Anesthesia, Labor Pain, Pain
Conditions
Keywords
Labor pain, Epidural, Obstetric, Labor Analgesia
Brief summary
Neuraxial labor analgesia is performed by the administration of a local anesthetic/opioid mixture in the epidural space. The delivery method is a combination of continuous infusion, provider-administered boluses and patient-administered boluses (patient controlled epidural analgesia \[PCEA\]) via epidural catheter. The anesthetic solution administered through the lumbar epidural catheter must spread cephalad in the epidural space to reach the T10 nerve roots and spinal cord, and must spread caudad to reach the caudal nerve roots in the epidural space. Epidural infusion pumps capable of delivering PIEB of local anesthetic with PCEA have become commercially available and many studies have attempted to assess the optimal parameter settings (including volume of programmed bolus, bolus interval, rate of bolus administration) to provide superior labor analgesia. Traditionally higher concentration local anesthetic solutions have been associated with increased motor blockade leading to a higher incidence of instrumental vaginal delivery. Several local anesthetic solutions with varying drug concentrations are available for labor analgesia and are used clinically in the United States. We plan to perform a randomized, controlled, double-blind study to test the hypothesis that patients whose labor analgesia is maintained using PIEB with low-volume bolus (6.25 mL) of a higher local anesthetic concentration solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) will require less supplemental analgesia (manual provider re-doses) than patients whose PIEB is delivered with a high-volume bolus (10 mL) of lower density local anesthetic solution (0.0625% bupivacaine with fentanyl 2.0 mcg/mL). The aim of this study is to evaluate the association between bolus volume and concentration of local anesthetic during maintenance of labor analgesia with programmed intermittent epidural bolus (PIEB) analgesia. The hypothesis of this study is: patients whose labor analgesia is maintained using PIEB with low-volume bolus (6.25 mL) of higher local anesthetic concentration solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) will have a longer duration of adequate analgesia (time to first manual re-dose request) than patients whose PIEB is delivered with a high-volume bolus (10 mL) of lower concentration local anesthetic solution (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).
Interventions
DRUGLow volume bolus
Administration of a low-volume bolus (6.25 mL) of greater density solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump.
DRUGHigh volume bolus
Administration of a high-volume bolus (10 mL) of lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump.
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The participant and outcomes assessor will be blinded to the assigned randomization.
Intervention model description
Two group randomized controlled trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years and above * Nulliparous parturients * Present to the labor and delivery unit for an induction of labor or who are in spontaneous labor * Request neuraxial labor analgesia at ≤5 cm cervical dilation
Exclusion criteria
* Patients who are not eligible to receive a combined spinal epidural (CSE) technique with 25 mcg of intrathecal fentanyl * Non-English speaking * Failed initiation of CSE analgesia (VAS pain score \>10 15 minutes after intrathecal dose) * Need to have the epidural catheter replaced during labor * Who deliver within 90 minutes of initiation of labor analgesia * Require re-dose within 90 minutes of initiation of labor analgesia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anesthesia Provider Administered Bolus | 72 hours | Anesthesia provider (MD) administered boluses of additional anesthetic administered prior to the delivery of the baby. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| VAS Score After Delivery | 24 hours | VAS score (Visual Analogue Scale) on a score of 0 (no pain,good) to 100 (worst pain imaginable,bad) immediately after delivery of baby |
| Intrascapular Pain | 72 hours | Number of participants who experienced intrascapular pain (pain in your shoulder blade) during the study period. |
| Provider Administered Bolus | 72 hours | Number of participants requiring anesthesia provider administration of additional bolus doses of pain medication. |
| Number of Participants Who Required Additional Provider Redoses | 72 hours | Additional number of participants who required additional anesthesia care provider redoses of pain medication. |
| Time to First Anesthesiology Provider Bolus | 72 hours | Time elapsed in minutes from epidural set up to time to request supplemental analgesia provided by the anesthesiology care provider. |
| VAS Score Prior to First Provider Bolus Dose | 72 hours | Patient reported visual analogue scale score (0 no pain,good-100 worst pain imaginable, bad) prior to the first anesthesiology care provider bolus dose of anesthetic (pain medication). |
