Perioperative Ketamine for Pain With Gastric Bypass

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT03448068
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arms: 2
• Actual Duration (Months): 20.8
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

Opioid medications such as morphine, hydrocodone and oxycodone are standard for treating pain after surgery, however there are disadvantages. Because of the way opioids work, gastric bypass patients may have an increased risk of having sedation or problems with breathing. In patients with sleep apnea, opioids may increase the risk of severe apnea.

Ketamine is an alternative pain medicine that can be used to treat pain after surgery and may have fewer effects on breathing. Using ketamine as part of the regimen may be a better choice for laparoscopic gastric bypass patients.

This study is being done to find out if intraoperative ketamine infusion combined with continuation for twenty-four hours post-surgery provides superior pain control and decreases post-operative opioid use versus standard non-ketamine therapy.

Condition or Disease	Intervention/Treatment	Phase
Laparoscopic Gastric Bypass Surgery; Ketamine	Drug: Ketamine; Drug: Standard therapy	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Low-dose Ketamine Infusions for Perioperative Pain Management in Patients Undergoing Laparoscopic Gastric Bypass
• Actual Study Start Date: Apr 16, 2018
• Actual Primary Completion Date: Jan 9, 2020
• Actual Study Completion Date: Jan 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketamine Therapy Ketamine 0.3 mg/kg (IBW) bolus with induction. Ketamine infusion 0.2 mg/kg/hr. (IBW) initiated after induction and terminated after 24 hours. Ketamine infusion will not be titrated. Remaining care will be identical to standard therapy group.	Drug: Ketamine; Ketamine 0.3 mg/kg (IBW) bolus with induction. Ketamine infusion 0.2mg/kg/hr. (IBW) initiated after induction and terminated after 24 hours. Ketamine infusion not titrated.
Active Comparator: Standard Therapy Calculation ideal body weight (IBW) Pre-op dexamethasone Pre-op midazolam at discretion of anesthesiologist Anesthesia Induction - Propofol and fentanyl, anesthesiologist discretion. Neuromuscular block with succinylcholine and/or rocuronium at discretion of anesthesiologist. Orotracheal intubation. Anesthesia Maintenance - Sevoflurane/rocuronium. Addl. doses of fentanyl, discretion of anesthesiologist. Emergence from anesthesia - Acetaminophen, Ketorolac and Ondansetron unless contraindicated. Sugammadex depending on twitch response per drug manufacturer recommended protocol. Post-Op Analgesia - Hydromorphone, acetaminophen and ketorolac Other post-op care as per usual surgical routine	Drug: Standard therapy; Pre-op dexamethasone 4mg IV and midazolam 1-2mg IV Anesthesia Induction - Propofol 2-3mg/kg IV, Fentanyl 1mcg/kg IV, neuromuscular block w/succinylcholine and/or rocuronium, orotracheal intubation Anesthesia maintenance - Sevoflurane/rocuronium, fentanyl 0.5-1mcg/kg Anesthesia emergence - Acetaminophen 1g, ketorolac 30 mg IV, ondansetron 4mg IV, sugammadex 2mg/kg or 4 mg/kg dose depending on twitch Post-op anesthesia - Hydromorphone patient-controlled analgesia (PCA) 0.2 mg/8 min, acetaminophen 1 g IV Q8 around the clock (ATC) x 3 addl. doses, ketorolac 15 mg IV Q6 ATC x 3 addl. doses. Other standard surgical post-op care

Outcome Measures

Primary Outcome Measures

1. Total Cumulative Perioperative Opioid Dose [approximately 48 hours after induction of anesthesia]

   Measured in oral morphine equivalents

Secondary Outcome Measures

1. Average Pain Score 0-12 Hours [approximately 0-12 hours post operatively]

   Patient reported pain scores at 0-12 hours post operatively. Measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 for no pain and 100 mm for extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain. A higher score indicates great pain intensity.

