Efficacy and safety of perioperative ketamine for the prevention of chronic postsurgical pain: A meta‐analysis

Abstract Study Objective Assessment of the efficacy and safety of perioperative intravenous ketamine in reducing incidence and severity of chronic postsurgical pain. Study Design A systematic review and meta‐analysis of randomized controlled trials (RCTs). Data Source s The following data sources were systematically searched: MEDLINE, CENTRAL, and EMBASE (till 02/2021). Patients Adult patients undergoing any surgery. Interventions Perioperative use of intravenous ketamine as an additive analgesic drug compared to placebo, no active control treatment, and other additive drugs. Measurements Primary outcomes were number of patients with chronic postsurgical pain after 6 months and ketamine related adverse effects. Secondary outcomes were chronic postsurgical pain incidence after 3 and 12 months, chronic postsurgical neuropathic pain incidence, chronic postsurgical moderate to severe pain incidence, intensity of chronic postsurgical pain at rest, and during movement, oral morphine consumption after 3, 6, and 12 months and incidence of opioid‐related adverse effects. Main Results Thirty‐six RCTs were included with a total of 3572 patients. Ketamine compared to placebo may result in no difference in the number of patients with chronic postsurgical pain after 6 months (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.71–1.05; I 2 = 34%; 16 studies; low‐certainty evidence). Ketamine may reduce the incidence of chronic postsurgical neuropathic pain after 3 months in comparison to placebo (RR 0.78, 95% CI 0.62–0.99, I 2 = 31%, seven trials, low‐certainty evidence). Ketamine compared to placebo may increase the risk for postoperative nystagmus (RR 9.04, 95% CI 1.15–70.90, I 2 30%, two trials, low‐certainty evidence) and postoperative visual disturbances (RR 2.29, 95% CI 1.05–4.99, I 2 10%, seven trials, low‐certainty evidence). Conclusions There is low‐certainty evidence that perioperative ketamine has no effect on chronic postsurgical pain in adult patients. Low‐certainty evidence suggests that ketamine compared to placebo may reduce incidence of chronic postsurgical neuropathic pain after 3 months. Questions like ideal dosing, treatment duration and more patient‐related outcome measures remain unanswered, which warrants further studies. Protocol Registration Prospero CRD42021223625, 07.01.2021.