Efficacy of lipid emulsion therapy in treating cardiotoxicity from diphenhydramine ingestion: a review and analysis of case reports

Introduction Lipid emulsion therapy (LET) has been most thoroughly studied to reverse local anesthetic systemic toxicity (LAST). Case reports suggest that LET can successfully rescue cardiovascular collapse from bupropion, amitriptyline, and propranolol. The efficacy of LET against refractory hypotension and dysrhythmias from diphenhydramine, a commonly ingested lipophilic cardiotoxic agent, is less well described. Objective Summarize the evidence that LET rescues cardiac ion channel blockade (QRS, QTc widening) or hypotension attributable to diphenhydramine overdose. Methods We searched MEDLINE, EMBASE, and Google Scholar for English-language full-length case reports of diphenhydramine (DPH) intoxication in patients 17 years of age or older. We extracted data with a PRISMA-compliant protocol, dividing the case reports into two groups, one that received LET and one that did not. We performed a pooled analysis to compare the change in mean arterial pressure (MAP), QRS duration, and QTc duration between the two groups. Results We identified 23 reports (25 patients). Lipid emulsion therapy (LET) was used in 6 cases because the patient suffered from hypotension refractory to traditional resuscitation. Those who received LET and those who did not were comparable in age, gender, amount ingested, and frequency of seizures. The mean arterial pressure (MAP) decreased by 4.5 +/- 11.5 mm Hg in those who did not receive LET compared to an increase in MAP 37 +/- 17.5 mm Hg in those who did receive LET. The QRS narrowed by 29 +/- 33.9 ms (no LET group) vs 68 +/- 49.5 ms (LET group) and QTc by 168.5 +/- 126.75 ms (no LET group) vs 134 +/- 88 ms (LET group). All values are expressed as median +/- interquartile range. One out of the 6 patients who received LET died after withdrawal of care. In the group that did not receive LET 4 out of 19 died and 3 had no outcome reported. Discussion LET may improve MAP in patients with hypotension refractory to vasopressors due to diphenhydramine toxicity. We found no significant effect of LET on QRS or QTc duration. These results are limited by a small sample size, reporting bias of case reports, incomplete data, and heterogeneity. Conclusion An analysis of pooled case reports suggests that LET may rescue hypotension when other methods have failed in patients with hypotension attributable to diphenhydramine overdose.