A randomized, noninferiority, controlled trial of two doses of intravenous subdissociative ketamine for analgesia in the emergency department.

Abstract

This study aimed to determine if 0.15mg/kg intravenous (IV) subdissociative ketamine is noninferior to 0.3mg/kg in emergency department (ED) patients with acute pain. This randomized, prospective, double-blinded, noninferiority trial included patients' age 18 to 59years presenting to the ED with acute moderate to severe pain. Subjects were randomized to IV subdissociative ketamine, 0.15mg/kg ("low" dose) or 0.30mg/kg ("high" dose), over 15 minutes. The primary endpoint was the 11-point numeric rating scale (NRS) pain score between groups at 30 minutes. Secondary endpoints included NRS pain scores at 15 and 60 minutes; change in NRS at 15, 30, and 60 minutes; rescue analgesia; and adverse effects. The noninferiority limit, δ0 , was set to 1.3. Forty-nine patients were included in each group. After the differences in the baseline NRS score were adjusted for, the mean NRS score at 30 minutes was 4.7 (95% confidence interval [CI]= 3.8 to 5.5) in the low-dose group and 5.0 (95% CI= 4.2 to 5.8) in the high-dose group (mean difference= 0.4, 95% CI= -0.8 to 1.5), indicating that the low-dose subdissociative ketamine was noninferior to the high dose (lower limit of 95% CI=-0.8 to ≥1.3= -δ0 ). Adverse effects were similar at 30 minutes. At 15 minutes, the high-dose group experienced greater change in NRS; however, more adverse effects occurred. Our data did not detect a large difference in analgesia or adverse effect profile between0.15mg/kg IV ketamine and0.30mg/kg in the short-term treatment of acute pain in the ED.