Pain Management in Pregnant Women
Conditions
Brief summary
Purpose: To determine if IV acetaminophen can 1) decrease pain in pregnancy women, 2)reduce the amount of opioid use in pregnant women who encounter pain, 3) reduce maternal and fetal adverse effects compared to opioids. Design: This is a comparative effective trial that is a randomized, controlled trial of IV acetaminophen vs. IV morphine in pregnant women. Procedures: Women meeting inclusion/exclusion criteria will be randomized to IV acetaminophen or IV morphine. The IV acetaminophen group will get up to four standard doses of IV acetaminophen during their stay at the hospital. The second group will get up to six standard doses of morphine. Subjects will complete a pain scale after medication administration and will be asked about any side effects.
Detailed description
Rationale for this clinical trial The goal of analgesia in pregnancy is to reduce pain while minimizing both maternal and fetal adverse effects. Current opioids used in pregnancy provide minimal pain relief and are associated with adverse effects. IV acetaminophen has been shown to significantly improve pain control following cesarean section and in the first stage of labor. Moreover, IV acetaminophen reduces the need and consumption of opioids following surgery. If IV acetaminophen can be as effective in controlling pain associated with maternal medical conditions and uterine contractions with labor, then the use of parenteral opioids in pregnant women and its exposure to the fetus could be reduced. This could provide new opportunities in the medical management of pain in pregnancy. Thus we propose a comparative effectiveness trial of IV acetaminophen compared to IV morphine. Hypothesis: We hypothesize that IV acetaminophen is as effective as IV morphine in reducing pain in pregnant women. In doing so, IV acetaminophen can reduce the amount of narcotics needed in women with pain. Objectives: To determine if IV acetaminophen can: 1. Decrease pain in pregnant women 2. Reduce the amount of opioid use in pregnant women who encounter pain 3. Reduce maternal and fetal adverse effects compared to opioids Study Design: For this comparative effective trial, we propose a randomized, controlled trial of IV acetaminophen vs. IV morphine in pregnant women. Prior studies have confirmed that IV acetaminophen is effective in controlling pain compared to placebo.\[14,20\] Thus, administering just a placebo for pain control is not justified at this time. We will include 3 different groups of pregnant populations who encounter pain for different reasons. Group 1: Pregnant women with uterine contractions, but not in labor Group 2: Pregnant women with uterine contractions in the first stage of labor Group 3: Pregnant women with a medical condition associated with pain.
Interventions
DRUGIV Acetaminophen
IV Acetaminophen
DRUGIV Morphine
IV Morphine
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Group 1. We will include pregnant women greater than 24 weeks of pregnancy who present with uterine contractions, but are not in labor and who are warranting treatment with intravenous medication for pain control as part of their routine treatment. This will be defined as the presence of uterine contractions documented on the tocodynamometer. However, the cervix remains less than 2 cm dilated and has not changed after 1 hour after re-examining her cervix.\[23\] Group 2. We will include pregnant women greater than 34 weeks of pregnancy who present with uterine contractions and are in the first stage of labor and who are warranting treatment with intravenous medication for pain control as part of their routine treatment. This will be defined as the presence of uterine contractions documented on the tocodynamometer and cervical dilation greater than 2 cm, but less than 6 cm. \[23\] Group 3. We will include pregnant women greater than 16 weeks of pregnancy who present with pain due to a maternal medical condition including sickle cell crisis, pyelonephritis, pancreatitis, cholecystitis, nephrolithiasis or headache and who are warranting treatment with intravenous medication for pain control as part of their routine treatment.
