Individually determined postpartum magnesium sulfate therapy

with clinical parameters to safely and cost-effectively shorten

treatment for pre-eclampsia
Marian H. Ascarelli, MD, Vanessia Johnson, RN, Warren L. May, PhD, Rick W. Martin, MD, and
James N. Martin, Jr, MD
Jackson, Mississippi

OBJECTIVE: The purpose of this study was to investigate the safety of treating pre-eclampsia with magne-
sium sulfate, with clinical determinants used for drug discontinuation.
STUDY DESIGN: One hundred sixty-eight patients were enrolled. After delivery, women with mild pre-
eclampsia received a minimum of 6 hours of intravenous magnesium sulfate, whereas women with severe
pre-eclampsia received a minimum of 12 hours. Magnesium sulfate was discontinued in the absence of clini-
cal symptoms associated with spontaneous diuresis, minimal protein by urinary dipstick, and satisfaction of
predetermined blood pressure criteria.
RESULTS: Patients with mild pre-eclampsia required significantly less magnesium sulfate (mean 9.5 4.2
hours) than did those with severe pre-eclampsia alone (mean 16 5.9 hours); pre-eclampsia superimposed
on chronic hypertension (mean 16 5.8 hours); or hemolysis, elevated liver enzyme, and low platelet count
syndrome (mean 20 6.7 hours). With this protocol there was no eclampsia, and recovery room time was re-
duced by 50%.
CONCLUSION: Individual determination of postpartum magnesium sulfate therapy for pre-eclampsia ap-
pears to be a safe approach that carries minimal risk of eclampsia. (Am J Obstet Gynecol 1998;179:952-6.)

Key words: Hemolysis, elevated liver enzymes, and low platelet count syndrome; magnesium
sulfate; pre-eclampsia

Hypertensive diseasewhich includes chronic hyper-
tension; pregnancy-induced hypertension (either as ges-
tational hypertension, pre-eclampsia, or eclampsia); he-
molysis, elevated liver enzymes, and low platelet count
(HELLP) syndrome; and chronic hypertension with su-
perimposed pre-eclampsiacomplicates between 5%
and 10% of all pregnancies.1 Standard treatment of pre-
eclampsia in the United States includes antiseizure pro-
phylaxis with parenteral magnesium sulfate during partu-
rition and continuation of the drug variably into the
puerperium until the signs and symptoms of disease have
abated and the risk of eclampsia is minimal. In some hos-
pitals this period of treatment is extended as long as 48
hours. A shortened period of magnesium sulfate infusion
during the postpartum period could be equally effica-
cious in prevention of eclampsia.
From the Department of Obstetrics and Gynecology, University of
Mississippi Medical Center.
Supported in part by the Vicksburg Hospital Medical Foundation.
Presented at the Eighteenth Annual Meeting of the Society of Perinatal
Obstetricians, Miami, Florida, February 2-7, 1998.
Reprint requests: Marian Ascarelli, MD, c/o Obstetrics and Gynecology
Publication Office, Department of Obstetrics and Gynecology, University
of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-
4505.
Copyright 1998 by Mosby, Inc.
0002-9378/98 $5.00 + 0 6/6/92027
The purpose of this study was to investigate the effi-
cacy of treating pre-eclampsia during the postpartum pe-
riod with clinical parameters as determinants for discon-
tinuation of the drug, rather than universally treating
patients for a fixed period. The goal was to implement
cost-effective treatment and simultaneously decrease the
maternal morbidity associated with pre-eclampsia, with-
out increasing the risk of eclampsia.
Material and methods
All patients delivered of an infant at >20 weeks gesta-
tion with diagnoses of pregnancy-related hypertensive
disease were eligible for inclusion into the study. Patients
with mild pre-eclampsia had blood pressure elevations to
140 mm Hg systolic, 90 mm Hg diastolic, or both but
elevation to <160/105 mm Hg during labor without the
use of antihypertensive medication; urinary protein >100
mg/dL on dipstick evaluation of a catheterized speci-
men or <5 g urinary protein in a recent 24-hour collec-
tion; absence of visual changes or epigastric or right
upper quadrant pain; absence of fetal growth restriction;
and laboratory data with platelets of >150,000 cells/L,
lactic dehydrogenase <400 IU/L, and normal values for
aspartate aminotransferase.
Patients classified as having severe pre-eclampsia in-
cluded those with sustained systolic blood pressures 160

