia can be managed with the appropriate cardiac medicine per advanced life support guidelines. [74] In diphenhydramine overdoses, bicarbonate may be helpful in treating QRS complex abnormalities and cardiac dysrhythmias. Treatment with bicarbonate in this overdose should be used in concert with poison center or medical toxicology consultation.
Successful use of intravenous lipid emulsion treatment for DPH overdose has been reported. [75]
Rhabdomyolysis is managed by ensuring adequate hydration to maintain urine output at 2 mg/kg/h. Furosemide or mannitol may be needed to maintain diuresis. Consider using a solution of sodium bicarbonate and potassium chloride to alkalinize the urine to a pH of at least 7.5. Monitor serum pH to avoid inducing severe alkalemia. Chart strict intake and output. Consult a nephrologist for oliguria or renal failure, and arrange hemodialysis for the anuric or severely acidotic patient.
Muscle rigidity and hyperactivity are secondary to sympathomimetic toxicity and can be controlled with neuromuscular paralysis.
Hyperthermia associated with sympathomimetics can be controlled with external evaporative cooling, removing the patient's clothes, and spraying with tepid water and fanning.
Use of Physostigmine
Use of physostigmine in antihistamine poisoning is extremely controversial, and it should not be given unless directed by a regional poison control center or in direct consultation with a medical toxicologist. Physostigmine, an anticholinesterase, may be indicated in the suspected anticholinergic poisoning for its therapeutic value.
Physostigmine is a tertiary amine that crosses the blood brain barrier and reverses both the central and the peripheral effects of anticholinergics. Reversal of anticholinergic signs and symptoms is not long-lasting because physostigmine has a relatively short duration of action (20-60 min). Indications are severe life-threatening complications, such as coma, hypotension with dysrhythmias unresponsive to other attempts at treatment, and intractable seizures.
Adolescent and adult trial dosages are 2 mg IV slowly every 5 minutes. To administer, dilute the dose of physostigmine in 10 mL of dextrose 5% in water (D5W) or in 10 mL of isotonic sodium chloride solution.
Hospital Admission
Patients with suspected cough, cold, or allergy preparation poisoning with persistent or significant hypertension, dysrhythmia, or CNS stimulation require admission for monitoring. For all intentional overdoses, a psychiatric evaluation is necessary. The decision to admit the patient to the intensive care unit should be based on the following:
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Initial presentation
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Comorbid diseases
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Nature and number of the involved agents
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Potential for delayed toxicity
Long-Term Monitoring
Most regional poison control centers have their own protocols on who may be observed at home; contact them if ingestion has occurred. As a general rule, patients who ingest less than 3 times the maximum daily dose can be observed at home.
If symptoms are present (other than mild somnolence) or ingestion is more than 4 times the maximum daily dose, the patient should be referred to a health care facility. The patient should be observed for 4-6 hours following ingestion of liquid and immediate-release solid preparations. Ingestion of sustained-release products may result in delayed onset of symptoms and may require longer periods of observation.
Patients who have ingested less than 10 mg/kg of dextromethorphan can be treated at home. If the patient has ingested a long-acting dextromethorphan preparation, refer the patient to a health care facility for evaluation.
If the ingestion was intentional, prompt psychiatric evaluation and admission is warranted. Additional counseling and social work involvement may be required for patients engaging in recreational abuse.
With children, further outpatient treatment should include teaching the patient's caretaker about medication storage and safety.
Consultations
The following consultations may be necessary:
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Regional poison control center or a medical toxicologist as soon as possible
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Intensivist for invasive monitoring and hemodynamic support in complicated cases
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Nephrology service in the case of rhabdomyolysis and acute renal failure
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Psychiatry for intentional overdoses
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Neurology for neurologic complications
Prevention
Medications should be labeled and stored safety. Child-resistant closures should be applied to all medications and substances that can cause significant toxicity, such as cough and cold medications. Childproof safety caps and clear labeling have been shown to decrease toxic exposures in young children and elderly individuals. Elderly persons should not use anticholinergics as sleep aids.
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Dextromethorphan.
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Terfenadine is the antihistamine most commonly associated with torsade de pointes in both acute overdose and therapeutic administration.
