Postoperative Pain
Conditions
Keywords
Ketamine, Postoperative pain, Opioid dependent patients, Acute pain control
Brief summary
Patients who are dependent on opioids often have poor pain relief after major surgery. This study tests the hypothesis that adding intravenous ketamine to a postoperative regimen of intravenous opioids for postoperative pain will improve pain relief in this subset of patients.
Interventions
DRUGKetamine
Intravenous (IV) ketamine 0.2 mg/kg/hr for 24-48 hours postoperatively.
DRUGPlacebo
Patients who received ketamine-matching placebo were given saline infusions
Intravenous hydromorphone PCA
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic pain \> 6 months * Long term use of opioids * Major surgery
Exclusion criteria
* Use of regional anesthetic techniques * No need for intravenous (IV) patient controlled analgesia (PCA) after surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Postoperative Pain Score | Participants were followed for the duration of hospital stay, an average of approximately 3 days. | Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for worst, average, and least pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average postoperative pain score for each treatment arm is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Worst Postoperative Pain Score | Participants were followed for the duration of hospital stay, an average of approximately 3 days. | Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for worst, average, and least pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average worst postoperative pain score for each treatment arm is reported. |
| Least Postoperative Pain Score | Participants were followed for the duration of hospital stay, an average of approximately 3 days. | Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for worst, average, and least pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average least postoperative pain score for each treatment arm is reported. |
| 24-Hour Postoperative Opioid Use | For 24 hours following surgery | Opioid use is defined as the total milligrams of hydromorphone plus other home or oral opioid used per 24 hours, converted to oral morphine equivalents. |
| Number of Participants With Treatment Related Adverse Events (AEs) | Participants were followed for the duration of hospital stay, an average of approximately 3 days. | Participants were asked to complete a Side Effects Checklist to assess for any unwanted side effects (AEs) of drugs that were administered. The determination of whether or not an AE was treatment related was at the discretion of the Investigator. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively. | 29 |
| Placebo Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively. | 30 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discharged Prior to Study Completion | 2 | 1 |
| Overall Study | Participant Opted for Morphine PCA | 1 | 1 |
Baseline characteristics
| Characteristic | Ketamine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 48.5 years STANDARD_DEVIATION 11.9 | 55 years STANDARD_DEVIATION 11.2 | 52.2 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 16 Participants | 17 Participants | 33 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 27 | 2 / 28 |
| serious Total, serious adverse events | 0 / 27 | 2 / 28 |
Outcome results
Primary
Average Postoperative Pain Score
Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for worst, average, and least pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average postoperative pain score for each treatment arm is reported.
Time frame: Participants were followed for the duration of hospital stay, an average of approximately 3 days.
Population: All randomized participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Average Postoperative Pain Score | 6.0 units on a scale | Standard Deviation 2.2 |
| Placebo | Average Postoperative Pain Score | 7.3 units on a scale | Standard Deviation 2.2 |
p-value: 0.0241Wilcoxon (Mann-Whitney)
Secondary
24-Hour Postoperative Opioid Use
Opioid use is defined as the total milligrams of hydromorphone plus other home or oral opioid used per 24 hours, converted to oral morphine equivalents.
Time frame: For 24 hours following surgery
Population: All randomized participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | 24-Hour Postoperative Opioid Use | 726 oral morphine mg equivalents | Standard Deviation 489 |
| Placebo | 24-Hour Postoperative Opioid Use | 770 oral morphine mg equivalents | Standard Deviation 560 |
p-value: 0.748Wilcoxon (Mann-Whitney)
Secondary
Least Postoperative Pain Score
Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for worst, average, and least pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average least postoperative pain score for each treatment arm is reported.
Time frame: Participants were followed for the duration of hospital stay, an average of approximately 3 days.
Population: All randomized participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Least Postoperative Pain Score | 4.4 units on a scale | Standard Deviation 3.1 |
| Placebo | Least Postoperative Pain Score | 5.6 units on a scale | Standard Deviation 3 |
p-value: 0.1085Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Treatment Related Adverse Events (AEs)
Participants were asked to complete a Side Effects Checklist to assess for any unwanted side effects (AEs) of drugs that were administered. The determination of whether or not an AE was treatment related was at the discretion of the Investigator.
Time frame: Participants were followed for the duration of hospital stay, an average of approximately 3 days.
Population: All randomized participants who completed the study and also completed the Side Effects Checklist.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ketamine | Number of Participants With Treatment Related Adverse Events (AEs) | Hallucination | 1 participants |
| Ketamine | Number of Participants With Treatment Related Adverse Events (AEs) | Sedation | 25 participants |
| Ketamine | Number of Participants With Treatment Related Adverse Events (AEs) | Pruritis | 5 participants |
| Ketamine | Number of Participants With Treatment Related Adverse Events (AEs) | Nausea | 7 participants |
| Ketamine | Number of Participants With Treatment Related Adverse Events (AEs) | Respiratory depression | 0 participants |
| Placebo | Number of Participants With Treatment Related Adverse Events (AEs) | Nausea | 5 participants |
| Placebo | Number of Participants With Treatment Related Adverse Events (AEs) | Respiratory depression | 0 participants |
| Placebo | Number of Participants With Treatment Related Adverse Events (AEs) | Hallucination | 0 participants |
| Placebo | Number of Participants With Treatment Related Adverse Events (AEs) | Pruritis | 2 participants |
| Placebo | Number of Participants With Treatment Related Adverse Events (AEs) | Sedation | 24 participants |
Secondary
Worst Postoperative Pain Score
Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for worst, average, and least pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average worst postoperative pain score for each treatment arm is reported.
Time frame: Participants were followed for the duration of hospital stay, an average of approximately 3 days.
Population: All randomized participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Worst Postoperative Pain Score | 8.7 units on a scale | Standard Deviation 2 |
| Placebo | Worst Postoperative Pain Score | 9.0 units on a scale | Standard Deviation 1.9 |
p-value: 0.4102Wilcoxon (Mann-Whitney)