The Impact of Perioperative Ketamine Infusion on Surgical Recovery

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04625283

Enrollment

1570

Registered

2020-11-12

Start date

2021-04-12

Completion date

2024-02-01

Last updated

2025-02-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

ERAS, Enhanced Recovery After Surgery, Ketamine, Opioid, Learning Healthcare System

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.

Interventions

DRUGKetamine

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

DRUGPlacebo

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

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.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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 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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Total Consumption of Inpatient Opioids	From hospital admission until discharge, typically 3-5 days	Inpatient opioid consumption measured in morphine milligram equivalents
Number of Participants With Ileus	From hospital admission until discharge, typically 3-5 days	Number of participants reporting ileus requiring gastric decompression as defined by orogastric or nasogastric tube placement in the postoperative period.
Number of Participants Who Encounter Rapid Response Team Activation	From hospital admission until discharge, typically 3-5 days	Number of participants who encounter rapid response team activation within 72 hours post-operation. This is as a binary outcome
Number of Participants Who Experienced ICU Transfer	From hospital admission until discharge, typically 3-5 days	Number of participants who experienced transfer to ICU. This is as a binary outcome
Number of Participants Who Experienced Adverse Side Effects	From hospital admission until discharge, typically 3-5 days	Total number of side effects (hallucination, sedation, lightheadedness, patient request) as adverse reactions requiring early cessation.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	770
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. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.	752
Total	1,522

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	post randomization exclusion	28	20

Baseline characteristics

Characteristic	Ketamine	Saline	Total
Age, Continuous	58.9 years	57.8 years	58.3 years
BMI (kg/m²)	27.3 kg/m²	27.6 kg/m²	27.4 kg/m²
Opioid status Exposed	82 Participants	76 Participants	158 Participants
Opioid status Naive	688 Participants	676 Participants	1364 Participants
Race/Ethnicity, Customized Asian	3 Participants	11 Participants	14 Participants
Race/Ethnicity, Customized Black or African American	58 Participants	67 Participants	125 Participants
Race/Ethnicity, Customized Hispanic/Latino	3 Participants	3 Participants	6 Participants
Race/Ethnicity, Customized Other	15 Participants	9 Participants	24 Participants
Race/Ethnicity, Customized Unknown	5 Participants	2 Participants	7 Participants
Race/Ethnicity, Customized White	686 Participants	660 Participants	1346 Participants
Region of Enrollment United States	770 Participants	752 Participants	1522 Participants
Sex: Female, Male Female	371 Participants	380 Participants	751 Participants
Sex: Female, Male Male	399 Participants	372 Participants	771 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 770	0 / 752
other Total, other adverse events	322 / 770	163 / 752
serious Total, serious adverse events	0 / 770	1 / 752

Outcome results

Primary

Length of Stay

The participants length of stay, from anesthesia beginning to discharge, measured in days

Time frame: From surgery start until discharge, typically 3-5 days

Arm	Measure	Value (MEDIAN)
Ketamine	Length of Stay	5.0 days
Saline	Length of Stay	5.0 days

Secondary

Number of Participants Who Encounter Rapid Response Team Activation

Number of participants who encounter rapid response team activation within 72 hours post-operation. This is as a binary outcome