Pain After Scheduled Cesarean Delivery: Spinal Morphine With or Without Levobupivacaine Wound Infiltration (LEVO-CS)

Background and rationale Intrathecal morphine is the gold standard for analgesia after cesarean delivery. However, 25-80% of women still report moderate to severe pain during the first 24-48 hours. Poorly controlled pain may delay mobilization, increase systemic opioid use, interfere with breastfeeding and newborn care, and has been associated with chronic pain and postpartum depression. International recommendations (PROSPECT, ERAS) support multimodal analgesia. Local anesthetic wound infiltration is simple, inexpensive and reproducible, but evidence on its added benefit over intrathecal morphine is limited and heterogeneous in dose, technique and anatomical plane. Levobupivacaine, the pure S-enantiomer of bupivacaine, has lower cardiovascular and central nervous system toxicity.

Design This is a prospective, single-center, analytical observational cohort study at Fundación Santa Fe de Bogotá, a high-complexity teaching hospital in Bogotá, Colombia, with about 2,000 births per year. Patients are enrolled consecutively over 10 months. Exposure is determined only by the usual clinical practice of each attending obstetrician. The investigators do not assign, randomize or suggest the exposure.

Exposure Exposed cohort: subcutaneous and subfascial infiltration with levobupivacaine 0.75%, 75 mg (one 10 mL ampoule diluted in 10 mL of saline), after closure of the aponeurosis. The drug is Bupinest®, INVIMA registration 2016 M-013339-R2. The total local anesthetic dose, including the spinal dose, stays within the maximum of 2 mg/kg.

Unexposed cohort: no wound infiltration.

Standard institutional analgesia (both cohorts) Spinal anesthesia with intrathecal morphine 100 mcg and fentanyl 25 mcg. Ketorolac 30 mg IV after delivery of the newborn. Acetaminophen 1 g IV at the end of surgery. During the 48-hour hospital stay: oral celecoxib every 12 hours (unless contraindicated), oral acetaminophen 1 g every 8 hours, and IV hyoscine butylbromide 20 mg every 8 hours.

Rescue systemic opioid for pain score >7 or at the patient's request.

Blinding and data collection Outcome assessment and statistical analysis are blinded to exposure. Patient-reported outcomes (pain scale and the validated Spanish version of the ObsQoR-10) are self-administered through automated REDCap surveys sent by WhatsApp or email, which reduces inter-observer variability. Clinical and surgical data are taken from the electronic medical record.

Sample size Sample size was calculated with Epidat 4.2 for comparison of two independent means, using 24-hour pain scores from published data. The parameters were 95% confidence, 80% power and a 1:1 ratio. The result is 336 participants (168 per cohort).

Statistical analysis Pain trajectory (24 h, 48 h, 7 days): linear mixed model for repeated measures. Fixed effects are exposure, time and the exposure × time interaction; the patient is a random effect. Mean between-group differences at each time point are reported with 95% CIs. If model assumptions are not met, robust or ordinal models will be used.

Secondary outcomes:

Time to first ambulation: t-test or Mann-Whitney, and Kaplan-Meier with log-rank if exact times are available.

Rescue analgesia: chi-square or Fisher's exact test, and logistic regression. ObsQoR-10: as a continuous score, and dichotomized at ≥70 points as good recovery.

Adjusted models: multivariable models adjust for confounders, including maternal age, BMI and previous cesarean delivery.

Exploratory subgroups: age, parity, BMI category and previous cesarean delivery.

Significance is set at p <0.05. The analysis will be done in Rstudio.

Ethics The study is classified as minimal risk under Colombian Resolution 8430 of 1993. It has been approved by the Corporate Research Ethics Committee (CCEI) of Fundación Santa Fe de Bogotá. As an observational Phase IV study of a marketed medicine, it will be notified to INVIMA, the Colombian National Food and Drug Surveillance Institute, before enrollment begins. All participants give electronic informed consent through REDCap. Results will be published regardless of direction.