Comparative Efficacy of Intravenous Dexamethasone, Intravenous Dexmedetomidine, and Intrathecal Dexmedetomidine for Prophylaxis of Postoperative Nausea and Vomiting After Cesarean Delivery: A Six-Arm Randomized Triple-Blind Controlled Trial

Abstract

Background: Postoperative nausea and vomiting (PONV) is a common complication following cesarean delivery under spinal anesthesia, particularly when intrathecal opioids are used. Although dexamethasone is widely used for PONV prophylaxis, alternative regimens with comparable efficacy and acceptable safety profiles remain of clinical interest. Dexmedetomidine, an alpha-2 adrenergic agonist with sedative and sympatholytic properties, may reduce PONV and improve perioperative hemodynamic stability. Objectives: This randomized controlled trial compared the efficacy of different prophylactic regimens of intravenous dexamethasone, intravenous dexmedetomidine, and intrathecal dexmedetomidine for preventing PONV after elective cesarean delivery under spinal anesthesia. Methods: In this six-arm, triple-blind, randomized controlled trial, 300 parturients undergoing elective cesarean delivery under spinal anesthesia with 12 mg hyperbaric bupivacaine were allocated equally to six groups (n = 50 each): placebo, intravenous dexamethasone 2 mg, intravenous dexamethasone 4 mg, intravenous dexamethasone 6 mg, intravenous dexmedetomidine 10 µg, and intrathecal dexmedetomidine 10 µg. A double-dummy design was used to maintain blinding. Per-protocol analysis included 285 participants who completed the study. The primary outcome was the incidence and severity of PONV during the first 24 postoperative hours, assessed using a 4-point ordinal scale. Hemodynamic parameters were recorded from baseline to 120 minutes after spinal anesthesia. Data were analyzed using multivariable ordinal logistic regression and linear mixed-effects models. Results: Of the 300 randomized participants, 285 completed the study (placebo, n = 47; dexamethasone 2 mg, n = 48; dexamethasone 4 mg, n = 46; dexamethasone 6 mg, n = 49; intravenous dexmedetomidine, n = 47; intrathecal dexmedetomidine, n = 48). Baseline characteristics were comparable across groups (all P > 0.05). Compared with placebo, the lowest incidences of PONV were observed with intravenous dexamethasone 6 mg (12%; adjusted OR, 0.07; 95% CI, 0.03 - 0.13; absolute risk reduction, 66%; number needed to treat, 1.5) and intrathecal dexmedetomidine (14%; adjusted OR, 0.08; 95% CI, 0.04 - 0.16; absolute risk reduction, 64%; number needed to treat, 1.6). In linear mixed-effects analyses, intrathecal dexmedetomidine and intravenous dexamethasone 6 mg were associated with better maintenance of systolic blood pressure than placebo, with intrathecal dexmedetomidine showing the smallest maximum decline. Obesity (BMI ≥ 30 kg/m2) was independently associated with higher odds of more severe PONV (adjusted OR, 2.44; P < 0.001), whereas gravidity ≥ 4 was associated with lower odds (adjusted OR, 0.38; P < 0.001). Conclusions: Among the evaluated prophylactic regimens, intravenous dexamethasone 6 mg and intrathecal dexmedetomidine 10 µg were associated with the most favorable profiles for reducing PONV after elective cesarean delivery under spinal anesthesia. Given its ease of administration and noninvasive route, intravenous dexamethasone 6 mg may be a practical first-line prophylactic option. Trial Registration: IRCT20240221061070N10