| VAS at 10 Centimeters Dilation of Cervix | 24 hours | VAS (visual analogue scale) at 10 centimeters dilation of cervix on a scale of 0 (no pain,good) to 100 (worst pain imaginable,bad) |
| Bupivacaine Consumption Per Hour | 72 hours | Average consumption of bupivacaine in milligrams per hour. |
| Maximum Oxytocin Dose | 72 hours | Maximum oxytocin dose administered intravenously in international units. |
| Time of Intrathecal Administration to Delivery | 72 hours | Elapsed time in minutes from the intrathecal administration of anesthetic by anesthesiology provider to time of delivery of baby. |
| Number of Participants Categorized by Mode of Delivery | 72 hours | Mode of delivery identified as: normal vaginal delivery, instrumental vaginal delivery, cesarean delivery or emergency cesarean delivery |
| PCA Boluses | 72 hours | Number of Patient-Controlled Epidural Analgesia (PCEA) boluses of pain medication requested and number of PCEA medication boluses administered. |
| PCA Boluses Ratio | 72 hours | The ratio of the number of Patient-Controlled Epidural Analgesia (PCEA) pain medication boluses requested and number of PCEA pain medication boluses administered by the PCEA pump. |
| VAS Score 30 Minutes After Anesthetic Care Provider Dose | 72 hours | Patient reported visual analogue scale score (0 no pain, good -100 worst pain imaginable, bad) 30 minutes after the first anesthesiology care provider bolus dose of anesthetic was administered to the participant for pain relief. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited within Prentice Women's Hospital labor and delivery unit. Recruitment period start date was 1/21/2020 and the end date for recruitment was 09/01/2022.
Pre-assignment details
146 subjects consented to participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| Low Volume Bolus 0.1% Bupivacaine 6.25 mL administration at 250 ml per hour of a greater density solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL)
Low volume bolus: Administration of a low-volume bolus (6.25 mL) of greater density solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump. | 67 |
| High Volume Bolus .0625% Bupivacaine 10 mL administration of a lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).
High volume bolus: Administration of a high-volume bolus (10 mL) of lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump. | 62 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Fentanyl and or clonidine administered via epidural catheter | 1 | 2 |
| Overall Study | First redose of anesthetic by anesthesiologist administered under 90 minutes after catheter placed | 1 | 1 |
| Overall Study | Greater than 3 redoses of anesthetic by the anesthesiologist using the epidural catheter | 1 | 0 |
| Overall Study | MD withdrew (pump settings changed d/t interscapular pain) | 1 | 1 |
| Overall Study | No cerebral spinal fluid obtained during epidural procedure a straight catheter was used | 0 | 1 |
| Overall Study | Physician Decision | 2 | 5 |
| Overall Study | Unintentional dural puncture during epidural procedure | 0 | 1 |
Baseline characteristics
| Characteristic | Low Volume Bolus 0.1% Bupivacaine | High Volume Bolus .0625% Bupivacaine | Total |
|---|---|---|---|
| Age, Customized Age | 32.6 Years | 32.9 Years | 32.8 Years |
| BMI kg/m^2 | 29.8 kg/m^2 | 32.0 kg/m^2 | 31 kg/m^2 |
| Cervical dilation at labor analgesia request (cm) | 3 Centimeters | 4 Centimeters | 3 Centimeters |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 8 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 54 Participants | 113 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fetal position Non-vertex position | 2 Participants | 0 Participants | 2 Participants |
| Fetal position Vertex position | 65 Participants | 62 Participants | 127 Participants |
| Gestational age | 39.3 Weeks | 39.6 Weeks | 39.4 Weeks |
| Labor type Induction of labor | 28 Participants | 33 Participants | 61 Participants |
| Labor type Spontaneous labor | 39 Participants | 29 Participants | 68 Participants |
| Number of times pregnant 1 time pregnant | 44 Participants | 52 Participants | 96 Participants |
| Number of times pregnant 2 times pregnant | 20 Participants | 6 Participants | 26 Participants |
| Number of times pregnant 3 times pregnant or greater | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 9 Participants | 23 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) White | 43 Participants | 46 Participants | 89 Participants |
| Region of Enrollment United States | 67 participants | 62 participants | 129 participants |
| Sex: Female, Male Female | 67 Participants | 62 Participants | 129 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| VAS scores (0 to 100) at labor analgesia request | 70 units on a scale (0 low (good)-100 high) | 70 units on a scale (0 low (good)-100 high) | 70 units on a scale (0 low (good)-100 high) |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 62 |
| other Total, other adverse events | 0 / 67 | 3 / 62 |
| serious Total, serious adverse events | 0 / 67 | 0 / 62 |
Outcome results
Primary
Anesthesia Provider Administered Bolus
Anesthesia provider (MD) administered boluses of additional anesthetic administered prior to the delivery of the baby.
