Analgesia, Epidural, Labor
Conditions
Keywords
analgesia, tubal ligation, chloroprocaine
Brief summary
Epidural chloroprocaine is often used in obstetrical anesthesia because of its fast onset and short duration. These properties make it an ideal drug to use for epidural anesthesia in patients undergoing postpartum tubal ligation. When epidural morphine is given after chloroprocaine, there is a decreased efficacy of analgesia as compared to lidocaine (1). Several studies have hypothesized a specific opioid receptor mediated antagonism of chloroprocaine (2,3). Karambelkar raised the question whether this decreased efficacy is due to a disparity between the time the chloroprocaine anesthesia resolves and the onset of epidural morphine analgesia, resulting in a time window of pain (2). The duration of action of epidural 2-CP anesthesia is 30-45 minutes and the onset of epidural morphine analgesia is 60-70 minutes, therefore the regression of sensory blockade before the onset of the morphine analgesia could result in a window of pain (2). Hess and colleagues studied epidural morphine analgesia and women who had a Cesarean delivery under spinal bupivacaine anesthesia (3). Subjects were randomized to receive epidural 2-CP and morphine or epidural saline and morphine. There was no difference in postoperative analgesia between the two groups (3 and personal communication, Dr. Philip Hess). A literature search cross referencing epidural chloroprocaine, using Pub Med, did not produce any articles comparing epidural morphine given before the procedure (in an attempt to time the onset of analgesia with the resolution of chloroprocaine anesthesia) to the standard administration time after the procedure.
Detailed description
Women undergoing post partum tubal ligation with an epidural in-situ will be randomly double blindedly selected into one of three groups for pain control. The groups are epidural 1) epidural morphine-chloroprocaine 2) epidural chloroprocaine-morphine 3) epidural morphine-lidocaine. Groups 1 and 3 will receive morphine 30 minutes prior to local anesthetic dosing followed by saline placebo after local dosing. Group 2 will receive placebo 30 minutes prior to local anesthetic dosing followed by epidural morphine. Pain scores and supplemental analgesic requirements will be evaluated 30 minutes, 1hr, 2hr, 4hr and every 4 hrs for the first 24hrs.
Interventions
DRUGMorphine-CP-saline (MCS)
3mg of preservative free morphine will be administered epidurally 30 min prior to epidural anesthesia. Epidural 3% 2CP will be used to achieve a T4 dermatomal level for surgical anesthesia for PPTL. 6ml of epidural saline will be administered at skin incision
DRUGsaline-2CP-morphine (SCM)
6ml of saline will be administered epidurally 30 min prior to epidural anesthesia. Epidural 3% 2CP will be used to achieve a T4 dermatomal level for surgical anesthesia for PPTL. 3mg of preservative free morphine will be administered at skin incision
DRUGsaline-lidocaine-morphine (SLM)
3mg of preservative free morphine will be administered epidurally 30 min prior to epidural anesthesia. Epidural 2% lidocaine with epinephrine 1:200,000 will be used to achieve a T4 dermatomal level for surgical anesthesia for PPTL. 6ml of epidural saline will be administered at skin incision
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 60 Years
Healthy volunteers
Yes
Inclusion criteria
* All patients with an epidural catheter in situ for labor analgesia, status post a vaginal delivery, and scheduled for a postpartum tubal ligation under epidural anesthesia will be eligible
Exclusion criteria
* Allergy/hypersensitivity to morphine * Allergy/hypersensitivity to ester-linked local anesthetics or para-amino benzoic acid (PABA) * Body Mass Index \>40 kg/m2 * Patients using chronic opioids * History of obstructive sleep apnea * Any contraindication to epidural anesthesia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Continuing Analgesia | 48 hours | Time to first request for supplemental analgesia |
| Supplemental Analgesia in First 90 Minutes | 90 min | Participants requesting supplemental analgesia in the first 90 minutes following study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Verbal Rating Score (0 to 10) for Pain (VRPS) | At recovery room entry | Verbal Rating Pain Score (VRPS) at time of post-anesthesia recovery room entry, where 0 = no pain and 10 = worst pain imaginable |
| Supplemental Analgesia in First 48 Hours | 48 hours | Participants requesting supplemental analgesia in first 48 hours |
Countries
United States
Participant flow
Recruitment details
136 subjects approached and assessed for eligibility
