Analgesic Effects of Preoperative Combination of Oral Pregabalin and Intravenous Magnesium Sulfate on Postoperative Pain in Patients Undergoing Posterolateral Spinal Fusion Surgery: A 4-arm, Randomized, Double-blind, Placebo-controlled Trial

Background: Multimodal perioperative pain management including nonopioid analgesia is a major pillar of enhanced recovery after surgery programs. The aim of this study was to investigate the analgesic efficacy of the preoperative combination of 2 nonopioid drugs, oral pregabalin and intravenous magnesium sulfate, in patients undergoing posterolateral lumbar spinal fusion. Methods: This 4-arm, randomized, double-blind, placebo-controlled trial included 104 patients randomly allocated to receive: magnesium sulfate and pregabalin (MP), magnesium sulfate and oral placebo (M), 0.9% saline and oral pregabalin (P), and 0.9% saline and oral placebo (C). The study drugs were administered 1 hour preoperatively. The primary outcome was the cumulative morphine consumption on postoperative day 1. Secondary outcomes included visual analog scale scores for leg pain at rest and with movement, and postoperative nausea and vomiting (PONV) in the first 48 hours after surgery. Results: Cumulative morphine consumption on postoperative day 1 was lower in group MP (19.6±8.0 mg) compared with group M (32.6±9.5 mg; P <0.001), group P (28.9±9.4 mg; P =0.001), or group C (38.8±10.3 mg; P <0.001). Multiple linear regression demonstrated a significant association between group MP and cumulative morphine consumption (B=−5.4 [95% CI, −7.1, −3.7], P <0.001). Visual analog scale scores for leg pain at rest and with movement were lower in group MP compared with other groups ( P =0.006 and <0.001). The incidence of PONV was also lowest in group MP ( P =0.032). Conclusions: Preoperative administration of oral pregabalin and intravenous magnesium sulfate resulted in reduced morphine consumption and greater analgesic effect than the use of each drug individually or placebo in patients undergoing posterolateral lumbar spinal fusion.