Risk factors for pulmonary edema in triplet pregnancies.

OBJECTIVE: Multiple gestations are known to be at increased risk for pulmonary edema. Our objective was to characterize this morbidity in a cohort of triplet pregnancies. STUDY DESIGN: Charts from triplet pregnancies managed by the Georgetown University Hospital Maternal-Fetal Medicine service were abstracted for demographic information and complications. Cases who developed pulmonary edema were compared with those who did not using Fisher exact test, chi(2) and Student's t-test with p <0.05 considered significant. RESULTS: Of 66 triplet pregnancies with complete records, 15 (22.7%) were complicated by pulmonary edema. Patients developing this condition were more likely to be receiving magnesium sulfate therapy than those who did not [14/15 (93.3%) vs 32/51 (62.7%) p=0.049]. There was no difference between patients developing pulmonary edema and those who did not in terms of maternal age (mean+/-SD: 34.5+/-6.8 vs 34+/-4.3 years, p=0.8) or gestational age at delivery (33.3+/-2.3 vs 32.8+/-3.5 weeks, p=0.6), but the former group had smaller babies than the latter (1739+/- 369 vs 1891+/-538 g, p=0.04). Among the patients treated with magnesium sulfate, those who developed the more severe form of pulmonary edema were more likely than those who did not to have been treated for pre-eclampsia than preterm labor (6/10 (60%) vs 7/33 (21.2%), p=0.04). CONCLUSIONS: Pulmonary edema is a common complication of triplet pregnancy. Patients receiving magnesium sulfate, having pre-eclampsia or fetal growth restriction are at increased risk for pulmonary edema, particularly in its worst clinical presentation.     

The effect of oxytocin infusion on the pharmacokinetics of intramuscular magnesium sulfate therapy

The effect of oxytocin infusion on the pharmacokinetics of standard intramuscular magnesium sulfate therapy was determined in 18 women with preeclampsia; the results were compared with those in seven women with preeclampsia who did not receive oxytocin. Oxytocin had no significant effects on the maternal serum magnesium and calcium ion concentrations, nor did oxytocin appear to affect the magnesium or calcium concentrations in fetal umbilical cord blood. Urinary excretion of magnesium rose 21-fold and calcium excretion rose threefold in patients receiving intramuscular magnesium sulfate in both the oxytocin and the nonoxytocin groups. Sixty-five percent of the administered magnesium was excreted during the treatment period, again with no significant differences between the oxytocin and the nonoxytocin groups. These results indicate that oxytocin does not affect the pharmacokinetics of intramuscular magnesium sulfate and no dosage adjustment of magnesium sulfate is required when oxytocin is used to induce or augment labor or when it is given during the postpartum period.     

Pregnancy and severe chronic hypertension: maternal outcome.

OBJECTIVE: To determine the maternal outcome associated with severe chronic hypertension during the second half of pregnancy. METHODS: An analysis of data obtained of women with severe chronic hypertension (> or = 160/110 mm Hg) and > or = 20 weeks' gestation who were hospitalized and delivered during a 5-year period. The pregnancy outcome data were collected retrospectively from medical records. Each patient was observed closely throughout hospitalization with intensive monitoring of the clinical status of both mother and fetus. Antihypertensive drugs were used for systolic or diastolic blood pressure > or = 160 and > or = 110 mm Hg, respectively. Women with superimposed preeclampsia received magnesium sulfate. The main outcome measures were peak of blood pressure, superimposed preeclampsia, and major maternal complications. RESULTS: Of 154 women studied, 111 (72%) had pregestational chronic hypertension, and 120 (78%) developed superimposed preeclampsia. The mean weeks' gestation was 34.5 +/- 4.6. Overall, 110 (71.4%) pregnancies were delivered by cesarean section. Maternal age and parity were significantly higher among women who had pregestational chronic hypertension than those who had chronic hypertension diagnosed during the first half of pregnancy. Abruptio placentae (8.4%), HELLP syndrome (8.4%), acute renal insufficiency (3.9%), pulmonary edema (1.3%), and postpartum hypertensive encephalopathy (1.3%) were the most frequent maternal complications. There were no maternal deaths, disseminated intravascular coagulation, or eclampsia. CONCLUSION: Three-quarters of women with severe chronic hypertension in the second half of pregnancy developed superimposed preeclampsia. Intensive monitoring of the clinical status of the mother was associated with low maternal morbidity and the absence of maternal deaths. Pregestational chronic hypertension does not change the maternal prognosis.     

