[Skip to Content]
[Skip to Content Landing]

Postoperative Multimodal Analgesia Pain Management With Nonopioid Analgesics and TechniquesA Review

Educational Objective To identify the advantages and disadvantages of nonopioid techniques commonly included in the enhanced recovery after surgery protocol.
1 Credit CME

Importance  Amid the current opioid epidemic in the United States, the enhanced recovery after surgery pathway (ERAS) has emerged as one of the best strategies to improve the value and quality of surgical care and has been increasingly adopted for a broad range of complex surgical procedures. The goal of this article was to outline important components of opioid-sparing analgesic regimens.

Observations  Regional analgesia, acetaminophen, nonsteroidal anti-inflammatory agents, gabapentinoids, tramadol, lidocaine, and/or the N-methyl-d-aspartate class of glutamate receptor antagonists have been shown to be effective adjuncts to narcotic analgesia. Nonsteroidal anti-inflammatory agents are not associated with an increase in postoperative bleeding. A meta-analysis of 27 randomized clinical trials found no difference in postoperative bleeding between the groups taking ketorolac tromethamine (33 of 1304 patients [2.5%]) and the control groups (21 of 1010 [2.1%]) (odds ratio [OR], 1.1; 95% CI, 0.61-2.06; P = .72). After adoption of the multimodal analgesia approach for a colorectal ERAS pathway, most patients used less opioids while in the hospital and many did not need opioids after hospital discharge, although approximately 50% of patients received some opioid during their stay.

Conclusions and Relevance  Multimodal analgesia is readily available and the evidence is strong to support its efficacy. Surgeons should use this effective approach for patients both using and not using the ERAS pathway to reduce opioid consumption.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Corresponding Author: Elizabeth C. Wick, MD, Department of Surgery, University of California, San Francisco, 513 Parnassus Ave, Room S549, San Francisco, CA 94143 (elizabeth.wick@ucsf.edu).

Accepted for Publication: March 4, 2017.

Published Online: May 31, 2017. doi:10.1001/jamasurg.2017.0898

Author Contributions: Dr Wick had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition, analysis, or interpretation of data: Wick.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: Wick, Grant.

Administrative, technical, or material support: Wick, Grant.

Study supervision: Wick, Wu.

Conflict of Interest Disclosures: None reported.

