Caesarean Section, Postoperative Pain
Conditions
Keywords
Caesarean section, Cesarean section, Cesarean delivery, Caesarean delivery, Postoperative pain, Intrathecal morphine, Spinal morphine, elective caesarean
Brief summary
The goal of this clinical trial is to learn if morphine added to the spinal anaesthesia can improve postoperative pain treatment for patients undergoing caesarean section, without increasing the risk of serious adverse events in mother and baby. The main questions it aims to answer are: * Is the treatment effective in preventing postoperative pain? * Is the treatment safe for both mother and baby? Participants will be given a normal spinal anaesthesia with addition of either morphine or sodium chloride (inactive substance). All participants will receive standard postoperative pain treatment, including morphine tablets as needed. Researchers will collect data from the electronic medical record and ask the participants to fill out questionnaires about pain levels and possible side effects.
Detailed description
BACKGROUND AND OBJECTIVE: Caesarean section is surgical procedure associated with moderate to severe postoperative pain, which can negatively affect recovery, mother-child bonding and the initiation of breastfeeding. Intrathecal morphine may offer pain relief for up to 24 hours, and is widely implemented and recommended as part of multimodal postoperative pain management. Despite the widespread use, there is limited evidence for the balance between benefits and harms of low-dose intrathecal morphine in patients undergoing caesarean section. The objective of the trial is to evaluate analgesic efficacy as well as maternal and neonatal safety associated with addition of low-dose (80 µg) intrathecal morphine versus placebo to standard multimodal postoperative pain management in patients undergoing planned caesarean section. The trial is a superiority, investigator-initiated, pragmatic, randomised, blinded, placebo-controlled multicentre trial. TRIAL SIZE: A total of 1,312 participants is required to show/reject a 35% relative increase in the composite co-primary safety outcome, with an estimated baseline incidence of 21% without intrathecal morphine and a power of 80%. We adjust statistically for having two primary outcomes by using an alpha of 2.5%. We reach a power of 99.9% for the co-primary outcome of pain score with an estimated mean Numeric Rating Scale (0-10) of 4.88, standard deviation of 2.0 and relevant mean difference of 1.0. ETHICAL CONSIDERATIONS: Intrathecal morphine for caesarean delivery represents a common medical practice which is not supported by robust evidence. High-quality data on efficacy and safety of the treatment will enable clinicians to tailor postoperative pain treatment to each patient, thus improving care for future patients. Choosing low-dose morphine minimises the risk of adverse effects, and all trial participants will receive standard multimodal pain treatment. There is no evidence of any harmful neonatal effects. All trial participants will give informed consent, and the trial will adhere to the Declaration of Helsinki as well as national and international standards of good clinical practice. PLANNED SUBSTUDIES: * Incidence of desaturation and bradypnea during the first 24 hours following surgery, assessed using continuous wireless respiratory monitoring in a subpopulation of 100 patients at 3 trial sites. * Efficacy and safety of intrathecal morphine in participant subgroups: The influence of different pre-existing factors on the primary outcomes
Interventions
DRUGIntrathecal Morphine
80 μg preservative-free morphine (0.2 ml) added to a single-shot spinal anaesthesia consisting of 11.5 mg hyperbaric bupivacaine and 10 μg fentanyl
0.2 ml of isotonic sodium chloride added to a single-shot spinal anaesthesia consisting of 11.5 mg hyperbaric bupivacaine and 10 μg fentanyl.
Sponsors
Anne Juul Wikkelsø
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 years * Singleton pregnancy * Scheduled for planned caesarean section performed under spinal anaesthesia * Written informed consent
Exclusion criteria
* Allergy to or contraindications towards trial medication * Patients planned for postoperative epidural due to expected difficult postoperative pain management * Patients planned for combined spinal-epidural as primary anaesthesia * Inability to understand and read Danish * Previous inclusion in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of pain when mobilising from supine to sitting position within 24 hours | 6, 12, 18 and 24 hours following spinal anaesthesia | Longitudinal measurements of NRS (0-10) at 6, 12, 18 and 24 hours with most focus on the 24-hour pain level |
| Maternal and neonatal serious adverse events | Within 7 days from discharge | Binary composite outcome: 1. Death of either participant or neonate within 7 days 2. Participants with clinically significant respiratory depression within 24 hours, defined as respiratory depression documented in the electronic medical record, e.g. need for airway management or pharmacological intervention (subjective assessment by treating clinician, validated by 2 investigators) 3. Neonates needing admission to neonatal intensive care unit within 48 hours 4. Hospitalisation of either participant or neonate within 7 days after discharge 5. Participants with severe vomiting or nausea within 24 hours, defined as ≥5 points on the 'Simplified postoperative nausea and vomiting impact scale'63 at any time point (6, 12, 18 and 24 hours) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Opioid consumption within 24 hours | Within 24 hours following spinal anaesthesia | Mg oral morphine equivalents |
| Morphine associated adverse effects within 24 hours | Within 24 hours following spinal anaesthesia | Binary composite outcome: participants experiencing either: 1. Vomiting (patient reported, yes/no) 2. Nausea 3. Dizziness 4. Pruritus Nausea, dizziness, and pruritus is assessed as "none", "little", "moderate", or "severe" with patients reporting "moderate" or "severe" categorised as having a positive outcome 5. Urinary retention, defined as need for re-catheterisation within 24 hours |
| Obstetric quality of recovery score at 24 hours | Within 24 hours following spinal anaesthesia | Obs-QoR-10 (0-100) |
| Participants satisfaction with postoperative pain-treatment during the first 24 hours | Within 24 hours following spinal anaesthesia | NRS 0-10 |
| Established breastfeeding at 30 days | 30 days from surgery | Proportion of neonates being exclusively breastfed at 30 days |
Countries
Denmark
Contacts
CONTACTAnneline B Seegert, MD
CONTACTAnne J Wikkelsø, MD, PhD
Outcome results
None listed