Hypertensive complications of pregnancy

  • Overview/procedure description

    Hypertension during pregnancy includes a number of conditions and occurs in 6-8% of all pregnancies. These conditions include gestational hypertension, pre eclampsia/eclampsia, and chronic hypertension and are responsible for considerable maternal and perinatal morbidity and mortality.1

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    Definition of Terms

    Hypertension

    Blood pressure taken in the sitting position (with the right arm horizontal) that is persistently recorded as being more than 30 mm Hg systolic and/or more than 15 mm Hg diastolic above pre-pregnancy or early pregnancy values or, in the absence of knowledge of pre-pregnancy or early pregnancy values, >140 mm Hg systolic and/or >90 mm Hg diastolic (diastolic blood pressure is recorded with disappearance of the Korotkoff V sound).2

    Proteinuria

    Urine protein that is >300mg/24 hour collection or a spot urine protein:creatinine ratio >25mg/mmol are the two recognised determinants of proteinuria. Note: Semi quantification by dipstick testing may be unreliable.

    Oedema

    Oedema is no longer included in the definition of pre eclampsia as it occurs equally in women with and without this condition.

    Classification of hypertension in pregnancy

    Gestational hypertension

    Development of an elevated blood pressure after 20 weeks of pregnancy or in the first 24 hours postpartum. No other signs or symptoms of pre eclampsia or evidence of hypertensive vascular disease is present. Resolution of blood pressure elevation occurs by 12 weeks postpartum. Some women with gestational hypertension will progress to develop the clinical syndrome of pre eclampsia; the rate of progression is determined by the gestational age at the time of diagnosis of gestational hypertension, the earlier in gestation the diagnosis the greater the risk of progression.3

    Pre eclampsia

    Mild pre eclampsia

    Onset of mild hypertension (an increase of 20 mm Hg systolic and/or more than 10 mm Hg diastolic above pre-pregnancy or early pregnancy values or, in the absence of knowledge of pre-pregnancy or early pregnancy values, 140 systolic and/or 90 diastolic) after the 20th week of gestation with proteinuria (>300mg/24 hour collection or spot urine protein : creatinine ratio > 25mg of protein/mmol creatinine), uncomplicated by neurologic symptoms or criteria for the diagnosis of severe pre eclampsia

    Severe pre eclampsia

    Severe pre eclampsia is diagnosed when:

    • Blood pressure >170 mm Hg systolic and/or 110 mm Hg diastolic

    The diagnosis should also be considered in women with lesser degrees of hypertension, but who have one or more of the following:

    • Severe proteinuria ( >5 grams in a 24 hour specimen).
    • Oliguria (<400mL in 24 hours).
    • CNS dysfunction (severe headaches, blurred vision, changing sensorium).
    • Thrombocytopenia (platelet counts considered consistent with severe pre-eclampsia are those <100,000; excessive bleeding associated with trauma or surgery is uncommon unless the patient's platelet count is <50,000/mL4 with significant spontaneous bleeding limited to patients with platelet counts <10,000/mL).
    • Liver disease - elevated liver enzymes.
    • Severe epigastric and right upper quadrant pain.
    • Pulmonary oedema.
    • Intrauterine growth restriction (IUGR).

    Eclampsia

    The occurrence of convulsions or coma (not caused by trauma or coincidental neurologic disease such as epilepsy) in a woman whose condition also fulfils the criteria for the diagnosis of pre eclampsia.

    Note: Use of the term Pregnancy Induced Hypertension is discouraged because it inadequately defines what is a complex multi-system disease condition.

    Procedure details

    Baseline assessment

    Maternal

    • History and physical examination.
    • Full blood examination.
    • Urinalysis.
    • Spot urine protein:creatinine ratio or 24 hr urine collection for total protein and creatinine clearance.
    • Liver function and uric acid.

    Fetal

    • Non-stress cardiotocography (CTG).
    • Complete ultrasound examination if not recently performed (fetal growth parameters, amniotic fluid volume measurement, umbilical arterial Doppler measurements).

    Management

    The only definitive treatment for the hypertensive complications of pregnancy is delivery.  For this reason, delivery is indicated in women with hypertensive complications at term (37 or more completed weeks) of any severity and in preterm pregnancies with severe disease. There are however several exceptions to these general rules.

    Term

    Delivery may be delayed in a term pregnancy to achieve cervical favourability by ripening, if:

    • blood pressure is mildly elevated
    • there is minimal proteinuria
    • there is no evidence of end-organ compromise
    • there is no evidence of fetal compromise.

    Preterm

    Pregnancies < 32-34 weeks with severe disease responsive to anti-hypertensive and anti-seizure therapy may be observed with maternal and fetal surveillance, in a high level multi-disciplinary unit setting, to achieve greater fetal maturity.

