Restricted accessResearch articleFirst published online 2023-9
Opioid-free anesthesia versus opioid-based anesthesia in patients undergoing cardiovascular and thoracic surgery: a meta-analysis and systematic review
Despite their extensive clinical use, opioids are characterized by several side effects. These complications, coupled with the ongoing opioid epidemic, have favored the rise of opioid-free-anesthesia (OFA). Herein, we perform the first pairwise meta-analysis of clinical outcomes for OFA vs opioid-based anesthesia (OBA) in patients undergoing cardiovascular and thoracic surgery.
Methods
We comprehensively searched medical databases to identify studies comparing OFA and OBA in patients undergoing cardiovascular or thoracic surgery. Pairwise meta-analysis was performed using the Mantel–Haenszel method. Outcomes were pooled as risk ratios (RR) or standard mean differences (SMD) and their 95% confidence intervals (95% CI).
Results
Our pooled analysis included 919 patients (8 studies), of whom 488 underwent surgery with OBA and 431 with OFA. Among cardiovascular surgery patients, compared to OBA, OFA was associated with significantly reduced post-operative nausea and vomiting (RR, 0.57; P = .042), inotrope need (RR .84, P = .045), and non-invasive ventilation (RR, .54; P = .028). However, no differences were observed for 24hr pain score (SMD, −.35; P = .510) or 48hr morphine equivalent consumption (SMD, −1.09; P = .139). Among thoracic surgery patients, there was no difference between OFA and OBA for any of the explored outcomes, including post-operative nausea and vomiting (RR, 0.41; P = .025).
Conclusion
Through the first pooled analysis of OBA vs OFA in a cardiothoracic-exclusive cohort, we found no significant difference in any of the pooled outcomes for thoracic surgery patients. Although limited to 2 cardiovascular surgery studies, OFA was associated with significantly reduced postoperative nausea and vomiting, inotrope need, and non-invasive ventilation in these patients. With growing use of OFA in invasive operations, further studies are needed to assess their efficacy and safety in cardiothoracic patients.
RosenblumAMarschLAJosephHPortenoyRK. Opioids and the Treatment of Chronic Pain: Controversies, Current Status, and Future Directions. Exp Clin Psychopharmacol2008;16(5):405-416. doi:10.1037/a0013628.
2.
ForgetP. Opioid-free anaesthesia. Why and how? A contextual analysis. Anaesth Crit Care Pain Med2019; 38(2): 169-172. doi:10.1016/j.accpm.2018.05.002.
3.
KwantenLEO’BrienBAnwarS. Opioid-Based Anesthesia and Analgesia for Adult Cardiac Surgery: History and Narrative Review of the Literature. J Cardiothorac Vasc Anesth2019; 33(3): 808-816. doi:10.1053/j.jvca.2018.05.053.
4.
FerryNHancockLEDhanjalS. Opioid Anesthesia. [Updated 2022 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from:https://www.ncbi.nlm.nih.gov/books/NBK532956/
BeloeilH. Opioid-free anesthesia. Best Pract Res Clin Anaesthesiol2019; 33(3): 353-360. doi:10.1016/j.bpa.2019.09.002.
11.
ToleskaMDimitrovskiA. Is Opioid-Free General Anesthesia More Superior for Postoperative Pain Versus Opioid General Anesthesia in Laparoscopic Cholecystectomy?Pril (Makedon Akad Nauk Umet Odd Med Nauki)2019; 40(2): 81-87. doi:10.2478/prilozi-2019-0018.
12.
HubletSGallandMNavezJPatriziaLClossetJForgetP, et al. Opioid-free versus opioid-based anesthesia in pancreatic surgery. BMC Anesthesiol2022;22:9. doi:10.1186/s12871-021-01551-y.
13.
ChoiHSongJYOhEJChaeMSSanghyuckYMoonYE. The Effect of Opioid-Free Anesthesia on the Quality of Recovery After Gynecological Laparoscopy: A Prospective Randomized Controlled Trial. J Pain Res2022;15:2197-2209. doi:10.2147/JPR.S373412.
14.
TripathySRathSAgrawalSRaoPBPandaAMishraTS, et al. Opioid-free anesthesia for breast cancer surgery: An observational study. J Anaesthesiol Clin Pharmacol2018;34(1):35-40. doi:10.4103/joacp.JOACP_143_17.
