Ketamine and postoperative pain – a quantitative systematic review of randomised trials

Abstract

Ketamine, an N-methyl-D-aspartate receptor antagonist, is known to be analgesic and to induce psychomimetic effects. Benefits and risks of ketamine for the control of postoperative pain are not well understood. We systematically searched for randomised comparisons of ketamine with inactive controls in surgical patients, reporting on pain outcomes, opioid sparing, and adverse effects. Data were combined using a fixed effect model. Fifty-three trials (2839 patients) from 25 countries reported on a large variety of different ketamine regimens and surgical settings. Sixteen studies tested prophylactic intravenous ketamine (median dose 0.4 mg/kg, range (0.1-1.6)) in 850 adults. Weighted mean difference (WMD) for postoperative pain intensity (0-10 cm visual analogue scale) was -0.89 cm at 6 h, -0.42 at 12 h, -0.35 at 24 h and -0.27 at 48 h. Cumulative morphine consumption at 24 h was significantly decreased with ketamine (WMD -15.7 mg). There was no difference in morphine-related adverse effects. The other 37 trials tested in adults or children, prophylactic or therapeutic ketamine orally, intramuscularly, subcutaneously, intra-articulary, caudally, epidurally, transdermally, peripherally or added to a PCA device; meta-analyses were deemed inappropriate. The highest risk of hallucinations was in awake or sedated patients receiving ketamine without benzodiazepine; compared with controls, the odds ratio (OR) was 2.32 (95%CI, 1.09-4.92), number-needed-to-harm (NNH) 21. In patients undergoing general anaesthesia, the incidence of hallucinations was low and independent of benzodiazepine premedication; OR 1.49 (95%CI 0.18-12.6), NNH 286. Despite many published randomised trials, the role of ketamine, as a component of perioperative analgesia, remains unclear.

The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double‐blind, controlled study

“…However, each drug and the combination produced a statistically significant and clinically important morphine-sparing effect. In fact, we observed a 37% reduction in total 48-h morphine use (26 mg) in the ketamine-only group, which is similar to the morphine-sparing effect reported previously [5]. Benefit in patients given pregabalin alone was similar.…”

Preemptive analgesia effects of Ketamine in patients undergoing surgery. A meta-analysis

“…This meta-analysis has some advantages compared with the previous review 27 . The first one is that the included studies were updated up to 2012.…”

Preventive Analgesia and Novel Strategies for the Prevention of Chronic Post-Surgical Pain

“…While the use of ketamine to reduce CPSP is empirically promising, the results still remain controversial due to the wide variability in clinical settings, ketamine regimens, and reported outcomes. In addition, some of the positive results have been obtained using clinical anesthesia regimens which are not accepted as standard treatments [55,56]. Since Chaparro et al's systematic review no ketamine trials were identified which examined CPSP outcomes.…”