Preventive effects of first-generation antihistamine on emergence agitation or delirium: a systematic review

Eur J Clin Pharmacol. 2024 Dec;80(12):1883-1892. doi: 10.1007/s00228-024-03748-9. Epub 2024 Sep 12.

Abstract

Purpose: The effects of first-generation antihistamines in preventing postoperative emergence agitation or delirium are unclear. Determining the postoperative effects of first-generation antihistamines may provide important insights into the management of patient safety. Therefore, we performed a systematic review of randomized controlled trials (RCTs) evaluating the efficacy and safety of postoperative first-generation antihistamines.

Methods: Patients who used first-generation antihistamines in the intensive care unit or operating room were included. Primary outcomes were assessed postoperative emergence agitation or delirium with binary and continuous variables. The secondary outcome was any adverse event.

Results: Nine studies were included. The frequency of postoperative emergence agitation, measured using binary variables, tended to be lower in patients receiving chlorpheniramine or diphenhydramine than those receiving saline. However, evaluation using the Richmond Agitation-Sedation Scale as a continuous variable revealed that only chlorpheniramine was effective at lowering postoperative emergence agitation. Only one study assessed delirium but found no benefit of first-generation antihistamines. Adverse events for first-generation antihistamines did not differ from that of other drugs.

Conclusion: Our results provide limited evidence that some first-generation antihistamines may prevent postoperative emergence agitation and are safe. To further verify this possibility, new RCTs with clear and universal assessment criteria for postoperative emergence agitation or delirium should be conducted.

Keywords: Delirium; Histamine H1 antagonists; Postoperative period; Systematic review.

Publication types

  • Systematic Review

MeSH terms

  • Chlorpheniramine / therapeutic use
  • Delirium / prevention & control
  • Diphenhydramine / administration & dosage
  • Diphenhydramine / adverse effects
  • Diphenhydramine / therapeutic use
  • Emergence Delirium* / prevention & control
  • Histamine Antagonists / adverse effects
  • Histamine Antagonists / therapeutic use
  • Histamine H1 Antagonists / adverse effects
  • Histamine H1 Antagonists / therapeutic use
  • Humans
  • Postoperative Complications / prevention & control
  • Psychomotor Agitation / prevention & control
  • Randomized Controlled Trials as Topic

Substances

  • Chlorpheniramine
  • Diphenhydramine
  • Histamine Antagonists
  • Histamine H1 Antagonists