Is there a benefit to administering magnesium (Mg) for refractory diphenhydramine (Benadryl) overdose?

From the Guidelines

Administering magnesium sulfate may provide benefit in cases of refractory diphenhydramine (Benadryl) overdose, particularly when standard treatments have failed. For severe cases not responding to conventional therapy, IV magnesium sulfate can be considered at doses of 2-4 grams administered over 20 minutes, with careful cardiac monitoring, as supported by the 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care 1. Magnesium works by competing with sodium at the cardiac sodium channels, potentially counteracting the sodium channel blockade caused by diphenhydramine toxicity. This mechanism may help resolve refractory ventricular dysrhythmias and QRS prolongation that can occur in severe overdoses. Some key points to consider when administering magnesium sulfate include:

• Monitoring for hypotension, respiratory depression, and loss of deep tendon reflexes, which can indicate magnesium toxicity
• Using magnesium as an adjunct to, not a replacement for, standard treatments including sodium bicarbonate, benzodiazepines for seizures, and supportive care
• Being aware that evidence is limited to case reports and small series, but magnesium represents a reasonable option when facing life-threatening diphenhydramine toxicity unresponsive to conventional management, as noted in the study by 1. Key considerations for the use of magnesium sulfate in this context include:
• The potential for magnesium to counteract sodium channel blockade and improve cardiac function
• The importance of careful monitoring and dose adjustment to avoid magnesium toxicity
• The need for further research to fully establish the efficacy and safety of magnesium sulfate in refractory diphenhydramine overdose.

From the Research

Treatment of Refractory Benadryl Overdose

There are several studies that discuss the treatment of diphenhydramine (Benadryl) overdose, including refractory cases.

• The use of magnesium and sodium bicarbonate is recommended in some cases 2.
• Physostigmine may be reserved for administration in a hospital 2.
• Benzodiazepines may be administered if agitation or seizures are present 2.
• Intravenous lipid emulsion has been used in the treatment of severe diphenhydramine overdose, with some cases showing improvement 3, 4.
• Activated charcoal may be used as an adjunct in the treatment of antihistamine overdose, with maximal and multiple doses recommended 5.

Administration of Magnesium

The administration of magnesium is mentioned in the context of treating diphenhydramine overdose, particularly in cases with widened QRS intervals 3.

• However, there is limited information on the specific use of magnesium in refractory Benadryl overdose.

Current Research and Recommendations

Current research suggests that more study is needed to determine the ideal therapeutic approach to treating antihistamine overdoses 6.

• The use of newer treatments such as donepezil, dexmedetomidine, and lipid emulsion therapy may be considered in refractory cases 6, 3, 4.
• It is essential to consider the individual patient's circumstances and the severity of the overdose when determining the best course of treatment 2.