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

• ClinicalTrials.gov Identifier: NCT00487084
• Recruitment Status: Completed
• First Posted: June 15, 2007
• Results First Posted: April 18, 2011
• Last Update Posted: April 14, 2014
• Sponsor: Northwestern University
• Information provided by (Responsible Party): Cynthia Wong, Northwestern University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Labor; Analgesia, Epidural	Drug: Morphine-CP-saline (MCS); Drug: saline-2CP-morphine (SCM); Drug: saline-lidocaine-morphine (SLM)	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 136 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Interaction Between Epidural 2-chloroprocaine and Epidural Morphine: Effect of Timing on Efficacy of Morphine Analgesia After 2-chloroprocaine Anesthesia
• Study Start Date: August 2004
• Actual Primary Completion Date: September 2008
• Actual Study Completion Date: September 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Duration of Continuing Analgesia [ Time Frame: 48 hours ]
   Time to first request for supplemental analgesia
2. Supplemental Analgesia in First 90 Minutes [ Time Frame: 90 min ]
   Participants requesting supplemental analgesia in the first 90 minutes following study drug

Secondary Outcome Measures :

1. Verbal Rating Score (0 to 10) for Pain (VRPS) [ Time Frame: 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
2. Supplemental Analgesia in First 48 Hours [ Time Frame: 48 hours ]
   Participants requesting supplemental analgesia in first 48 hours

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

Investigators

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

More Information

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.

Karambelkar DJ, Ramanathan S. 2-Chloroprocaine antagonism of epidural morphine analgesia. Acta Anaesthesiol Scand. 1997 Jun;41(6):774-8.

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.

• Responsible Party: Cynthia Wong, Professor of Anesthesiology, Northwestern University
• ClinicalTrials.gov Identifier: NCT00487084
• Other Study ID Numbers: 0524-021
• First Posted: June 15, 2007
• Results First Posted: April 18, 2011
• Last Update Posted: April 14, 2014
• Last Verified: March 2014

Keywords provided by Cynthia Wong, Northwestern University:

analgesia; tubal ligation; chloroprocaine

Additional relevant MeSH terms:

Agnosia; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Lidocaine; Morphine; Anesthetics; Chloroprocaine; Procaine; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, Local; Sensory System Agents; Peripheral Nervous System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Analgesics, Opioid; Narcotics; Analgesics