Magnesium and bupivacaine-induced convulsions in awake pregnant rats.
BACKGROUND
Magnesium sulfate (MgSO(4)) is widely used for the treatment and prevention of convulsions associated with preeclampsia. The aim of this study was to determine whether it alters the dose of bupivacaine required to produce convulsions in awake pregnant rats.


METHODS
Twelve pregnant rats were pretreated with an intravenous infusion of either MgSO(4) or saline. Following 2 h of the pretreatment, bupivacaine was concomitantly infused in all animals until the onset of convulsions. Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout. Serial arterial samples were obtained during the infusion. At the onset of convulsions, fetuses were delivered and maternal and fetal blood, as well as various tissue samples, were obtained. All samples were assayed for bupivacaine and magnesium concentrations.


RESULTS
Maternal MAP and HR decreased significantly shortly after the initiation of MgSO(4), while saline did not affect these measurements. Baseline concentrations of magnesium in plasma were similar in both MgSO(4) and saline groups; magnesium increased significantly during the infusion of MgSO(4). The dose (mean+/-SD) of bupivacaine required to produce convulsions in the animals receiving MgSO(4) was significantly larger (10.2+/-1.9 mg/kg) than that in the saline group (5.9+/-1.0 mg/kg) (P<0.05). As a consequence, bupivacaine concentrations in the brain and liver at the onset of convulsions were greater in animals receiving MgSO(4) (16.0+/-8.4 and 18.2+/-4.3 microg/g wet weight, respectively) than in those given saline (12.1+/-2.2 and 9.9+/-2.0 microg/g wet weight, respectively). Fetal bupivacaine concentrations at the onset of convulsions in the MgSO(4) group were also higher than those in saline group. However, the rate of placental transfer of this drug was similar between MgSO(4) and saline animals.


CONCLUSIONS
This study demonstrates that the clinically used concentration of magnesium sulfate increased the threshold of bupivacaine-induced convulsions in awake rats.
Okutomi
T
T
Departments of Anesthesiology and Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA. toshiyukiokutomi@hotmail.com
Zhang
Y
Y
Cooper
T B
TB
Morishima
H O
HO
D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D005260:Female; D008278:Magnesium Sulfate / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control; D014851:Wakefulness
D000779:Anesthetics, Local; D008278:Magnesium Sulfate; D002045:Bupivacaine