Cesarean Section Complications, Post-operative Pain, Post-partum Pain
Conditions
Keywords
ketorolac, opiate, cesarean section
Brief summary
To evaluate the efficacy of increased ketorolac in reducing opioid use after cesarean section.
Detailed description
This was a single-center, randomized, double-blind, parallel-group trial to assess pain management following cesarean section with increased ketorolac versus placebo. All patients undergoing cesarean section with neuraxial anesthesia received two doses of 30mg IV ketorolac postoperatively per hospital protocol and were then randomized to receive an additional four doses of 30 mg of IV ketorolac or placebo every 6 hours. The primary outcome was the total morphine milligram equivalents (MME) used in the first 72 postoperative hours. Secondary outcomes included the number of patients that used no opioid postoperatively, postoperative pain scores, postoperative change in hematocrit and creatinine, and postoperative satisfaction with inpatient care and pain management. A sample size of 74 per group (n=148) was planned.
Interventions
DRUGKetorolac
The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.
Sponsors
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The subjects, care providers, and investigators will be blinded to the assignments of groups.
Intervention model description
Randomized controlled trial
Eligibility
Sex/Gender
FEMALE
Age
16 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Women presenting for care at Tufts Medical Center as an outpatient in obstetrics clinic or on Labor and Delivery. * The subject must have had a cesarean section for any indication at Tufts Medical Center to be randomized to the study * The subject is willing to have a phone call follow up conversation 2 weeks after their surgery.
Exclusion criteria
* Patients with allergy to ketorolac, NSAIDS or aspirin * Patients with peptic ulcer disease, preexisting kidney or liver disease. * Duramorph is not used as the anesthetic for the spinal/epidural during the cesarean section. * Patient is hemodynamically unstable due to hemorrhage. * Patient requires therapeutic anticoagulation in the post-operative period * Patients with peripartum cardiomyopathy * Provider decision to exclude patient. * Patient diagnosis of chronic hypertension, gestational hypertension, preeclampsia, HELLP syndrome, or eclampsia * A study subject may participate in another research study while participating in this research study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Total Morphine Milligram Equivalents (MME) Used in the First 72 Postoperative Hours | Within 72 postoperative hours | The amount of MME's will be monitored for each group. MME's will be determined by the amount of opiate mediations administered. The MME value can range from 0 to typically 200 MME's, however there is no upper limit of measureable MME's. The MME's for each patient will be a sum of MME's administered throughout the course of the hospitalization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients That Used no Opioid Postoperatively | Within 72 post-operative hours | The number of patients in each arm that required no opioids for pain control postoperatively. |
| Postoperative Change in Hematocrit | Change in pre-operative hematocrit to POD1 hematocrit | The change in patient hematocrit from baseline to POD1 |
| Number of Participants With a Pain Score Greater Than 3 | 2 weeks | The patient reported pain scores will be recorded and analyzed for each group. The Pain Score is determined by the patient using a visual analog scale with a range from 0-10, where 0 is no pain at all and 10 is the worst pain imaginable for the patient. Pain scores were collected by postpartum nursing staff per institutional policy. The number of patients with a pain score greater than 3 will be reported. A pain score greater than 3 was chosen as a cutoff as this is the pain score at which an opioid may be indicated for analgesia at our institution. |
| Postoperative Satisfaction With Inpatient Pain Control | Inpatient pain control satisfaction as reported at two weeks postpartum | Two weeks after cesarean section, subjects were contacted by telephone to complete a survey on postpartum pain management. At least three attempts were made to contact subjects by telephone. In the follow-up phone call, patients were asked to rate their satisfaction with their postpartum care: very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied. The number below describes the number of patients who reported they were very satisfied with their care. |
| Postoperative Satisfaction With Their Inpatient Postpartum Care. | Satisfaction with inpatient care as reported at two weeks postpartum | Two weeks after cesarean section, subjects were contacted by telephone to complete a survey on their overall postpartum care. At least three attempts were made to contact subjects by telephone. In the follow-up phone call, patients were asked to rate their satisfaction with their postpartum care: very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied. The number below describes the number of patients that reported they were very satisfied with their care. |
| Change in Creatinine | Change in creatinine from POD1 to POD2 | The change in patient's creatinine from POD1 to POD2 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Protocol Subjects randomized to the standard group will receive the standard postoperative pain protocol that is currently used at Tufts Medical Center. It includes two doses of IV Ketorolac every 6 hours as needed for postoperative pain. Ibuprofen would be ordered 6 hours following the last dose after the last study drug. | 74 |
| Ketorolac Protocol Subjects randomized to the Ketorolac protocol will receive the study postoperative pain protocol. This includes 6 doses of IV Ketorolac, scheduled every 6 hours. The first dose is administered in the operating room or post-operative care unit.
