Postoperative Pain
Conditions
Keywords
cesarean, morphine, multimodal analgesia
Brief summary
This is a randomized double blinded non-inferiority study comparing the duration of pain relief when patients receive one of three doses of spinal morphine. Enrolled patients will be randomly assigned to receive either 50 mcg, 150 mcg, or 250 mcg. All patients will receive standardized postoperative care, including multimodal analgesia. The primary outcome will be the time until the patient requests additional opioid pain medications.
Detailed description
Prospective, randomized, double-blind, controlled trial, with a non-inferiority design. Patients will be randomly assigned to receive either intrathecal morphine 50 mcg, 150 mcg, or 250 mcg based on a pre-assigned randomization sequence. This medication will be administered as part of their spinal anesthesia for cesarean delivery. the patient, clinician who administers the spinal anesthesia, and investigator who follows the patient will all be blinded to the dose of medication. All patients will receive standard of care for cesarean delivery and routine nursing care. This includes: preoperative intravenous catheter placement with preoperative IV fluid, standard American Society of Anesthesiologists monitoring, and neuraxial anesthesia placement (either spinal or combined spinal epidural) in sterile fashion. Each patient will receive standard cesarean induction dose of intrathecal medication consisting of 1.5ml of 0.75% hyperbaric bupivacaine, fentanyl 25 mcg. At end of surgery, all patients will receive standard dose of ketorolac 30 mg IV and acetaminophen 1 gm IV and continue with redosing every 6 and 8 hours (respectively) for 24 hours. On arrival to PACU, all patients will receive standard nursing care with standard monitoring of side effects. On discharge from PACU, patients will be transferred to postpartum floor and receive standard nursing care and monitoring. Over the following 24 hours, the patient will receive all standard post-cesarean care. For treatment of breakthrough pain, medications will provided be per standard care: oxycodone 5-10 mg PO every four hours PRN for pain. If the patient is not comfortable after receiving oral oxycodone they will be assessed by an anesthesia provider for either regional nerve block or additional opioids, as a one-time dose or by patient controlled analgesia (PCA). For treatment for side effects, medications will provided be per standard care: ondansetron 4mg IV as first-line for nausea/vomiting, promethazine 6.25 mg IV or Haloperidol 0.5-1mg IV for refractory nausea/vomiting. Naloxone 0.04 mg IV for refractory pruritus.
Interventions
Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief
Sponsors
Study design
Masking description
Randomization maintained in the research pharmacy. Blinded syringe delivered to the investigator for the study.
Intervention model description
Prospective randomized
Eligibility
Inclusion criteria
* Healthy women (ASA 2) * Between 18 and 45 years old * Singleton term pregnancies * Planned neuraxial anesthesia
Exclusion criteria
* Refusal to participate * Known allergy or contraindication to any medication used in the study * Significant medical or obstetrical disease (ASA ≥ 3) * Opioid use disorder * Chronic pain syndrome * Daily or near daily opioid use within last 3 weeks. * Patient receiving a Monoamine oxidase inhibitors (MOAi)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Pain Relief | 72 hours after delivery | Time to patient request for first dose of oral rescue pain medicine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Scores | 24 hours after delivery | Visual analogue pain scores reported by the patient. Scale measured on a line from 0 to 100 mm, with 0 representing 'no pain' and 100 representing 'worst possible pain' |
| Quality of Recovery | 24 hours after delivery | Quality of Recovery Score following Cesarean Delivery Questionnaire (ObsQoR-11). This is a multi-dimensional wellness scale ranging from 0 (worst) to 120 (best) along 12 axis items. |
| Nausea | 24 hours after delivery | Incidence of nausea and vomiting requiring treatment with a medication |
| Pruritus | 24 hours after delivery | Incidence of pruritus requiring treatment with a medication |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50 Micrograms Patients in this arm will receive 50 micrograms of morphine administered in the spinal fluid as part of their anesthesia for cesarean delivery
Morphine Sulfate: Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief | 23 |
| 150 Micrograms Patients in this arm will receive 150 micrograms of morphine administered in the spinal fluid as part of their anesthesia for cesarean delivery
Morphine Sulfate: Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief | 23 |
| 250 Micrograms Patients in this arm will receive 250 micrograms of morphine administered in the spinal fluid as part of their anesthesia for cesarean delivery
Morphine Sulfate: Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief | 24 |
| Total | 70 |
Baseline characteristics
| Characteristic | 50 Micrograms | 150 Micrograms | 250 Micrograms | Total |
|---|---|---|---|---|
| Age, Continuous | 36.0 Years STANDARD_DEVIATION 3.8 | 33.9 Years STANDARD_DEVIATION 4.8 | 36.8 Years STANDARD_DEVIATION 4.9 | 35.6 Years STANDARD_DEVIATION 4.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 20 Participants | 23 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) White | 12 Participants | 16 Participants | 19 Participants | 47 Participants |
| Sex: Female, Male Female | 23 Participants | 23 Participants | 24 Participants | 70 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 | 0 / 24 |
| other Total, other adverse events | 0 / 23 | 0 / 23 | 0 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 | 0 / 24 |
Outcome results
Duration of Pain Relief
Time to patient request for first dose of oral rescue pain medicine
Time frame: 72 hours after delivery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50 Micrograms | Duration of Pain Relief | 24.5 hours |
| 150 Micrograms | Duration of Pain Relief | 29.4 hours |
| 250 Micrograms | Duration of Pain Relief | 32 hours |
Nausea
Incidence of nausea and vomiting requiring treatment with a medication
Time frame: 24 hours after delivery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 Micrograms | Nausea | 4.3 percentage of participants |
| 150 Micrograms | Nausea | 8.7 percentage of participants |
| 250 Micrograms | Nausea | 12.5 percentage of participants |
Pain Scores
Visual analogue pain scores reported by the patient. Scale measured on a line from 0 to 100 mm, with 0 representing 'no pain' and 100 representing 'worst possible pain'
Time frame: 24 hours after delivery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50 Micrograms | Pain Scores | 2.2 score on a scale |
| 150 Micrograms | Pain Scores | 1.8 score on a scale |
| 250 Micrograms | Pain Scores | 1.9 score on a scale |
Pruritus
Incidence of pruritus requiring treatment with a medication
Time frame: 24 hours after delivery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 Micrograms | Pruritus | 8.7 percentage of participants |
| 150 Micrograms | Pruritus | 4.3 percentage of participants |
| 250 Micrograms | Pruritus | 4.1 percentage of participants |
Quality of Recovery
Quality of Recovery Score following Cesarean Delivery Questionnaire (ObsQoR-11). This is a multi-dimensional wellness scale ranging from 0 (worst) to 120 (best) along 12 axis items.
Time frame: 24 hours after delivery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50 Micrograms | Quality of Recovery | 72 score on a scale |
| 150 Micrograms | Quality of Recovery | 93 score on a scale |
| 250 Micrograms | Quality of Recovery | 95 score on a scale |