Preeclampsia remote from term. The role of magnesium in the management of patients with preeclampsia remote from term (less than 34 weeks of gestation), when continuation of the pregnancy can provide fetal benefit, also is unclear. We administer magnesium sulfate for the first 24 to 48 hours of hospitalization in patients with severe preeclampsia.
The multiple mechanisms by which magnesium counters preeclampsia-induced vasoconstriction have the potential to improve blood flow in the pulmonary, renal, hepatic, gastrointestinal, and placental circulations, as well as the central nervous system, thus delaying the need for delivery. Whether prolonged infusion of magnesium can be an effective component of therapy to delay delivery and improve fetal outcome remains to be determined.
Abruptio placentae. Magnesium also may reduce the risk of abruptio placentae,1 although 1 small study did not find IV magnesium infusion beneficial in this setting.20
A look at pathophysiology
Over the normal range of arterial pressure, cerebral blood flow and capillary hydrostatic pressures remain relatively constant thanks to accompanying adjustments in cerebral vascular resistance. But when arterial pressures are high, elevations in vascular resistance may not completely compensate for them. Thus, capillary blood flow and hydrostatic pressure are increased, disrupting endothelial tight junctions and promoting leakage of small ions and water into the brain parenchyma. The result is cerebral edema and convulsions.
Yet an increase in arterial pressure cannot be the sole mechanism at work, since eclampsia can occur in apparently normotensive patients. Nor is the risk of seizures in preeclamptic women directly proportional to the rise in arterial pressure. Cerebral vasogenic edema may also result from disruptions in cerebral vascular resistance and/or from increased capillary permeability due to endothelial dysfunction or injury, which are unrelated to changes in arterial pressure.1,2 Cytotoxic edema as a result of vasoconstriction or infarction3,4 is another possible mechanism, as are disturbances in brain metabolism.
Imaging studies. Until recently, imaging studies were unable to distinguish between vasogenic and cytotoxic edema; both present as hypodensities on computed tomography and magnetic resonance imaging.5-7 But diffusion-weighted imaging techniques demonstrate that focal vasogenic edema, which disappears with resolution of clinical symptoms, is more consistently observed in eclamptic women.8,9 Petechial brain hemorrhages also have been detected in patients with eclampsia or severe preeclampsia.10
REFERENCES
1. Bhatia RK, Bottoms SF, Saleh AA, Norman GS, Mammen EF, Sokol RJ. Mechanisms for reduced colloid osmotic pressure in preeclampsia. Am J Obstet Gynecol. 1987;157:106.-
2. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: An endothelial cell disorder. Am J Obstet Gynecol. 1989;161:1200-1204.
3. Sheehan JL, Lynch JB. Pathology of Toxaemia of Pregnancy. London: Churchill Livingston; 1973;524:582.-
4. McKay DG. Clinical significance of the pathology of toxemia of pregnancy. Circulation. 1964;30(suppl 2):66-75.
5. Milliez J, Dohoun A, Boudraa M. Computed tomography of the brain in eclampsia. Obstet Gynecol. 1990;75:975-980.
6. Dahmus MA, Barton JR, Sibai BM. Cerebral imaging in eclampsia: magnetic resonance imaging versus computed tomography. Am J Obstet Gynecol. 1992;167:935-941.
7. Cunningham FG, Twickler D. Cerebral edema complicating eclampsia. Am J Obstet Gynecol. 2000;182:94-100.
8. Kanki T, Tsukimori K, Mihara F, Nakano H. Diffusion-weighted images and vasogenic edema in eclampsia. Obstet Gynecol. 1999;93:821-823.
9. Friese S, Fetter M, Küker W. Extensive brainstem edema in eclampsia: Diffusion weighted MRI may indicate a favourable prognosis. J Neurol. 2000;247:465-466.
10. Drislane FW, Wang A-M. Multifocal cerebral hemorrhage in eclampsia and severe pre-eclampsia. J Neurol. 1997;244:194-198.
Administration
Protocols based on observational data. Therapeutic magnesium concentrations in maternal plasma have been deduced from empiric studies.21 In a protocol for eclampsia, both IV and intramuscular (IM) administration of magnesium sulfate were associated with initial maternal plasma magnesium levels of 7 to 9 mEq/L, with subsequent stabilization at 4 to 7 mEq/L. For patients with preeclampsia, IM administration of magnesium resulted in concentrations of 3.5 to 6 mEq/L. Because these protocols were generally effective, 4 to 7 mEq/L has been used as a therapeutic range, though no formal dose-response testing has been performed.
The lower limit of target plasma magnesium concentrations is about twice the mean physiologic concentration (approximately 1.7 mEq/L).
Optimum IV infusion rate. Continuous IV infusion of magnesium sulfate—rather than IM injection—is now the norm in most US hospitals.22 However, the infusion rate of 1 g/h, which is generally effective for prophylaxis and treatment of seizures,22 often fails to meet target maternal serum magnesium concentrations.19 Thus, an infusion rate of 2 g/h is recommended (TABLE 2).
We generally start with a loading dose of 4 to 6 g over 10 to 15 minutes in women with normal renal function, using the hydrated form of the drug. In patients with oliguria, we give a loading dose of 4 g over 15 minutes, followed by a maintenance infusion of 1 g/h. Even at the higher infusion rate (2 g/h), plasma levels are usually in the lower therapeutic range.19