Combined intrathecal and epidural magnesium sulfate supplementation of spinal anesthesia to reduce post-operative analgesic requirements: a prospective, randomized, double-blind, controlled trial in patients undergoing major orthopedic surgery

BACKGROUND: New ways of decreasing post-operative analgesic drug requirements are of special interest after major surgery. Magnesium sulfate (MgSO(4)) alters pain processing and reduces the induction and maintenance of central sensitization by blocking the N-methyl-D-aspartate (NMDA) receptor in the spinal cord. We investigated whether supplementation of spinal anesthesia with combined intrathecally and epidurally infused MgSO(4) reduced patients' post-operative analgesia requirements. METHODS: In a randomized, prospective, double-blind, placebo-controlled trial, we enrolled 120 consecutive patients undergoing orthopedic surgery during spinal anesthesia (levobupivacaine and sufentanil). Patients were randomly assigned to receive intrathecal MgSO(4) (94.5 mg, 6.3%), epidural MgSO(4) (2%, 100 mg/h), intrathecal and epidural MgSO(4) combined or spinal anesthesia alone (controls). Post-operative morphine consumption was assessed in all groups by patient-controlled analgesia (PCA). RESULTS: Of the 120 patients enrolled, 103 (86%) completed the study. Morphine consumption at 36 h after surgery was 38% lower in patients receiving spinal anesthesia plus epidural MgSO(4) [- 14.963 mg; 95% confidence interval (CI), - 1.44 to - 28.49 mg], 49% lower in those receiving spinal anesthesia plus intrathecal MgSO(4) (- 18.963 mg; 95% CI, - 5.27 to - 32.65 mg) and 69% lower in the intrathecal-epidural combined group (- 26.963 mg; 95% CI, - 13.73 to - 40.19 mg) relative to control patients receiving spinal anesthesia alone. No complications developed during the post-operative course or at 1 month after surgery. CONCLUSION: In patients undergoing orthopedic surgery, supplementation of spinal anesthesia with combined intrathecal and epidural MgSO(4) significantly reduces patients' post-operative analgesic requirements.