HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Isler, C. M. Articles by Martin, J. N. Search for Related Content PubMed PubMed Citation Articles by Isler, C. M. Articles by Martin, J. N., Jr

Postpartum Seizure Prophylaxis: Using Maternal Clinical Parameters to Guide Therapy

From the Department of Obstetrics and Gynecology, East Carolina University Brody School of Medicine, Greenville, North Carolina; and Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi.

Address reprint requests to: Christy M. Isler, MD, East Carolina University Brody School of Medicine, Department of Obstetrics and Gynecology, PCMH TA Room 150, Greenville, NC 27858-4354; E-mail: islerc{at}mail.ecu.edu.

	ABSTRACT

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
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.

Hypertensive disease complicates 5–8% of pregnancies in the United States and ranks second only to thromboembolic disease as the leading cause of maternal mortality.¹ The goal of treatment in preeclampsia is to prevent eclamptic seizures and their resultant morbidity whereas, in eclamptic patients, the goal is to prevent recurrent seizures. Magnesium sulfate has been shown to be the optimal anticonvulsant for this indication.^2,3 Traditionally, seizure prophylaxis has been administered intrapartum and continued postpartum for an arbitrary time, usually 12–24 hours. Some investigators have used individual patient parameters to determine the duration of postpartum seizure prophylaxis,⁴ whereas other investigators have questioned whether prophylaxis is needed at all in patients with mild disease.¹ Ascarelli et al⁴ used a combination of patient signs (blood pressure, urinary output), symptoms (headache, visual changes), and laboratory assessments (proteinuria determination by dip-stick analysis) to guide postpartum magnesium sulfate duration. Because of the regulations implemented by the Clinical Laboratory Improvement Amendment, many nursing units no longer perform dipstick urine analysis.

The purpose of this study was to determine if the duration of postpartum magnesium sulfate seizure prophylaxis is administered in patients with the spectrum of hypertensive disorders of pregnancy (including mild preeclampsia, severe preeclampsia, chronic hypertension with superimposed preeclampsia, hemolysis, elevated liver enzymes, low platelets [HELLP] syndrome, and eclampsia) could be guided by clinical parameters alone, without the use of laboratory parameters.

	MATERIALS AND METHODS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
This prospective clinical study was conducted at the University of Mississippi Medical Center between July 1998 and August 2000. The protocol was approved by the Institutional Review Board, and informed consent was obtained from all patients. All gravidas with the diagnosis of preeclampsia or eclampsia at the time of delivery were invited to participate. Patients were classified according to the American College of Obstetricians and Gynecologists criteria¹ into one of five categories (based on status at the time of delivery): mild preeclampsia, severe preeclampsia, chronic hypertension with superimposed preeclampsia, eclampsia, or HELLP syndrome. Patients diagnosed with HELLP syndrome demonstrated the characteristic triad of laboratory abnormalities (lactate dehydrogenase greater than or equal to 600 U/L, aspartate aminotransferase greater than or equal to 70 U/L, and platelet count less than or equal to 100,000/µL). Patients with a history of seizure disorder were excluded from this investigation.

All patients received intravenous magnesium sulfate seizure prophylaxis during the intrapartum period consisting of a 4-g loading dose and a 2-g per hour maintenance dose. After delivery, a 2-g per hour maintenance dose was continued until the patient fulfilled clinical criteria for discontinuation of seizure prophylaxis. These criteria included: absence of persistent headache, visual changes, and epigastric pain; greater than 50% of the hourly postpartum blood pressures less than 150 mm Hg systolic and less than 100 mm Hg diastolic (including the hour immediately before medication discontinuation); no indication for acute antihypertensive therapy within the preceding 2 hours (systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 110 mm Hg); and spontaneous diuresis of more than 100 mL per hour for 2 hours or more consecutively. By these predetermined criteria, all patients received a minimum of 2 hours of postpartum magnesium sulfate prophylaxis. Laboratory assessments (including dipstick proteinuria) were not used as criteria for medication discontinuation. Intravenous fluids were administered at a total rate of 125 mL per hour. Vital signs and urinary output were assessed hourly during the intrapartum and postpartum periods until the patient was discharged from the labor/delivery/recovery unit. Oral antihypertensive medications (except in patients with chronic hypertension on long-term therapy) and diuretic agents were not routinely initiated immediately postpartum. Patients with HELLP syndrome received high-dose corticosteroid therapy with intravenous dexa-methasone sodium phosphate 10 mg every 12 hours until disease resolution was evidenced by rising platelet count and decreasing serum transaminase levels. Patients were transferred to the postpartum ward after 2 hours of further observation in the labor/delivery/recovery unit. Vital signs were assessed every 4 hours until the time of hospital discharge. If the systolic blood pressure was greater than or equal to 160 mm Hg or the diastolic blood pressure was greater than or equal to 110 mm Hg, the hourly evaluation of vital signs was reinstituted until the previously stated criteria were achieved for 4 consecutive hours. Magnesium sulfate seizure prophylaxis was reinstituted in patients with a sustained blood pressure greater than 160 mm Hg systolic and 110 mm Hg diastolic for at least 2 hours associated with a headache or visual changes. This therapy was administered by convention for a 24-hour course.

