Effect of Timing on Efficacy of Morphine Analgesia After 2-chloroprocaine Anesthesia

Study Overview
=================
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.

Official Title
-----------------
Interaction Between Epidural 2-chloroprocaine and Epidural Morphine: Effect of Timing on Efficacy of Morphine Analgesia After 2-chloroprocaine Anesthesia

Conditions
-----------------
Labor, Analgesia, Epidural

Intervention / Treatment
-----------------
* Drug: Morphine-CP-saline (MCS)
* Drug: saline-2CP-morphine (SCM)
* Drug: saline-lidocaine-morphine (SLM)


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: morphine - 2CP-saline (MCS)<br>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 | Drug: Morphine-CP-saline (MCS)<br>* 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<br>|
| Experimental: saline-2CP-morphine (SCM)<br>saline will be administered 30 min prior to epidural anesthesia; 2CP will be used to achieve a T4 level;morphine will be administered at skin incision | Drug: saline-2CP-morphine (SCM)<br>* 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<br>|
| Active Comparator: saline-lidocaine-morphine (SLM)<br>Saline will be administered 30 min prior to epidural anesthesia; lidocaine will be used to achieve a T4 level; morphine will be administered at skin incision | Drug: saline-lidocaine-morphine (SLM)<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Continuing Analgesia | Time to first request for supplemental analgesia | 48 hours | 
| Supplemental Analgesia in First 90 Minutes | Participants requesting supplemental analgesia in the first 90 minutes following study drug | 90 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | At recovery room entry | 
| Supplemental Analgesia in First 48 Hours | Participants requesting supplemental analgesia in first 48 hours | 48 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
analgesia, tubal ligation, chloroprocaine