952
Volume 179, Number 4
Am J Obstet Gynecol
Table I. Demographic summary of patients enrolled in study period
Demographics Mild (n = 103) Severe (n = 44)
Age (y) 22 5.4 22 4.7
Weight (lb) 212 47.8 185 45.8
Primigravid (%) 58 56
Black (%) 71 73
Delivery GA (wk) 39 1.9 33 4.5
Patients with HELLP syndrome or chronic hypertension with superimposed pre-eclampsia were older and of higher gravidity, whereas
patients with mild pre-eclampsia were of significantly greater weight and achieved a significantly longer gestational age than did patients
in other 3 groups. CHTN, Chronic hypertension; GA, gestational age.
mm Hg, diastolic values 105 mm Hg, or the need for an-
tihypertensive medication for blood pressure control
during labor; oliguria (urine output <30 mL/h for 2 con-
secutive hours) unresponsive to 500 mL fluid challenge;
persistent headache, visual disturbance, epigastric or
right upper quadrant pain; pulmonary edema, evidence
of fetal growth restriction; or laboratory values reflecting
1 of the following: thrombocytopenia <150,000/L, lac-
tic dehydrogenase >400 IU/L, or aspartate aminotrans-
ferase elevation (>30 IU/L). Patients with hemolysis, ele-
vated liver enzymes, and low platelet count syndrome
included parturients with evidence of hemolysis, liver
dysfunction, and thrombocytopenia as defined, regard-
less of blood pressure values or urinary protein status.
Patients who were designated as having chronic hyper-
tension with superimposed pre-eclampsia included those
with diagnoses of underlying chronic hypertension be-
fore the current pregnancy and significant blood pres-
sure elevations above their established baseline (>30 mm
Hg systolic or >15 mm Hg diastolic) in association with
proteinuria, laboratory values reflecting the aforemen-
tioned aberrations, or clinical symptoms.
Classification of pre-eclampsia severity was made at
time of transfer from delivery suite to the postpartum re-
covery area. Patients with mild pre-eclampsia were desig-
nated to receive 6 hours of intravenous magnesium sul-
fate therapy at a rate of 2 g/h after a loading dose of 4 g
that was given over 20 minutes, whereas those with more
severe forms of the disease (severe pre-eclampsia,
chronic hypertension with superimposed pre-eclampsia,
and hemolysis, elevated liver enzymes, and low platelet
count syndrome) received 12 hours of parenteral mag-
nesium sulfate at the same rate of intravenous infusion
after the loading dose was administered.
Once minimum therapy had been delivered, 4 clinical
and laboratory parameters were used to determine
whether intravenous magnesium sulfate could be discon-
tinued: (1) preceding 6 hours characterized by absence of
persistent headache, visual change, or epigastric pain; (2)
>50% of hourly postpartum systolic blood pressures 150
mm Hg and diastolic values 100 mm Hg, with no single
systolic pressure 160 mm Hg or single diastolic pressure
105 mm Hg; (3) presence of a spontaneous diuresis of
Ascarelli et al 953
CHTN/pre-eclampsia Statistical
HELLP (n = 11) (n = 10) significance
29 6.6 31 7.8 P < .001
190 45.8 190 60.3 P < .020
18 10 P < .001
82 100 NS
31 5.0 34 3.6 P < .001
100 mL/h for 2 consecutive hours without a fluid chal-
lenge or furosemide stimulation; and (4) <100 mg/dL
urinary protein on dipstick evaluation of a catheterized
urine specimen. All criteria had to be met to permit dis-
continuation of magnesium sulfate therapy. After cessa-
tion of intravenous magnesium sulfate therapy, patients
were observed thereafter for an additional 2 hours in the
recovery room before transfer to the postpartum ward,
where vital signs and clinical symptoms were assessed
every 4 hours, and ad lib activity was prescribed until the
patient was discharged to home. The maximum duration
of postpartum magnesium sulfate infusion was arbitrarily
set at 48 hours. Laboratory data from periodic hemato-
logic tests were not used as a determinant for discontinu-
ation of magnesium sulfate therapy.
Inpatient hospitalization charges and recovery room
costs were obtained from the hospital billing department
and administration. Statistical analysis was performed
with analysis of variance and alternate methods
(Bonferroni, Kruskal-Wallis method) as appropriate. A P
value <.05 was considered significant.
Results
A total of 175 eligible patients were recruited for the
study; however, 7 patients refused to participate. A total
of 168 patients were enrolled in the study, 103 of whom
(61%) had mild pre-eclampsia. The demographic vari-
ables of the 4 categories of hypertensive patients are de-
picted in Table I. Note that patients with hemolysis, ele-
vated liver enzymes, and low platelet count syndrome or
with chronic hypertension with superimposed pre-
eclampsia were approximately 7 years older on average
and of higher gravidity than patients in the other 2
groups, whereas patients with mild and severe pre-
eclampsia were more likely to be primigravid. Patients
with mild pre-eclampsia had significantly greater weight
at admission (22-27 lb heavier than the 3 more severe
groups, with a mean weight of 212 47 lb), which may be
attributable to their having achieved a significantly more
advanced gestational age of 39 1.9 weeks, compared
with a mean gestational age between 31 and 34 weeks for
the 3 other groups with more severe forms of disease.
As expected, patients with mild pre-eclampsia received
954 Ascarelli et al October 1998
Am J Obstet Gynecol

