The Impact of Perioperative Ketamine Infusion on Surgical Recovery

Summary

In order to effectively treat surgical pain with the least amount of opioids required, a multi-modal approach must include medications with different mechanisms of actions at alternative receptors. In light of the opioid epidemic, medical providers at Vanderbilt University Medical Center (VUMC) are strategically combining these medications in a bundled pain-regimen after surgery. These regimens have been shown to decrease opioid consumption, improve surgical outcomes, and reduce hospital stays, thus coining the term 'enhanced recovery pathway'. The combination of these medications has an indisputable synergistic effect. However, it is unknown how each medication contributes individually to the overall efficacy of the pathway. This study will examine the effects of ketamine, within the constructs of a multimodal pain regimen, on a) length of stay, b) opioid consumption, and c) surgical outcomes after major abdominal surgery.

Timeline

Start

2021-04-12

Primary completion

2024-01-26

Completion

2024-02-01

Outcome

Missed primary endpoint

paper ketamine administration did not decrease length of stay (odds ratio [OR] 1.21; 95% confidence interval [CI] 1.00-1.47) PMID 40903379 ↗

Publications

• Background Boenigk K, Echevarria GC, Nisimov E, von Bergen Granell AE, Cuff GE, Wang J, Atchabahian A. Low-dose ketamine infusion reduces postoperative hydromorphone requirements in opioid-tolerant patients following spinal fusion: A randomised controlled trial. Eur J Anaesthesiol. 2019 Jan;36(1):8-15. doi: 10.1097/EJA.0000000000000877.
• Background Kaur S, Saroa R, Aggarwal S. Effect of intraoperative infusion of low-dose ketamine on management of postoperative analgesia. J Nat Sci Biol Med. 2015 Jul-Dec;6(2):378-82. doi: 10.4103/0976-9668.160012.
• Background Kim SH, Kim SI, Ok SY, Park SY, Kim MG, Lee SJ, Noh JI, Chun HR, Suh H. Opioid sparing effect of low dose ketamine in patients with intravenous patient-controlled analgesia using fentanyl after lumbar spinal fusion surgery. Korean J Anesthesiol. 2013 Jun;64(6):524-8. doi: 10.4097/kjae.2013.64.6.524. Epub 2013 Jun 24.
• Background Suppa E, Valente A, Catarci S, Zanfini BA, Draisci G. A study of low-dose S-ketamine infusion as "preventive" pain treatment for cesarean section with spinal anesthesia: benefits and side effects. Minerva Anestesiol. 2012 Jul;78(7):774-81. Epub 2012 Feb 29.
• Background Remerand F, Le Tendre C, Baud A, Couvret C, Pourrat X, Favard L, Laffon M, Fusciardi J. The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study. Anesth Analg. 2009 Dec;109(6):1963-71. doi: 10.1213/ANE.0b013e3181bdc8a0.
• Background Pergolizzi JV Jr, Rosenblatt M, LeQuang JA. Three Years Down the Road: The Aftermath of the CDC Guideline for Prescribing Opioids for Chronic Pain. Adv Ther. 2019 Jun;36(6):1235-1240. doi: 10.1007/s12325-019-00954-1. Epub 2019 Apr 23.
• Background Kent ML, Hurley RW, Oderda GM, Gordon DB, Sun E, Mythen M, Miller TE, Shaw AD, Gan TJ, Thacker JKM, McEvoy MD; POQI-4 Working Group. American Society for Enhanced Recovery and Perioperative Quality Initiative-4 Joint Consensus Statement on Persistent Postoperative Opioid Use: Definition, Incidence, Risk Factors, and Health Care System Initiatives. Anesth Analg. 2019 Aug;129(2):543-552. doi: 10.1213/ANE.0000000000003941.
• Background Brummett CM, Waljee JF, Goesling J, Moser S, Lin P, Englesbe MJ, Bohnert ASB, Kheterpal S, Nallamothu BK. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. JAMA Surg. 2017 Jun 21;152(6):e170504. doi: 10.1001/jamasurg.2017.0504. Epub 2017 Jun 21.
• Background Kurokawa Y, Kurokawa T, Tanimoto T. Opioid Prescription After Surgery. JAMA Surg. 2019 Jul 1;154(7):675. doi: 10.1001/jamasurg.2019.0573. No abstract available.
• Background Mercadante S. Opioid Analgesics Adverse Effects: The Other Side of the Coin. Curr Pharm Des. 2019;25(30):3197-3202. doi: 10.2174/1381612825666190717152226.
• Background McEvoy MD, Wanderer JP, King AB, Geiger TM, Tiwari V, Terekhov M, Ehrenfeld JM, Furman WR, Lee LA, Sandberg WS. A perioperative consult service results in reduction in cost and length of stay for colorectal surgical patients: evidence from a healthcare redesign project. Perioper Med (Lond). 2016 Feb 5;5:3. doi: 10.1186/s13741-016-0028-1. eCollection 2016.
