Journal: Acta Anaesthesiol Scand 51(7):482-489, 2007. 42 References
Reprint: Dept 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, Italy (S Palmisani, MD)
Faculty Disclosure: Abstracted by R. Klotz, who has nothing to disclose.
N-Methyl-D-aspartate (NMDA) receptor antagonists prevent central sensitization induced by peripheral nociceptive stimulation and abolish hypersensitization once it is established by blocking dorsal horn NMDA receptor activation induced by excitatory amino acid transmitters, such as glutamate and aspartate.
Magnesium is a non-competitive NMDA receptor antagonist that blocks ion channels in a voltage-dependent fashion. Numerous clinical studies have shown that magnesium sulfate (MgSO4) reduces the intraoperative consumption of hypnotic agents and analgesics, prolongs neuromuscular blockade and reduces postoperative analgesic requirements. The IV administration of MgSO4 does not seem to be associated with a corresponding increase in CSF ion concentrations, although this is probably its true site of action. Precisely how magnesium passes through the blood-brain barrier is unclear. Studies have shown that humans maintain normal CSF magnesium concentrations even in the presence of changes in the blood-brain barrier and in induced systemic hypermagnesemia. Direct intrathecal administration of MgSO4 prolongs the action of subarachnoid anesthesia in humans, and has been shown to be clinically safe in humans.
To the author’s knowledge, there has been no study that has investigated the effects of intrathecally injected MgSO4 on postoperative analgesia require-ments, or verified the anti-nociceptive effect of combined intrathecally and epidurally administered MgSO4. Therefore, the authors hypothesized that, like local anesthetics and opioids, MgSO4 administered via this route might rapidly reach and maintain therapeutic concentrations in the CSF.
A total of 120 consecutive patients undergoing orthopedic surgery (total hip or knee replacement) over a 4-month period were enrolled in the study. Patients were randomly assigned to 1 of 4 groups to receive as an adjunct to spinal anesthesia intrathecal MgSO4 (94.5 mg, 6.3%), epidural MgSO4 (2%, 100 mg/hr), intrathecal and epidural MgSO4 combined, or spinal anesthesia alone (controls). All patients received combined subarachnoid-epidural anesthesia.
All patients received postoperative IV analgesia delivered through a PCA pump loaded with morphine hydrochloride 1 mg/mL diluted in 0.9% NaCl, and programmed to deliver, on request, a 4-mg morphine bolus with a lock-out period of 20 minutes between 2 consecutive boluses. Postoperative follow-up lasted for 36 hours, starting at the end of surgery (T1) and then every 4 hours for 36 hours (T10). A blinded observer evaluated postoperative pain, motor function, the number of morphine boluses via PCA, the onset of PONV and any complications.
On the day of discharge and at 1 month after surgery, 118 patients (98%) underwent medical assessment, including neurologic exam focusing on motor and sensory function of the lower limbs and history taking of all possible neurologic symptoms arising after the procedure.
Of the 120 patients enrolled, 103 (86%) successfully completed the study (30 control, 25 epidural, 23 intrathecal and 25 intrathecal-epidural). No differences were found in cardiorespiratory variables between groups during surgery. Patients who received spinal anesthesia only (control) required larger postoperative morphine doses. At 36 hours postoperative, the control group required, on average 38.96 mg morphine, the epidural group 24.0 mg, the intrathecal group 20.0 mg and the intrathecal-epidural group only 12.0 mg. This illustrates that, compared to the control group, the epidural group’s morphine requirement was 38% lower, 49% lower in the intrathecal group and 69% lower in the intrathecal-epidural group. The incidence of PONV was similar between groups at 36 hrs postoperative, although the tendency was lower in MgSO4 treated patients.
For major orthopedic surgery, supplementation of spinal anesthesia with combined intrathecally injected and epidurally infused MgSO4 reduces patients’ postoperative PCA requirements considerably, compared with spinal alone. Therefore, once MgSO4 is approved for intrathecal and epidural use, a low-cost, simple change in clinical anesthesiology practice will do much to decrease patients’ postoperative analgesic needs. |