Fig 1. As expected, those with mild pre-eclampsia required significantly less magnesium sulfate (9.5 h 4.2 h) than did
other groups (severe pre-eclampsia alone or superimposed on chronic hypertension [CHTN], 16.0 h 5.9 h; HELLP
syndrome, 20 h 6.8 h; P < .05). There was no statistically significant difference among 3 severe groups. Although 3 pa-
tients (7%) with severe pre-eclampsia required reinitiation of magnesium sulfate because of blood pressure elevation
or symptoms, no postpartum elampsia developed.

Fig 2. Compared with former protocol in which all pre-eclamptic patients received minimum of 24 hours of intra-
venous magnesium sulfate post partum, current protocol saved at least 1985 hours (50% reduction) of recovery room
time and associated cost.

postpartum magnesium sulfate therapy for a significantly
shorter period (9.5 4.2 hours) compared with the more
severe groups (16 5.9 hours for severe pre-eclampsia
and chronic hypertension with superimposed pre-
eclampsia and 20 6.7 hours for patients with hemolysis,
elevated liver enzymes, and low platelet count syn-
drome), thereby shortening the overall recovery room
time (Fig 1). Among the 3 patient groups with more se-
vere forms of the disease there were no statistically signif-
icant differences in the amount of time required for clin-
ical parameters to be achieved before magnesium sulfate
could be discontinued. Regarding mode of delivery,
there was a slightly higher occurrence of cesarean deliv-
ery among patients with hemolysis, elevated liver en-
zymes, and low platelet count syndrome, but this differ-
ence was not significant (mild pre-eclampsia, n = 14/103,
14%; severe pre-eclampsia, n = 14/44, 32%; hemolysis, el-
evated liver enzymes, and low platelet count syndrome, n
= 6/11, 56%; and chronic hypertension with superim-
posed pre-eclampsia, n = 2/10, 20%; P = .053).
Further analysis of the 4 patient groups reveals no sta-
tistically significant differences among the 3 more severe
groups with respect to the number of patients that re-
quired antihypertensive medication to control blood
pressure during labor (severe pre-eclampsia, n = 17/44,
39%; hemolysis, elevated liver enzymes, and low platelet
count syndrome, n = 6/11, 45%; and chronic hyperten-
sion with superimposed pre-eclampsia, n = 3/10, 30%; P
> .05). There were, however, significant differences in the
number of patients who required oral antihypertensive
medications at the time of discharge from the hospital:
3% of patients with mild pre-eclampsia, 18% of patients
Volume 179, Number 4
Am J Obstet Gynecol
with severe pre-eclampsia, and 27% of patients with he-
molysis, elevated liver enzymes, and low platelet count
syndrome (P < .001). Patients with chronic hypertension
were most likely to receive these medications (80%).
There were 3 patients for whom magnesium sulfate was
reinitiated after discharge from the recovery area to the
postpartum ward. These patients all demonstrated ele-
vated blood pressures and clinical symptoms such as per-
sistent headache and visual changes. They each had a pre-
vious diagnosis of severe pre-eclampsia at delivery. Two of
the patients initially had met clinical criteria for discon-
tinuation of magnesium sulfate therapy after 12 hours,
and the third patient had received 24 hours of intra-
venous magnesium sulfate before its discontinuation. All
3 patients received an additional 24 hours of intravenous
magnesium sulfate therapy, with immediate amelioration
of signs and symptoms, and there was no eclampsia.
Compared with the previous hospital protocol of 24
hours of postpartum magnesium sulfate infusion for all
patients with pregnancy-related hypertensive disorders,
our protocol reduced the number of postpartum recov-
ery hours by nearly 50% (Fig 2). In our study the total
cost saving from reduced recovery room time was ap-
proximately $120,000, with the greatest reduction
achieved among patients with mild pre-eclampsia.
Comment
Hypertensive disorders of pregnancy are second only
