Postoperative Pain, Pregnancy, Obesity
Conditions
Keywords
Cesarean Delivery, Ropivicaine, TAP block
Brief summary
Since there have been no published dose-response studies investigating the effective analgesic dose of ropivacaine for use in a TAP block for post-Cesarean delivery analgesia, the investigators propose a study primarily examining the effect on 24 hour post-Cesarean delivery opioid consumption of using either a placebo, 0.25% ropivacaine, 0.5% ropivacaine, or 0.75% ropivacaine for TAP blocks.
Detailed description
Cesarean delivery is the most commonly performed surgical procedure in the United States today, with over 1.2 million cases performed in 2005. One of the most important aspects of cesarean delivery is the provision of safe, effective postoperative analgesia for the mother, while simultaneously ensuring minimal side effects for both the mother and neonate. Studies have suggested that a multimodal approach to post-cesarean pain utilizing both intravenous, oral, and neuraxial opioids and non-steroidal anti-inflammatory drugs is highly effective in providing effective analgesia. A significant component of post-cesarean pain is incisional pain from the Pfannenstiel incision on the anterior abdominal wall. The sensory supply to the skin, muscles, and parietal peritoneum of the anterior abdominal wall is derived from the anterior rami of T7-L1. After exiting the spinal column, these nerves proceed through the lateral abdominal wall within the transversus abdominal fascial plane, terminating in the anterior abdominal wall. Recent studies have suggested that blocking these afferent sensory nerves with local anesthetics, as part of a multimodal postoperative pain regimen, provides superior pain relief in terms of decreased pain scores and morphine consumption for up to 48 hours postoperatively. The technique utilized for these studies employed a surface anatomical approach to the transversus abdominal fascial plane via the lumbar triangle of Petit, a technique validated in both cadaveric and radiologic studies. However, as ultrasonography has emerged as the gold standard for initiating many nerve blocks, reports have described the successful use of ultrasound imaging for initiation of transversus abdominis plane (TAP) blocks for both abdominal surgeries and cesarean deliveries. In the published studies investigating the use of the TAP block for post-operative analgesia, either ropivacaine or bupivacaine was utilized in concentrations of 0.75% and 0.375%, respectively. Studies comparing ropivacaine with bupivacaine for use in interscalene, femoral, or sciatic nerve blocks have found no difference in terms of potency, time to onset or duration of postoperative analgesia between the two local anesthetics. Although no similar studies have been done with TAP blocks, one can assume that utilization of ropivacaine for this nerve block would yield similar results in terms postoperative analgesia. Moreover, the cardiotoxicity of ropivacaine has been shown to be significantly less than bupivacaine, making it a safer alternative for use in nerve blocks when used in high doses. Risk factors for respiratory depression after the administration of neuraxial opioids in the non-obstetric population include morbid obesity and obstructive sleep apnea. For the obstetric population, a study of 856 patients revealed that all 8 patients who experienced respiratory depression after intrathecal morphine for cesarean delivery were markedly obese. Furthermore, the onset of respiratory depression after intrathecal morphine can occur up to 12 hours after administration, a time period when the patient is not being as closely monitored as she is during the 1:1 nursing care in the recovery room. Therefore, it is the investigators policy on the Labor and Delivery unit to not administer intrathecal morphine to any parturient with a history of obstructive sleep apnea or a BMI \> 40 kg/m2. These patients often require intravenous opioid patient-controlled analgesia postoperatively, which has been shown to provide inferior pain relief and greater opioid consumption than neuraxial opioids. The current clinical standard is to administer the TAP block to those patients who have not received morphine in their neuraxial anesthetic. The TAP block offers a novel addition to the management of post-cesarean pain for this patient population.
Interventions
DRUG0.9% Normal Saline
The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side.
DRUG0.2% Ropivacaine
The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side.
DRUG0.5% Ropivacaine
The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side.
The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side.
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ASA II-III patient * \> 18 years of age who is pregnant * presenting for a cesarean delivery via Pfannenstiel incision who is eligible to receive a spinal anesthetic with 0.75% bupivacaine and fentanyl and whose is not eligible to receive intrathecal morphine due to a BMI \>40 kg/m2.