2. Average Pain Score 12-24 Hours [approximately 12-24 hours post operatively]

   Patient reported pain scores at 12-24 hours post operatively. Measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 for no pain and 100 mm for extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain. A higher score indicates great pain intensity.

3. Average Pain Score 24-48 Hours [approximately 24-48 hours post operatively]

   Patient reported pain scores at 24-48 hours post operatively. Measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 for no pain and 100 mm for extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain. A higher score indicates great pain intensity.

4. Post-Operative Nausea [12 hours, 24 hours, and 48 hours]

   Number of subject to experience post-operative nausea

5. Length of Stay in Hospital [Arrival at hospital until discharge from hospital, approximately 2 days]

   Length of hospital stay measured in hours

6. Patient Satisfaction With Pain Control at Time of Hospital Discharge [approximately 1-2 days post-operatively]

   Self-reported questionnaire at the time of discharge from the hospital rating satisfaction of pain treatment while in the hospital using a scale of 0= extremely dissatisfied, 10 = extremely satisfied.

7. Patient Satisfaction With Pain Control at Postoperative Visit [approximately 30 days post-operatively]

   Self-reported questionnaire at the time of first post-operative visit with the surgeon, rating the worst amount of pain since being discharged from the hospital using a scale of 0= no pain, 10 = worst pain possible.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Patients undergoing laparoscopic gastric bypass at Mayo Clinic in Arizona

2. BMI is ≥ 35 kg/m2

3. Consent is able to be obtained as per Mayo Clinic policy

Exclusion Criteria:

1. Intolerance to ketamine

2. History of schizophrenia, schizoaffective disorder, or other psychiatric diagnosis with psychotic features

3. Presence of unstable cardiovascular disease (presence of acute coronary syndrome, unstable angina, hypertension emergency, acute transient ischemic attack (TIA) or stroke)

4. Presence of acute elevation of intracranial or intraocular pressure

5. Presence of seizure disorder

6. History of substance abuse or addiction

7. Creatinine greater than 1.5 mg/dL

8. End-stage liver disease

9. Pregnancy

10. Patients with chronic pain and/or chronic opioid therapy will not be excluded to more closely replicate the study patient population of interest. However, patients taking greater than 50 morphine equivalents (ME) per day for greater than 1 month prior to surgery will be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Phoenix	Arizona	United States	85054

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Andrew W Gorlin, M.D., Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 12, 2019

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Andrew Gorlin, MD, Assistant Professor of Anesthesiology, College of Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03448068
• Other Study ID Numbers: 17-000301
• First Posted: Feb 27, 2018
• Last Update Posted: Apr 29, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Ketamine

Study Results

Participant Flow

Arm/Group Title	Ketamine Therapy	Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia
Period Title: Overall Study
STARTED	17	17
COMPLETED	17	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ketamine Therapy	Standard Therapy	Total
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia	Total of all reporting groups
Overall Participants	17	17	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.2 (11.5)	48.8 (10.2)	51.5 (11.0)
Sex: Female, Male (Count of Participants)
Female	12 70.6%	15 88.2%	27 79.4%
Male	5 29.4%	2 11.8%	7 20.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	17 100%	17 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Total Cumulative Perioperative Opioid Dose
Description	Measured in oral morphine equivalents
Time Frame	approximately 48 hours after induction of anesthesia

