Determining the Optimal Dose of Intrathecal Morphine for Post-Cesarean Analgesia

Summary

Using spinal or epidural anesthesia (known as neuraxial blocks) is the gold standard for pain control during childbirth, especially in cesarean sections (C-sections). However, many women experience moderate to severe pain after a C-section, which can affect both their physical and emotional well-being, and even impact their ability to care for their newborn. Unfortunately, this pain is often not treated effectively, which can lead to increased sensitivity to pain or even chronic postoperative pain.

One effective way to manage this pain is by giving opioids directly into the spinal fluid (subarachnoid space). This method allows doctors to use much smaller doses than would be needed if the same medication were given through a vein, which also helps avoid many of the common side effects of opioids like respiratory depression, nausea, pruritus, and constipation.

Common opioids used in this setting include fentanyl, sufentanil, and morphine. These drugs behave differently depending on their chemical properties. For example, drugs that are more fat-soluble work faster, while those that are less fat-soluble tend to last longer. Morphine, which is less fat-soluble than the others, provides strong and long-lasting pain relief. When injected spinally, its effect can last 18-24 hours, with the pain relief starting 1-2 hours after the injection. Its performance is comparable to that of epidural anesthesia or nerve blocks.

Researchers have studied a wide range of spinal morphine doses (from 20 to 500 micrograms) to find the most effective and safest dose. Most of these studies are small or use set doses without clear reasoning. Recently, a method called sequential allocation has become popular for finding the best dose more accurately.

About the Study This research aims to find the ideal dose of spinal morphine when it's given with a fixed amount of fentanyl and varying doses of ropivacaine (a local anesthetic) during spinal anesthesia for C-section in healthy full-term parturients. The goal is to find the dose that provides adequate analgesia (pain score under 3 out of 10) for at least 12 hours after surgery.

This is a prospective, non-randomized, double-blind study. The study follows ethical standards and all participants sign an informed consent form. Two anesthesiologists are involved in each case: one handles the spinal injection and dose decision (based on the previous patient's response), while the other monitors the patient and collects the data without knowing the dose used.

Anesthetic Technique Spinal anesthesia is done using standard procedures. A very fine needle (25 or 27 gauge) is used to inject a mixture of fentanyl (15 mcg), a variable dose of ropivacaine (based on somatometrics), and a variable dose of morphine (based on the algorithm). The mixture is injected slowly (1 ml every 10 seconds), with the needle facing toward the head. After surgery, all women receive additional pain medications like paracetamol and NSAIDs as part of a multimodal pain relief approach.

How the Morphine Dose is Decided

The dose of morphine changes based on whether the previous participant had effective pain relief. Pain relief is considered successful if the pain score stays at or below 3 (on a 0-10 scale) for at least 12 hours after the spinal injection. For the first woman in the study, the starting dose is chosen based on published research. Then:

* If the previous participant had good pain control (NRS ≤3 for 12 hours), the dose for the next woman is reduced by 20 micrograms.
* If pain control was poor (NRS \>3 within the first 12 hours), the dose is increased by 40 micrograms.

This up-and-down adjustment continues for each new participant.

Conditions

• Morphine
• Cesarean Section
• Postoperative Pain, Acute
• Spinal Analgesia
• Postoperative Pain

Interventions

DRUG

Intrathecal morphine

Intrathecal morphine with fixed-dose fentanyl and ropivacaine

Sponsors & Collaborators

• University of Ioannina

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-07-04

Primary Completion

2026-07-01

Completion

2026-09-01

Countries

• Greece

Study Locations