Postoperative Pain
Conditions
Keywords
cesarean, postoperative, morphine, genetics, opioid
Brief summary
HYPOTHESIS: The response to a given dose of morphine given via a spinal anesthetic for cesarean section will be affected by the genetics of the woman's mu-opioid receptor Most women undergoing elective cesarean section (CS) receive spinal anesthesia, and most receive a dose of preservative free morphine with the spinal anesthetic. Spinally-administered morphine provides 16-24 hours of high quality pain relief. The dose administered is usually 75-200 micrograms, but surprisingly few dose-response studies exist. The mu-opioid receptor (OPRM1 gene)is the site of action of endogenous opioid peptides and opioid analgesic drugs like morphine. There is a common genetic variant of this receptor at the 40th amino acid of the protein, with asparagine and asparate being present in different people. The less common variant (aspartate), present in 25-30% of the overall American population (higher in Asian populations, lower in Blacks) at codon 40 that has been shown in many studies to affect opioid analgesia. This will be a randomized, blinded study of 3 doses of spinal morphine (50, 100, 150 micrograms) given to women undergoing elective cesarean section at term pregnancy. 300 women will be studied (100 per dose). Blood will be obtained for genotyping of OPRM1 and other genes that may affect pain and analgesic responses. The primary outcome will be the amount of intravenous morphine patients self-administer in the 24 hours postsurgery. The primary outcome (use of intravenous morphine) will be analyzed by dose, and within each dose group by genotype of OPRM1. Secondary outcomes will include pain scores every 6 hours, satisfaction with analgesia, side effects (itching, nausea/vomiting) by dose and genotype. It is anticipated that there will be an interim data analysis at 150 evaluable subjects for assessment of the dose response to morphine in the overall population; then a final analysis at 300 subjects for the genetic effect assessment.
Interventions
DRUGMorphine
Morphine will be given via spinal injection at doses of 50, 100, 150 micrograms as part of a spinal anesthetic for cesarean section
Sponsors
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* healthy women undergoing elective cesarean
Exclusion criteria
* cardiovascular disease * analgesic medications * complications of pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively | 24 hours | IV morphine use in milligrams, by participant-controlled analgesia will be assessed every 6 hours for 24 hours postoperatively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale (VAS) Pain at 12 Hours | 12 hours post-operatively | Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement. |
| Visual Analog Scale (VAS) Pain at 18 Hours | 18 hours post-operatively | Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement. |
| Visual Analog Scale (VAS) Pain at 24 Hours | 24 hours post-operatively | Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement. |
| Visual Analog Scale- Nausea/Vomiting at 6 Hours | 6 hours post-operatively | Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm). |
| Visual Analog Scale- Nausea/Vomiting at 12 Hours | 12 hours post-operatively | Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm). |
| Visual Analog Scale- Nausea/Vomiting at 18 Hours | 18 hours post-operatively | Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm). |
| Visual Analog Scale (VAS) Pain at 6 Hours | 6 hours post-operatively | Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement. |
| Visual Analog Scale Pruritus (Itching) at 6 Hours | 6 hours post-operatively | Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm). |
| Visual Analog Scale Pruritus (Itching) at 12 Hours | 12 hours post-operatively | Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm). |
| Visual Analog Scale Pruritus (Itching) at 18 Hours | 18 hours post-operatively | Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm). |
| Visual Analog Scale Pruritus (Itching) at 24 Hours | 24 hours post-operatively | Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm). |
| Visual Analog Patient Satisfaction With Analgesia at 24 Hours | 24 hours postoperatively | Visual analog patient satisfaction scale measures satisfaction with analgesia on a 100mm scale. Participants make a mark on the scale with one end labeled Completely Dissatisfied (0mm) and the other labeled Completely Satisfied (100mm). |
| Visual Analog Scale- Nausea/Vomiting at 24 Hours | 24 hours post-operatively | Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50 Micrograms Spinal Morphine these subjects will receive 50 mcg spinal morphine | 47 |
| 100 Micrograms Spinal Morphine these subjects will receive 100 mcg spinal morphine | 54 |
| 150 Micrograms Spinal Morphine these subjects will receive 150 mcg spinal morphine | 43 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 6 | 4 |
| Overall Study | Protocol Violation | 6 | 3 | 3 |
Baseline characteristics
| Characteristic | 100 Micrograms Spinal Morphine | 150 Micrograms Spinal Morphine | 50 Micrograms Spinal Morphine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 43 Participants | 47 Participants | 144 Participants |
| Age, Continuous | 33 years STANDARD_DEVIATION 5 | 33 years STANDARD_DEVIATION 6 | 33 years STANDARD_DEVIATION 6 | 33 years STANDARD_DEVIATION 4 |
| Region of Enrollment United States | 54 participants | 43 participants | 47 participants | 144 participants |
| Sex: Female, Male Female | 54 Participants | 43 Participants | 47 Participants | 144 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 / 47 | 0 / 54 | 0 / 43 |
| other Total, other adverse events | 0 / 47 | 0 / 54 | 0 / 43 |
| serious Total, serious adverse events | 0 / 47 | 0 / 54 | 0 / 43 |
Outcome results
Primary
Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively
IV morphine use in milligrams, by participant-controlled analgesia will be assessed every 6 hours for 24 hours postoperatively.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively | 18 Milligrams |
| 100 Micrograms Spinal Morphine | Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively | 14 Milligrams |
| 150 Micrograms Spinal Morphine | Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively | 15 Milligrams |
Secondary
Visual Analog Patient Satisfaction With Analgesia at 24 Hours
Visual analog patient satisfaction scale measures satisfaction with analgesia on a 100mm scale. Participants make a mark on the scale with one end labeled Completely Dissatisfied (0mm) and the other labeled Completely Satisfied (100mm).
