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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


Dr Stefano Palmisani
Department of Anesthesia and Intensive Care Medicine
‘La Sapienza’ University of Rome
II Faculty of Medicine
S. Andrea Hospital
via di Grottarossa 1035–1039
00189 Rome


Background:  New ways of decreasing post-operative analgesic drug requirements are of special interest after major surgery. Magnesium sulfate (MgSO4) 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 MgSO4 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 MgSO4 (94.5 mg, 6.3%), epidural MgSO4 (2%, 100 mg/h), intrathecal and epidural MgSO4 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 MgSO4 [– 14.963 mg; 95% confidence interval (CI), – 1.44 to – 28.49 mg], 49% lower in those receiving spinal anesthesia plus intrathecal MgSO4 (– 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 MgSO4 significantly reduces patients’ post-operative analgesic requirements.