Slow Infusion of Low-dose Ketamine Reduces Bothersome Side Effects Compared to Intravenous Push: A Double-blind, Double-dummy, Randomized Controlled Trial.

Abstract

We compared the analgesic efficacy and incidence of side effects when low-dose (0.3 mg/kg) ketamine (LDK) is administered as a slow infusion (SI) over 15 minutes versus an intravenous push (IVP) over 1 minute. This was a prospective, randomized, double-blind, double-dummy, placebo-controlled trial of adult ED patients presenting with moderate to severe pain (numerical rating scale [NRS] score ≥ 5). Patients received 0.3 mg/kg ketamine administered either as a SI or a IVP. Our primary outcome was the proportion of patients experiencing any psychoperceptual side effect over 60 minutes. A secondary outcome was incidence of moderate or greater psychoperceptual side effects. Additional outcomes included reduction in pain NRS scores at 60 minutes and percent maximum summed pain intensity difference (%SPID). Fifty-nine participants completed the study. A total of 86.2% of the IVP arm and 70.0% of the SI arm experienced any side effect (difference = 16.2%, 95% confidence interval [CI] = -5.4 to 37.8). We found a large reduction in moderate or greater psychoperceptual side effects with SI administration-75.9% reported moderate or greater side effects versus 43.4% in the SI arm (difference = 32.5%, 95% CI = 7.9 to 57.1). Additionally, the IVP arm experienced more hallucinations (n = 8, 27.6%) than the SI arm (SI n = 2, 6.7%, difference = 20.9%, 95% CI = 1.8 to 43.4). We found no significant differences in analgesic efficacy. At 60 minutes, the mean %SPID values in the IVP and SI arms were 39.9 and 33.5%, respectively, with a difference of 6.5% (95% CI = -5.8 to 18.7). Most patients who are administered LDK experience a psychoperceptual side effect regardless of administration via SI or IVP. However, patients receiving LDK as a SI reported significantly fewer moderate or greater psychoperceptual side effects and hallucinations with equivalent analgesia.