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

NCT07023497 | Recruiting

• 1 other identifier: 8-1-2024/489
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Proportion of participants achieving adequate postoperative analgesia within 12 hours after spinal injection

  Adequate analgesia is defined as a Numerical Rating Scale (NRS, 0 to 10) pain score ≤3, maintained for at least 12 hours following intrathecal morphine administration for cesarean section. Each participant's outcome (success or failure) guides the dose selection for the next participant in accordance with the up-and-down sequential allocation method. The primary objective is to determine the ED50 and ED90 (median and 90% effective dose) of intrathecal morphine.

  0 to 24 hours post spinal anesthesia

Secondary Outcomes (10)

• Total analgesic consumption

  0 to 24 hours post surgery

• Duration of sensory block

  Intraoperative to early postoperative period (up to 6 hours)

• Duration of motor block

  Intraoperative to early postoperative period (up to 6 hours)

• Neonatal Apgar Score

  1 and 5 minutes post-delivery

• Maternal satisfaction

  At 24 hours postoperatively

Study Arms (1)

Dose-Finding Arm

EXPERIMENTAL

Participants receive spinal anesthesia with a fixed dose of fentanyl and ropivacaine, and a variable dose of morphine determined by the up-and-down sequential allocation method.

Drug: Intrathecal morphine

Interventions

Intrathecal morphine DRUG

Intrathecal morphine with fixed-dose fentanyl and ropivacaine

Dose-Finding Arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• term parturient
• single pregnancy
• elective cesarean delivery
• adult parturient
• ASA II

You may not qualify if:

• participants under the age of 18
• extreme somatometric characteristics
• lack of patient consent
• absolute contraindications for spinal anesthesia
• urgent cesarean section
• presence of known fetal anomalies
• onset of labor prior to administration of the block
• history of chronic pain
• use of opioids (systemic or otherwise) for any reason (e.g., chronic malignant pain)
• communication difficulties (e.g., language barriers, cognitive impairments)
• allergy or hypersensitivity to morphine
• severe arrhythmia or other serious cardiovascular conditions
• severe hepatic or renal insufficiency

Sponsors & Collaborators

• University of Ioannina: lead

Study Sites (1)

University Hospital of Ioannina

Ioannina, Epirus, 455 00, Greece

RECRUITING

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Central Study Contacts

Agathi Karakosta

CONTACT

+306948066243; akarakosta@uoi.gr

Dimitra Oikonomou

CONTACT

+306959136713; dimitra.oiknm@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is a single-arm dose-finding study using a double-blind design. The participant and outcome assessor are blinded to the morphine dose administered, but all participants receive the same intervention (intrathecal morphine) with dose variation based on sequential allocation. No multi-arm comparison is involved.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anaesthesiology

Model Details: We aim to employ an up-and-down sequential allocation method, a prospective, non-randomized, double-blind design commonly used in dose-finding studies. Each participant receives a dose of intrathecal morphine based on the analgesic response of the previous participant: the dose is increased following inadequate analgesia and decreased following effective pain relief.

Study Record Dates

• First Submitted: June 7, 2025
• First Posted: June 17, 2025
• Study Start: July 4, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: June 17, 2025

Record last verified: 2025-06

Locations

GR (1)