Effect of magnesium sulfate on plasma endothelin-1 levels in normal and preeclamptic pregnancies.

OBJECTIVE: We attempted to determine the effects of magnesium sulfate on: (1) endothelin-1 concentration in preeclampsia, preterm labor, and term pregnancy and (2) endothelin-1 release from human umbilical cord endothelial cells. STUDY DESIGN: Plasma samples were prospectively collected from eight women with preeclampsia, six preterm labor patients, and eight term patients undergoing external cephalic version before and 2 hours after magnesium sulfate infusion. Supernatants were collected from human umbilical cord endothelial cells exposed to magnesium sulfate and controls. All samples were assayed with a specific radioimmunoassay for endothelin-1. Paired Student t test and analysis of variance were used for statistical analysis. RESULTS: Magnesium sulfate infusion in preeclampsia lowered endothelin-1 levels compared with preinfusion values (6.6 +/- 3.81 before and 4.75 +/- 2.28 after infusion, p < 0.02). Magnesium sulfate did not have an effect on endothelin-1 concentration in preterm and term pregnancies. Magnesium sulfate did not alter the endothelin-1 release from human umbilical cord endothelial cells. CONCLUSION: A significant reduction of endothelin-1 plasma levels after magnesium sulfate therapy is limited to preeclampsia. In contrast, this lowering effect was not exhibited in women without preeclampsia or in normal endothelial cells.     

Magnesium sulfate prophylaxis in preeclampsia: Lessons learned from recent trials

In the US, the routine use of magnesium sulfate for seizure prophylaxis in women with preeclampsia is an ingrained obstetric practice. During the past decade, several observational studies and randomized trials have described the use of various regimens of magnesium sulfate to prevent or reduce the rate of seizures and complications in women with preeclampsia. There are only 2 double-blind, placebo-controlled trials evaluating the use of magnesium sulfate in mild preeclampsia. There were no instances of eclampsia among 181 women assigned to placebo, and there were no differences in the percentage of women who progressed to severe preeclampsia (12.5% in magnesium group vs 13.8% in the placebo group, relative risk [RR] 0.90; 95% CI 0.52-1.54). However, the number of women enrolled in these trials is too limited to draw any valid conclusions. There are 4 randomized controlled trials that compare the use of no magnesium sulfate, or a placebo vs magnesium sulfate, to prevent convulsions in patients with severe preeclampsia. The rate of eclampsia was 0.6% among 6343 patients assigned to magnesium sulfate vs 2.0 % among 6330 patients assigned to a placebo or control (RR 0.39; 95% CI 0.28-0.55). However, the reduction in the rate of eclampsia was not associated with a significant benefit in either maternal or perinatal outcome. In addition, there was a higher rate of maternal respiratory depression among those assigned magnesium sulfate (RR 2.06; 95% CI 1.33-3.18). The evidence to date confirms the efficacy of magnesium sulfate in reduction of seizures in women with eclampsia and severe preeclampsia; however, this benefit does not affect overall maternal and perinatal mortality and morbidities. The evidence regarding the benefit-to-risk ratio of magnesium sulfate prophylaxis in mild preeclampsia remains uncertain, and does not justify its routine use for that purpose.     

Magnesium sulfate in women with mild preeclampsia: a randomized controlled trial

OBJECTIVE: To determine whether magnesium sulfate prevents disease progression in women with mild preeclampsia. METHODS: A total of 222 women with mild preeclampsia were randomized to receive intravenous magnesium sulfate (n = 109) or matched placebo (n = 113). Mild preeclampsia was defined as blood pressure of at least 140/90 mm Hg taken on two occasions in the presence of new-onset proteinuria. Patients with chronic hypertension or severe preeclampsia were excluded. Patients were considered to have disease progression if they developed signs or symptoms of severe preeclampsia, eclampsia, or laboratory abnormalities of full or partial HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. RESULTS: The groups were similar with respect to maternal age, ethnicity, gestational age, parity, and maternal weight at enrollment. Fourteen women (12.8%) in the magnesium group and 19 (16.8%) in the placebo group developed severe preeclampsia after randomization (relative risk = 0.8, 95% confidence interval 0.4, 1.5, P =.41). None in either group developed eclampsia or thrombocytopenia. Women assigned magnesium had similar rates of cesarean delivery (30% versus 25%), chorioamnionitis (3% versus 2.7%), endometritis (5.3% versus 4.3%), and postpartum hemorrhage (1% versus 0.9%), compared to those assigned placebo. Neonates born to women assigned magnesium had similar mean Apgar scores at 1 and 5 minutes as those born to women assigned placebo (7.7 +/- 1.5 versus 7.8 +/- 1.6 and 8.7 +/- 0.7 versus 8.8 +/- 0.6, respectively). CONCLUSION: Magnesium sulfate does not have a major impact on disease progression in women with mild preeclampsia. Magnesium use does not seem to increase rates of cesarean delivery, infectious morbidity, obstetric hemorrhage, or neonatal depression.     

