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Prevention and treatment of postpartum hypertension

  1. Laura Magee1,*,
  2. Peter von Dadelszen2

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 30 APR 2013

Assessed as up-to-date: 12 FEB 2013

DOI: 10.1002/14651858.CD004351.pub3


How to Cite

Magee L, von Dadelszen P. Prevention and treatment of postpartum hypertension. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD004351. DOI: 10.1002/14651858.CD004351.pub3.

Author Information

  1. 1

    British Columbia Women's Hospital and Health Centre, Departments of Internal Medicine (UBC) and Specialized Women's Health (BC Women's Hospital), Vancouver, British Columbia, Canada

  2. 2

    University of British Columbia, Department of Obstetrics and Gynaecology, Vancouver, BC, Canada

*Laura Magee, Departments of Internal Medicine (UBC) and Specialized Women's Health (BC Women's Hospital), British Columbia Women's Hospital and Health Centre, 4500 Oak Street, Suite 1U59, Vancouver, British Columbia, V6H 3N1, Canada. lmagee@cw.bc.ca.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 30 APR 2013

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Characteristics of included studies [ordered by study ID]
Ascarelli 2005

MethodsSequentially numbered sealed opaque envelopes.
Randomisation method not stated.


Participants264 postpartum women.
Delivered > or equal to 20 weeks.
All with the diagnosis of mild or severe pre-eclampsia, or HELLP syndrome, or chronic hypertension with superimposed pre-eclampsia.
Excluded women with hypokalaemia, haemodynamic instability, those on diuretics or potassium supplements, and those who did not understand the consent form.


InterventionsFurosemide 20 mg po OD x 5 days plus potassium supplements (K-Dur 20 meq/day in 132 women).
No therapy in 132 women.
IV MgS04 discontinued before onset of trial in both groups, and all women experienced onset of spontaneous diuresis prior to enrolment.
Treatment goal: sBP < 150 and/or dBP < 100.


OutcomesChanges in BP.
Need for additional antihypertensive agent during hospitalisation.
Need for additional antihypertensive agent at the time of discharge.


NotesMany results are presented by type of hypertensive disorder but randomisation was not stratified for the type of hypertension.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation method not stated.

Allocation concealment (selection bias)Low riskSequentially numbered sealed opaque envelopes. 

Blinding (performance bias and detection bias)
All outcomes
Unclear riskFor participants, personnel and outcome assessors.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe number of women in the final paper differ from the number in the previously unpublished version, without explanation. There was no explanation for why in each group, one woman who was randomised was not presented in terms of baseline data or outcomes.

Selective reporting (reporting bias)High riskMany results are presented by type of hypertensive disorder but randomisation was not stratified for the type of hypertension. Study protocol not available.

Other biasLow riskNo other bias identified.

Barton 1990

Methods"Randomized...by sequential assignment from sealed envelopes based on a table of random numbers."
Method of randomisation by random number tables.


Participants31 postpartum women with antepartum diagnosis of pre-eclampsia.
sBP > 100 or dBP > 120 or sBP = 160-180 or dBP = 110-120 for > 2 hrs or sBP > 140 or dBP > 90 x 2, > 6 hrs apart.
Excluded women with reactions to calcium channel blockers and those requiring supplemental therapy for hypertension other than hydralazine.


InterventionsNifedipine 10 mg po every 4 hrs x 48 hrs (right after delivery) in 16 women.
Placebo po Q4H x 48 hrs in 15 women.
Both groups received 10 mg of hydralazine IV if sBP > 160 or dBP > 110 every 20 mins until BP <= 150/100.
If above failed x 3, then nitroprusside given.
All women were given continuous IV MgS04.
Treatment goal: BP < or equal to 160/110.


OutcomesNeed for additional antihypertensive therapy.
Change in treatment due to maternal side-effects.
Significant hypotension.
Duration of hospitalisation.
MAP.
U/O.
Urinary specific gravity.


NotesAuthor contacted re: doses of hydralazine needed in each group and the duration of hospitalisation for each group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number tables.

Allocation concealment (selection bias)Unclear riskEnvelopes not stated to be opaque. 

Blinding (performance bias and detection bias)
All outcomes
Low riskAdequate for participants, personnel, and outcome assessors.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Unclear riskRemote publication with no published protocol

Other biasLow riskNo other bias identified.

Fidler 1992

Methods"...randomly allocated..".
Method of randomisation not stated.