Exclusion criteria
* \< 18 years of age * contraindication to placement of a spinal anesthetic * contraindication to use of non-steroidal anti-inflammatory drugs (NSAIDs) * patients receiving medical therapies considered to result in tolerance to opioids * patients with a history of established chronic pain, (e.g. chronic low back pain, fibromyalgia or headaches), defined as requiring regular medical follow-up with pain specialists, as well as recent use (within the year preceding pregnancy) of opioid analgesics as an outpatient * patients with a history of diabetes mellitus * patients undergoing a vertical midline skin incision * patients who are undergoing a cesarean delivery after a failed vaginal trial of labor * patients who had a prior epidural placed for labor analgesia during the same hospital encounter.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morphine Equivalents 0-24 Hours (Mgs) | 24 hours | Total dose of morphine equivalents (IV equivalent of morphine) taken by the participant 0-24 hours after completion of the TAP block. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Morphine Equivalents Total (Mgs) | 72 hours | Total dose of morphine equivalents (IV equivalent of morphine) taken by the participant 0-72 hours after completion of the TAP block. |
| Time to First PCA Request | Elapsed time in minutes | The elapsed time in minutes of the first PCA (patient controlled analgesia) request in time (minutes) from the end of the TAP block. |
| Pain Scores at Rest | Request for first patient controlled analgesia then at 2,6,24,72 hours after initial PCA request | Pain scores at rest ( 0 low 10 high) using an 11 point VRS (verbal pain scale) at the following hour time points, at the first request for patient controlled analgesia (PCA) then at 2,6,24,and 74 hours after the first request for PCA (patient controlled analgesia). |
| Morphine Equivalents 24-72 Hours (Mgs) | 24-72 hours | Total dose of morphine equivalents (IV equivalent of morphine) taken by the participant 24-72 hours after completion of the TAP block. |
| Pain Burden at Rest | 72 hours | Pain burden at rest calculated as area under the pain score \* time (hr) curve 0-72 hours. |
| Pain Burden With Movement | 72 hours | Pain burden with movement calculated as area under the pain score \* time (hr) curve 0-72 hours. |
| Pain Scores With Movement | First PCA request then at 2,6,24,72 hours after first PCA request. | Pain scores with movement ( 0 low 10 high) using an 11 point VRS (verbal pain scale) at the first request for patient controlled analgesia (PCA) then at 2,6,24,and 74 hours after the first request for PCA (patient controlled analgesia). |
Countries
United States
Participant flow
Pre-assignment details
120 patients were randomized to one of four groups who received TAP blockade. Four patients subsequently were dropped from the study after randomization for pre-defined criteria. Substantive data was missing in one subject who was excluded from analysis. One patient received a morphine PCA instead of hydromorphone due to a drug shortage.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 TAP Block utilizing 15mL of 0.9% normal saline per side
0.9% Normal Saline: The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side. | 34 |
| Group 2 TAP Block utilizing 15ml of 0.2% ropivacaine per side
0.2% Ropivacaine: The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side. | 32 |
| Group 3 TAP Block utilizing 15ml of 0.5% ropivacaine per side
0.5% Ropivacaine: The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side. | 25 |
| Group 4 TAP Block utilizing 15ml of 0.75% ropivacaine per side
0.75% Ropivacaine: The abdominal muscle layers will be located by placing the ultrasound transducer perpendicular to the coronal anatomic plane at the T-10 dermatome level in the patient's midaxillary line. Under ultrasound guidance, a 70mm or 90mm, 21 gauge blunted Stimuplex needle will be advanced from the skin until the tip reaches the fascial layer between the internal oblique and transversus abdominis. 15ml of the study drug will be injected incrementally. The needle will then be removed and the process repeated in the same manner on the patient's opposite side. | 29 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Exclusion criteria met after consent | 1 | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Group 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 32 Participants | 25 Participants | 29 Participants | 120 Participants |
| BMI (kg/m^2) | 44.3 BMI (kg/m^2) | 43.7 BMI (kg/m^2) | 44.6 BMI (kg/m^2) | 44.5 BMI (kg/m^2) | 44.28 BMI (kg/m^2) |
| Estimated Gestational Age (EGA) | 39 weeks | 39 weeks | 39 weeks | 39 weeks | 39 weeks |
| # previous Cesarean deliveries > 1 Cesarean Deliveries | 0 Participants | 7 Participants | 2 Participants | 6 Participants | 15 Participants |
| # previous Cesarean deliveries 1 Cesarean Delivery | 21 Participants | 14 Participants | 11 Participants | 12 Participants | 58 Participants |
| # previous Cesarean deliveries No Cesarean Deliveries | 12 Participants | 9 Participants | 12 Participants | 9 Participants | 42 Participants |
| Race/Ethnicity Other | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity Race of Participants : African American | 9 Participants | 8 Participants | 7 Participants | 10 Participants | 34 Participants |
| Race/Ethnicity Race of Participants : Asian | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity Race of Participants : Caucasian | 19 Participants | 13 Participants | 12 Participants | 10 Participants | 54 Participants |
| Race/Ethnicity Race of Participants : Hispanic | 4 Participants | 8 Participants | 5 Participants | 7 Participants | 24 Participants |
| Region of Enrollment United States | 34 Participants | 32 Participants | 25 Participants | 29 Participants | 120 Participants |
| Sex: Female, Male Female | 34 Participants | 32 Participants | 25 Participants | 29 Participants | 120 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 32 | 0 / 25 | 0 / 29 |
| other Total, other adverse events | 11 / 34 | 8 / 32 | 12 / 25 | 10 / 29 |
| serious Total, serious adverse events | 0 / 34 | 0 / 32 | 0 / 25 | 0 / 29 |
Outcome results
Primary
Morphine Equivalents 0-24 Hours (Mgs)
Total dose of morphine equivalents (IV equivalent of morphine) taken by the participant 0-24 hours after completion of the TAP block.