15.
ChikweJAthanasiouT. Complications of cardiothoracic surgery. Surgical Complications. Singapore: World Scientific Publishing Co.; 2007:245-300.
16.
StroupDFBerlinJAMortonSCOlkinIWilliamsonGDRennieD, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008.
17.
PageMJMcKenzieJEBossuytPMBoutronIHoffmannTMulrowC, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ2021;372:n71. doi:10.1136/bmj.n71.
18.
OlaussonASvenssonCJAndréllPJildenstålPThörnSWolfA. Total opioid-free general anaesthesia can improve postoperative outcomes after surgery, without evidence of adverse effects on patient safety and pain management: A systematic review and meta-analysis. Acta Anaesthesiol Scand2022;66(2):170-185. doi:10.1111/aas.13994.
19.
SterneJACSavovićJPageMJElbersRGBlencoweNSBoutronI, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ2019;366:l4898. doi:10.1136/bmj.l4898.
HigginsJPTAltmanDGGøtzschePCJüniPMoherDOxmanAD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ2011;343:d5928. doi:10.1136/bmj.d5928.
23.
ChakravarthyM. Opioid Free Cardiac Anesthesia – A Flash in The Pan?Ann Card Anaesth2020; 23(2): 113-115. doi:10.4103/aca.ACA_68_19.
24.
PatvardhanCFerranteM. Opiate free anaesthesia and future of thoracic surgery anaesthesia. J Vis Surg2018; 4(0): 253. doi:10.21037/jovs.2018.12.08.
25.
GrantMCSuffrediniGChoBC. Is it time to eliminate the use of opioids in cardiac surgery?JTCVS Open2021; 7: 247-252. doi:10.1016/j.xjon.2021.03.022.
26.
ThotaRSRamkiranSGargRGoswamiJBaxiVThomasM. Opioid free onco-anesthesia: Is it time to convict opioids? A systematic review of literature. J Anaesthesiol Clin Pharmacol2019;35(4):441-452. doi:10.4103/joacp.JOACP_128_19.
27.
SaloméAHarkoukHFletcherDMartinezV. Opioid-Free Anesthesia Benefit–Risk Balance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med2021;10(10):2069. doi:10.3390/jcm10102069.
28.
WilliamsJBMcConnellGAllenderJEWoltzPKaneKSmithPK, et al. One-year results from the first US-based enhanced recovery after cardiac surgery (ERAS Cardiac) program. J Thorac Cardiovasc Surg2019;157(5):1881-1888. doi:10.1016/j.jtcvs.2018.10.164.
29.
EngelmanDTBen AliWWilliamsJBPerraultLPReddyVSAroraRC, et al. Guidelines for Perioperative Care in Cardiac Surgery: Enhanced Recovery After Surgery Society Recommendations. JAMA Surg2019;154(8):755-766. doi:10.1001/jamasurg.2019.1153.
30.
BatchelorTJPRasburnNJAbdelnour-BerchtoldEBrunelliACerfolioRJGonzalezM, et al. Guidelines for enhanced recovery after lung surgery: recommendations of the Enhanced Recovery After Surgery (ERAS®) Society and the European Society of Thoracic Surgeons (ESTS). Eur J Cardio Thorac Surg2019;55(1):91-115. doi:10.1093/ejcts/ezy301.
31.
MaghamiMAfazelMRAzizi-FiniIMaghamiM. The effect of aromatherapy with peppermint essential oil on nausea and vomiting after cardiac surgery: A randomized clinical trial. Compl Ther Clin Pract2020;40:101199. doi:10.1016/j.ctcp.2020.101199.
32.
RobertsGWBekkerTBCarlsenHHMoffattCHSlatteryPJMcClureAF. Postoperative Nausea and Vomiting Are Strongly Influenced by Postoperative Opioid Use in a Dose-Related Manner. Anesth Analg. EC; 2005;101: 1343-1348.
SawatzkyJAVRivetMArianoREHiebertBAroraRC. Post-operative nausea and vomiting in the cardiac surgery population: Who is at risk?Heart Lung2014;43(6):550-554. doi:10.1016/j.hrtlng.2014.07.002.
