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Anesth Analg. 2002 Sep;95(3):661-6, table of contents.

Intrathecal magnesium prolongs fentanyl analgesia: a prospective, randomized, controlled trial.

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  • 1Department of Anesthesiology, Rush Medical College at Rush-Presbyterian-St Luke's Medical Center, 1653 W Congress Parkway, Chicago, IL 60612, USA.


Magnesium is a noncompetitive, N-methyl-D-aspartate receptor antagonist that does not effectively cross the blood-brain barrier when given IV. Intrathecal magnesium potentiates opioid antinociception in rats, and the safety of intrathecal magnesium has been demonstrated in animals. This is the first prospective human study evaluating whether intrathecal magnesium could prolong spinal opioid analgesia. Fifty-two patients requesting analgesia for labor were randomized to receive either intrathecal fentanyl 25 micro g plus saline or fentanyl 25 micro g plus magnesium sulfate 50 mg as part of a combined spinal-epidural technique. The duration of analgesia of the intrathecal drug combination was defined by the time of patient request for additional analgesia. There was significant prolongation in the median duration of analgesia (75 min) in the magnesium plus fentanyl group compared with the fentanyl alone group (60 min). There was no associated increase in adverse events in the group that received intrathecal magnesium. Larger doses of intrathecal magnesium were not studied in this group of patients because of the limitations on cephalad spread when hyperbaric solutions are injected in the sitting position. Our data indicate that intrathecal magnesium prolongs spinal opioid analgesia in humans and suggest that the availability of an intrathecal N-methyl-D-aspartate antagonist could be of clinical importance for pain management.


Magnesium occurs naturally in the spinal cord and blocks the NMDA glutamate channel. In animal studies, intrathecal magnesium sulfate improves spinal morphine analgesia. For patients receiving spinal analgesia for labor, the addition of magnesium sulfate to the opioid fentanyl prolonged analgesia with no increase of side effects.

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