Clinical trial NCT03451695: Effect of Intrathecal Morphine on Chronic Pain After Elective Caesarean Section
Official title: Effect of Intrathecal Morphine on Chronic Pain After Elective Caesarean Section: A Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Pain Post-Procedural
Lead sponsor: B.P. Koirala Institute of Health Sciences
Sponsor class: OTHER
First posted: 2018-03-02
Enrollment: 290
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Primary outcomes:
measure: Number of participants with the incidence of post surgery chronic pain at 3 months following elective caesarean section
timeFrame: 3 months after elective caesarean section
Secondary outcomes:
measure: Number of participants with the incidence of post surgery chronic pain at 6 months following elective caesarean section
timeFrame: 6 month after elective caesarean section
measure: Brief pain inventory (BPI) pain severity scores at 3 and 6 month after elective caesarean section between those receiving intrathecal morphine and normal saline
timeFrame: 3 and 6 months after elective caesarean section
measure: Brief Pain Inventory (BPI) pain interference scores at 3 and 6 month after elective caesarean section between those receiving intrathecal morphine and normal saline
timeFrame: 3 and 6 months after elective caesarean section
measure: Any pain medication or treatment received for relieving pain. If so, the amount of pain relieved.
timeFrame: 3 and 6 months after elective caesarean section
measure: Numerical rating Scale (NRS) pain scores and opioid consumption post operatively
timeFrame: 24 and 48 hrs after surgery
Other outcomes:
Locations:
city: Dharān Bāzār
country: Nepal
facility: BP Koirala Institute of Health Sciences (BPKIHS)
state: Koshi
Study officials:
References:
citation: 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.