Time frame: 72 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | Anesthesia Provider Administered Bolus | 23 Participants |
| High Volume Bolus .0625% Bupivacaine | Anesthesia Provider Administered Bolus | 11 Participants |
Secondary
Bupivacaine Consumption Per Hour
Average consumption of bupivacaine in milligrams per hour.
Time frame: 72 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | Bupivacaine Consumption Per Hour | 13.1 milligrams/hour | Standard Deviation 4 |
| High Volume Bolus .0625% Bupivacaine | Bupivacaine Consumption Per Hour | 11.7 milligrams/hour | Standard Deviation 3.5 |
Secondary
Intrascapular Pain
Number of participants who experienced intrascapular pain (pain in your shoulder blade) during the study period.
Time frame: 72 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | Intrascapular Pain | 0 Participants |
| High Volume Bolus .0625% Bupivacaine | Intrascapular Pain | 3 Participants |
Secondary
Maximum Oxytocin Dose
Maximum oxytocin dose administered intravenously in international units.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | Maximum Oxytocin Dose | 12 International Units |
| High Volume Bolus .0625% Bupivacaine | Maximum Oxytocin Dose | 16 International Units |
Secondary
Number of Participants Categorized by Mode of Delivery
Mode of delivery identified as: normal vaginal delivery, instrumental vaginal delivery, cesarean delivery or emergency cesarean delivery
Time frame: 72 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | Number of Participants Categorized by Mode of Delivery | Vaginal Delivery | 45 Participants |
| Low Volume Bolus 0.1% Bupivacaine | Number of Participants Categorized by Mode of Delivery | Instrumental Delivery | 7 Participants |
| Low Volume Bolus 0.1% Bupivacaine | Number of Participants Categorized by Mode of Delivery | Cesarean Delivery | 15 Participants |
| High Volume Bolus .0625% Bupivacaine | Number of Participants Categorized by Mode of Delivery | Vaginal Delivery | 42 Participants |
| High Volume Bolus .0625% Bupivacaine | Number of Participants Categorized by Mode of Delivery | Instrumental Delivery | 4 Participants |
| High Volume Bolus .0625% Bupivacaine | Number of Participants Categorized by Mode of Delivery | Cesarean Delivery | 16 Participants |
Secondary
Number of Participants Who Required Additional Provider Redoses
Additional number of participants who required additional anesthesia care provider redoses of pain medication.
Time frame: 72 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 1 Redose | 9 Participants |
| Low Volume Bolus 0.1% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 3 Redoses | 5 Participants |
| Low Volume Bolus 0.1% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 2 Redoses | 8 Participants |
| Low Volume Bolus 0.1% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 4 Redoses | 1 Participants |
| Low Volume Bolus 0.1% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 0 Redoses | 44 Participants |
| High Volume Bolus .0625% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 4 Redoses | 0 Participants |
| High Volume Bolus .0625% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 0 Redoses | 51 Participants |
| High Volume Bolus .0625% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 1 Redose | 7 Participants |
| High Volume Bolus .0625% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 2 Redoses | 3 Participants |
| High Volume Bolus .0625% Bupivacaine | Number of Participants Who Required Additional Provider Redoses | 3 Redoses | 1 Participants |
Secondary
PCA Boluses
Number of Patient-Controlled Epidural Analgesia (PCEA) boluses of pain medication requested and number of PCEA medication boluses administered.