to thromboembolic disease as a cause of pregnancy-re-
lated maternal death.1 The most common manifestation
is mild pre-eclampsia, which constitutes 70% of preg-
nancy-related hypertensive disorders. A goal of treatment
for all patients with pre-eclampsia, whether mild or se-
vere, is to prevent eclamptic seizures because these can
be associated with significant morbidity and mortality.
Seizure activity is presumably a consequence of focal
cerebral ischemia caused by the underlying vasospastic
pathophysiology of pre-eclampsia.2 As many as a fourth
of eclamptic seizures occur during the postpartum pe-
riod, with the greatest risk observed to be within the first
12 to 24 hours after delivery.3 Thus intravenous or intra-
muscular magnesium sulfate is typically employed post
partum for a variable period as a standard practice for pa-
tients with pre-eclampsia. A standard regimen for the
treatment of all patients with pre-eclampsia for a prede-
termined period may not be required, because disease
expression has a broad clinical and laboratory spectrum.
More selective and individual cost-effective treatment
may be preferable and efficacious.
Certainly any protocol for seizure prevention among
parturients with pre-eclampsia, including the current
protocol, will not prevent all seizure activity. The inci-
dence of eclampsia among women with pre-eclampsia
who do not receive magnesium sulfate is 1.2%, versus
0.3% among women with pre-eclampsia who receive pro-
Ascarelli et al 955
phylactic magnesium sulfate therapy.4 Among treated pa-
tients who have eclampsia, half may have subtherapeutic
magnesium levels.5 Nonetheless, eclamptic seizures can
occur in the presence of therapeutic concentrations of
magnesium sulfate. Moreover, delayed eclamptic seizures
have been reported to occur as late as 3 weeks post par-
tum.6 Two authors noted that delayed postpartum
eclamptic seizures, occurring >48 hours after delivery, ac-
counted for 16% and 28% of all recorded episodes of
eclampsia observed in the 2 institutions under investiga-
tion.3, 6, 7 Of note is that severe headaches or visual dis-
turbances usually precede such convulsive activity.3
Delivery of the fetoplacental unit is the only definitive
treatment for pre-eclampsia. Postpartum reversal of the
aberrant pathophysiology inherent in pre-eclampsia usu-
ally begins within the first 24 to 48 hours post partum.
Patients with persistence or exacerbation of the signs and
symptoms of pre-eclampsia during the postpartum pe-
riod are at risk for development of renal failure, hepatic
infarction, hypertensive encephalopathy, eclampsia, and
other neurologic complications.8
The goal of our study was to use a panel of several eas-
ily assessed clinical parameters to signal cessation of pro-
phylactic magnesium sulfate treatment at the earliest
possible time, presumably coincident with declining va-
sospasm, hypoperfusion, and risk for eclampsia. Before
discontinuation of magnesium sulfate, both subjective
resolution of symptoms and objective evidence of the re-
versal of the preeclamptic pathophysiology were re-
quired, as noted by improvement in blood pressure,
reperfusion of the kidneys with a spontaneous diuresis,
and a minimum amount of urinary protein.
We elected to exclude the subjective assessment of
patellar reflexes as a clinical parameter because many
parturients without evidence of pre-eclampsia demon-
strate hyperreflexia or even clonus. Because patients
conditions were required to fulfill all 4 selected clinical
parameters before discontinuation of magnesium sul-
fate, we are unable to categorize the individual parame-
ters to conclude which of these criteria might be the
most important hallmark that signals reversal of the
preeclamptic process.
Most patients enrolled in our study had diagnoses of
mild disease (n = 103), as would be true in any patient
population because mild pre-eclampsia is far more preva-
lent than its severe counterparts. No patients in the mild