Time frame: 24 hours postoperatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Patient Satisfaction With Analgesia at 24 Hours | 85 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Patient Satisfaction With Analgesia at 24 Hours | 83 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Patient Satisfaction With Analgesia at 24 Hours | 84 mm |
Secondary
Visual Analog Scale- Nausea/Vomiting at 12 Hours
Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm).
Time frame: 12 hours post-operatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 12 Hours | 0 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 12 Hours | 0 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 12 Hours | 0 mm |
Secondary
Visual Analog Scale- Nausea/Vomiting at 18 Hours
Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm).
Time frame: 18 hours post-operatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 18 Hours | 0 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 18 Hours | 0 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 18 Hours | 0 mm |
Secondary
Visual Analog Scale- Nausea/Vomiting at 24 Hours
Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm).
Time frame: 24 hours post-operatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 24 Hours | 0 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 24 Hours | 0 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 24 Hours | 0 mm |
Secondary
Visual Analog Scale- Nausea/Vomiting at 6 Hours
Visual analog nausea/vomiting scale measures nausea and vomiting on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Nausea/Vomiting Imaginable (100mm).
Time frame: 6 hours post-operatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 6 Hours | 0 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 6 Hours | 7 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale- Nausea/Vomiting at 6 Hours | 0 mm |
Secondary
Visual Analog Scale Pruritus (Itching) at 12 Hours
Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm).
Time frame: 12 hours post-operatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 12 Hours | 10 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 12 Hours | 23 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 12 Hours | 25 mm |
Secondary
Visual Analog Scale Pruritus (Itching) at 18 Hours
Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm).
Time frame: 18 hours post-operatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 18 Hours | 9 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 18 Hours | 13 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 18 Hours | 5 mm |
Secondary
Visual Analog Scale Pruritus (Itching) at 24 Hours
Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm).
Time frame: 24 hours post-operatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 24 Hours | 7 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 24 Hours | 12 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 24 Hours | 6 mm |
Secondary
Visual Analog Scale Pruritus (Itching) at 6 Hours
Visual analog pruritus scale measures itching on a 100mm scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst Itching Imaginable (100mm).
Time frame: 6 hours post-operatively
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 6 Hours | 21 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 6 Hours | 37 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale Pruritus (Itching) at 6 Hours | 39 mm |
Secondary
Visual Analog Scale (VAS) Pain at 12 Hours
Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement.
Time frame: 12 hours post-operatively
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 12 Hours | Rest | 20 mm |
| 50 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 12 Hours | Movement | 30 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 12 Hours | Rest | 15 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 12 Hours | Movement | 35 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 12 Hours | Rest | 10 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 12 Hours | Movement | 30 mm |
Secondary
Visual Analog Scale (VAS) Pain at 18 Hours
Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement.
Time frame: 18 hours post-operatively
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 18 Hours | Rest | 17 mm |
| 50 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 18 Hours | Movement | 32 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 18 Hours | Rest | 11 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 18 Hours | Movement | 30 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 18 Hours | Rest | 5 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 18 Hours | Movement | 26 mm |
Secondary
Visual Analog Scale (VAS) Pain at 24 Hours
Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement.
Time frame: 24 hours post-operatively
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 24 Hours | Rest | 24 mm |
| 50 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 24 Hours | Movement | 43 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 24 Hours | Rest | 21 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 24 Hours | Movement | 41 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 24 Hours | Rest | 18 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 24 Hours | Movement | 41 mm |
Secondary
Visual Analog Scale (VAS) Pain at 6 Hours
Visual analog pain scale measures pain on a 100 millimeter (mm) scale. Participants make a mark on the scale with one end labeled None (0mm) and the other labeled Worst pain imaginable (100mm). Pain measured at rest and with movement.
Time frame: 6 hours post-operatively
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 50 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 6 Hours | Rest | 20 mm |
| 50 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 6 Hours | Movement | 43 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 6 Hours | Rest | 25 mm |
| 100 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 6 Hours | Movement | 43 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 6 Hours | Rest | 15 mm |
| 150 Micrograms Spinal Morphine | Visual Analog Scale (VAS) Pain at 6 Hours | Movement | 30 mm |