Time frame: 72 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | PCA Boluses | Boluses Requested | 7 Boluses |
| Low Volume Bolus 0.1% Bupivacaine | PCA Boluses | Boluses Delivered | 5 Boluses |
| High Volume Bolus .0625% Bupivacaine | PCA Boluses | Boluses Requested | 8 Boluses |
| High Volume Bolus .0625% Bupivacaine | PCA Boluses | Boluses Delivered | 5 Boluses |
Secondary
PCA Boluses Ratio
The ratio of the number of Patient-Controlled Epidural Analgesia (PCEA) pain medication boluses requested and number of PCEA pain medication boluses administered by the PCEA pump.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | PCA Boluses Ratio | 1.5 Ratio of requested to delivered boluses |
| High Volume Bolus .0625% Bupivacaine | PCA Boluses Ratio | 1.3 Ratio of requested to delivered boluses |
Secondary
Provider Administered Bolus
Number of participants requiring anesthesia provider administration of additional bolus doses of pain medication.
Time frame: 72 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | Provider Administered Bolus | 23 participants |
| High Volume Bolus .0625% Bupivacaine | Provider Administered Bolus | 11 participants |
Secondary
Time of Intrathecal Administration to Delivery
Elapsed time in minutes from the intrathecal administration of anesthetic by anesthesiology provider to time of delivery of baby.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | Time of Intrathecal Administration to Delivery | 468 Minutes |
| High Volume Bolus .0625% Bupivacaine | Time of Intrathecal Administration to Delivery | 575 Minutes |
Secondary
Time to First Anesthesiology Provider Bolus
Time elapsed in minutes from epidural set up to time to request supplemental analgesia provided by the anesthesiology care provider.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | Time to First Anesthesiology Provider Bolus | 270 Minutes |
| High Volume Bolus .0625% Bupivacaine | Time to First Anesthesiology Provider Bolus | 489 Minutes |
Secondary
VAS at 10 Centimeters Dilation of Cervix
VAS (visual analogue scale) at 10 centimeters dilation of cervix on a scale of 0 (no pain,good) to 100 (worst pain imaginable,bad)
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | VAS at 10 Centimeters Dilation of Cervix | 1 score on a scale 0 good 100 worst |
| High Volume Bolus .0625% Bupivacaine | VAS at 10 Centimeters Dilation of Cervix | 9 score on a scale 0 good 100 worst |
Secondary
VAS Score 30 Minutes After Anesthetic Care Provider Dose
Patient reported visual analogue scale score (0 no pain, good -100 worst pain imaginable, bad) 30 minutes after the first anesthesiology care provider bolus dose of anesthetic was administered to the participant for pain relief.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | VAS Score 30 Minutes After Anesthetic Care Provider Dose | 25 score on a scale 0 good-100 bad |
| High Volume Bolus .0625% Bupivacaine | VAS Score 30 Minutes After Anesthetic Care Provider Dose | 5 score on a scale 0 good-100 bad |
Secondary
VAS Score After Delivery
VAS score (Visual Analogue Scale) on a score of 0 (no pain,good) to 100 (worst pain imaginable,bad) immediately after delivery of baby
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | VAS Score After Delivery | 0 score on a scale 0 good-100 bad |
| High Volume Bolus .0625% Bupivacaine | VAS Score After Delivery | 0 score on a scale 0 good-100 bad |
Secondary
VAS Score Prior to First Provider Bolus Dose
Patient reported visual analogue scale score (0 no pain,good-100 worst pain imaginable, bad) prior to the first anesthesiology care provider bolus dose of anesthetic (pain medication).
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Volume Bolus 0.1% Bupivacaine | VAS Score Prior to First Provider Bolus Dose | 72 score on a scale 0 good-100 bad |
| High Volume Bolus .0625% Bupivacaine | VAS Score Prior to First Provider Bolus Dose | 61 score on a scale 0 good-100 bad |