The Impact of Perioperative Ketamine Infusion on Surgical Recovery

NCT ID: NCT04625283

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1570 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-12
• Study Completion Date: 2024-02-01

Brief 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.

Detailed Description

Opioids are powerful analgesic medications that can reduce pain through action at the mu receptor. Unfortunately, activation of the mu receptor also results in undesirable side effects, such as respiratory depression, sedation, bowel ileus, nausea, itching, and tolerance. Therefore, in order to effectively treat pain with the least amount of opioids required, a multi-modal approach must include medications with different mechanisms of actions at alternative receptors. Some examples of non-narcotic pain medications include acetaminophen (Tylenol), anti-inflammatories (NSAIDS), muscle relaxants, local anesthetics, gabapentinoids (Lyrica), and ketamine, to name a few. 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' or enhanced recovery after surgery (ERAS). 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. Ultimately, the investigators aim to perform a series of randomized controlled trials in which we isolate each component of the pathway to investigate its effects on length of stay, total opioid consumption, and surgical outcomes. The investigators will begin with studying ketamine.

Conditions

Opioid Use; Enhanced Recovery After Surgery; Anesthesia; Ketamine; Pain, Postoperative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine

Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

Participants in the ketamine arm will receive intraoperative and postoperative ketamine.

Saline

Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants in the placebo arm will receive intraoperative and postoperative saline.

Interventions

Ketamine

Participants in the ketamine arm will receive intraoperative and postoperative ketamine.

Intervention Type: DRUG

Placebo

Participants in the placebo arm will receive intraoperative and postoperative saline.

Intervention Type: DRUG

Other Intervention Names

Ketalar; Saline

Eligibility Criteria

Inclusion Criteria

• 18 years old or greater
• presenting at VUMC for abdominal surgery on the colorectal, ventral hernia or surgical oncology services on a weekday.

Exclusion Criteria

• allergy or contraindication to ketamine
• unable or refuse to receive a neuraxial or regional nerve block
• patient refusal
• direct transfer from operating room to intensive care unit with endotracheal tube placed
• treating team elects to exclude the patient prior to study drug administration
• abortion of planned surgical procedure

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Britany Lynn Raymond, MD

MD, Assistant Professor, Department of Anesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Britany L Raymond, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 30113350 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26283834 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23814653 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22374377 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19923527 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31016474 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30897590 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28403427 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31017640 (View on PubMed)

Mercadante S. Opioid Analgesics Adverse Effects: The Other Side of the Coin. Curr Pharm Des. 2019;25(30):3197-3202. doi: 10.2174/1381612825666190717152226.

Reference Type: BACKGROUND

PMID: 31333113 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26855773 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30334161 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29555468 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29750324 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24368573 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29927768 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30570761 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28673215 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29870457 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30077280 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30745263 (View on PubMed)

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 Sep 2:S0007-0912(25)00508-2. doi: 10.1016/j.bja.2025.08.001. Online ahead of print.

Reference Type: DERIVED

PMID: 40903379 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37391729 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36993617 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

200210

Identifier Type: -

Identifier Source: org_study_id