Exclusion criteria
We will exclude women less than 18 years of age, less than 16 weeks gestation, with weight less than 50 kg, and contraindications to acetaminophen including reported elevated liver function tests, hepatic injury, hepatic disorder, active liver disease, alcoholism, chronic malnutrition, known coagulopathy, hemorrhage, creatinine \> 1.0, or known allergy or hypersensitivity to acetaminophen. We will also exclude women who have received any opioids within the last 24 hours.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Intensity as Assessed by a Visual Analogue Scale (VAS) | baseline, 120 minutes after administration | The visual analogue scale (VAS) ranges from 0mm to 140mm. The subject will be asked to mark with a pen on the scale to rate their pain. Negative differences in scores indicated a pain score worse than baseline and positive differences indicated an improved pain score from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Received Rescue Medications | 24 hours after administration | — |
| Quantity of Rescue Medication Over 24 Hours | 24 hours after administration | — |
| Total Amount of Study Drug Administered | 24 hours after administration | — |
| Pain Relief Based on a 5 Point Verbal Scale | 24 hrs | — |
| Number of Participants With Maternal Side Effects | 1 hour after administration | Maternal side effects include nausea, vomiting, headache, pruritus, insomnia, and drowsiness. |
| Number of Participants With Fetal Heart Rate Changes | 1 hour after administration | Changes in fetal heart rate tracing include acceleration, decelerations, and variability. |
| Patient's Global Satisfaction at 24 Hours | 24hrs | This will be patient reported. |
Countries
United States
Participant flow
Pre-assignment details
163 were enrolled, including those in Group 1 (Pregnant women with uterine contractions, but not in labor), Group 2 (Pregnant women with uterine contractions in the first stage of labor), and Group 3 (Pregnant women with a medical condition associated with pain). The participant flow only reflects participants enrolled in Group 1 and Group 2, and not those in Group 3.
Participants by arm
| Arm | Count |
|---|---|
| IV Acetaminophen IV acetaminophen for pain control
IV Acetaminophen: IV Acetaminophen | 48 |
| IV Morphine IV morphine for pain control
IV Morphine: IV Morphine | 52 |
| Total | 100 |
Baseline characteristics
| Characteristic | IV Morphine | Total | IV Acetaminophen |
|---|---|---|---|
| Age, Continuous | 27.5 years STANDARD_DEVIATION 6 | 27.3 years STANDARD_DEVIATION 5.8 | 27.0 years STANDARD_DEVIATION 5.5 |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 24 Participants | 43 Participants | 19 Participants |
| Race/Ethnicity, Customized Caucasian | 8 Participants | 13 Participants | 5 Participants |
| Race/Ethnicity, Customized Hispanic | 21 Participants | 40 Participants | 19 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment United States | 52 participants | 100 participants | 48 participants |
| Sex: Female, Male Female | 52 Participants | 100 Participants | 48 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 / 48 | 0 / 52 |
| other Total, other adverse events | 21 / 43 | 15 / 51 |
| serious Total, serious adverse events | 1 / 48 | 0 / 52 |
Outcome results
Primary
Change in Pain Intensity as Assessed by a Visual Analogue Scale (VAS)
The visual analogue scale (VAS) ranges from 0mm to 140mm. The subject will be asked to mark with a pen on the scale to rate their pain. Negative differences in scores indicated a pain score worse than baseline and positive differences indicated an improved pain score from baseline.
Time frame: baseline, 120 minutes after administration
Population: For the IV Acetaminophen arm, data were collected for 24 out of 30 participants in pre-labor and 18 out of 18 participants in the 1st stage of labor. For the IV morphine arm, data were collected for 30 out of 32 participants in pre-labor and 20 out of 20 participants in the 1st stage of labor.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Acetaminophen | Change in Pain Intensity as Assessed by a Visual Analogue Scale (VAS) | pre-labor group | 2.67 score on a scale | Standard Deviation 3.8 |
| IV Acetaminophen | Change in Pain Intensity as Assessed by a Visual Analogue Scale (VAS) | first stage of labor group | -18.2 score on a scale | Standard Deviation 13.2 |
| IV Morphine | Change in Pain Intensity as Assessed by a Visual Analogue Scale (VAS) | pre-labor group | 3.2 score on a scale | Standard Deviation 5.1 |
| IV Morphine | Change in Pain Intensity as Assessed by a Visual Analogue Scale (VAS) | first stage of labor group | -4.8 score on a scale | Standard Deviation 12.5 |
Secondary
Number of Participants Who Received Rescue Medications
Time frame: 24 hours after administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Acetaminophen | Number of Participants Who Received Rescue Medications | 30 Participants |
| IV Morphine | Number of Participants Who Received Rescue Medications | 19 Participants |
Secondary
Number of Participants With Fetal Heart Rate Changes
Changes in fetal heart rate tracing include acceleration, decelerations, and variability.
