1. 2023;26;E111-E122Effects of Ketamine on Chronic Postsurgical Pain in Patients Undergoing Surgery: A Systematic Review and Meta-analysis
   Systematic Review
   Wanchen Sun, MD, Yang Zhou, MD, Juan Wang, MD, Yuxuan Fu, MD, Jingyi Fan, MD, Yidan Cui, MD, Yishuang Wu, MD, Lianjie Wang, MD, Yun Yu, MD, and Ruquan Han, MD, PhD.

BACKGROUND: Chronic postsurgical pain (CPSP) has become a common complication during the perioperative period. The efficacy of one of the most potent strategies, ketamine, remains unclear.

OBJECTIVES: The aim of this meta-analysis was to evaluate the effect of ketamine on CPSP in patients undergoing common surgeries..

STUDY DESIGN: Systematic review and meta-analysis.

METHODS: English-language randomized controlled trials (RCTs) published in MEDLINE, Cochrane Library, and EMBASE from 1990 through 2022 were screened. RCTs with a placebo control group that evaluated the effect of intravenous ketamine on CPSP in patients undergoing common surgeries were included. The primary outcome was the proportion of patients who experienced CPSP 3 – 6 months postsurgery. The secondary outcomes included adverse events, emotional evaluation, and 48 hour postoperative opioid consumption. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pooled effect sizes were measured using the common-effects model or random-effects model, and several subgroup analyses were conducted.

RESULTS: Twenty RCTs were included with 1,561 patients. Our pooled meta-analysis showed a significant difference between ketamine and placebo in the treatment of CPSP (Relative Risk [RR] = 0.86; 95% CI, 0.77 – 0.95; P = 0.02; I2 = 44%). In the subgroup analyses, our results indicated that compared with placebo, intravenous ketamine might decrease the prevalence of CPSP 3 – 6 months postsurgery (RR = 0.82; 95% CI, 0.72 – 0.94; P = 0.03; I2 = 45%). For adverse events, we observed that intravenous ketamine might lead to hallucinations (RR = 1.61; 95% CI, 1.09 – 2.39; P = 0.27; I2 = 20%) but did not increase the incidence of postoperative nausea and vomiting (RR = 0.98; 95% CI, 0.86 – 1.12; P = 0.66; I2 = 0%).

LIMITATIONS: Inconsistent assessment tools and follow-up for chronic pain may contribute to the high heterogeneity and limitation of this analysis.

CONCLUSIONS: We discovered that intravenous ketamine may reduce the incidence of CPSP in patients undergoing surgery, especially 3 – 6 months postsurgery. Because of the small sample size and high heterogeneity of the included studies, the effect of ketamine in the treatment of CPSP still needs to be explored in future large-sample, standardized-assessment studies.

KEY WORDS: Ketamine, chronic postsurgical pain, perioperative period, meta-analysis, randomized controlled trial