eMedicine Specialties > Emergency Medicine > Toxicology
Toxicity, Antihistamine: Treatment & Medication
Updated: Jun 10, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Prehospital Care
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.
Emergency Department Care
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, can retain 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 unprotected airway. 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 one 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, although the development of ileus generally limits its use.
- Agitation
- Anticholinergic-induced delirium ranges from mild confusion to severe agitation with associated hyperthermia and rhabdomyolysis. The administration 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, physostigmine is safe and effective for the treatment of antihistamine-induced agitated delirium, provided that the ECG does not demonstrate conduction disturbances (ie, PR and QRS prolongation); a recent study suggests that physostigmine is more effective and just as safe as benzodiazepines to control antihistamine-induced agitated delirium.39
- Neuroleptic agents, such as haloperidol, have been used but have anticholinergic effects and may exacerbate hyperthermia or provoke a dystonic reaction and their use should be discouraged.
- Physostigmine, a naturally occurring alkaloid obtained from the Ordeal bean Physostigma venenosum, is the only reversible acetylcholinesterase inhibitor lacking a charged quaternary amine moiety. As a tertiary amine, physostigmine traverses the blood-brain barrier and binds to central acetylcholinesterase, increasing acetylcholine levels and, thus, reversing central anticholinergic delirium. Peripheral signs and symptom also are reversed. Considering that patients with anticholinergic symptoms usually fare well with supportive therapy alone, physostigmine is indicated only in the following limited circumstances:
- Single-drug (anticholinergic) exposure39
- Pronounced hallucinations, delirium, or agitation (suggesting a CNS effect) unresponsive to benzodiazepines
- Intractable seizures resistant to all other treatments
- Absence of QRS prolongation on ECG
- Physostigmine should not be used in known antidepressant overdoses. Case series of patients taking maprotiline indicated that seizures developed in 6 out of 7 patients treated with physostigmine. Other reports describe development of asystole for the administration of physostigmine after cyclic antidepressant poisoning. In a series of 21 patients receiving physostigmine, 2 patients experienced seizures and 2 experienced cholinergic reactions (hypersalivation in one patient, bradycardia and hypotension in the other). Thus, use physostigmine cautiously.
- Always have atropine at bedside when using physostigmine in order to reverse excessive cholinergic activity (eg, bradycardia, salivation)
- Manage hyperthermia, especially when severe agitation is present, with neuromuscular paralysis, evaporative cooling, and ice-bath immersion if temperature is higher than 105°F. Use of dantrolene or bromocriptine is controversial.
- Cardiovascular toxicity
- Sinus tachycardia usually does not require treatment. Sedation with a benzodiazepine may be helpful when agitation is also present. Intravenous 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.
- Case reports suggest that physostigmine ends seizures, but clinical experience is limited and no proof of its efficacy for seizure control exists. Treat antihistamine-induced seizures with benzodiazepines and barbiturates. Reserve physostigmine for refractory seizures. One case of using flumazenil for successful reversal of antihistamine-induced depressed mental status in a 7-month-old infant was reported in 2003.40 Evidence to recommend this therapy is insufficient.
The American Association of Poison Control Centers has issued evidence-based consensus guidelines on the out-of-hospital management of diphenhydramine and dimenhydrinate poisoning.41
Consultations
- Regional poison control center or a medical toxicologist as soon as possible
- Intensivist for invasive monitoring and hemodynamic support in complicated cases
- Nephrology service in the case of rhabdomyolysis and acute renal failure
- Psychiatry for intentional overdoses
Medication
Most poisonings result from first-generation antihistamines. Most patients present with anticholinergic symptoms and generally have good outcomes with simple observation and meticulous attention to supportive care. Limit treatment with physostigmine to severe cases. For treatment of cardiac toxicity, include careful monitoring and aggressive treatment of conduction delays or torsade de pointes.
GI decontaminant
These agents are used to limit absorption of ingested antihistamine. Protect the patient’s airway if the patient has diminished mental status.
Activated charcoal (Liqui-Char)
May be administered as long as 4 h postingestion with potential benefit. Anticholinergic features of antihistamines may delay gastric emptying.
Available as aqueous solution or with cathartic (sorbitol 70%).
Adult
1 g/kg PO (with or without cathartic)
Pediatric
<2 years: 1-2 g/kg PO without cathartic
>2 years: 1-2 g/kg PO
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix charcoal with sherbet, milk, or ice cream (decreases adsorptive properties)
Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies; unprotected airway with absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Protect airway in patients at risk of aspiration; not very effective in poisonings of ethanol, methanol, and iron salts; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black
Benzodiazepines
These agents are indicated for the control of anxiety, agitation, and seizures.
Lorazepam (Ativan)
By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. DOC because of more prolonged anticonvulsant effects than diazepam or midazolam (4-6 h vs 1-3 h). Excellent safety profile.
