Intraperitoneal Hydrocortisone for Postoperative Pain and CRP after Cesarean Section: A Randomized Controlled Trial

Abstract

Background: Postoperative pain and acute surgical peritoneal injury following cesarean section (CS) induce substantial local nociception and systemic inflammatory surges. Intraperitoneal instillation of hydrocortisone—an endogenous mammalian glucocorticoid—exerts anti-inflammatory properties, but its incremental clinical utility within an already optimized modern multimodal analgesia (MMA) regimen remains undefined.
Methods: In a prospective, double-blind, parallel-group, randomized controlled trial (ClinicalTrials.gov Identifier: NCT07892547), 50 parturients undergoing elective CS under spinal anesthesia (12.5 mg hyperbaric bupivacaine 0.5% + 50 µg intrathecal morphine), bilateral ultrasound-guided transversus abdominis plane (TAP) blocks (50 mg levobupivacaine per side), and 1 g intravenous paracetamol were randomized 1:1 using computer-generated permuted blocks with sequentially numbered opaque sealed envelopes. Following uterine repair, subjects received either 100 mg hydrocortisone in 100 mL 0.9% NaCl (Group H, n=25) or 100 mL 0.9% NaCl placebo (Group P, n=25) instilled into the peritoneal cavity. Primary outcome was Visual Analog Scale (VAS) pain intensity at 6, 12, and 24 hours. Secondary outcomes included serum C-reactive protein (CRP) concentrations (baseline, 12h, 24h), dynamic changes (ΔVAS, ΔCRP), rescue fentanyl consumption, and safety parameters.
Results: All 50 randomized subjects completed the 24-hour protocol without dropout. VAS pain scores did not differ significantly between Group H and Group P at 6 hours (3.04±0.98 vs. 3.04±0.20 cm; p=0.324), 12 hours (2.80±0.41 vs. 3.00±0.87 cm; p=0.611), or 24 hours (3.20±0.82 vs. 3.48±1.50 cm; p=1.000). Serum CRP concentrations increased significantly over time in both cohorts (Friedman p<0.001), with no between-group differences at baseline (10.75±11.43 vs. 15.58±38.80 mg/L; p=0.682), 12 hours (20.14±22.74 vs. 22.95±25.67 mg/L; p=0.726), 24 hours (50.71±33.62 vs. 57.76±43.67 mg/L; p=0.900), or in net ΔCRP (39.96±31.28 vs. 42.18±33.21 mg/L; p=1.000). Supplemental fentanyl requirements (24% vs. 28%; p=1.000) and adverse event profiles were equivalent, with 0% pruritus and 0% hyperglycemia. In exploratory correlation analysis, dynamic pain change and inflammatory surge correlated positively in the placebo group (ΔVAS 6→24h vs. ΔCRP 12→24h: Spearman r=+0.465, p=0.019), but this association was uncoupled in the hydrocortisone group (r=-0.173, p=0.408).
Conclusion: Intraperitoneal hydrocortisone 100 mg provided no incremental analgesic or anti-inflammatory benefit over placebo in parturients receiving comprehensive multimodal analgesia with bilateral TAP block, primarily attributable to an analgesic floor effect. Routine peritoneal corticosteroid instillation is not warranted when baseline regional analgesia is optimized.