The Impact of Perioperative Ketamine Infusion on Surgical Recovery

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04625283

Collaborator

(none)

1,600

Enrollment

Location

Arms

17.6

Anticipated Duration (Months)

90.7

Patients Per Site Per Month

Study Details

Study Description

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, c) pain scores, and d) surgical outcomes after major abdominal surgery.

Condition or Disease	Intervention/Treatment	Phase
Opioid Use Enhanced Recovery After Surgery Anesthesia Ketamine Pain, Postoperative	Drug: Ketamine Drug: Placebo	Phase 4

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, pain scores, and surgical outcomes. The investigators will begin with studying ketamine.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This study will be performed as a pragmatic controlled clinical trial with parallel group assignment. Randomization will be in a cluster format.This study will be performed as a pragmatic controlled clinical trial with parallel group assignment. Randomization will be in a cluster format.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Effect and Contribution of a Perioperative Ketamine Infusion in an Established Enhanced Recovery Pathway

Actual Study Start Date :

Apr 12, 2021

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 mg/kg/min, up to 100kg max) for 48 hours.	Drug: Ketamine Participants in the ketamine arm will receive intraoperative and postoperative ketamine. Other Names: Ketalar
Placebo Comparator: 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.	Drug: Placebo Participants in the placebo arm will receive intraoperative and postoperative saline. Other Names: Saline

Arm

Intervention/Treatment

Experimental: 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 mg/kg/min, up to 100kg max) for 48 hours.

Drug: Ketamine

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

Other Names:

Ketalar

Placebo Comparator: 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.

Drug: Placebo

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

Other Names:

Saline

Outcome Measures

Primary Outcome Measures

Hospital Length of Stay [From hospital admission until discharge, typically 3-5 days]
The participants total hospital length of stay measured in days

Secondary Outcome Measures

Total consumption of inpatient opioids [From hospital admission until discharge, typically 3-5 days]
Inpatient opioid consumption measured in morphine milligram equivalents
Pain scores [Inpatient baseline day through inpatient day 3]
Numerical pain scores, ranging from 0 to 10 with 0 being no pain and 10 being worse pain possible
Incidence of Surgical Outcomes - Return of bowel function [From hospital admission until discharge, typically 3-5 days]
Return of bowel function measured in hours
Incidence of Surgical Outcomes - Gastrointestinal Complications [From hospital admission until discharge, typically 3-5 days]
Incidence of ileus and/or nausea
Incidence of Surgical Outcomes - Rapid Response [From hospital admission until discharge, typically 3-5 days]
Rapid response as a binary outcome
Incidence of Surgical Outcomes - ICU Transfer [From hospital admission until discharge, typically 3-5 days]
Transfer to ICU as a binary outcome
Incidence of Adverse Side Effects [From hospital admission until discharge, typically 3-5 days]
Total incidence of side effects (hallucination, sedation, lightheadedness, patient request) as adverse reactions requiring early cessation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 regional nerve block
patient refusal
direct transfer from operating room to intensive care unit with endotracheal tube placed