Ketamine and Postoperative Opioid Consumption
Ketamine administered intraoperatively decreases postoperative opioid consumption.
Anesthesia and Analgesia in Total Joint Arthroplasty (2021)
Developed by: American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, The Hip Society, and The Knee Society

Rationale

Six high quality studies evaluated the influence of intraoperative ketamine on opioid consumption after primary TJA.[2–7] Three of these studies also included a postoperative ketamine intravenous infusion for 24 hours.[2,3,6] Five of the six studies found reduced postoperative opioid consumption after primary TJA when intraoperative ketamine was administered.[2–6] The one study that did not demonstrate this finding from Tan et al. compared intraoperative ketamine administered at 6mcg/kg/ minute to placebo and found no difference in opioid consumption at 24 hours postoperatively. Due to heterogeneity in the dosing of ketamine administered intraoperatively, we were unable to conduct a meta-analysis.

Seven high quality studies evaluated the influence of intraoperative ketamine on pain after primary TJA.[2–8] Four of these studies also included a postoperative ketamine infusion for 24 hours.[2,3,6,8] Four studies, two intraoperative only and two intraoperative plus postoperative ketamine, found decreased pain in the first 48 hours after primary TJA.[3,4,7,8] The three other studies found no difference in postoperative pain between ketamine and placebo at all timepoints.[2,5,6] Although all studies that evaluated postoperative pain are high quality, the workgroup downgraded this recommendation to moderate because of the mixed evidence on the influence of intraoperative ketamine on postoperative pain.

Four high quality studies evaluated the effects of intraoperative ketamine on postoperative nausea and vomiting.[4–6,8] A meta-analysis of these four studies with limited heterogeneity (I2 = 4.9%) found that ketamine significantly reduces postoperative nausea and vomiting. (0.68 relative risk [RR]; 95% confidence interval [CI] 0.50 to 0.92). The workgroup downgraded this recommendation to moderate as this is not the primary purpose of intraoperative ketamine. While the anti-emetic effect is a beneficial secondary effect of ketamine, ketamine is primarily used as an anesthetic for sedation and as an analgesic for pain control.

Four high quality studies evaluated the adverse effects of intraoperative ketamine for primary TJA.[4–6,8] All four studies found no increase in adverse events with the use of intraoperative ketamine, including delirium and urinary retention. A meta-analysis of three studies with no heterogeneity (I2 = 0) found no increased risk of postoperative delirium with intraoperative ketamine administration (0.70 RR; 95% CI 0.29 to 1.69).[4–6] Another metaanalysis of three studies with no heterogeneity (I2 = 0) found no increased risk of postoperative urinary retention with intraoperative ketamine administration (1.02 RR; 95% CI 0.53 to 1.94).[5,6,8] Although the meta-analyses demonstrate no increased risk of postoperative delirium or postoperative urinary retention, the rarity of the event makes it more difficult to study in randomized clinical trials. Database studies might be better suited to evaluate rare adverse events such as delirium. Two database studies have evaluated the association between intraoperative ketamine and delirium, with conflicting results between the studies.[9,10]. In one study using claims data from the Premier database evaluating nearly 1.7 million total hip/knee arthroplasties between 2006-2016, no increase in delirium was observed with the use of ketamine [10]. However, in a single institution retrospective review of 41,766 hip/knee arthroplasties between 2005-2014, the use of intraoperative ketamine (OR 1.27 CI 1.01 – 5.26 – 1.59) or a postoperative ketamine infusion did increase the risk of postoperative delirium (OR 10.59 CI 5.26-19.91) [9]. The authors were unable to determine a threshold dose of intraoperative ketamine beyond which the risk of delirium increases.