preeclamptic group required reinitiation of magnesium
sulfate therapy for recurrent blood pressure elevation or
deterioration in clinical symptoms. The time required
for parenteral magnesium sulfate with our protocol com-
pared with conventional therapy in this group of patients
alone was decreased by 60%. Our recovery room charge
is $60/h, and the cost saving in the group with mild pre-
eclampsia, which comprised most of the total cost saving
($120,000) for all 4 groups, was $90,540 ($840/patient).
956 Ascarelli et al
The cost reduction for patients with severe pre-eclampsia
was $480/patient. For patients with chronic hypertension
with superimposed pre-eclampsia and those with hemoly-
sis, elevated liver enzymes, and low platelet count syn-
drome, the cost saving was $240/patient. In many other
American hospitals the hourly cost of postpartum recov-
ery room care is much higher, and the financial saving
from such a protocol would thus be much more signifi-
cant. A further savings might have accrued had the pro-
tocol permitted cessation of magnesium sulfate on the
basis of purely clinical criteria and without a mandatory
infusion period of 6 hours.
There were no differences in the amounts of time re-
quired for clinical parameters to be satisfied among pa-
tients enrolled in the 3 more severe groups. A mean infu-
sion time of only 4 to 8 hours was saved by our protocol
compared with a standard regimen (24 hours) of post-
partum magnesium sulfate therapy. Although 3 patients
did require reinitiation of parenteral magnesium sulfate
therapy after they had been discharged to the postpar-
tum ward, eclamptic seizures developed in none of these
3 patients.
The treatment of most clinical disorders is moderated
by the patients response to the therapeutic modality
being used. Our study demonstrates that, if effectively
monitored, clinical parameters can be used to individu-
ally tailor postpartum magnesium sulfate therapy for pa-
tients with pregnancy-related hypertensive disease with-
out jeopardizing maternal welfare. Early patient
ambulation may favor a decrease in such postpartum and
particularly postoperative complications as pneumonia,
October 1998
Am J Obstet Gynecol
thromboembolic disease, and urinary tract infection. It
also facilitates earlier discharge of patients, to promote
cost-effective health care. Because eclampsia is such a
rare event, we are unable to conclude from this study
whether our regimen is as efficacious as standard therapy
for the prevention of eclamptic seizures. Although larger,
randomized trials in multiple centers are needed before
a definitive recommendation can be made, the findings
of this pilot study support the concept of individually de-
termined postpartum magnesium sulfate treatment for
the shortest possible time.
REFERENCES
1. American College of Obstetrics and Gynecology. Hypertension
in pregnancy. Washington: The College; 1996. p. 1-8. Technical
Bulletin No.: 219.
2. Morris MC, Twickler DM, Hatab MR, Clarke GD, Peshock RM,
Cunningham FG. Cerebral blood flow and cranial magnetic res-
onance imaging in eclampsia and severe preeclampsia. Obstet
Gynecol 1997;89:561-8.
3. Miles JF, Martin JN Jr, Blake PG, Perry KG Jr, Martin RW, Meeks
GR. Postpartum eclampsia: a recurring perinatal dilemma.
Obstet Gynecol 1990;76:328-31.
4. Usta IM, Sibai BM. Emergent management of perpetual eclamp-
sia. Obstet Gynecol Clin North Am 1995;22:2:315-35.
5. Sibai BM, Abdella TN, Spinnato JA. Eclampsia, V: the incidence
on nonpreventable eclampsia. Am J Obstet Gynecol
1986;154:561-6.
6. Lubarsky SL, Barton JR, Friedman SA, Nasredine S, Ramadan
MK, Sibai BM. Late postpartum eclampsia revisited. Obstet
Gynecol 1994;83:502-5.
7. Brown CE, Cunningham FG, Pritchard JA. Convulsions in hy-
pertensive, proteinuric primiparas more than 24 hours after de-
livery: eclampsia or some other cause? J Reprod Med
1987;32:499-503.
8. Magann EF, Martin JN Jr. Complicated postpartum preeclampsia-
eclampsia. Obstet Gynecol Clin North Am 1995;22:337-55.