Adult
0.05-0.10 mg/kg (2-7 mg) IV/IM initial over 1-2 min
Status epilepticus: 4 mg IV over 2-5 min; may repeat second dose in 10-15 min, if needed; not to exceed 8 mg
Pediatric
Children: 0.05 mg/kg IV (range, 0.02-0.1 mg/kg)
Adolescents: Administer as in adults
Status epilepticus:
Neonates: 0.05 mg/kg IV over 2-5 min; may repeat in 10-15 min, if needed
Infants and children: 0.1 mg/kg IV slowly over 2-5 min; second dose of 0.05 mg/kg IV at 10-15 min, if needed; not to exceed 4 mg
Adolescents: 0.7 mg/kg IV; not to exceed 4 mg IV slowly over 2-5 min; second dose in 10-15 min, if needed
Alcohol, phenothiazines, barbiturates, and MAOIs increase CNS toxicity
Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor for respiratory depression with high or repeated doses; contains benzyl alcohol, which may be toxic to infants in high doses; caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, Parkinson disease, or patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
Midazolam (Versed)
Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Second-line agent because of shorter anticonvulsant effect and shorter duration of sedation.
Adult
0.05 mg/kg IV; not to exceed 2.5 mg
Pediatric
<32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion
Sedative effects may be antagonized by theophyllines; narcotics and erythromycin may accentuate sedative effects because of decreased clearance; may potentiate sedative effects of other sedatives including H1 blockers; reduce dose of thiopental by 15% when using together
Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages in patients with organic brain syndrome and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
Diazepam (Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.
Third-line agent for agitation or seizures because of shorter duration of anticonvulsive effects and accumulation of active metabolites that may prolong sedation.
Adult
5-10 mg IV q10-15min until symptoms resolve; not to exceed 30 mg
Pediatric
<30 days: Not established
30 days to 5 years: 0.2-0.5 mg IV (slowly) q2-5min until symptoms resolve; not to exceed 5 mg
>5 years: 1 mg IV (slowly) q2-5min until symptoms resolve; not to exceed 10 mg
Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, H1 blockers, barbiturates, alcohols, and MAOIs
Documented hypersensitivity; hypotension; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with other CNS depressants, low albumin levels, or renal and hepatic disease (may increase toxicity); monitor for respiratory depression with high or repeated doses
Cholinergic agents
Acetylcholinesterase inhibitors are indicated to reverse central and peripheral toxicity of anticholinergic substances.
Physostigmine (Antilirium)
Reversible cholinesterase inhibitor that increases concentration of ACh in the myoneural junction. Readily crosses the blood-brain barrier to produce desired CNS effects.
Adult
1-2 mg IV slowly over 3-5 min; may repeat q10min until cessation of life-threatening condition
Pediatric
0.02-0.06 mg IV at a slow, controlled rate; not to exceed 0.5 mg/min or 2 mg as a single dose; clinical effects last 20-60 min; may repeat prn
Atropine antagonizes muscarinic effects of neostigmine; effects of neuromuscular agents are increased
Documented hypersensitivity; asthma; gangrene; diabetes; CV disease; intestinal obstruction; urogenital obstruction; patients receiving choline esters or depolarizing neuromuscular blockers
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor heart rate and rhythm during use; IV injection contains benzyl alcohol, not for use in neonates; anticholinesterase insensitivity can develop for brief or prolonged periods
Cardiovascular agents
These agents alter the electrophysiologic mechanisms responsible for arrhythmia.
Sodium bicarbonate (Neut)
First-line agent for prolongation of QRS interval after overdose with antihistamine with quinidinelike effects.
Adult
1 mg/kg slow IV push; if continuous infusion is desired, may add 2-3 amps of 50 mEq sodium bicarbonate to 1 L D5W and infuse to maintain serum pH of 7.45-7.55
Pediatric
Administer as in adults
Urinary alkalinization, induced by increased sodium bicarbonate concentrations, may cause decreased levels of lithium, tetracyclines, chlorpropamide, methotrexate, and salicylates; increases levels of amphetamines, pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine; may inactivate catecholamines
Documented hypersensitivity; alkalosis (pH>7.5); volume overload; severe hypernatremia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May shift oxygen hemoglobin dissociation curve to left; only use to treat documented metabolic acidosis and hyperkalemia-induced cardiac arrest; can cause alkalosis, decreased plasma potassium, hypocalcemia, and hypernatremia; caution in electrolyte imbalances such as patients with CHF, cirrhosis, edema, corticosteroid use, or renal failure; avoid extravasation since can cause tissue necrosis
Magnesium sulfate
First-line agent in the treatment of antihistamine-associated torsade de pointes.
Adult
2-4 g slow IV push over 3-5 min; follow with infusion of 3-20 mg/min for 5-24 h
Pediatric
25-50 mg/kg/dose IV over 3-5 min; infuse at 60 mg/kg/d IV
Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade observed with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants and betamethasone; may increase cardiotoxicity of ritodrine
Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
May alter cardiac conduction leading to heart block in digitalized patients; monitor respiratory rate, deep tendon reflex, and renal function when electrolyte is administered parenterally; caution when administering magnesium dose because may produce significant hypertension or asystole; in overdose, calcium gluconate (10-20 mL IV of 10% solution) can be administered as antidote for clinically significant hypermagnesemia
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Further Reading
Keywords
antihistamine toxicity, antihistamine overdose, alkylamine, antihistamine exposure, antihistamine poisoning, brompheniramine, cetirizine, clemastine, cyproheptadine, desloratadine, diphenhydramine, doxylamine, ethanolamine, ethylenediamine, fexofenadine, H1-receptor antagonists, H2-receptor antagonists, levocetirizine, loratadine, meclizine, nonsedating H1 blockers, phenothiazine, piperazine, promethazine, tripelennamine, triprolidine
