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Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis
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  • Published on:
    Reply to: Diphenhydramine should be co-administered with intravenous prochlorperazine to prevent akathisia
    • Ryan S D'Souza, Anesthesiologist Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN
    • Other Contributors:
      • Anthony Donato, Internal Medicine Physician and Professor of Medicine

    Dear Editor,
    We thank Drs. Vinson et al. for their thoughtful comments as well as their important research that was the basis for our systematic review.1 While we proposed that difference in administration time was one possible explanation for the heterogeneity that we identified, Dr. Vinson’s proposal that the between-drug differences could also explain the heterogeneity is just as plausible. Although we did not include the two trials investigating different administration times of prochlorperazine since we limited our inclusion criteria to trials that used diphenhydramine prophylaxis, we do acknowledge the importance that infusion time of prochlorperazine does not affect the incidence of akathisia given the current evidence.2 3 We completely concur with Dr. Vinson’s conclusion that the differences between prochlorperazine and metoclopramide deserve to be further explored in a randomized trial, but until then, his suggestions of how to proceed appear consistent with our study’s findings.

    1. D'Souza RS, Mercogliano C, Ojukwu E, et al. Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis. Emerg Med J 2018.
    2. Collins RW, Jones JB, Walthall JD, et al. Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, contro...

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    Conflict of Interest:
    None declared.
  • Published on:
    Diphenhydramine should be co-administered with intravenous prochlorperazine to prevent akathisia
    • David R Vinson, Emergency physician and clinical researcher The Permanente Medical Group and the KP CREST Network, Oakland, California, USA
    • Other Contributors:
      • Benjamin W Friedman, Emergency physician and clinical researcher

    Dear Editor,

    We commend Dr D’Souza et al for their systematic review of the effects of prophylactic diphenhydramine in the reduction of akathisia induced by intravenous dopamine D2 antagonist antiemetics.1 Akathisia is a dysphoric feeling of restlessness that ranges from mild to severe, the more severe expressions of which can be quite distressing to patients.2 Attention to its prevention is welcome. We took particular interest in the systematic review because we led three of the four studies included in the meta-analysis.2-4

    The authors conclude that adjunct diphenhydramine reduces akathisia when dopamine D2 antagonist antiemetics are administered over 2 minutes, but diphenhydramine fails to augment the reduction in akathisia achieved by simply slowing the antiemetic infusion to 15 minutes. They report moderately high heterogeneity among the four included studies (I2 =43%).5 This reveals an inconsistency in results between studies that precludes a one-size-fits-all recommendation on the use of prophylactic diphenhydramine. Such an elevated I2 requires explanation. The authors attribute this heterogeneity to rates of infusion and determine that a 15-minute infusion is less likely to cause akathisia.

    But another explanation for the heterogeneity is at hand that the authors did not explore: prochlorperazine and metoclopramide behave differently when it comes to akathisia preventio...

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    Conflict of Interest:
    None declared.