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine Therapy	Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia
Measure Participants	17	17
Mean (Standard Deviation) [Morphine Equivalents]	179.9 (113.1)	248.6 (91.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine Therapy, Standard Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Average Pain Score 0-12 Hours
Description	Patient reported pain scores at 0-12 hours post operatively. Measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 for no pain and 100 mm for extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain. A higher score indicates great pain intensity.
Time Frame	approximately 0-12 hours post operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine Therapy	Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia
Measure Participants	17	17
Mean (Standard Deviation) [mm]	3.4 (2.2)	4.2 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine Therapy, Standard Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2252
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Average Pain Score 12-24 Hours
Description	Patient reported pain scores at 12-24 hours post operatively. Measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 for no pain and 100 mm for extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain. A higher score indicates great pain intensity.
Time Frame	approximately 12-24 hours post operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine Therapy	Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia
Measure Participants	17	17
Mean (Standard Deviation) [mm]	2.6 (1.9)	3.7 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine Therapy, Standard Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0610
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Average Pain Score 24-48 Hours
Description	Patient reported pain scores at 24-48 hours post operatively. Measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 for no pain and 100 mm for extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain. A higher score indicates great pain intensity.
Time Frame	approximately 24-48 hours post operatively

Outcome Measure Data

Analysis Population Description

2 subjects were discharged early so data was not collected or analyzed for 1 subject from the ketamine therapy group and 1 subject from the standard therapy group

Arm/Group Title	Ketamine Therapy	Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia
Measure Participants	16	16
Mean (Standard Deviation) [mm]	3.1 (1.9)	3.8 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine Therapy, Standard Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2720
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Post-Operative Nausea
Description	Number of subject to experience post-operative nausea
Time Frame	12 hours, 24 hours, and 48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine Therapy	Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia
Measure Participants	17	17
Nausea 1st 12 hours	10 58.8%	9 52.9%
Nausea 2nd 12 hours	6 35.3%	2 11.8%
Nausea 2nd 24 hours	3 17.6%	3 17.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine Therapy, Standard Therapy
	Comments	Nausea 1st 12 hours for Ketamine Therapy vs Standard Therapy
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7298
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ketamine Therapy, Standard Therapy
	Comments	Nausea 2nd 12 hours for Ketamine Therapy vs Standard Therapy
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1058
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ketamine Therapy, Standard Therapy
	Comments	Nausea 2nd 24 hours for Ketamine Therapy vs Standard Therapy
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Length of Stay in Hospital
Description	Length of hospital stay measured in hours
Time Frame	Arrival at hospital until discharge from hospital, approximately 2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine Therapy	Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia
Measure Participants	17	17
Mean (Standard Deviation) [Hours]	43.9 (18.0)	36.7 (14.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine Therapy, Standard Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Patient Satisfaction With Pain Control at Time of Hospital Discharge
Description	Self-reported questionnaire at the time of discharge from the hospital rating satisfaction of pain treatment while in the hospital using a scale of 0= extremely dissatisfied, 10 = extremely satisfied.
Time Frame	approximately 1-2 days post-operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine Therapy	Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia
Measure Participants	17	17
Mean (Standard Deviation) [score on a scale]	9.5 (0.9)	8.3 (1.9)

8. Secondary Outcome

Title	Patient Satisfaction With Pain Control at Postoperative Visit
Description	Self-reported questionnaire at the time of first post-operative visit with the surgeon, rating the worst amount of pain since being discharged from the hospital using a scale of 0= no pain, 10 = worst pain possible.
Time Frame	approximately 30 days post-operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine Therapy	Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours	Subjects received standard of care anesthesia
Measure Participants	17	17
Mean (Standard Deviation) [score on a scale]	3.6 (3.4)	6.2 (2.3)

Adverse Events

Time Frame	Adverse events were collected 30 days following surgery for each participant, over a study duration of approximately 48 months
Arm/Group Title	Ketamine Therapy		Standard Therapy
Arm/Group Description	Subjects received a ketamine bolus (0.3 mg/kg IV IBW) with induction; a ketamine infusion (0.2 mg/kg/hr IBW) was started after induction and terminated the next morning after surgical team rounds or at 24 hours		Subjects received standard of care anesthesia
All Cause Mortality
	Ketamine Therapy		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)
Serious Adverse Events
	Ketamine Therapy		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Ketamine Therapy		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/17 (76.5%)		11/17 (64.7%)
General disorders
Nausea	13/17 (76.5%)	19	11/17 (64.7%)	14

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.