Statistical analysis was performed with analysis of variance (plus Tukey test), Kruskal-Wallis, and ² techniques as appropriate for the data. A P value of <.05 was considered significant. Before initiation of this study, it was hypothesized (from the institution’s patient population) that one-half of the patients enrolled would have mild preeclampsia and the remaining patients would be equally divided between the severe preeclampsia, chronic hypertension with superimposed preeclampsia, and HELLP syndrome groups. The number of eclamptic patients was anticipated to be minimal and not used in the sample size analysis. To detect a mean difference of 4 hours of magnesium therapy assuming an of 0.05 and a power of 0.80, each group would require 74 patients. Using the hypothesized patient population, 444 patients would be required for enrollment, not including the patients with eclampsia. To insure adequate enrollment, this number was arbitrarily rounded to 500.

	RESULTS

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Five hundred three patients were enrolled in this investigation over a period of 25 months. Demographic data for the five patient classifications are shown in Table 1. The results derived from the intrapartum and postpartum course of study participants are depicted in Table 2. The duration of postpartum magnesium sulfate administration and route of delivery were similar between all groups. Although not reaching statistical significance, the HELLP syndrome patients took a longer time to achieve spontaneous diuresis postpartum, and subsequently required a longer postpartum course of magnesium sulfate prophylaxis. Patients with chronic hypertension with superimposed preeclampsia required reinstitution of magnesium sulfate seizure prophylaxis for disease exacerbation more often than the patients without underlying chronic hypertension (P = .02) (Table 2). No patient in this investigation had a postpartum eclamptic seizure.

	DISCUSSION

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

Current theories regarding the pathogenesis of preeclampsia postulate the disorder commences with abnormal placental implantation. However, the clinical manifestations of the disease result from widespread vasoconstriction. Eclampsia is believed to be caused by ischemia from cerebral under-perfusion resulting from this vasoconstriction, although some cases of eclampsia may be caused by hypertensive encephalopathy from cerebral over-perfusion.⁷ We propose that the onset of diuresis signals a reversal of the vasoconstriction found in this disorder, thereby decreasing the risk of eclampsia from cerebral under-perfusion. Likewise, the strict blood pressure criteria in this protocol decrease the risk of eclampsia resulting from over-perfusion caused by hypertensive encephalopathy.

The current study raises several points for further investigation. It is unclear which subpopulations of hypertensive gravidas might be at increased risk of disease exacerbation after a shortened postpartum magnesium therapy. Certainly, patients with chronic hypertension and superimposed preeclampsia were at a greater risk of disease exacerbation requiring reinstitution of magnesium sulfate therapy. It is also unclear why patients with more severe forms of disease (severe preeclampsia, HELLP syndrome) did not require longer magnesium courses than patients with milder disease (mild preeclampsia). These questions, along with other investigators’ concerns regarding the need for seizure prophylaxis at all in patients with mild preeclampsia, lead us to favor a large, multicenter trial to investigate the optimal patient population and duration of postpartum magnesium sulfate for seizure prophylaxis in hypertensive diseases of pregnancy.

	Footnotes

 
This study was supported in part by the Vicksburg Hospital Medical Foundation, Vicksburg, Mississippi.

Presented at the 2001 Annual Clinical Meeting of the American College of Obstetricians and Gynecologists, Chicago, Illinois, May 2001.

PII S0029-7844(02)02317-7

Received April 11, 2002. Received in revised form June 17, 2002. Accepted August 1, 2002.

	REFERENCES

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
1. American College of Obstetrics and Gynecology. Diagnosis and management of preeclampsia and eclampsia. ACOG practice bulletin no. 33. Washington: American College of Obstetricians and Gynecologists, 2002:159–167.

2. The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995;345:1455–63.[Medline]

3. Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995;333:201–5.[Abstract/Free Full Text]

4. Ascarelli MH, Johnson V, May WL, Martin RW, Martin JN Jr. Individually determined postpartum magnesium sulfate therapy with clinical parameters to safely and cost-effectively shorten treatment for preeclampsia. Am J Obstet Gynecol 1998;179:952–6.[Medline]

5. Coetzee EJ, Dommisse J, Anthony J. A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe preeclampsia. Br J Obstet Gynaecol 1998;105:300–3.[Medline]

6. Witlin AG. Prevention and treatment of eclamptic convulsions. Clin Obstet Gynecol 1999;42:507–18.[Medline]

7. Belfort MA, Anthony J, Saade BR. Prevention of eclampsia. Sem Perinatol 1999:23;65–78.

This article has been cited by other articles:

				H. M. Ehrenberg and B. M. Mercer Abbreviated postpartum magnesium sulfate therapy for women with mild preeclampsia: a randomized controlled trial. Obstet. Gynecol., October 1, 2006; 108(4): 833 - 838. [Abstract] [Full Text] [PDF]

				W. W. Hurd, G. Ventolini, A. Stolfi, M. D. Fejgin, S. B. Goldberger, and C. M. Isler Postpartum Seizure Prophylaxis: Using Maternal Clinical Parameters to Guide Therapy Obstet. Gynecol., July 1, 2003; 102(1): 196 - 198. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Isler, C. M. Articles by Martin, J. N. Search for Related Content PubMed PubMed Citation Articles by Isler, C. M. Articles by Martin, J. N., Jr