Morphine Plus Placebo vs Morphine Plus Acetaminophen for Acute Pain in the Emergency Department: A Randomized Clinical Trial
Abstract
IMPORTANCE: Intravenous (IV) acetaminophen is widely used in multimodal analgesia with opioids for the initial management of acute pain in emergency departments (EDs), but its additive benefit when combined with titrated morphine is uncertain.
OBJECTIVE: To determine whether titrated IV morphine plus placebo is noninferior to titrated IV morphine plus acetaminophen for pain relief in the first hour in adults seen in the ED with acute traumatic or nontraumatic pain.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, double-blind, randomized, placebo-controlled noninferiority clinical trial was conducted in 11 French EDs from December 3, 2019, to December 31, 2024, with 60 minutes of follow-up. Adults (aged ≥18 years) with severe acute pain (numeric rating scale [NRS] score ≥5 on a scale from 0 [no pain] to 10 [worst pain]) of traumatic or nontraumatic origin were eligible. Prespecified analyses were planned for traumatic and nontraumatic pain.
INTERVENTIONS: All patients received weight-based titrated IV morphine. In the control group, patients also received 1 g IV acetaminophen; in the intervention group, patients received matching placebo.
MAIN OUTCOMES AND MEASURES: The primary outcome was the mean change in NRS pain score from baseline to 30 minutes. The noninferiority margin was 1 point. Analyses were conducted in modified intention-to-treat (mITT) and per-protocol (PP) populations.
RESULTS: Among 430 randomized patients (median age, 42 years [IQR, 29-57 years]; 220…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 430 participants or records.
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