The Optimal Dosage of Intrathecal Morphine for Peripartum Analgesia

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01146457
• Collaborator: (none)
• Enrollment: 83
• Location: 1
• Arms: 5
• Duration (Months): 54
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the ideal dosage of intrathecal morphine for intra and post partum analgesia, while minimizing the side effect profile.

Condition or Disease	Intervention/Treatment	Phase
Labor Pain	Drug: Morphine; Drug: Saline	N/A

Detailed Description

Regional anesthesia techniques such as combined spinal epidural (CSE) analgesia are very effective for the management of intrapartum pain. The advantages of these techniques are that they are safe when properly conducted and that they provide excellent analgesia while allowing the patient to remain awake and participate in the labor and delivery. The risks of maternal aspiration and fetal drug depression associated with general anesthesia are minimized. Finally, the effective analgesia associated with regional techniques blunt the hemodynamic effects caused by painful contractions and reduce maternal catecholamines, resulting in increased placental perfusion.1

Opioids in combination with local anesthetics in the spinal space provide effective pain relief during labor with minimal side effects. The advantages of spinal opioid administration include lack of motor blockade and faster onset of analgesia.2 In addition, since the opiate receptors are in the spinal space, a smaller amount of opioid can be used to provide excellent pain relief while minimizing the side effects. At Beth Israel Deaconess Medical Center (BIDMC), the obstetric anesthesiology group uses a standard spinal dosing for CSE during labor which includes: 1 ml of 0.25% bupivicaine with 12.5 mcg of fentanyl.

Yeh and colleagues have found that morphine 150 mcg added to the fentanyl-bupivicaine spinal injection can prolong the duration of spinal analgesia but was associated with increased side effects. 3 The side effect profile of spinal narcotics include: nausea, vomiting, pruritus, and urinary retention. Although these side effects for the most part can be easily treated, they can be bothersome to the post partum patient. In a previous study performed from our institution, the addition of 100 mcg of morphine to spinal bupivicaine and fentanyl reduced the rate of breakthrough pain during labor analgesia and prolonged the time to first request for supplementation. Overall, it was found that the incidence of side effects was low but the group that received the spinal morphine did have more nausea and vomiting compared with the placebo group. 4

In this current investigation, we would like to assess whether an even smaller dose of spinal morphine would provide an effective, pain free recovery from vaginal delivery while decreasing the incidence of side effects, specifically nausea and vomiting. We would like to perform a formal dose response study to identify the ideal dose of intrathecal morphine that would not compromise the pain relief during labor while minimizing the side effects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Optimal Dosage of Intrathecal Morphine for Peripartum Analgesia
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Saline; Saline Control; Other Names: Saline added to solution
Active Comparator: Morphine 25	Drug: Morphine; Active dosage; Other Names: Dose of morphine added to solution
Active Comparator: Morphine 50	Drug: Morphine; Active dosage; Other Names: Dose of morphine added to solution
Active Comparator: Morphine 75	Drug: Morphine; Active dosage; Other Names: Dose of morphine added to solution
Active Comparator: Morphine 100	Drug: Morphine; Active dosage; Other Names: Dose of morphine added to solution

Outcome Measures

Primary Outcome Measures

1. Rate of Breakthrough Pain [Participants were followed for the duration of delivery, an average of 7 hours]

   Rate of breakthrough pain is the number of episodes of breakthrough pain divided by the number of hours of labor. Time measured from placement of the neuraxial anesthetic, until delivery of the neonate. Because duration of labor is different for all patients, the rate of breakthrough pain per hour is used as the primary outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• singleton pregnancy,

• at least 36 weeks gestational age,

• active labor (≤ 5 cm dilation) requesting neuraxial analgesia,

• ASA I or II,

• not currently taking pain medications.

Exclusion Criteria:

• multiple gestation,

• preterm labor,

• systemic opioids in the past 4 hours,

• chronic pain syndromes,

• chronic opioid use,

• contraindications to regional anesthesia,

• allergies to opioids,

• significant co existing medical problems,

• severe pregnancy induced hypertension,

• sedatives,

• magnesium therapy,

• diabetes type 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center

Investigators

• Principal Investigator: Philip E Hess, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Phillip Hess, Chief of Obstetric Anesthesia, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01146457
• Other Study ID Numbers: 2009P000197
• First Posted: Jun 17, 2010
• Last Update Posted: Apr 25, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Phillip Hess, Chief of Obstetric Anesthesia, Beth Israel Deaconess Medical Center: Obstetric anesthesia; labor analgesia; morphine; epidural analgesia
• Additional relevant MeSH terms: Labor Pain; Morphine; Pharmaceutical Solutions

Study Results

Participant Flow

Arm/Group Title	Placebo	Morphine 25	Morphine 50	Morphine 75	Morphine 100
Arm/Group Description	Saline: Saline Control	Morphine 25 micrograms: Active dosage	Morphine 50 micrograms: Active dosage	Morphine 75 micrograms: Active dosage	Morphine 100 micrograms: Active dosage
Period Title: Overall Study
STARTED	19	17	21	13	13
COMPLETED	19	17	20	13	13
NOT COMPLETED	0	0	1	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Morphine 25	Morphine 50	Hine 75	Morphine 100	Total
Arm/Group Description	Saline control	Morphine 25 micrograms	Morphine 50 micrograms	Morphine 75 micrograms	Morphine 100 micrograms	Total of all reporting groups
Overall Participants	19	17	21	13	13	83
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.3 (5.3)	31.5 (5.3)	31.3 (6.6)	32.5 (5.5)	32.4 (5.7)	32.3 (5.7)
Sex: Female, Male (Count of Participants)
Female	19 100%	17 100%	21 100%	13 100%	13 100%	83 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Rate of Breakthrough Pain
Description	Rate of breakthrough pain is the number of episodes of breakthrough pain divided by the number of hours of labor. Time measured from placement of the neuraxial anesthetic, until delivery of the neonate. Because duration of labor is different for all patients, the rate of breakthrough pain per hour is used as the primary outcome.
Time Frame	Participants were followed for the duration of delivery, an average of 7 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Morphine 25	Morphine 50	Morphine 75	Morphine 100
Arm/Group Description	Saline Control	Morphine 25 micrograms	Morphine 50 micrograms	Morphine 75 micrograms	Morphine 100 micrograms
Measure Participants	19	17	21	13	13
Mean (Standard Deviation) [episodes of breakthrough pain per hour]	0.25 (0.29)	0.28 (0.35)	0.25 (0.25)	0.23 (0.26)	0.17 (0.21)

Adverse Events

Arm/Group Title	Placebo		Morphine 25		Morphine 50		Morphine 75		Morphine 100
Arm/Group Description	Saline: Saline Control		Morphine: Active dosage		Morphine: Active dosage		Morphine: Active dosage		Morphine: Active dosage
All Cause Mortality
	Placebo		Morphine 25		Morphine 50		Morphine 75		Morphine 100
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Morphine 25		Morphine 50		Morphine 75		Morphine 100
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/17 (0%)		0/21 (0%)		0/13 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Morphine 25		Morphine 50		Morphine 75		Morphine 100
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/17 (0%)		0/21 (0%)		0/13 (0%)		0/13 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.