Effects of Ketamine on Postoperative Pain After Remifentanil-Based Anesthesia for Major and Minor Surgery in Adults: A Systematic Review and Meta-Analysis.

Juan F García-Henares,Jose A Moral-Munoz,Alejandro Salazar,Esperanza Del Pozo

doi:10.3389/fphar.2018.00921

Abstract

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been postulated as an adjuvant analgesic for preventing remifentanil-induced hyperalgesia after surgery. This systematic review and meta-analysis aims to assess the effectiveness of ketamine [racemic mixture and S-(+)-ketamine] in reducing morphine consumption and pain intensity scores after remifentanil-based general anesthesia. We performed a literature search of the PubMed, Web of Science, Scopus, Cochrane, and EMBASE databases in June 2017 and selected randomized controlled trials using predefined inclusion and exclusion criteria. To minimize confounding and heterogeneity, studies of NMDA receptor antagonists other than ketamine were excluded and the selected studies were grouped into those assessing minor or major surgery. Methodological quality was evaluated with the PEDro and JADA scales. The data were extracted and meta-analyses were performed where possible. Twelve RCTs involving 156 adults who underwent minor surgery and 413 adults who underwent major surgery were included in the meta-analysis. When used as an adjuvant to morphine, ketamine reduced postoperative morphine consumption in the first 24 h and postoperative pain intensity in the first 2 h in the minor and major surgery groups. It was also associated with significantly reduced pain intensity in the first 24 h in the minor surgery group. Time to the first rescue analgesia was longer in patients who received ketamine and underwent major surgery. No significant differences in the incidence of ketamine-related adverse effects were observed among patients in the intervention group and controls. This systematic review and meta-analysis show that low-dose (≤0.5 mg/kg for iv bolus or ≤5 μg/kg/min for iv perfusion) of ketamine reduces postoperative morphine consumption and pain intensity without increasing the incidence of adverse effects.

Highlights

Management of chronic postsurgical pain remains a challenge for anesthesiologists and surgeons
Only two meta-analyses, each analyzing 14 randomized controls trials (RCTs), have been conducted (Liu et al, 2012; Wu et al, 2015) and they reported conflicting findings One of the analyses found no significant evidence that NMDA antagonists prevented remifentanil-associated hyperalgesia (Wu et al, 2015), while the other one showed that ketamine significantly reduced postoperative pain and cumulative morphine consumption (Wu et al, 2015)
Two of the RCTs were excluded because morphine was not used for postoperative analgesia (Launo et al, 2004; Choi et al, 2015) and one was excluded because the manuscript was written in Chinese (Launo et al, 2004)

Summary

Introduction

Management of chronic postsurgical pain remains a challenge for anesthesiologists and surgeons. 240 million surgical procedures are performed worldwide each year, and an estimated 12% of patients still report moderate to intense pain 1 year after surgery (Fletcher et al, 2015). Acute postoperative pain is a risk factor for the development of chronic postsurgical pain (Perkins and Kehlet, 2000), and the relationship appears to be directly proportional, with more intense or longer-lasting pain linked to a higher incidence of chronic pain (Mion and Villevieille, 2013; Pozek et al, 2016; Reddi, 2016). Its potency as an opioid agonist combined with a short elimination half-life without accumulating with prolonged infusion allows anesthesiologists to maintain hemodynamic stability during surgery without risk of delayed awakening. Intraoperative remifentanil infusion has, been associated with opioid-induced hyperalgesia (Joly et al, 2005; Fletcher and Martinez, 2014)

Methods

Results

Discussion

Conclusion