Acute pulmonary edema in pregnancy

OBJECTIVE: To describe the incidence, predisposing conditions, and inciting factors culminating in pulmonary edema in the pregnant patient. METHODS: A review of 62,917 consecutive pregnancies delivered at our institution from January 1, 1989 to June 1, 1999 was undertaken for the diagnosis of pulmonary edema. Each chart was reviewed for maternal demographics, admission diagnoses, medication use, gestational age at diagnosis, fluid balance, coexisting maternal illness, tocolytic use, evidence of preeclampsia, and diagnostic criteria. After careful review of the records, the most likely cause of pulmonary edema was assigned. RESULTS: Fifty-one women (0.08%) were diagnosed with acute pulmonary edema during pregnancy or in the postpartum period. The mean patient age at the time of diagnosis was 27.6 +/- 6.4 years. The mean gestational age at the time of diagnosis was 31.5 +/- 6.8 weeks. The diagnosis of pulmonary edema was made during the antepartum period in 24 patients (47%), the intrapartum period in seven (14%), and the postpartum period in 20 (39%). The most common attributable causes were tocolytic use (13 patients [25.5%]), cardiac disease (13 patients [25.5%]), fluid overload (11 patients [21.5%]), and preeclampsia (nine patients [18%]). Those with fluid overload identified as the likely etiology had a significantly greater mean positive fluid balance (6022 +/- 3340 mL). All patients whose pulmonary edema was secondary to tocolytic use received multiple simultaneous tocolytic agents; the most common combination was intravenous magnesium sulfate and subcutaneous terbutaline. Six of the 13 women with cardiac disease were found to have previously undiagnosed structural heart disease. CONCLUSION: The most common causes of pulmonary edema are the use of tocolytic agents, underlying cardiac disease, fluid overload, and preeclampsia.     

Calcitonin gene- and parathyroid hormone-related peptides in preeclampsia: effects of magnesium sulfate

OBJECTIVE: To determine whether circulating levels of calcitonin gene-related peptide (CGRP) and parathyroid hormone-related peptide (PTHrP) are altered in preeclampsia, and to assess the effects of magnesium sulfate therapy on circulating levels of these two peptides. METHODS: The study population included 25 women with preeclampsia and 25 normotensive controls of similar gestational age. The effects of magnesium sulfate therapy were evaluated in 17 of the 25 preeclamptic women. Circulating levels of immunoreactive CGRP and PTHrP, including calcium, magnesium, and phosphate in the maternal and umbilical cord serum were measured. RESULTS: The frequency of preeclampsia subjects with nondetectable PTHrP (under 3 pg/mL) was significantly higher (92% versus 48%, P <.001), whereas maternal serum CGRP levels were significantly lower (50 +/- 19 versus 90 +/- 23 pg/mL, P <.001). Similarly, the frequency of newborns with nondetectable PTHrP levels in umbilical serum was significantly higher (68% versus 36%, P <.05), whereas the levels of CGRP were significantly lower (67 +/- 17 versus 79 +/- 16 pg/mL, P <.05). Magnesium sulfate treatment resulted in a significant increase in maternal circulating CGRP levels (64 +/- 17 versus 47 +/- 18 pg/mL, P <.05) with no changes in PTHrP. CONCLUSION: Maternal circulating PTHrP and CGRP concentrations were significantly lower in women with preeclampsia, which may contribute to the development and maintenance of hypertension during pregnancy. Furthermore, magnesium sulfate therapy increased the levels of CGRP in the maternal circulation.     

