Pain, Postoperative Depression
Conditions
Keywords
perioperative period, pain, gastric bypass
Brief summary
This is a randomized, double-blind, placebo-controlled, two-arm parallel, single-center study. One hundred subjects (50 in each arm) will be enrolled. Subjects, between the ages 18 and 65, undergoing laparoscopic gastric bypass or sleeve gastrectomy will be recruited and consented during the preadmission visit prior to surgery.
Detailed description
This is a randomized, double-blind, placebo-controlled, two-arm parallel, single-center study. One hundred subjects (50 in each arm) will be enrolled. Subjects, between the ages 18 and 65, undergoing laparoscopic gastric bypass or sleeve gastrectomy will be recruited and consented during the preadmission visit prior to surgery. Eligible subjects will be randomized to one of the two treatment group in a 1:1 ratio to receive either IV ketamine (0.4mg/kg) or matching placebo. Both men and women will be recruited, and there is no limitation as to racial and ethnic origin. In the PACU, patients will receive either 0.4mg/kg IV ketamine or placebo. All patients will also receive standard post-anesthetic monitoring and care, as well as routine care after transfer out of the PACU. Patients are followed until the date of discharge, and endpoints (see below) are collected from patient reports as well as from medical charts. During their hospital stay (and once after their discharge from the hospital), patients will fill out five questionnaires which provide estimates of their postoperative pain control, mood and function, and quality of postsurgical recovery. An additional component of the study, which is entirely optional, is to obtain patient serum samples (about two teaspoons) in the operating room and 15 minutes and 4 hours after ketamine infusion. The investigators will use these samples to assess levels of IL-1, IL-6, TNF-α, and BDNF, which are markers for pain. In addition, with patient consent, the investigators will also store serum samples for future research use to measure other cytokines and neurotrophic factors and molecular markers associated with pain and depression.
Interventions
DRUGKetamine
0.4mg/kg infusion
OTHERPlacebo Comparator
0.4mg/kg infusion
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adults, \>18 years, \<65 years, who will undergo gastric bypass or sleeve gastrectomy. 2. Subject is non-lactating and is either: * Not of childbearing potential; or * Of childbearing potential but is not pregnant at time of baseline as determined by pre-operative pregnancy testing. 3. Subject is ASA physical status 1, 2, or 3. 4. Subject who is deemed medically stable
Exclusion criteria
1. \<18 years of age; \>65 years of age 2. Pregnant or breastfeeding 3. Does not speak or understand English (the study forms used are copy-righted in English) 4. Cognitively impairment (by history) or clinical signs of altered mental status 5. History of misuse or abuse of ketamine 6. History of chest pain or chest pain in the PACU 7. Use of a medication that interferes with metabolism of ketamine within the last 24 hours 8. A diagnosis of schizophrenia and/ or a history of chronic antipsychotic medication use 9. History of head trauma 10. History of intracranial mass or hemorrhage 11. History of stroke 12. History of cardiac arrhythmia 13. Subject for whom ketamine is contraindicated 14. Unwillingness to give informed consent according to HIC guidelines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Scores | Baseline (DOS) to 7 days (Post Op) | VAS Scores will be assessed on Day of Surgery (DOS), Post-op Day (POD) 1, 2 and 7. If patients have been discharged, coordinators will contact patient by home. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay During Hospitalization | 8 days | LOS will be recorded from medical record. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to Out of Bed to Chair (OOB) | 7 Days | Patient will be asked to record and report the time to OOB |
| Spirometry Use 4 Hours After the Termination of Ketamine Infusion | 1 day | Spirometry use will be assessed by a study team member to determine whether the patient is meeting the goal set by the surgical team 4 hours after ketamine infusion. |
| Change in Serum Level of IL-1 After Ketamine Infusion | 1 day | changes in serum levels of IL-1, which will be collected at baseline (in the OR preoperatively), and 15 min and 4 hours after the termination of ketamine infusion. |
| Survey Scores - McGill's Short Form | Pre-op,Day of Surgery through Post-op Day 8 | Change in survey scores -- McGill's short form |
| Survey Scores - Becks Depression Index (BDI) | Pre-op,Day of Surgery through Post-op Day 8 | Change in survey scores for Becks Depression Index (BDI) |
| Opioid Usage Per Hour During the PACU Stay Before and After Ketamine Infusion | 8 Days | Length of stay and opioid usage will be recorded from electronic medical chart |