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Morphine Equivalents 0-24 Hours (Mgs) | 54 Morphine equivalents (mg) |
| Group 2 | Morphine Equivalents 0-24 Hours (Mgs) | 38 Morphine equivalents (mg) |
| Group 3 | Morphine Equivalents 0-24 Hours (Mgs) | 32 Morphine equivalents (mg) |
| Group 4 | Morphine Equivalents 0-24 Hours (Mgs) | 45 Morphine equivalents (mg) |
p-value: 0.050.975% CI: [1.25, 1.25]Kruskal-Wallis
Secondary
Morphine Equivalents 24-72 Hours (Mgs)
Total dose of morphine equivalents (IV equivalent of morphine) taken by the participant 24-72 hours after completion of the TAP block.
Time frame: 24-72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Morphine Equivalents 24-72 Hours (Mgs) | 67 Morphine equivalents (mgs) |
| Group 2 | Morphine Equivalents 24-72 Hours (Mgs) | 60 Morphine equivalents (mgs) |
| Group 3 | Morphine Equivalents 24-72 Hours (Mgs) | 67 Morphine equivalents (mgs) |
| Group 4 | Morphine Equivalents 24-72 Hours (Mgs) | 67 Morphine equivalents (mgs) |
Secondary
Morphine Equivalents Total (Mgs)
Total dose of morphine equivalents (IV equivalent of morphine) taken by the participant 0-72 hours after completion of the TAP block.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Morphine Equivalents Total (Mgs) | 120 Morphine equivalents (mgs) |
| Group 2 | Morphine Equivalents Total (Mgs) | 96 Morphine equivalents (mgs) |
| Group 3 | Morphine Equivalents Total (Mgs) | 98 Morphine equivalents (mgs) |
| Group 4 | Morphine Equivalents Total (Mgs) | 112 Morphine equivalents (mgs) |
Secondary
Pain Burden at Rest
Pain burden at rest calculated as area under the pain score \* time (hr) curve 0-72 hours.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Pain Burden at Rest | 129 score on scale * (hr) |
| Group 2 | Pain Burden at Rest | 79 score on scale * (hr) |
| Group 3 | Pain Burden at Rest | 79 score on scale * (hr) |
| Group 4 | Pain Burden at Rest | 151 score on scale * (hr) |
Secondary
Pain Burden With Movement
Pain burden with movement calculated as area under the pain score \* time (hr) curve 0-72 hours.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Pain Burden With Movement | 265 pain score * time (hr) curve 72 hours |
| Group 2 | Pain Burden With Movement | 202 pain score * time (hr) curve 72 hours |
| Group 3 | Pain Burden With Movement | 233 pain score * time (hr) curve 72 hours |
| Group 4 | Pain Burden With Movement | 327 pain score * time (hr) curve 72 hours |
Secondary
Pain Scores at Rest
Pain scores at rest ( 0 low 10 high) using an 11 point VRS (verbal pain scale) at the following hour time points, at the first request for patient controlled analgesia (PCA) then at 2,6,24,and 74 hours after the first request for PCA (patient controlled analgesia).