Ketorolac: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively. | 74 |
| Total | 148 |
Baseline characteristics
| Characteristic | Ketorolac Protocol | Total | Standard Protocol |
|---|---|---|---|
| Age, Continuous | 32.6 years STANDARD_DEVIATION 5.2 | 32.5 years STANDARD_DEVIATION 5 | 32.4 years STANDARD_DEVIATION 5 |
| Race/Ethnicity, Customized Race/Ethnicity Asian | 6 Participants | 10 Participants | 4 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black | 8 Participants | 23 Participants | 15 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 14 Participants | 29 Participants | 15 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Not reported | 9 Participants | 17 Participants | 8 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White | 37 Participants | 69 Participants | 32 Participants |
| Region of Enrollment United States | 74 participants | 148 participants | 74 participants |
| Sex: Female, Male Female | 74 Participants | 148 Participants | 74 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 74 |
| other Total, other adverse events | 0 / 74 | 0 / 74 |
| serious Total, serious adverse events | 1 / 74 | 1 / 74 |
Outcome results
Primary
The Total Morphine Milligram Equivalents (MME) Used in the First 72 Postoperative Hours
The amount of MME's will be monitored for each group. MME's will be determined by the amount of opiate mediations administered. The MME value can range from 0 to typically 200 MME's, however there is no upper limit of measureable MME's. The MME's for each patient will be a sum of MME's administered throughout the course of the hospitalization.
Time frame: Within 72 postoperative hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Protocol | The Total Morphine Milligram Equivalents (MME) Used in the First 72 Postoperative Hours | 60.0 MME |
| Ketorolac Protocol | The Total Morphine Milligram Equivalents (MME) Used in the First 72 Postoperative Hours | 30 MME |
Secondary
Change in Creatinine
The change in patient's creatinine from POD1 to POD2
Time frame: Change in creatinine from POD1 to POD2
Population: Post operative day 1 and 2 creatinine was collected on 68 patients in the standard group and 65 patients in the ketorolac group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Protocol | Change in Creatinine | .03 mg/dL | Standard Deviation 0.05 |
| Ketorolac Protocol | Change in Creatinine | .59 mg/dL | Standard Deviation 0.01 |
Secondary
Number of Participants With a Pain Score Greater Than 3
The patient reported pain scores will be recorded and analyzed for each group. The Pain Score is determined by the patient using a visual analog scale with a range from 0-10, where 0 is no pain at all and 10 is the worst pain imaginable for the patient. Pain scores were collected by postpartum nursing staff per institutional policy. The number of patients with a pain score greater than 3 will be reported. A pain score greater than 3 was chosen as a cutoff as this is the pain score at which an opioid may be indicated for analgesia at our institution.
Time frame: 2 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Protocol | Number of Participants With a Pain Score Greater Than 3 | 40 Participants |
| Ketorolac Protocol | Number of Participants With a Pain Score Greater Than 3 | 19 Participants |
Secondary
Postoperative Change in Hematocrit
The change in patient hematocrit from baseline to POD1
Time frame: Change in pre-operative hematocrit to POD1 hematocrit
Population: Post-operative day 1 hematocrit was available on 72 patients in the standard group and 73 patients in the ketorolac group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Protocol | Postoperative Change in Hematocrit | -5.5 percentage of red blood cells in blood | Standard Deviation 3.5 |
| Ketorolac Protocol | Postoperative Change in Hematocrit | -5.5 percentage of red blood cells in blood | Standard Deviation 2.6 |
Secondary
Postoperative Satisfaction With Inpatient Pain Control
Two weeks after cesarean section, subjects were contacted by telephone to complete a survey on postpartum pain management. At least three attempts were made to contact subjects by telephone. In the follow-up phone call, patients were asked to rate their satisfaction with their postpartum care: very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied. The number below describes the number of patients who reported they were very satisfied with their care.
Time frame: Inpatient pain control satisfaction as reported at two weeks postpartum
Population: 52 patients in the standard protocol and 52 patients in the ketorolac group responded to the 2 week postpartum survey.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Protocol | Postoperative Satisfaction With Inpatient Pain Control | 35 Participants |
| Ketorolac Protocol | Postoperative Satisfaction With Inpatient Pain Control | 29 Participants |
Secondary
Postoperative Satisfaction With Their Inpatient Postpartum Care.
Two weeks after cesarean section, subjects were contacted by telephone to complete a survey on their overall postpartum care. At least three attempts were made to contact subjects by telephone. In the follow-up phone call, patients were asked to rate their satisfaction with their postpartum care: very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied. The number below describes the number of patients that reported they were very satisfied with their care.
Time frame: Satisfaction with inpatient care as reported at two weeks postpartum
Population: 52 patients in the standard protocol and 52 patients in the ketorolac group responded to the 2 week postpartum survey.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Protocol | Postoperative Satisfaction With Their Inpatient Postpartum Care. | 39 Participants |
| Ketorolac Protocol | Postoperative Satisfaction With Their Inpatient Postpartum Care. | 39 Participants |
Secondary
The Number of Patients That Used no Opioid Postoperatively
The number of patients in each arm that required no opioids for pain control postoperatively.
Time frame: Within 72 post-operative hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Protocol | The Number of Patients That Used no Opioid Postoperatively | 24 Participants |
| Ketorolac Protocol | The Number of Patients That Used no Opioid Postoperatively | 9 Participants |