Pre-assignment details
Excluded from randomization (n=37), 26 refused to participate, 11 did not meet exclusion criteria
Participants by arm
| Arm | Count |
|---|---|
| Morphine - 2 Chloroprocaine - Saline (MCS) morphine will be administered 30 min prior to epidural anesthesia; 2CP will be used to achieve a T4 level; saline will be administered at skin incision | 33 |
| Saline-2 Chloroprocaine - Morphine (SCM) saline will be administered 30 min prior to epidural anesthesia; 2-chloroprocaine will be used to achieve a T4 level; morphine will be administered at skin incision | 33 |
| Saline - Lidocaine - Morphine (SLM) Saline administered 30 minutes prior to lidocaine to achieve a T4 anesthesia level. Morphine administered at skin incision. | 33 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not receive intervention | 4 | 3 | 5 |
Baseline characteristics
| Characteristic | Saline-2 Chloroprocaine - Morphine (SCM) | Saline - Lidocaine - Morphine (SLM) | Morphine - 2 Chloroprocaine - Saline (MCS) | 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 | 33 Participants | 33 Participants | 33 Participants | 99 Participants |
| Age, Continuous | 31 years STANDARD_DEVIATION 5 | 29 years STANDARD_DEVIATION 4 | 33 years STANDARD_DEVIATION 4 | 30 years STANDARD_DEVIATION 4 |
| Region of Enrollment United States | 33 participants | 33 participants | 33 participants | 99 participants |
| Sex: Female, Male Female | 33 Participants | 33 Participants | 33 Participants | 99 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 | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 29 | 0 / 30 | 0 / 28 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 | 0 / 28 |
Outcome results
Primary
Duration of Continuing Analgesia
Time to first request for supplemental analgesia
Time frame: 48 hours
Population: All participants receiving the intervention were analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Morphine - 2 Chloroprocaine - Saline (MCS) | Duration of Continuing Analgesia | 28.6 hours |
| Saline-2 Chloroprocaine - Morphine (SCM) | Duration of Continuing Analgesia | 2.2 hours |
| Saline - Lidocaine - Morphine (SLM) | Duration of Continuing Analgesia | 25.8 hours |
Comparison: A sample of 56 was estimated to have an 80% power to detect a 30% difference in the proportion of subjects with continuing analgesia in the MCS versus the SCM groups when 50% of the subjects in the SCM had requested supplemental analgesia. 28 subjects was added to compare the influence of time of morphine and 2-chloroprocaine administration to lidocaine-morphine analgesia. The primary outcome was compared using Kaplan-Meier survival analysis and the log-rank test.p-value: 0.006Log Rank
p-value: 0.83Log Rank
p-value: 0.009Log Rank
Primary
Supplemental Analgesia in First 90 Minutes
Participants requesting supplemental analgesia in the first 90 minutes following study drug
Time frame: 90 min
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Morphine - 2 Chloroprocaine - Saline (MCS) | Supplemental Analgesia in First 90 Minutes | 0 participants |
| Saline-2 Chloroprocaine - Morphine (SCM) | Supplemental Analgesia in First 90 Minutes | 10 participants |
| Saline - Lidocaine - Morphine (SLM) | Supplemental Analgesia in First 90 Minutes | 0 participants |
p-value: 0.01Chi-squared, Corrected
p-value: 0.01Chi-squared, Corrected
Secondary
Supplemental Analgesia in First 48 Hours
Participants requesting supplemental analgesia in first 48 hours
Time frame: 48 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Morphine - 2 Chloroprocaine - Saline (MCS) | Supplemental Analgesia in First 48 Hours | 12 Participants |
| Saline-2 Chloroprocaine - Morphine (SCM) | Supplemental Analgesia in First 48 Hours | 8 Participants |
| Saline - Lidocaine - Morphine (SLM) | Supplemental Analgesia in First 48 Hours | 12 Participants |
p-value: 0.2Chi-squared, Corrected
Secondary
Verbal Rating Score (0 to 10) for Pain (VRPS)
Verbal Rating Pain Score (VRPS) at time of post-anesthesia recovery room entry, where 0 = no pain and 10 = worst pain imaginable
Time frame: At recovery room entry
Population: Verbal Rating Score for Pain (0-10) where 0 = no pain and 10 = worst pain imaginable
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Morphine - 2 Chloroprocaine - Saline (MCS) | Verbal Rating Score (0 to 10) for Pain (VRPS) | 2 Scores on a scale |
| Saline-2 Chloroprocaine - Morphine (SCM) | Verbal Rating Score (0 to 10) for Pain (VRPS) | 2 Scores on a scale |
| Saline - Lidocaine - Morphine (SLM) | Verbal Rating Score (0 to 10) for Pain (VRPS) | 0 Scores on a scale |
p-value: <0.05Kruskal-Wallis
p-value: <0.05Kruskal-Wallis