• Background Hawkins AT, Geiger TM, King AB, Wanderer JP, Tiwari V, Muldoon RL, Ford MM, Dmochowski RR, Sandberg WS, Martin B, Hopkins MB, McEvoy MD. An enhanced recovery program in colorectal surgery is associated with decreased organ level rates of complications: a difference-in-differences analysis. Surg Endosc. 2019 Jul;33(7):2222-2230. doi: 10.1007/s00464-018-6508-2. Epub 2018 Oct 17.
• Background King AB, Spann MD, Jablonski P, Wanderer JP, Sandberg WS, McEvoy MD. An enhanced recovery program for bariatric surgical patients significantly reduces perioperative opioid consumption and postoperative nausea. Surg Obes Relat Dis. 2018 Jun;14(6):849-856. doi: 10.1016/j.soard.2018.02.010. Epub 2018 Feb 13.
• Background Li Z, Zhao Q, Bai B, Ji G, Liu Y. Enhanced Recovery After Surgery Programs for Laparoscopic Abdominal Surgery: A Systematic Review and Meta-analysis. World J Surg. 2018 Nov;42(11):3463-3473. doi: 10.1007/s00268-018-4656-0.
• Background Greco M, Capretti G, Beretta L, Gemma M, Pecorelli N, Braga M. Enhanced recovery program in colorectal surgery: a meta-analysis of randomized controlled trials. World J Surg. 2014 Jun;38(6):1531-41. doi: 10.1007/s00268-013-2416-8.
• Background Doan LV, Wang J. An Update on the Basic and Clinical Science of Ketamine Analgesia. Clin J Pain. 2018 Nov;34(11):1077-1088. doi: 10.1097/AJP.0000000000000635.
• Background Brinck EC, Tiippana E, Heesen M, Bell RF, Straube S, Moore RA, Kontinen V. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018 Dec 20;12(12):CD012033. doi: 10.1002/14651858.CD012033.pub4.
• Background Peyton PJ, Wu C, Jacobson T, Hogg M, Zia F, Leslie K. The effect of a perioperative ketamine infusion on the incidence of chronic postsurgical pain-a pilot study. Anaesth Intensive Care. 2017 Jul;45(4):459-465. doi: 10.1177/0310057X1704500408.
• Background Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466. doi: 10.1097/AAP.0000000000000806.
• Background Allen CA, Ivester JR Jr. Low-Dose Ketamine for Postoperative Pain Management. J Perianesth Nurs. 2018 Aug;33(4):389-398. doi: 10.1016/j.jopan.2016.12.009. Epub 2017 Jun 10.
• Background Plyler SS, Muckler VC, Titch JF, Gupta DK, Rice AN. Low-Dose Ketamine Infusion to Decrease Postoperative Delirium for Spinal Fusion Patients. J Perianesth Nurs. 2019 Aug;34(4):779-788. doi: 10.1016/j.jopan.2018.11.009. Epub 2019 Feb 10.
• Clifton JC, Raymond BL, Freundlich RE, Allen BFS, Stallings EG, Kertai MD. Ketamine Infusion and Risk of Postoperative Nausea and Vomiting and Adverse Outcomes in Surgical Patients: A Secondary Analysis of the IMPAKT Randomized Trial. Anesth Analg. 2026 Jun 29. doi: 10.1213/ANE.0000000000008205. Online ahead of print. No abstract available.
• Raymond BL, Allen BFS, Freundlich RE, McEvoy MD, Parrish CG, Ruble SR, Scharfman KH, Wanderer JP, Gao Y, Choi L, Dear ML, Master H, Rice TW, Kertai MD; Vanderbilt Learning Healthcare System Platform Investigators. IMpact of PerioperAtive KeTamine on Enhanced Recovery After abdominal Surgery (IMPAKT ERAS): a pragmatic randomised single-cluster trial. Br J Anaesth. 2025 Dec;135(6):1770-1778. doi: 10.1016/j.bja.2025.08.001. Epub 2025 Sep 3.
• Raymond BL, Allen BFS, Freundlich RE, Parrish CG, Jayaram JE, Wanderer JP, Rice TW, Lindsell CJ, Scharfman KH, Dear ML, Gao Y, Hiser WD, McEvoy MD; Vanderbilt Learning Healthcare System Platform Investigators. The IMpact of PerioperAtive KeTamine on Enhanced Recovery after Abdominal Surgery (IMPAKT ERAS): protocol for a pragmatic, randomized, double-blinded, placebo-controlled trial. BMC Anesthesiol. 2023 Jun 30;23(1):227. doi: 10.1186/s12871-023-02177-y.
• Raymond BL, Allen BFS, Freundlich RE, Parrish CG, Jayaram JE, Wanderer JP, Rice TW, Lindsell CJ, Scharfman KH, Dear ML, Gao Y, Hiser WD, McEvoy MD. The IMpact of PerioperAtive KeTamine on Enhanced Recovery after Abdominal Surgery (IMPAKT ERAS): protocol for a pragmatic, randomized, double-blinded, placebo-controlled trial. Res Sq [Preprint]. 2023 Mar 24:rs.3.rs-2639840. doi: 10.21203/rs.3.rs-2639840/v1.

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Indications