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

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

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.

Study Overview

• Status: Completed
• Conditions: Labor; Analgesia, Epidural
• Intervention / Treatment: Drug: Morphine-CP-saline (MCS); Drug: saline-2CP-morphine (SCM); Drug: saline-lidocaine-morphine (SLM)

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.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: morphine - 2CP-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	Drug: Morphine-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
Experimental: saline-2CP-morphine (SCM); 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); 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
Active Comparator: saline-lidocaine-morphine (SLM); 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); 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

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

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Cynthia A Wong, M.D., Northwestern University

Publications and helpful links

General Publications

• Eisenach JC, Schlairet TJ, Dobson CE 2nd, Hood DH. Effect of prior anesthetic solution on epidural morphine analgesia. Anesth Analg. 1991 Aug;73(2):119-23. doi: 10.1213/00000539-199108000-00003.
• Karambelkar DJ, Ramanathan S. 2-Chloroprocaine antagonism of epidural morphine analgesia. Acta Anaesthesiol Scand. 1997 Jun;41(6):774-8. doi: 10.1111/j.1399-6576.1997.tb04782.x.
• Camann WR, Hartigan PM, Gilbertson LI, Johnson MD, Datta S. Chloroprocaine antagonism of epidural opioid analgesia: a receptor-specific phenomenon? Anesthesiology. 1990 Nov;73(5):860-3. doi: 10.1097/00000542-199011000-00011.

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: June 13, 2007
• First Submitted That Met QC Criteria: June 14, 2007
• First Posted (Estimate): June 15, 2007

Study Record Updates

• Last Update Posted (Estimate): April 14, 2014
• Last Update Submitted That Met QC Criteria: March 17, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: analgesia; tubal ligation; chloroprocaine
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Agnosia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine; Morphine
• Other Study ID Numbers: 0524-021