Participants80 untreated postpartum women.
dBP of 95-105 x 2, 24 hrs apart.
No antihypertensive treatment for 48 hrs prior to onset of study.
Excluded women with diabetes, multiple gestation, and those already receiving antihypertensive therapy.


InterventionsTimolol 5 mg po TID in 40 women.
Methyldopa 250 mg po TID.
In both cases, dose was doubled every 24 hrs x 2 if dBP > 95.
If dBP > 95 after 2 attempts at doubling dose, po hydralazine was added.


OutcomesNeed for additional antihypertensive therapy.
Change in treatment due to maternal side-effects.
BP changes.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of randomisation not stated.

Allocation concealment (selection bias)Unclear riskUnclear. 

Blinding (performance bias and detection bias)
All outcomes
High riskNo stated blinding of participants, personnel, or outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Unclear riskRemote publication with no published protocol

Other biasLow riskNo other bias identified.

Griffis 1989

Methods"..sealed envelope...envelopes contained odd and even numbers generated at random."
Randomisation by random number selection.


Participants26 postpartum women with antepartum or intrapartum hypertension and proteinuria.
Postpartum dBP > or equal to 96 x 2.
Excluded: women with history of chronic hypertension or hepatic disease and those who had antihypertensive treatment during pregnancy other than what was used for intrapartum PIH.


InterventionsHydralazine 20 mg IM every 6 hrs in 12 women.
Methyldopa 250 mg IV every 6 hrs in 12 women.
Doses doubled if 2 successive dBP > 110.
All women received IV MgS04 at 1.5 g/hr x 12 hrs.
Treatment goal: dBP < 110.


OutcomesNeed for additional antihypertensive therapy.
Change in treatment due to maternal side-effects.
Need for augmentation of dose.
Time to diurese.
Changes in MAP.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation by random number selection.

Allocation concealment (selection bias)Low riskAdequate.

Blinding (performance bias and detection bias)
All outcomes
High riskNo stated blinding of participants, personnel, or outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Unclear riskRemote publication with no published protocol

Other biasLow riskNo other bias identified.

Hladunewich 2006

MethodsQuality score: AAA
Randomisation by computer-generated random number tables with the allocation performed centrally by pharmacy.


Participants45 women with pre-eclampsia antenatally or postnatally; most patients were treated only postpartum (30/45).
Excluded: women with chronic renal disease.


InterventionsL-arginine (3.5 g po every 6 hr or 10 g IV every 8 hr if unable to take po medication) taken before delivery or within 24 hr postpartum and continued for 3 days postpartum, or placebo taken before delivery or within 24 hr postpartum and continued for 3 days postpartum.


OutcomesData on the following clinically important outcomes were obtained from the primary author: severe postpartum hypertension (day 3 postpartum) and use of antihypertensive therapy (day 3 postpartum)


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation by computer-generated random number tables.

Allocation concealment (selection bias)Low riskAllocation performed centrally by pharmacy.

Blinding (performance bias and detection bias)
All outcomes
Low riskPlacebo used to blind participants and personnel (as well as those assessing outcomes)

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)High riskPublished report does not include all expected outcomes

Other biasLow riskNo other bias identified.

Matthews 1997

Methods"Randomization was performed by pharmacy."
Randomisation method not stated.


Participants19 postpartum women enrolled at 12-24 hrs postdelivery.
Diagnosis of pre-eclampsia.
Excluded: women with hepatic or renal impairment or hypovolaemia.


InterventionsFurosemide 40 mg po x 7 days in 10 women (2/10 received IV MgS04).
Placebo 40 mg po x 7 days in 8 women (3/8 received IV MgS04).
Acute control by bolus of IV hydralazine.
Treatment goal: not stated.


OutcomesNeed for additional antihypertensive therapy at discharge.
Change in treatment due to maternal side-effects.
Number of medical attendances: routine and ER visits.
Mean length of puerperal hospital stay.
Average fall in potassium 48 hrs postdelivery.
Oliguria postdelivery.
Fall in MAP.
Hypertension at postnatal visit.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation method not stated.

Allocation concealment (selection bias)Low riskA - Adequate.

Blinding (performance bias and detection bias)
All outcomes
Low riskPlacebo used to blind participants and personnel (as well as those assessing outcome)

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Unclear riskRemote publication with no published protocol

Other biasLow riskNo other bias identified.

Sayin 2005

MethodsRandomisation method not stated in the official translation of this Turkish paper.


Participants83 women with "hypertension" 24 hours after birth.

Excluded women with gestational hypertension or superimposed pre-eclampsia.


