The Optimal Dosage of Intrathecal Morphine for Peripartum Analgesia

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

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.

Official Title
-----------------
The Optimal Dosage of Intrathecal Morphine for Peripartum Analgesia

Conditions
-----------------
Labor Pain

Intervention / Treatment
-----------------
* Drug: Morphine
* Drug: Saline


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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Saline<br>* Saline Control<br>* Other names: Saline added to solution;|
| Active Comparator: Morphine 25<br> | Drug: Morphine<br>* Active dosage<br>* Other names: Dose of morphine added to solution;|
| Active Comparator: Morphine 50<br> | Drug: Morphine<br>* Active dosage<br>* Other names: Dose of morphine added to solution;|
| Active Comparator: Morphine 75<br> | Drug: Morphine<br>* Active dosage<br>* Other names: Dose of morphine added to solution;|
| Active Comparator: Morphine 100<br> | Drug: Morphine<br>* Active dosage<br>* Other names: Dose of morphine added to solution;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Breakthrough Pain | 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. | Participants were followed for the duration of delivery, an average of 7 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Obstetric anesthesia, labor analgesia, morphine, epidural analgesia