| Survey Scores - MADRS | Pre-op,Day of Surgery through Post-op Day 8 | Change in scores for MADRS |
| Change in Serum Level of IL-6 After Ketamine Infusion | 1 day | changes in serum levels of IL-1, which will be collected at baseline (in the OR preoperatively), and 15 min and 4 hours after the termination of ketamine infusion. |
| Change in Serum Level of TNF-α After Ketamine Infusion | 1 day | changes in serum levels of IL-1, which will be collected at baseline (in the OR preoperatively), and 15 min and 4 hours after the termination of ketamine infusion. |
| Change in Serum Level of BDNF After Ketamine Infusion | 1 day | changes in serum levels of IL-1, which will be collected at baseline (in the OR preoperatively), and 15 min and 4 hours after the termination of ketamine infusion. |
| Survey Scores - QoR15 | Pre-op,Day of Surgery through Post-op Day 8 | Change in scores for Quality of Recovery 15 - QoR15 |
| Opioid Usage Per Day Throughout the Hospital Stay | 8 days | recorded from medical chart |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo Comparator: 0.4mg/kg saline infusion | 46 |
| Ketamine Ketamine: 0.4mg/kg infusion | 44 |
| Total | 90 |
Baseline characteristics
| Characteristic | Placebo | Ketamine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 44 Participants | 90 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 9 Participants | 17 Participants |
| Race/Ethnicity, Customized White | 37 Participants | 35 Participants | 72 Participants |
| Region of Enrollment United States | 46 participants | 44 participants | 90 participants |
| Sex: Female, Male Female | 29 Participants | 33 Participants | 62 Participants |
| Sex: Female, Male Male | 17 Participants | 11 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 44 |
| other Total, other adverse events | 9 / 46 | 7 / 44 |
| serious Total, serious adverse events | 0 / 46 | 0 / 44 |
Outcome results
Primary
Change in Pain Scores
VAS Scores will be assessed on Day of Surgery (DOS), Post-op Day (POD) 1, 2 and 7. If patients have been discharged, coordinators will contact patient by home.
Time frame: Baseline (DOS) to 7 days (Post Op)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment/Placebo | Change in Pain Scores | 1.45 score on a scale | Standard Deviation 0.23 |
| Treatment | Change in Pain Scores | 1 score on a scale | Standard Deviation 0.18 |
Secondary
Length of Stay During Hospitalization
LOS will be recorded from medical record.
Time frame: 8 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment/Placebo | Length of Stay During Hospitalization | 1.3 Days |
| Treatment | Length of Stay During Hospitalization | 1.2 Days |
Other Pre-specified
Change in Serum Level of BDNF After Ketamine Infusion
changes in serum levels of IL-1, which will be collected at baseline (in the OR preoperatively), and 15 min and 4 hours after the termination of ketamine infusion.
Time frame: 1 day
Other Pre-specified
Change in Serum Level of IL-1 After Ketamine Infusion
changes in serum levels of IL-1, which will be collected at baseline (in the OR preoperatively), and 15 min and 4 hours after the termination of ketamine infusion.
Time frame: 1 day
Other Pre-specified
Change in Serum Level of IL-6 After Ketamine Infusion
changes in serum levels of IL-1, which will be collected at baseline (in the OR preoperatively), and 15 min and 4 hours after the termination of ketamine infusion.
Time frame: 1 day
Other Pre-specified
Change in Serum Level of TNF-α After Ketamine Infusion
changes in serum levels of IL-1, which will be collected at baseline (in the OR preoperatively), and 15 min and 4 hours after the termination of ketamine infusion.
Time frame: 1 day
Other Pre-specified
Opioid Usage Per Day Throughout the Hospital Stay
recorded from medical chart
Time frame: 8 days
Other Pre-specified
Opioid Usage Per Hour During the PACU Stay Before and After Ketamine Infusion
Length of stay and opioid usage will be recorded from electronic medical chart
Time frame: 8 Days
Other Pre-specified
Spirometry Use 4 Hours After the Termination of Ketamine Infusion
Spirometry use will be assessed by a study team member to determine whether the patient is meeting the goal set by the surgical team 4 hours after ketamine infusion.
Time frame: 1 day
Other Pre-specified
Survey Scores - Becks Depression Index (BDI)
Change in survey scores for Becks Depression Index (BDI)
Time frame: Pre-op,Day of Surgery through Post-op Day 8
Other Pre-specified
Survey Scores - MADRS
Change in scores for MADRS
Time frame: Pre-op,Day of Surgery through Post-op Day 8
Other Pre-specified
Survey Scores - McGill's Short Form
Change in survey scores -- McGill's short form
Time frame: Pre-op,Day of Surgery through Post-op Day 8
Other Pre-specified
Survey Scores - QoR15
Change in scores for Quality of Recovery 15 - QoR15
Time frame: Pre-op,Day of Surgery through Post-op Day 8
Other Pre-specified
Time to Out of Bed to Chair (OOB)
Patient will be asked to record and report the time to OOB
Time frame: 7 Days