Time frame: Request for first patient controlled analgesia then at 2,6,24,72 hours after initial PCA request
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1 | Pain Scores at Rest | 24 hours after first PCA request | 2 units on a scale |
| Group 1 | Pain Scores at Rest | 2 hous after first PCA request | 3 units on a scale |
| Group 1 | Pain Scores at Rest | 72 hours after first PCA reqest | 1 units on a scale |
| Group 1 | Pain Scores at Rest | 6 hours after first PCA request | 3 units on a scale |
| Group 1 | Pain Scores at Rest | At first PCA request | 3 units on a scale |
| Group 2 | Pain Scores at Rest | 6 hours after first PCA request | 2 units on a scale |
| Group 2 | Pain Scores at Rest | 24 hours after first PCA request | 1 units on a scale |
| Group 2 | Pain Scores at Rest | 72 hours after first PCA reqest | .5 units on a scale |
| Group 2 | Pain Scores at Rest | 2 hous after first PCA request | 1 units on a scale |
| Group 2 | Pain Scores at Rest | At first PCA request | 3 units on a scale |
| Group 3 | Pain Scores at Rest | 6 hours after first PCA request | 2 units on a scale |
| Group 3 | Pain Scores at Rest | At first PCA request | 2 units on a scale |
| Group 3 | Pain Scores at Rest | 2 hous after first PCA request | 0 units on a scale |
| Group 3 | Pain Scores at Rest | 24 hours after first PCA request | 1 units on a scale |
| Group 3 | Pain Scores at Rest | 72 hours after first PCA reqest | 1 units on a scale |
| Group 4 | Pain Scores at Rest | 24 hours after first PCA request | 3 units on a scale |
| Group 4 | Pain Scores at Rest | 2 hous after first PCA request | 2 units on a scale |
| Group 4 | Pain Scores at Rest | At first PCA request | 2 units on a scale |
| Group 4 | Pain Scores at Rest | 6 hours after first PCA request | 2 units on a scale |
| Group 4 | Pain Scores at Rest | 72 hours after first PCA reqest | 1 units on a scale |
Secondary
Pain Scores With Movement
Pain scores with movement ( 0 low 10 high) using an 11 point VRS (verbal pain scale) at the first request for patient controlled analgesia (PCA) then at 2,6,24,and 74 hours after the first request for PCA (patient controlled analgesia).
Time frame: First PCA request then at 2,6,24,72 hours after first PCA request.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1 | Pain Scores With Movement | 24 hours after first PCA request | 4 units on a scale |
| Group 1 | Pain Scores With Movement | 2 hous after first PCA request | 4 units on a scale |
| Group 1 | Pain Scores With Movement | 72 hours after first PCA reqest | 3.5 units on a scale |
| Group 1 | Pain Scores With Movement | 6 hours after first PCA request | 4 units on a scale |
| Group 1 | Pain Scores With Movement | At first PCA request | 5 units on a scale |
| Group 2 | Pain Scores With Movement | 6 hours after first PCA request | 4 units on a scale |
| Group 2 | Pain Scores With Movement | 24 hours after first PCA request | 3 units on a scale |
| Group 2 | Pain Scores With Movement | 72 hours after first PCA reqest | 2 units on a scale |
| Group 2 | Pain Scores With Movement | 2 hous after first PCA request | 2 units on a scale |
| Group 2 | Pain Scores With Movement | At first PCA request | 3.5 units on a scale |
| Group 3 | Pain Scores With Movement | 6 hours after first PCA request | 5 units on a scale |
| Group 3 | Pain Scores With Movement | At first PCA request | 3.5 units on a scale |
| Group 3 | Pain Scores With Movement | 2 hous after first PCA request | 3 units on a scale |
| Group 3 | Pain Scores With Movement | 24 hours after first PCA request | 4 units on a scale |
| Group 3 | Pain Scores With Movement | 72 hours after first PCA reqest | 3 units on a scale |
| Group 4 | Pain Scores With Movement | 24 hours after first PCA request | 5 units on a scale |
| Group 4 | Pain Scores With Movement | 2 hous after first PCA request | 3 units on a scale |
| Group 4 | Pain Scores With Movement | At first PCA request | 4 units on a scale |
| Group 4 | Pain Scores With Movement | 6 hours after first PCA request | 4 units on a scale |
| Group 4 | Pain Scores With Movement | 72 hours after first PCA reqest | 4 units on a scale |
Secondary
Time to First PCA Request
The elapsed time in minutes of the first PCA (patient controlled analgesia) request in time (minutes) from the end of the TAP block.
Time frame: Elapsed time in minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1 | Time to First PCA Request | 90 Minutes |
| Group 2 | Time to First PCA Request | 118 Minutes |
| Group 3 | Time to First PCA Request | 126 Minutes |
| Group 4 | Time to First PCA Request | 83 Minutes |