Diphenhydramine, Sodium Bicarbonate, or Combination for Acute Peripheral Vertigo: A Randomized Clinical Trial.

Importance: Intravenous diphenhydramine is commonly used to treat acute peripheral vertigo but may cause sedation. Sodium bicarbonate, an alternative therapy used in Eastern countries, may relieve vertigo symptoms without lethargy. However, comparative evidence is limited. Objective: To evaluate the efficacy and safety of diphenhydramine, sodium bicarbonate, and their combination in treating acute peripheral vertigo among emergency department (ED) patients. Design, Setting, and Participants: A triple-arm, double-blind, randomized clinical trial was conducted at the National Taiwan University Hospital, Yunlin Branch ED, from January 17 to November 14, 2023. Adults with peripheral vertigo within 24 hours of onset were enrolled. Exclusion criteria included refusal, pregnancy, prior antivertigo medication use, symptom duration of more than 24 hours, heart failure, chronic kidney disease, or drug allergy. Interventions: Patients were randomized in a 1:1:1 ratio to receive 30 mg of intravenous diphenhydramine (group A), 66.4 mEq (approximately 1 mEq/kg) of sodium bicarbonate (group B), or both agents (group C). Main Outcomes and Measures: The primary outcome was change in vertigo severity using a 10-point visual analog scale (VAS) at 60 minutes after treatment. Key secondary outcomes included change in nausea severity using a 10-point VAS, rescue medication use, ED length of stay, and adverse effects. Analysis was performed on a modified intention-to-treat basis. Results: Among 222 patients (mean [SD] age, 57.9 [17.6] years; 150 women [67.6%%]), group C had greater improvement in vertigo severity than group A (mean [SD] VAS score, -5.6 [2.1] vs -4.4 [2.7]; P = .01), with the treatment effect most pronounced among younger male patients without a history of vertigo. Group B showed similar VAS improvement compared with group A (mean [SD] VAS score, -5.1 [2.2] vs -4.4 [2.7]; P = .34). Rescue therapy was used less frequently in group C (17.8% [13 of 73]) than in group A (46.7% [35 of 75]; P < .001). No differences were observed between groups in nausea scores or ED length of stay. Lethargy was more common in diphenhydramine groups than in the sodium bicarbonate group (moderate lethargy: group A, 38.7% [29 of 75] and group C, 30.1% [22 of 73] vs group B, 8.1% [6 of 74]; P < .001). Injection discomfort was more common with sodium bicarbonate (group A, 8.0% [6 of 75]; group B, 17.6% [13 of 74]; group C, 28.8% [21 of 73]; P = .004). Conclusions and Relevance: In this randomized clinical trial of patients with acute peripheral vertigo, combination therapy provided better symptom relief than diphenhydramine alone. Further studies should focus on the determination of peripheral vertigo types that can benefit from sodium bicarbonate and the underlying mechanisms. Trial Registration: ClinicalTrials.gov Identifier: NCT05676216.