Effect of Intrathecal Morphine on Chronic Pain After Elective Caesarean Section

NCT ID: NCT03451695

Last Updated: 2021-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 290 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-01
• Study Completion Date: 2021-03-30

Brief Summary

The incidence of chronic post-surgical pain (CPSP) after caesarean section (CS) is reported to be as high as 18%, reflecting it to be a significant clinical problem. Studies related to prevention of progression of acute post-CS pain to its chronicity are sparse. Current guidelines on post-CS analgesia recommend the use of intrathecal (IT) opioids to spinal anaesthesia for improved post-CS pain relief. Despite its frequent use, studies related to the IT morphine use and its association with post-CS chronic pain are lacking.

A recent prospective observation study revealed a significant reduction in persistent pain after CS when IT morphine was used as an adjuvant to spinal anaesthesia. However, there is no any randomized controlled trial (RCT) that has explored this association to date. We hypothesized that spinal morphine would reduce the incidence of persistent pain after CS.

Detailed Description

This prospective, randomised, double-blind trial will take place at B.P Koirala Institute of Health Sciences, a University hospital situated in Nepal. Approval for the study has been obtained from the institution ethical committee. After the trial is registered, recruitment of the patient will be initiated. Consent for the participation in the study will be obtained during pre-anaesthetic assessment visits in the evening before surgery. During this visit, preoperative anxiety level (hospital anxiety and depression scale), pain catastrophizing (assessed with pain catastrophizing scale), preoperative pain sensitivity (assessed with pain pressure threshold and tolerance) will be recorded. The investigator will also educate the patients regarding the use of NRS scores for postoperative pain and satisfaction ratings.

Patients will be randomly assigned in a 1:1 ratio to one of the two groups (morphine and placebo groups). Randomization will be done in variable block sizes (4/6/8) by an internet based random-number generator list.

Morphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml). Placebo group will receive 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10μg of fentanyl (0.2 ml) and normal saline (0.1ml).

Postoperatively, pain, opioid consumption, sedation, nausea or vomiting, pruritus, and respiratory depression in the postanesthesia care unit (time 0 hours) and at 2, 6, 12, 24, and 48 hours will be evaluated. The area of hyperalgesia around the surgical incision will be assessed at 48 hrs postoperatively using a von Frey filament.

Patient satisfaction from postoperative analgesia will be assessed using a 5-point scale (1 = very unsatisfied, 2 = unsatisfied, 3 = fair, 4 = satisfied and 5 = very satisfied). At 8 wks patients will be assessed for post-natal depression using Edinburgh postnatal depression scale.

Patients will be contacted by telephone by one of the blinded investigator at 3, 6 months after the surgery. The short form brief pain inventory will be used to determine post-CS chronic pain

Conditions

Chronic Pain Post-Procedural

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Morphine group

Morphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml).

Group Type: EXPERIMENTAL

Morphine

Intervention Type: DRUG

Morphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml).

Placebo group

Placebo group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and normal saline (0.1 ml).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo group will receive 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and normal saline (0.1ml)

Interventions

Morphine

Morphine group will receive intrathecal 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and 100 μg of preservative free morphine (0.1 ml).

Intervention Type: DRUG

Placebo

Placebo group will receive 11 mg of hyperbaric bupivacaine (2.2 mL 0.5%), 10 μg of fentanyl (0.2 ml) and normal saline (0.1ml)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Woman in American Society of Anesthesiologists (ASA) physical status classification II with full-term singleton pregnancy undergoing planned CS under spinal anesthesia.

Exclusion Criteria

• contraindication to spinal anaesthesia, height<150 cm, ASA > II, BMI> 40, allergy to any drug used in the study, recent opioid exposure, substance abuse, significant cardiovascular, renal, or hepatic disease; and known fetal abnormalities.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

B.P. Koirala Institute of Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Dr Asish Subedi

Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

BP Koirala Institute of Health Sciences (BPKIHS)

Dharān, Koshi, Nepal

Countries

Nepal

References

Subedi A, Schyns-van den Berg AMJV, Thapa P, Limbu PM, Trikhatri Y, Poudel A, Dhakal Y, Bhandari S. Intrathecal morphine does not prevent chronic postsurgical pain after elective Caesarean delivery: a randomised controlled trial. Br J Anaesth. 2022 Apr;128(4):700-707. doi: 10.1016/j.bja.2021.11.036. Epub 2022 Jan 26.

Reference Type: DERIVED

PMID: 35090722 (View on PubMed)

Other Identifiers

IRC/1183/017

Identifier Type: -

Identifier Source: org_study_id