Phillips  DM.  JCAHO pain management standards are unveiled.  JAMA. 2000;284(4):428-429.PubMedGoogle ScholarCrossref
Kozol  RA, Voytovich  A.  Misinterpretation of the fifth vital sign.  Arch Surg. 2007;142(5):417-420.PubMedGoogle ScholarCrossref
Manchikanti  L, Helm  S  II, Fellows  B,  et al.  Opioid epidemic in the United States.  Pain Physician. 2012;15(3)(suppl):ES9-ES38.PubMedGoogle Scholar
Okie  S.  A flood of opioids, a rising tide of deaths.  N Engl J Med. 2010;363(21):1981-1985.PubMedGoogle ScholarCrossref
Hanna  MN, Murphy  JD, Kumar  K, Wu  CL.  Regional techniques and outcome: what is the evidence?  Curr Opin Anaesthesiol. 2009;22(5):672-677.PubMedGoogle ScholarCrossref
Pöpping  DM, Elia  N, Van Aken  HK,  et al.  Impact of epidural analgesia on mortality and morbidity after surgery: systematic review and meta-analysis of randomized controlled trials.  Ann Surg. 2014;259(6):1056-1067. PubMedGoogle ScholarCrossref
Block  BM, Liu  SS, Rowlingson  AJ, Cowan  AR, Cowan  JA  Jr, Wu  CL.  Efficacy of postoperative epidural analgesia: a meta-analysis.  JAMA. 2003;290(18):2455-2463.PubMedGoogle ScholarCrossref
Liu  H, Hu  X, Duan  X, Wu  J.  Thoracic epidural analgesia (TEA) vs. patient controlled analgesia (PCA) in laparoscopic colectomy: a meta-analysis.  Hepatogastroenterology. 2014;61(133):1213-1219.PubMedGoogle Scholar
Hughes  MJ, Ventham  NT, McNally  S, Harrison  E, Wigmore  S.  Analgesia after open abdominal surgery in the setting of enhanced recovery surgery: a systematic review and meta-analysis.  JAMA Surg. 2014;149(12):1224-1230.PubMedGoogle ScholarCrossref
Horlocker  TT, Wedel  DJ, Rowlingson  JC,  et al.  Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition).  Reg Anesth Pain Med. 2010;35(1):64-101.PubMedGoogle ScholarCrossref
Meylan  N, Elia  N, Lysakowski  C, Tramèr  MR.  Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: meta-analysis of randomized trials.  Br J Anaesth. 2009;102(2):156-167.PubMedGoogle ScholarCrossref
American Society of Anesthesiologists Task Force on Neuraxial Opioids; Horlocker  TT, Burton  AW, Connis  RT,  et al.  Practice guidelines for the prevention, detection, and management of respiratory depression associated with neuraxial opioid administration.  Anesthesiology. 2009;110(2):218-230.PubMedGoogle Scholar
De Oliveira  GS  Jr, Castro-Alves  LJ, Nader  A, Kendall  MC, McCarthy  RJ.  Transversus abdominis plane block to ameliorate postoperative pain outcomes after laparoscopic surgery: a meta-analysis of randomized controlled trials.  Anesth Analg. 2014;118(2):454-463.PubMedGoogle ScholarCrossref
Baeriswyl  M, Kirkham  KR, Kern  C, Albrecht  E.  The analgesic efficacy of ultrasound-guided transversus abdominis plane block in adult patients: a meta-analysis.  Anesth Analg. 2015;121(6):1640-1654.PubMedGoogle ScholarCrossref
Joshi  GP, Bonnet  F, Shah  R,  et al.  A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia.  Anesth Analg. 2008;107(3):1026-1040. PubMedGoogle ScholarCrossref
Tan  M, Law  LS, Gan  TJ.  Optimizing pain management to facilitate Enhanced Recovery After Surgery pathways.  Can J Anaesth. 2015;62(2):203-218.PubMedGoogle ScholarCrossref
Bamigboye  AA, Hofmeyr  GJ.  Local anaesthetic wound infiltration and abdominal nerves block during caesarean section for postoperative pain relief.  Cochrane Database Syst Rev. 2009;(3):CD006954.PubMedGoogle Scholar
Gupta  A, Favaios  S, Perniola  A, Magnuson  A, Berggren  L.  A meta-analysis of the efficacy of wound catheters for post-operative pain management.  Acta Anaesthesiol Scand. 2011;55(7):785-796. PubMedGoogle ScholarCrossref
Richards  D.  The Oxford Pain Group League table of analgesic efficacy.  Evid Based Dent. 2004;5(1):22-23. doi:10.1038/sj.ebd.6400237Google ScholarCrossref
Elia  N, Lysakowski  C, Tramèr  MR.  Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? meta-analyses of randomized trials.  Anesthesiology. 2005;103(6):1296-1304.PubMedGoogle ScholarCrossref
Straube  S, Derry  S, McQuay  HJ, Moore  RA.  Effect of preoperative Cox-II-selective NSAIDs (coxibs) on postoperative outcomes: a systematic review of randomized studies.  Acta Anaesthesiol Scand. 2005;49(5):601-613.PubMedGoogle ScholarCrossref
