Severe symptoms include delirium, psychosis, seizures, coma, and death. In mild cases, patients may experience anticholinergic toxidrome. 10,11ĭiphenhydramine is an antihistamine that can cause life-threatening complications in the setting of overdoses. There is also anecdotal evidence for the use of IV lipid emulsion and extracorporeal membrane oxygenation in severe cases. 3 The anticonvulsant of choice for treating seizures from diphenhydramine are benzodiazepines, not physostigmine. Other treatment modalities for diphenhydramine overdoses include sodium bicarbonate for QRS widening. 9 Overall, physostigmine improves anticholinergic delirium in the majority of patients with few adverse events. When compared to benzodiazepines, physostigmine is far more effective in reversing agitation and delirium (87% for physostigmine vs 24% for benzodiazepines). 8 The death was not temporally related to physostigmine administration. A retrospective cohort study from 2003 to 2012 on patients who received physostigmine found the following adverse event rates: none (95.3%), emesis (2.1%), QTc prolongation (1%), seizure (1%), and death (0.5%). Physostigmine is very safe when given to patients with anticholinergic delirium. 3 This can be avoided by diluting each physostigmine dose of 0.5 to 1 mg in 10 mL D5W or normal saline and administering as a slow IV push over 2 to 5 minutes. Precipitation of seizures is another concern for physostigmine. Under these circumstances, physostigmine may worsen conduction disturbances, and cause bradyarrythmias or asystole. Thus, physostigmine should be avoided in patients with a widened QRS, AV block, or bradycardia. 3 Such patients are not suffering anticholinergic delirium and instead require resuscitation with fluids, pressors, benzodiazepines, and sodium bicarbonate. 7 Hence, physostigmine is contraindicated in tricyclic antidepressant overdose. The fear of physostigmine comes from early case reports that resulted in two deaths after overdosing on tricyclic antidepressants and receiving the physostigmine. Administration of physostigmine can potentially prevent a patient from being intubated and/or receiving copious amounts of sedatives, including benzodiazepines and antipsychotics. ![]() 3Īntilirium® (physostigmine), as a true anticholinergic antidote, should be strongly considered for diphenhydramine-induced delirium and agitation. 6 Fatal deaths have also been reported with oral doses greater than 20 mg/kg. 5 There is an even greater risk of seizures, coma, and death when ingestions are greater than 1.5 grams of diphenhydramine. With ingestions greater than 1 gram, diphenhydramine may result in delirium, psychosis, seizures, coma, and death. 2 Diphenhydramine-induced QRS widening and QTc prolongation can be seen on an electrocardiogram. Common signs and symptoms of overdose include confusion, urinary retention, tachycardia, blurry vision, dry mouth, irritability, and hallucinations. The toxicities associated with diphenhydramine are dose dependent. Additionally, there is concern for diphenhydramine’s cardiotoxic effects that derive from sodium and potassium channel blockade at higher doses. 3 The antihistamine is a lipophilic drug, which allows it to readily cross the blood-brain barrier. This fad was brought into the media spotlight in more recent months, but diphenhydramine has been one of the most common intentional ingestions even prior to the trend.ĭiphenhydramine is a peripherally and centrally acting first generation H1-antagonist with anticholinergic, antitussive, antiemetic, and local anesthetic properties. 2 Teenagers and young adults have been participating in the “Benadryl Challenge” on TikTok, where they post videos of themselves taking large quantities of diphenhydramine. 1 Reports of adolescents overdosing on diphenhydramine has drawn national attention. Food and Drug Administration released a warning in September 2020 regarding the dangers of taking more than the recommended doses for over-the-counter Benadryl® (diphenhydramine) allergy medication. Call the Utah Poison Control Center at 1-80 at any time 24/7 for assistance in managing anticholinergic toxicity and administering physostigmine. ![]() Physostigmine is a safe and effective antidote for anticholinergic poisoning. ![]()
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