Intravenous infusion of magnesium sulfate and regional redistribution of fetal blood flow during maternal hemorrhage in late-gestation gravid ewes.
OBJECTIVE
Even though magnesium sulfate is commonly prescribed for women with preeclampsia as prophylaxis against seizure and for women with preterm labor as a tocolytic agent there is limited information about its effects on the fetus. It is of particular concern that women with preeclampsia or in premature labor are at high risk for abruptio placentae with consequent compromise of fetal oxygenation. Magnesium sulfate is a vasodilator and thus may exert cardiovascular effects on the fetus. The goal of this study was to evaluate the effects of magnesium sulfate on fetal organ blood flow, especially regional cerebral blood flow, during the stressful condition of maternal hemorrhage.


METHODS
Studies were performed with 11 long-term instrumented pregnant ewes and their fetuses at 121 to 128 days' gestation (term, 147 days' gestation). Animals were randomly allocated to either the experimental (n = 5) or the control (n = 6) group. After a 60-minute baseline period, experimental fetuses received intravenous magnesium sulfate diluted in 0.9% sodium chloride (0.3 g loading dose, then 0.3 g/h at a rate of 3 mL/h) and control fetuses were infused with an equivalent volume of intravenous 0.9% sodium chloride. After 60 minutes of this infusion-only period, the infusions were continued and ewes were intermittently bled 4 times at a rate of 5 mL/kg for 10 minutes with 5 minutes between hemorrhages. The total blood lost at the end of the hemorrhage-plus-infusion hour was 20 mL/kg. The infusions were continued and the sheep were observed for 1 hour after this period (posthemorrhage period). At the end of baseline, infusion-only, and hemorrhage-plus-infusion periods, fetal and maternal blood pressures and blood gas values were measured and fetal organ blood flows were determined through a fluorescent microsphere technique. Repeated-measures analysis of variance and Wilcoxon tests were used to determine the significance of changes in hemodynamic, blood gas, and organ blood flow parameters between different time points within each group. Comparisons between groups were made with rank sum tests (Mann-Whitney tests).


RESULTS
There were no significant differences between groups or within groups for baseline and infusion-only measurements in any measured hemodynamic or hematologic factor. Mean maternal blood pressure decreased significantly (P <.05) after hemorrhage, with similar median decrements in both control and experimental groups of 41 mm Hg (interquartile range, 24-57 mm Hg) and 41 mm Hg (interquartile range, 12-43 mm Hg), respectively. There were no significant differences between groups in fetal blood gas values or hemodynamic parameters. Fetal arterial PO(2) decreased significantly after hemorrhage plus infusion, with similar mean (+/-SEM) decreases in control and experimental groups of 5.9 +/- 1.4 mm Hg and 4.5 +/- 1.5 mm Hg, respectively. Fetal pH also decreased significantly in both groups. After hemorrhage plus infusion there were significant increases in fetal regional cerebral and myocardial blood flows in both groups. Adrenal blood flow increased significantly from baseline (214%, 183%-294%) in the control group after hemorrhage plus infusion but not in the experimental group. No other difference in organ blood flow between control and experimental groups was observed. Significant regional variations in cerebral blood flow were not observed in either group at any time.


CONCLUSIONS
In these initially healthy, late-gestation fetal lambs magnesium sulfate exposure did not impair cardiac output redistribution, nor did it cause fetal death in response to maternal hemorrhage.
Moon
P F
PF
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Ramsay
M M
MM
Nathanielsz
P W
PW
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000633:toxicity*; D001921:Brain / Q000098:blood supply / Q000196:embryology; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000098:blood supply / Q000187:drug effects*; D007262:Infusions, Intravenous; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000633:toxicity*; D014592:Uterine Hemorrhage / Q000503:physiopathology*
D000927:Anticonvulsants; D015149:Tocolytic Agents; D008278:Magnesium Sulfate