35.
ChampionSZiegerLHemeryC. Prophylaxis of Postoperative Nausea and Vomiting after Cardiac Surgery in High-risk Patients: A Randomized Controlled Study. Ann Card Anaesth2018; 21(1):8-14. doi:10.4103/aca.ACA_122_17.
CaspiONaamiRHalfinEAronsonD. Adverse dose-dependent effects of morphine therapy in acute heart failure. Int J Cardiol2019;293:131-136. doi:10.1016/j.ijcard.2019.06.015.
38.
EstafanousFGBrumJMRibeiroMPEstafanousMStarrNFerrarioC. Analysis of heart rate variability to assess hemodynamic alterations following induction of anesthesia. J Cardiothorac Vasc Anesth1992;6(6):651-657. doi:10.1016/1053-0770(92)90045-9.
39.
BaddalNConkbayirCErdemliOKaradenizUTezcanBOztasDM, et al. Comparison of fentanil and remifentanil for coronary artery surgery with low ejection fraction. Arch Med Sci Atheroscler Dis2020;5:e20-e26. doi:10.5114/amsad.2020.93528.
40.
KazmaierSHanekopGGBuhreWWeylandABuschTRadkeOC, et al. Myocardial consequences of remifentanil in patients with coronary artery disease. Br J Anaesth2000;84(5):578-583. doi:10.1093/bja/84.5.578.
41.
MaddaliMMKurianEFahrJ. Extubation time, hemodynamic stability, and postoperative pain control in patients undergoing coronary artery bypass surgery: an evaluation of fentanyl, remifentanil, and nonsteroidal antiinflammatory drugs with propofol for perioperative and postoperative management. J Clin Anesth2006; 18(8): 605-610. doi:10.1016/j.jclinane.2006.03.022.
42.
LoskutovODanchynaTDzubaDDruzinaO. The use of multimodal low-opioid anesthesia for coronary artery bypass grafting surgery in conditions of artificial blood circulation. Kardiochir Torakochirurgia Pol2020;17(3):111-116. doi:10.5114/kitp.2020.99072.
43.
van der SchierRRoozekransMvan VelzenMDahanANiestersM. Opioid-induced respiratory depression: reversal by non-opioid drugs. F1000Prime Rep2014;6:79. doi:10.12703/P6-79.
44.
VargaAGReidBTKiefferBLLevittES. Differential impact of two critical respiratory centres in opioid-induced respiratory depression in awake mice. J Physiol2020;598(1):189-205. doi:10.1113/JP278612.
45.
MauermannERuppenWBandschappO. Different protocols used today to achieve total opioid-free general anesthesia without locoregional blocks. Best Pract Res Clin Anaesthesiol2017; 31(4): 533-545. doi:10.1016/j.bpa.2017.11.003.
46.
BeloeilHGarotMLebuffeGGerbaudABilaJCuvillonP, et al. Balanced Opioid-free Anesthesia with Dexmedetomidine versus Balanced Anesthesia with Remifentanil for Major or Intermediate Noncardiac Surgery: The Postoperative and Opioid-free Anesthesia (POFA) Randomized Clinical Trial. Anesthesiology2021;134(4):541-551. doi:10.1097/ALN.0000000000003725.
47.
BelloMOgerSBedon-CarteSVielstadteCLeoFZaouterC, et al. Effect of opioid-free anaesthesia on postoperative epidural ropivacaine requirement after thoracic surgery: A retrospective unmatched case-control study. Anaesth Crit Care Pain Med2019;38(5):499-505. doi:10.1016/j.accpm.2019.01.013.
48.
DevineGChengMMartinezGPatvardhanCAresuGPerytA, et al. Opioid-Free Anesthesia for Lung Cancer Resection: A Case-Control Study. J Cardiothorac Vasc Anesth2020;34(11):3036-3040. doi:10.1053/j.jvca.2020.05.022.
49.
AnGZhangYChenNFuJZhaoBZhaoX. Opioid-free anesthesia compared to opioid anesthesia for lung cancer patients undergoing video-assisted thoracoscopic surgery: A randomized controlled study. PLoS One2021;16(9):e0257279. doi:10.1371/journal.pone.0257279.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