Lee  A, Cooper  MG, Craig  JC, Knight  JF, Keneally  JP.  Effects of nonsteroidal anti-inflammatory drugs on postoperative renal function in adults with normal renal function.  Cochrane Database Syst Rev. 2007;(2):CD002765.PubMedGoogle Scholar
Gobble  RM, Hoang  HL, Kachniarz  B, Orgill  DP.  Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials.  Plast Reconstr Surg. 2014;133(3):741-755. PubMedGoogle ScholarCrossref
Strom  BL, Berlin  JA, Kinman  JL,  et al.  Parenteral ketorolac and risk of gastrointestinal and operative site bleeding: a postmarketing surveillance study.  JAMA. 1996;275(5):376-382.PubMedGoogle ScholarCrossref
Apfel  CC, Turan  A, Souza  K, Pergolizzi  J, Hornuss  C.  Intravenous acetaminophen reduces postoperative nausea and vomiting: a systematic review and meta-analysis.  Pain. 2013;154(5):677-689. PubMedGoogle ScholarCrossref
Hurley  RW, Cohen  SP, Williams  KA, Rowlingson  AJ, Wu  CL.  The analgesic effects of perioperative gabapentin on postoperative pain: a meta-analysis.  Reg Anesth Pain Med. 2006;31(3):237-247.PubMedGoogle Scholar
Mishriky  BM, Waldron  NH, Habib  AS.  Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis.  Br J Anaesth. 2015;114(1):10-31.PubMedGoogle ScholarCrossref
Sun  Y, Li  T, Wang  N, Yun  Y, Gan  TJ.  Perioperative systemic lidocaine for postoperative analgesia and recovery after abdominal surgery: a meta-analysis of randomized controlled trials.  Dis Colon Rectum. 2012;55(11):1183-1194. PubMedGoogle ScholarCrossref
Bai  Y, Miller  T, Tan  M, Law  LS, Gan  TJ.  Lidocaine patch for acute pain management: a meta-analysis of prospective controlled trials.  Curr Med Res Opin. 2015;31(3):575-581.PubMedGoogle ScholarCrossref
Radbruch  L, Glaeske  G, Grond  S,  et al.  Topical review on the abuse and misuse potential of tramadol and tilidine in Germany.  Subst Abus. 2013;34(3):313-320.PubMedGoogle ScholarCrossref
Klotz  U.  Tramadol—the impact of its pharmacokinetic and pharmacodynamic properties on the clinical management of pain.  Arzneimittelforschung. 2003;53(10):681-687. PubMedGoogle Scholar
Beakley  BD, Kaye  AM, Kaye  AD.  Tramadol, pharmacology, side effects, and serotonin syndrome: a review.  Pain Physician. 2015;18(4):395-400.PubMedGoogle Scholar
Bell  RF, Dahl  JB, Moore  RA, Kalso  E.  Perioperative ketamine for acute postoperative pain.  Cochrane Database Syst Rev. 2006;(1):CD004603.PubMedGoogle Scholar
De Oliveira  GS  Jr, Castro-Alves  LJ, Khan  JH, McCarthy  RJ.  Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials.  Anesthesiology. 2013;119(1):178-190.PubMedGoogle ScholarCrossref
King  MR, Ladha  KS, Gelineau  AM, Anderson  TA.  Perioperative dextromethorphan as an adjunct for postoperative pain: a meta-analysis of randomized controlled trials.  Anesthesiology. 2016;124(3):696-705.PubMedGoogle ScholarCrossref
Levy  B, Paulozzi  L, Mack  KA, Jones  CM.  Trends in opioid analgesic-prescribing rates by specialty, U.S., 2007-2012.  Am J Prev Med. 2015;49(3):409-413.PubMedGoogle ScholarCrossref
Hupp  JR.  The surgeon’s roles in stemming the prescription opioid abuse epidemic.  J Oral Maxillofac Surg. 2016;74(7):1291-1293. PubMedGoogle ScholarCrossref
Page  AJ, Gani  F, Crowley  KT,  et al.  Patient outcomes and provider perceptions following implementation of a standardized perioperative care pathway for open liver resection.  Br J Surg. 2016;103(5):564-571.PubMedGoogle ScholarCrossref
Talboys  R, Mak  M, Modi  N, Fanous  N, Cutts  S.  Enhanced recovery programme reduces opiate consumption in hip hemiarthroplasty.  Eur J Orthop Surg Traumatol. 2016;26(2):177-181. PubMedGoogle ScholarCrossref
Sarin  A, Litonius  ES, Naidu  R, Yost  CS, Varma  MG, Chen  LL.  Successful implementation of an Enhanced Recovery After Surgery program shortens length of stay and improves postoperative pain, and bowel and bladder function after colorectal surgery.  BMC Anesthesiol. 2016;16(1):55.PubMedGoogle ScholarCrossref
Chapman  JS, Roddy  E, Ueda  S, Brooks  R, Chen  LL, Chen  LM.  Enhanced Recovery Pathways for improving outcomes after minimally invasive gynecologic oncology surgery.  Obstet Gynecol. 2016;128(1):138-144.PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience

Lookup An Activity



My Saved Searches

You currently have no searches saved.

With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right