InterventionsMethyldopa 250 mg po TID in 41 women (until sBP was < 150 mmHg and dBP was < 100 mmHg).

Nifedipine 10 mg po QID in 42 women (until sBP was < 150 mmHg and dBP was < 100 mmHg).

If BP was > 140/90 mmHg, gave metoprolol 100 mg po per day.

If BP was "still too high", then a cardiologies was consulted regarding therapy with amlodipine 5 mg po OD or perindopril 4 mg po OD.

Women were discharged from hospital when sBP was < 140 mmHg and dBP was < 90 mmHg.


OutcomesNumber and duration of antihypertensive therapy.

Length of hospitalisation.


NotesNo information on adverse effects.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation method not stated in the Turkish translation of the paper.

Allocation concealment (selection bias)Unclear risk"randomly divided into 2 groups."

Blinding (performance bias and detection bias)
All outcomes
High riskNo stated blinding of participants, personnel, or outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskPublished report appears to contain all expected outcomes

Other biasLow riskNo other bias identified.

Vigil-De Gracia 2007

Methods"Randomized."
Randomisation method not stated.


Participants82 women with a hypertensive disorder of pregnancy postpartum.

sBP >/ 160 mmHg or dBP >/ 110 mmHg.

Were at least 24 hours after their last dose of IV antihypertensive therapy antepartum or intrapartum.

No concurrent antihypertensive therapy.

No contraindication to labetalol or hydralazine.


InterventionsHydralazine 5 mg "slow" IV bolus (every 5 minutes to a maximum of 5 doses) in 42 women.

Labetalol 20 mg IV (then if BP effect not achieved in 20 minutes, 40 mg IV was given, and then similarly, 80 mg IV every 5 minutes to a maximum of 300 mg, equivalent to 5 doses) in 40 women.

All women were prescribed bedrest, magnesium sulphate (4 g IV bolus then an infusion of 1 g/hr until 24 hours postpartum), plasma volume expansion (900 mL of Ringer's Lactate with 100 mL of 25% albumin or 1000 mL of Ringer's Lactate, @ 75 mL/hr for 12 hr).

Oliguria was treated with 1 or 2 "fluid" boluses of 300-500 mL.


OutcomesBP including hypotension.

Number of doses of antihypertensive medication required.

Adverse effects.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation method not stated.

Allocation concealment (selection bias)Unclear risk"randomized."

Blinding (performance bias and detection bias)
All outcomes
High riskNo stated blinding of participants, personnel, or outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskPublished report appears to contain all expected outcomes

Other biasLow riskNo other bias identified.

Walss Rodriguez 1991

MethodsRandomisation by random number tables.


Participants38 postpartum women with diagnosis of severe pre-eclampsia and dBP > or equal to 110.
Excluded: women with chronic hypertension, renal disease and those in the ICU.


InterventionsHydralazine 40 mg po every 6 hrs, plus nifedipine 10 mg sl if dBP > or equal to 110 in 18 women.
No antihypertensive agent but nifedipine 10 mg sl if dBP > or equal to 110 in 10 women.

Additional antihypertensive agent given if dBP > or equal to 110 persistently.
Treatment goal: dBP < 110.


OutcomesNeed for additional antihypertensive therapy.
Interval time for nifedipine doses needed.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation by random number tables

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
High riskNo stated blinding of participants, personnel, or outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Unclear riskRemote publication with no published protocol

Other biasLow riskNo other bias identified.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Adarsh 2006Postpartum curettage as a therapeutic option has been excluded from this review.

Alkan 2006Postpartum curettage as a therapeutic option has been excluded from this review.

Barrilleaux 2003A trial of dexamethasone for postpartum treatment of the end-organ complications of severe pre-eclampsia (not hypertension).

Belfort 1988A prospective study; not a RCT.

Ehrenberg 2006This is a trial of magnesium sulphate for pre-eclampsia and there is a separate review on this topic.

Garden 1982No clinical outcomes reported specifically for postpartum patients.

Gomez 2005Postpartum curettage as a therapeutic option has been excluded from this review.

Hennessy 2007This is an antenatal RCT.

Jia 2007The intervention (self-prescribed Xiaobai Decoction) was administered to decrease proteinuria, not to affect BP.

Keiseb 2002Prospective randomised single blinded trial studying severe pre-eclampsia/eclampsia related oliguria in the immediate postpartum period.
No BP information was provided in the study.
There was no response from the authors upon our request for the required additional information.