Effect of preeclampsia, magnesium sulfate prophylaxis, and maternal weight on labor induction: a retrospective analysis

BACKGROUND: Our purposes were to determine the effect of preeclampsia, magnesium sulfate prophylaxis, and maternal weight on labor induction in women with preeclampsia and identify risk factors associated with its failure. METHODS: Fifty-five preeclamptic women and 176 non-preeclamptic women requiring labor induction over an 18-month period were studied retrospectively. Prostaglandin E(2) (dinoprostone) and oxytocin were used for labor induction. Women with rupture of the membranes, spontaneous contraction resulting in cervical change, or an initial cervical examination showing more than 2 cm dilatation and 50% effacement were excluded. Statistics were analyzed with chi(2) test, Fisher's exact test, Student t test, Mann-Whitney U test, and multiple logistic regression. RESULTS: The women with preeclampsia had a significantly higher rate of failed induction than did those without preeclampsia (p = 0.01). However, the women with preeclampsia had a higher mean maternal weight and an increased use of magnesium sulfate, and labor was induced at earlier gestational age than in those without preeclampsia (p < 0.05 for each). Multiple logistic regression showed that the use of magnesium sulfate, higher maternal weight, and unfavorable cervix, but not preeclampsia, were significantly associated with an increased risk of failed induction after correction for known confounding variables. CONCLUSIONS: Although the risk of failed induction is increased in preeclamptic women, preeclampsia is not an independent risk factor for failed induction. The use of magnesium sulfate, higher maternal weight, and unfavorable cervix are independent risk factors for failed induction.     

Magnesium sulfate and beta-mimetic dual-agent tocolysis in preterm labor after single-agent failure

Twenty-three patients in preterm labor failed to respond to single-agent tocolytic therapy or could not tolerate the dosage necessary to inhibit contractions. A combination of magnesium sulfate and ritodrine or terbutaline was used to inhibit labor in these patients. Fourteen patients (60.9%) responded to dual-agent tocolysis by delaying delivery for 48 hours or more. Six patients had delivery delayed for more than one week. Five patients had multiple gestations; three of them had delivery delayed more than 48 hours. Five patients developed pulmonary edema under treatment with dual-agent tocolysis; all responded to diuretic and/or oxygen therapy after the termination of tocolysis. Dual-agent tocolysis may significantly prolong some pregnancies complicated by preterm labor, but only at some risk to maternal well-being.     

The effect of magnesium sulfate on large cerebral artery blood flow in preeclampsia.

OBJECTIVES: To determine the effect of a 6 gram intravenous bolus of magnesium sulfate on maternal cerebral blood flow in women with preeclampsia. STUDY DESIGN: Velocity-encoded phase-contrast magnetic resonance imaging studies were performed on twelve preeclamptic women prior to and immediately after infusion of a 6 gram magnesium sulfate loading dose. Cerebral blood flow was determined at the bilateral proximal middle and posterior cerebral arteries. Study participants returned 6 weeks postpartum for a non-pregnant measurement of cerebral blood flow. The Wilcoxon paired-sample test was used with statistical significance defined as p<0.05. RESULTS: There was no significant difference in cerebral vessel diameter nor blood flow for any of the examined arteries between the pre- and post magnesium sulfate therapy states. CONCLUSIONS: The absence of a significant difference in cerebral blood flow of the middle and posterior cerebral arteries before and after infusion of a 6 gram loading dose of magnesium sulfate in women with preeclampsia could suggest the absence of vasoconstriction of the large cerebral arteries in preeclampsia and question the role of magnesium sulfate as a vasodilator of these arteries.     

Evaluation of maternal fluid dynamics during tocolytic therapy with ritodrine hydrochloride and magnesium sulfate.

