The Impact of Perioperative Ketamine Infusion on Surgical Recovery

Study Overview
=================
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.

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

Conditions
-----------------
Opioid Use, Enhanced Recovery After Surgery, Anesthesia, Ketamine, Pain, Postoperative

Intervention / Treatment
-----------------
* Drug: Ketamine
* Drug: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will be performed as a pragmatic controlled clinical trial with parallel group assignment. Randomization will be in a cluster format.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine<br>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. | Drug: Ketamine<br>* Participants in the ketamine arm will receive intraoperative and postoperative ketamine.<br>* Other names: Ketalar;|
| Placebo Comparator: Saline<br>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<br>* Participants in the placebo arm will receive intraoperative and postoperative saline.<br>* Other names: Saline;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Stay | The participants length of stay, from anesthesia beginning to discharge, measured in days | From surgery start until discharge, typically 3-5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total consumption of inpatient opioids | Inpatient opioid consumption measured in morphine milligram equivalents | From hospital admission until discharge, typically 3-5 days | 
| Incidence of Surgical Outcomes - Gastrointestinal Complications | Incidence of ileus requiring gastric decompression as defined by orogastric or nasogastric tube placement in the postoperative period. | From hospital admission until discharge, typically 3-5 days | 
| Incidence of Surgical Outcomes - Rapid Response | Rapid response as a binary outcome | From hospital admission until discharge, typically 3-5 days | 
| Incidence of Surgical Outcomes - ICU Transfer | Transfer to ICU as a binary outcome | From hospital admission until discharge, typically 3-5 days | 
| Incidence of Adverse Side Effects | Total incidence of side effects (hallucination, sedation, lightheadedness, patient request) as adverse reactions requiring early cessation. | From hospital admission until discharge, typically 3-5 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Learning Healthcare System, ERAS, Enhanced Recovery After Surgery, Ketamine, Opioid