Livingston 2003This is a trial of magnesium sulphate for pre-eclampsia and there is a separate review on this topic.

Mabie 1987No BP or other maternal outcomes reported within the postpartum group.

Magann 1993Postpartum curettage as a therapeutic option has been excluded from this review.

Magann 1994Postpartum curettage as a therapeutic option has been excluded from this review.

Mantel 1997A double-blind RCT studying effects of Dopamine in postpartum preeclamptic women with oliguria.
No BP information was provided in the study.
There was no response from the authors upon our request for the required additional information.

Marsoni 1985A trial of postpartum hypotension not hypertension.

Montenegro 1985A double-blind RCT with cross-over with placebo.
Number of patients in each treatment arm is unknown.
No clinical outcomes reported.
There was no response from the authors upon our request for the required additional information.

Morrison 1993Postpartum curettage as a therapeutic option has been excluded from this review.

Vermillion 1999A double-blind RCT.
No stratification of postpartum patients therefore, no abstractable data.

Weiner 1984A double-blind RCT with cross-over with placebo.
Number of women who crossed over from the ketanserin group is unknown.
Number of women who were in the placebo group first and achieved a dBP < 95 is unknown.
There was no response from the authors upon our request for the required additional information.

 
Characteristics of ongoing studies [ordered by study ID]
Aina-Mumuney 2006

Trial name or titleHypertonic saline use for volume expansion in postpartum pre-eclampsia. [NCT 00181077]

MethodsRandomised, open label, active control, single group assignment, safety/efficacy trial.

ParticipantsPre-eclampsia, postpartum.

Excluding: maternal age < 18 years, non-English speaking or otherwise unable to give informed consent, serum creatinine of 1.6 mg/dL or higher, medically unstable, serum Na < 130 or > 150 mEq/L, co-morbid conditions that affect renal function.

Interventions2% buffered hypertonic saline infused at the rate of 75 mL/hr or lactated Ringer's solution at 75 mL/hr.

All women will receive magnesium sulphate.

OutcomesPrimary: fluid input to output ratios.

Secondary: laboratory evaluation of inflammatory parameters (platelet count, IL-1, IL-6), liver enzymes, weight.

Starting dateJune 2003.

Contact informationAbimbola Aina-Mumuney, John Hopkins University.

NotesEstimated study completion is listed as April 2006, but the information was last updated on May 23, 2006.

 
Comparison 1. Routine postnatal oral antihypertensive therapy for prevention of postpartum hypertension

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Maternal death2295Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.1 Furosemide versus placebo/no therapy
1264Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Routine antihypertensive versus placebo
131Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Maternal organ failure1264Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.1 Furosemide versus placebo/no therapy
1264Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Severe hypotension131Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.1 Routine antihypertensive versus placebo
131Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Severe hypertension145Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.60, 1.39]

    4.1 L-arginine vs. placebo
145Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.60, 1.39]

 5 Postnatal antihypertensive use in hospital1264Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.55, 1.00]

    5.1 Furosemide versus placebo/no therapy
1264Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.55, 1.00]

 6 Postnatal antihypertensive use at hospital DISCHARGE3325Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.58, 1.08]

    6.1 Furosemide vs. placebo/no therapy
2282Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.59, 1.12]

    6.2 L-arginine vs. placebo
143Risk Ratio (M-H, Fixed, 95% CI)0.64 [0.21, 1.94]

 7 Medication changed secondary to maternal side-effects131Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.1 Routine antihypertensive versus placebo
131Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Oral antihypertensive therapy for treatment of postpartum hypertension

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Maternal death2106Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.1 Antihypertensive agent versus another for mild-moderate postpartum hypertension
2106Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Maternal hypotension182Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.1 Antihypertensive agent versus another for severe postpartum hypertension
182Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Need for additional antihypertensive therapy5309Risk Ratio (M-H, Random, 95% CI)0.70 [0.25, 1.96]

    3.1 Antihypertensive agent versus another for mild-moderate postpartum hypertension
3189Risk Ratio (M-H, Random, 95% CI)0.92 [0.20, 4.20]

    3.2 Antihypertensive agent versus another for severe postpartum hypertension
2120Risk Ratio (M-H, Random, 95% CI)0.58 [0.04, 9.07]

 4 Medication changed secondary to maternal side-effects2106Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.05, 5.30]

    4.1 Antihypertensive agent versus another for mild-moderate postpartum hypertension
2106Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.05, 5.30]

   4.2 Antihypertensive therapy for severe postpartum hypertension
00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]