Time frame: 1 hour after administration
Population: Data for this outcome measure were not collected for 6 in the IV Acetaminophen arm and 4 in the IV morphine arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Acetaminophen | Number of Participants With Fetal Heart Rate Changes | absence of accelerations | 4 Participants |
| IV Acetaminophen | Number of Participants With Fetal Heart Rate Changes | late decelerations | 1 Participants |
| IV Acetaminophen | Number of Participants With Fetal Heart Rate Changes | minimal or absent variability | 4 Participants |
| IV Morphine | Number of Participants With Fetal Heart Rate Changes | absence of accelerations | 12 Participants |
| IV Morphine | Number of Participants With Fetal Heart Rate Changes | late decelerations | 1 Participants |
| IV Morphine | Number of Participants With Fetal Heart Rate Changes | minimal or absent variability | 3 Participants |
Secondary
Number of Participants With Maternal Side Effects
Maternal side effects include nausea, vomiting, headache, pruritus, insomnia, and drowsiness.
Time frame: 1 hour after administration
Population: Data for this outcome measure were not collected for 5 in the IV Acetaminophen arm and 1 in the IV morphine arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Acetaminophen | Number of Participants With Maternal Side Effects | headache | 5 Participants |
| IV Acetaminophen | Number of Participants With Maternal Side Effects | nausea | 2 Participants |
| IV Acetaminophen | Number of Participants With Maternal Side Effects | vomiting | 0 Participants |
| IV Acetaminophen | Number of Participants With Maternal Side Effects | pruritus | 2 Participants |
| IV Acetaminophen | Number of Participants With Maternal Side Effects | insomnia | 5 Participants |
| IV Acetaminophen | Number of Participants With Maternal Side Effects | drowsiness | 17 Participants |
| IV Morphine | Number of Participants With Maternal Side Effects | insomnia | 7 Participants |
| IV Morphine | Number of Participants With Maternal Side Effects | pruritus | 4 Participants |
| IV Morphine | Number of Participants With Maternal Side Effects | nausea | 2 Participants |
| IV Morphine | Number of Participants With Maternal Side Effects | drowsiness | 15 Participants |
| IV Morphine | Number of Participants With Maternal Side Effects | vomiting | 3 Participants |
| IV Morphine | Number of Participants With Maternal Side Effects | headache | 6 Participants |
Secondary
Pain Relief Based on a 5 Point Verbal Scale
Time frame: 24 hrs
Population: Data were not collected for this outcome measure.
Secondary
Patient's Global Satisfaction at 24 Hours
This will be patient reported.
Time frame: 24hrs
Population: Data were not collected for this outcome measure.
Secondary
Quantity of Rescue Medication Over 24 Hours
Time frame: 24 hours after administration
Population: Data were not collected for this outcome measure.
Secondary
Total Amount of Study Drug Administered
Time frame: 24 hours after administration
Population: For the IV Acetaminophen arm, data were collected for 30 out of 30 participants in pre-labor and 18 out of 18 participants in the 1st stage of labor. For the IV morphine arm, data were collected for 32 out of 32 participants in pre-labor and 20 out of 20 participants in the 1st stage of labor.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Acetaminophen | Total Amount of Study Drug Administered | pre-labor group | 1600 milligrams | Standard Deviation 952.2 |
| IV Acetaminophen | Total Amount of Study Drug Administered | 1st stage of labor group | 1055 milligrams | Standard Deviation 229 |
| IV Morphine | Total Amount of Study Drug Administered | pre-labor group | 6.4 milligrams | Standard Deviation 1.9 |
| IV Morphine | Total Amount of Study Drug Administered | 1st stage of labor group | 2.3 milligrams | Standard Deviation 0.72 |