OBJECTIVE: The purpose of the study was to observe and compare the effects of ritodrine hydrochloride and magnesium sulfate on maternal fluid dynamics. STUDY DESIGN: Fourteen women in preterm labor were prospectively studied during tocolytic therapy with either ritodrine hydrochloride or magnesium sulfate. The cardiovascular and renal effects of a pretreatment crystalloid infusion were compared with those observed during tocolytic therapy. Profile analysis and repeated measures of variance were used to analyze the data. RESULTS: Ritodrine hydrochloride was associated with decreased colloid osmotic pressure, hematocrit, and serum proteins and increased maternal and fetal heart rates. Arginine vasopressin levels increased during the first 2 hours of therapy, then returned to baseline. Sodium excretion was reduced and there was marked fluid retention. Intravenous magnesium sulfate also resulted in a reduction of colloid osmotic pressure, but hematocrit, serum protein concentration, arginine vasopressin, maternal and fetal heart rates, and mean arterial pressure were minimally affected. Sodium excretion increased to a maximum at 6 to 8 hours of treatment, then returned to baseline. A positive fluid balance was also noted in magnesium sulfate-treated patients but to a lesser degree than with ritodrine. CONCLUSIONS: Sodium retention appears to be the primary cause of plasma volume expansion in ritodrine-treated patients, whereas volume expansion during magnesium sulfate therapy is probably related to intravenous overhydration. In the absence of risk factors for pulmonary capillary membrane injury, available evidence supports volume overload as the principal mechanism for pulmonary edema during tocolytic therapy.     

Perinatal death and tocolytic magnesium sulfate

OBJECTIVE: To determine whether there is a significant association between perinatal mortality and exposure to total doses of tocolytic magnesium sulfate larger than 48 g. METHODS: We did a case-control study in which cases were defined as neonates or fetuses who died after being exposed to tocolytic magnesium sulfate and controls were those who survived exposure. The study included fetuses and neonates who weighed between 700 and 1249 g and whose mothers had received tocolytic magnesium sulfate at Chicago Lying-in Hospital between January 1, 1986, and March 31, 1999. We excluded women who received prophylactic magnesium sulfate for preeclampsia or preeclampsia superimposed on chronic hypertension, and fetuses or neonates with major congenital anomalies. Data were analyzed by Fisher exact test, chi(2) test, Student t test, Mann-Whitney U test, multivariable logistic regression, and Cochrane-Armitage trend test. RESULTS: Controlling for birth weight or gestational age, year of delivery, receipt of betamethasone, acute maternal disease, and maternal race in a multivariable model, we found that exposure to total doses of tocolytic magnesium sulfate exceeding 48 g was significantly associated with increased perinatal mortality (adjusted odds ratio 4. 7; 95% confidence interval 1.1, 20.0; P =.035). Using the Cochrane-Armitage trend test, we found that a significant dose response was present (P =.03), but one that was most consistent with a threshold effect. CONCLUSION: Our findings support the hypothesis that high doses of tocolytic magnesium sulfate are associated with increased perinatal mortality among fetuses and neonates weighing 700-1249 g.     

A comparison of intravenous and intramuscular magnesium sulfate regimens in preeclampsia

A prospective study comparing continuous intravenous magnesium sulfate to intramuscular magnesium sulfate was performed in 32 preeclamptic patients. Eighteen patients received the intramuscular regimen for mild and severe preeclampsia as recommended by Pritchard. The remaining 14 patients received an intravenous regimen consisting of a 4 gm loading dose administered over 15 minutes followed by a maintenance dose of either 1 gm/hr (n = 7) or 2 gm/hr (n = 7). All groups were similar regarding maternal age, height, weight, fetal gestational age, and laboratory findings. The intravenous regimen with a maintenance dose of 1 gm/hr produced serum magnesium levels that were much lower than those achieved with the intramuscular regimen. There was no significant difference after 3 hours of therapy between the mean magnesium levels achieved with the intramuscular regimen and the levels achieved with the intravenous regimen with a maintenance dose of 2 gm/hr. However, during the first 3 hours of therapy the intramuscular regimen for severe preeclampsia produced mean magnesium levels that were significantly higher than those levels obtained with the intravenous regimen with a maintenance dose of 2 gm/hr (p less than 0.001). Both methods were safe. However, the intravenous regimen with a maintenance dose of 1 gm/hr is inadequate in management of preeclamptic patients.     

