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

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age18-50
SponsorUniversity of Ioannina

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

term parturient

single pregnancy

elective cesarean delivery

adult parturient

Disqualifiers

participants under the age of 18

extreme somatometric characteristics

lack of patient consent

absolute contraindications for spinal anesthesia

Trial design

Design model

Single group

Treatments tested in this trial

  • Intrathecal morphine

    Drug

    Intrathecal morphine with fixed-dose fentanyl and ropivacaine

Treatment groups

100 Participants
are divided into 1 treatment group
Group A: Dose-Finding ArmExperimental treatment 1 intervention

Trial outcomes

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.

Time frame
0 to 24 hours post spinal anesthesia

Secondary outcomes

1

Total analgesic consumption

Cumulative dose of all systemic analgesics (opioids and non-opioids) administered during the first 24 hours postoperatively, recorded in morphine milligram equivalents (MME) where applicable.

Time frame
0 to 24 hours post surgery
2

Duration of sensory block

Time interval from spinal injection to full regression of sensory block to S2 dermatome, assessed using pinprick or cold test.

Time frame
Intraoperative to early postoperative period (up to 6 hours)
3

Duration of motor block

Time from spinal injection to complete recovery of motor function, defined as a modified Bromage score of 0. The modified Bromage scale ranges from 0 to 3, where 0 indicates no motor block/full movement of the lower limbs and 3 indicates complete motor block; higher scores indicate greater motor block.

Time frame
Intraoperative to early postoperative period (up to 6 hours)
4

Neonatal Apgar Score

Apgar score assessed at 1 and 5 minutes after birth to evaluate newborn status. The Apgar score ranges from 0 to 10, with higher scores indicating better neonatal condition.

Time frame
1 and 5 minutes post-delivery

Other outcomes

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