256 Intravenous Sub-Dissociative Dose Ketamine for Analgesia in the Emergency Department: A Dosing Comparison

Abstract

Sub-dissociative ketamine (SDK) is a safe and efficacious alternative and adjunctive agent to opioids in the treatment of acute pain in the emergency department (ED). While SDK via short intravenous (IV) infusion has shown decreased side effects compared to IV push, there is a wide range of acceptable analgesic dose. The purpose of this study is to compare the analgesic efficacy and safety of IV SDK at 0.15 mg/kg versus 0.3 mg/kg in ED patients with acute pain. This was a randomized, prospective, double-blinded, non-inferiority trial. A convenience sample of patients age 18-59 years with acute abdominal, flank, back, musculoskeletal pain, or headache with visual analog scale (VAS) pain score of ≥5 were included. Subjects were randomized to either IV SDK 0.15mg/kg (“low” dose) or 0.3 mg/kg (“high” dose) over 15 minutes. The primary endpoint was change in 11-point VAS pain score from baseline to 30 minutes after administration. Secondary endpoints included change in VAS at 15 and 60 minutes, and rescue analgesia. Safety endpoints included patient-reported adverse effects according to the Side Effects Rating Scale of Dissociative Anesthetics (SERSDA), and Richmond Agitation Sedation Scale (RASS) at 15, 30 and 60 minutes post-administration. Of the 93 patients screened, 65 (70%) were included (low dose group: n=33; high dose group: n=32). Most exclusions were due to patient refusal (n= 25; 68%). The most common type of pain was abdominal (45%) or musculoskeletal (32%) pain. Pain onset was <24 hours of presentation for most (53%) patients. Baseline comorbidities were similar between groups, with the exception of diabetes (27% low dose group vs. 5.7% high dose group, p=0.03), depression (2.7% low dose group vs. 20% high dose group, p=0.03) and anxiety (0% low dose group vs. 11.4% high dose group, p=0.03) (Table 1). Median ketamine dose was 13.6 mg and 25.3 mg, respectively. Median baseline pain scores were similar between groups (10 [IQR 8-10] vs. 9 [IQR 7 -10] , p =0.07). There was no difference in the primary endpoint of median change in VAS score from baseline to 30 minutes (- 4 [IQR [-2 to -6] low dose group vs. -3.5 high dose group [IQR -1 to -5], p=.43). Additionally, there were no differences in median pain scores or adverse effects at any time point (Table 1). IV SDK 0.15 mg/kg was non-inferior to SDK 0.3 mg/kg for treatment of acute pain in the ED with similar adverse effects between groups. Clinicians should consider using 0.15 mg/kg for treatment of acute pain as it is efficacious, and there is no apparent benefit to higher doses.