A prospective randomized trial of magnesium sulfate in severe preeclampsia: use of diuresis as a clinical parameter to determine the duration of postpartum therapy

OBJECTIVE: The purpose of this study was to assess the use of the onset of diuresis in the determination of the duration of postpartum magnesium sulfate therapy among patients with severe preeclampsia. STUDY DESIGN: A prospective randomized trial of postpartum therapy with magnesium sulfate was conducted. The control group received 24 hours of therapy, and the study group received therapy until the onset of diuresis (urine output >100 mL/hr for 2 consecutive hours). The Student t test, chi 2 test, and Fisher's exact test were used for analysis of data; a probability value of <.05 was considered statistically significant. RESULTS: There were 50 patients in the control group and 48 patients in the study group. There was no difference in maternal demographic data, severe disease criteria, blood pressure, 24-hour postpartum urine output, or need for antihypertensive therapy. The study group had a significantly shorter duration of therapy, and no patient had eclampsia or required the re-initiation of therapy. CONCLUSION: The use of the onset of diuresis in the postpartum period as the determinant clinical parameter for the discontinuation of magnesium sulfate in patients with severe preeclampsia was associated with no untoward outcomes or need for the re-initiation of treatment.     

Magnesium sulfate effectively reduces blood pressure in an animal model of preeclampsia.

OBJECTIVE: We tested the ability of magnesium sulfate to reduce hypertension and neonatal growth retardation in an animal model of preeclampsia. STUDY DESIGN: On day 17 of pregnancy, osmotic minipumps were inserted subcutaneously to continuously deliver either vehicle (saline control group), or N-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg/day), or L-NAME (50 mg/kg/day) in combination with magnesium sulfate (60 mg/kg/day). Prior to insertion, blood pressure and heart rate were monitored with a pneumatic tail cuff device. Blood pressure measurements were repeated on days 18, 20, and 21 of pregnancy. Blood was obtained on days 17 and 21, along with urine, to assess magnesium levels and degree of proteinuria. Pups were weighed and measured at 48 hours postpartum. RESULTS: Rats receiving L-NAME developed hypertension within 24 hours of implantation (108 +/- 3.9 vs. 123 +/- 3.4 mmHg, p < 0.05). Magnesium sulfate, given along with L-NAME did not prevent mean blood pressure from increasing, but reduced it by day 21 compared to L-NAME given alone (107 +/- 3.4 vs. 122 +/- 8.7 mmHg, respectively, p < 0.05). Magnesium sulfate reduced neonatal growth retardation by improving the weight of the pups compared to pups from maternal rats given L-NAME alone (6.1 +/- 0.1 vs. 5.2 +/- 0.3 grams, respectively, p < 0.05). CONCLUSION: Maternal magnesium sulfate reduces blood pressure and increases neonatal size compared to L-NAME without magnesium. These findings support a beneficial effect of magnesium in preeclampsia.     

Pharmacokinetics of ionized versus total magnesium in subjects with preterm labor and preeclampsia

OBJECTIVE: Intravenous magnesium sulfate is widely used in obstetrics for the treatment of both preterm labor and preeclampsia. Although therapeutic levels of total magnesium have been proposed, the levels remain controversial. Because the active form of magnesium is the free or ionized form, it is essential to determine whether ionized magnesium and total magnesium levels are highly correlated in vivo. We sought to examine the correlation between ionized magnesium and total magnesium under basal and therapeutic conditions and to define the initiation and elimination pharmacokinetics of both forms during intravenous magnesium sulfate infusion. STUDY DESIGN: Twenty-four singleton pregnant patients who were candidates for magnesium sulfate were studied (preterm labor, 15; preeclampsia, 9). Serial blood samples were taken before the magnesium sulfate infusion, during the first 4 hours after the initiation of magnesium sulfate infusion and for 4 hours after the discontinuation of the infusion. RESULTS: Baseline levels of total magnesium and ionized magnesium were not different between patients with preterm labor and with preeclampsia. Among patients with preeclampsia, although not patients with preterm labor, the initial apparent volume of distribution was significantly smaller for total magnesium than for ionized magnesium (16,397 +/- 1441 vs 23,856 +/- 2745 mL, respectively; P =.03), and the elimination half-life was greater for total magnesium as compared to ionized magnesium (707 +/- 160 vs 313 +/- 29 minutes;P <.05). Linear regression analysis demonstrated a lack of correlation between ionized magnesium and total magnesium during the pretreatment period and during the steady state infusion for both preterm labor and preeclampsia. CONCLUSION: The measurement of total magnesium may not be adequate for the titration of therapeutic magnesium infusions in patients with preeclampsia or preterm labor because of the lack of correlation between total magnesium and the physiologically active ionized magnesium. Further studies may determine whether the measurement of ionized magnesium is a superior method for following the adequacy and safety of the treatment of preeclampsia and preterm labor.     

