Opioid-Free Anesthesia Benefit-Risk Balance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Arthur Salomé,Valeria Martinez,Hakim Harkouk,Dominique Fletcher

doi:10.3390/jcm10102069

Abstract

Opioid-free anesthesia (OFA) is used in surgery to avoid opioid-related side effects. However, uncertainty exists in the balance between OFA benefits and risks. We searched for randomized controlled trials (RCTs) comparing OFA to opioid-based anesthesia (OBA) in five international databases. The co-primary outcomes were postoperative acute pain and morphine consumption at 2, 24, and 48 h. The secondary outcomes were the incidence of postoperative chronic pain, hemodynamic tolerance, severe adverse effects, opioid-related adverse effects, and specific adverse effects related to substitution drugs. Overall, 33 RCTs including 2209 participants were assessed. At 2 h, the OFA groups had lower pain scores at rest MD (0.75 (−1.18; −0.32)), which did not definitively reach MCID. Less morphine was required in the OFA groups at 2 and 24 h, but with very small reductions: 1.61 mg (−2.69; −0.53) and −1.73 mg (p < 0.05), respectively, both not reaching MCID. The reduction in PONV in the OFA group in the PACU presented an RR of 0.46 (0.38, 0.56) and an RR of 0.34 (0.21; 0.56), respectively. Less sedation and shivering were observed in the OFA groups with an SMD of −0.81 (−1.05; −0.58) and an RR of 0.48 (0.33; 0.70), respectively. Quantitative analysis did not reveal differences between the hemodynamic outcomes, although severe side effects have been identified in the literature. No clinically significant benefits were observed with OFA in terms of pain and opioid use after surgery. A clear benefit of OFA use was observed with respect to a reduction in PONV. However, more data on the safe use of OFAs should be collected and caution should be taken in the development of OFA.

Highlights

Opioids have long been used to supplement general anesthesia
Opioids are associated with well-recognized side effects such as nausea and vomiting, sedation, ileus, confusion and delirium, respiratory depression, increased postoperative pain and morphine consumption, immunodepression, hyperalgesia and chronic postoperative pain, addiction, and misuse [1]
The common practice of administering opioids during anesthesia was challenged by clinical studies suggesting that opioid-free anesthesia (OFA) may be effective in providing adequate pain control, while reducing postoperative opioid consumption and hopefully reducing opioid-related side effects [3]

Summary

Introduction

Opioids have long been used to supplement general anesthesia. The common practice of administering opioids during anesthesia was challenged by clinical studies suggesting that opioid-free anesthesia (OFA) may be effective in providing adequate pain control, while reducing postoperative opioid consumption and hopefully reducing opioid-related side effects [3]. Opioids should be avoided during surgery and should be replaced by hypnotic or analgesic drugs to control the consequences of surgical trauma during anesthesia, but this suggestion has never been validated. The definition of OFA varies in the literature and between centers, lidocaine, ketamine, and alpha-2 agonists such as clonidine or dexmedetomidine have been proposed to replace opioids alone or in combination [3]

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Discussion

Conclusion