Postpartum seizure prophylaxis: using maternal clinical parameters to guide therapy

OBJECTIVE: To use individual patient clinical parameters to signal cessation of postpartum magnesium sulfate seizure prophylaxis for the spectrum of pregnancy-related hypertensive disorders. METHODS: This was a prospective study using clinical symptoms (absence of headache, visual changes, epigastric pain) and signs (sustained blood pressure less than 150/100 without need for acute antihypertensive therapy, spontaneous diuresis more than 100 mL per hour for no less than 2 hours) to signal cessation of intravenous magnesium sulfate postpartum in gravidas diagnosed with preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelets syndrome. Laboratory assessments (including proteinuria) were not used as criteria for drug discontinuation. RESULTS: Five hundred three patients were enrolled and classified according to American College of Obstetricians and Gynecologists criteria (mild preeclampsia, severe preeclampsia, chronic hypertension with superimposed preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelets syndrome). Maternal age, gestational age, and hours of magnesium therapy before delivery were not statistically different among groups. There was no significant difference in the duration of postpartum magnesium sulfate therapy among groups with the median duration of therapy 4 hours (range 2-77 hours). No eclamptic seizures occurred after magnesium discontinuation. Thirty-eight patients (7.6%) required reinstitution of magnesium therapy for 24 hours because of exacerbation of blood pressure (sustained blood pressure more than 160/110) associated with headache or visual changes. CONCLUSION: Clinical criteria, when compared with arbitrary protocols, can be used successfully to shorten the duration of postpartum magnesium sulfate administration for seizure prophylaxis in patients with pregnancy-related hypertensive disorders.     

The effect of magnesium sulfate treatment on blood biochemistry and bleeding time in patients with severe preeclampsia

Objective.?The objective of this study was to observe the effects of magnesium sulfate on various blood biochemical parameters and coagulation status of patients with preeclampsia.

Methods.?During a period of 4 years, 50 patients with severe or mild preeclampsia progressing to severe preeclampsia were included in the cross-sectional study. Prothrombine (PT), activated limited thromboplastin time (aPTT), magnesium level, biochemistry parameters, systolic, and diastolic blood pressure (BP) were measured. These parameters were remeasured in the second hour of magnesium sulfate treatment.

Results.?After magnesium sulfate therapy; creatinine levels are decreased (p?<?0.05), bleeding time is increased and serum magnesium levels are increased (p?<?0.01), systolic and diastolic BP values decreased significantly (p?<?0.01). PT, aPTT, platelet levels, and coagulation time did not change after treatment.

Conclusion.?Magnesium sulfate infusion prolonged bleeding time in patients with severe preeclampsia. This is clinically important because it worsens the present condition and causes possible complications.     

Magnesium for seizure prophylaxis in patients with mild preeclampsia

OBJECTIVE: To estimate whether magnesium therapy is the optimal management for women with mild preeclampsia. METHODS: A decision analytic model was designed for women with mild preeclampsia to estimate whether empiric magnesium therapy or no magnesium therapy is the optimal management strategy. The model considered relevant clinical events: seizure, placental abruption, and magnesium toxicity. Modeled outcomes were maternal mortality, neonatal mortality, and neurologic neonatal compromise. The two strategies were compared based on the probability of clinical events and outcomes and the utilities or values assigned to the outcomes by prior research. Probabilities and utilities were derived from the literature. RESULTS: The base-case analysis showed that although the no-magnesium strategy results in a 15% reduction in neonatal mortality and avoids most maternal drug toxicity, it produces a twofold increase in maternal death and more neurologically compromised neonates compared with empiric magnesium. The two strategies are essentially equivalent with regard to aggregate maternal and neonatal outcomes (0.9792 compared with 0.9781 utilities). Multivariable sensitivity analysis using Monte Carlo simulation confirmed the decision to be a "toss-up," yielding a similar mean utility for no-magnesium and magnesium strategies (0.9789+/-0.1374 compared with 0.9784+/-0.1390, respectively). CONCLUSION: Our decision model indicates that either strategy, using or not using empiric magnesium sulfate therapy, is acceptable. The clinical decision of whether to use magnesium in patients with mild preeclampsia for seizure prophylaxis should be determined by the physician or institution, considering patient values or preferences and the unique risk-benefit trade-off of each strategy.