    Outpatient management

    Rest at home can be used in women with mild gestational hypertension as long as:

    • there are no obstetric contraindications
    • there are no geographic contraindications
    • there is no evidence of fetal compromise
    • the patient has her blood pressure regularly monitored at home
    • the patient visits the clinic 1-2 times per week

    Any evidence of maternal and or fetal compromise or failure to respond to outpatient treatment requires hospitalisation.

    Inpatient management

    Maternal

    • Evaluate patient to determine if the admission should be to Delivery Suite or to antepartum ward.
    • Perform baseline laboratory evaluations.
    • Review by senior staff at least daily (including weekends and public holidays)5-6 to evaluate the patient for evidence of maternal deterioration (headaches, visual changes, or epigastric distress).

    Fetal

    • Fetal surveillance by CTG, Doppler studies and/or Biophysical Profile 2-3 times per week.
    • Administer betamethasone 11.4mg IM 24 hours apart for 2 doses.

    Special management issues for patients with hypertensive crises (BP of >170/110).

    • Admit to a high dependency area for close observation and antepartum care. Manage in this high dependency manner postpartum until the crisis has resolved.
    • Obstetrician immediately available and 1:1 midwife to patient ratio.
    • Evaluate and stabilise with continuous maternal and fetal surveillance.
    • Anaesthesia: May consider epidural/spinal anaesthesia if maternal platelet count is >100,000 and platelet function is normal.

    Transfer to a tertiary setting is indicated for:

    • Pre-term pregnancies with severe pre eclampsia, eclampsia or HELLP syndrome.
    • Term pregnancies complicated by eclampsia or HELLP syndrome.
    • Any pregnancy in which the health care provider believes his/her health care facility would be unable to manage the complications of hypertension in pregnancy.

    Note:

    Magnesium sulphate therapy should be considered prior to transfer in women with severe pre eclampsia, eclampsia or HELLP syndrome.

    Assessment of severity in pre eclampsia

    All patients with pre eclampsia must be regarded as being at risk of major maternal and fetal complications, but there are certain indicators of particular concern, when they occur in a woman with definite pre eclamspia:

    • HELLP syndrome - see below
    • Severe hypertension refractory to usual treatment
    • Renal impairment - creatinine greater than 0.09 micromoles/l
    • Massive oedema - beware laryngeal oedema
    • Pulmonary oedema
    • Persistent neurological symptoms - headache / altered mental state / clonus
    • "Pre eclamptic angina" - severe epigastric pain and/or vomiting with abnormal liver enzymes
    • Fetal growth restriction

    Pre eclampsia usually pursues a course of deterioration, sometimes slowly and sometimes quickly. It may evolve from mild to moderate to severe over a period of hours or days, and requires frequent reassessment by medical staff.

    HELLP syndrome

    The HELLP Syndrome is a form of severe pre eclampsia. Maternal mortality is reported to be as high as 1-2% .

    The elements of this variety of severe pre eclampsia are:

    • thrombocytopenia (common)
    • haemolysis (rare) and
    • elevated liver enzymes (ALT, LDH - common).

    The presence of any one of

    • maternal platelet count of less than 100,000
    • transaminase level or LDH more than double the normal upper limit
    • any haemolysis

    in a woman with pre eclampsia is an indicator of severe disease, even if not suggested on other criteria such as severity of hypertension.

    Timing of delivery

    Deferral of delivery

    Consider in patients between 23 and 32 weeks with severe pre eclampsia:

    • whose disease improves with bed-rest and interim therapy and
    • where there is no evidence of fetal compromise (abnormal fetal heart rate tracing or IUGR).7-8

    Indicated delivery

    • Mature fetus in a patient with severe pre eclampsia.
    • Premature pregnancy with severe pre eclampsia, chronic hypertension with superimposed pre eclampsia.
    • Eclampsia.
    • Maternal deterioration.
    • IUGR or evidence of fetal intolerance of the intrauterine environment.

    Treatment of pre eclampsia

    Given the earlier statement that "The only definitive treatment for the hypertensive complications of pregnancy is delivery", the decision to deliver a woman because of pre eclampsia is a complex one and should take into account all the above indicators of maternal and fetal status, as well as fetal maturity.  At very early gestations, it may be justifiable to delay delivery even where there are maternal abnormalities that would provoke delivery at a later gestation. Close maternal and fetal monitoring are mandatory if such a conservative course is pursued, in a high level multi-disciplinary unit setting.

    The final decision about timing and mode of delivery in severe pre eclampsia should be made by an Obstetric Consultant, often after Paediatric, Anaesthetic and/or Medical consultation

    Except in the situation of acute fetal compromise, urgent delivery is not helpful in pre eclampsia and the mother should be resuscitated before being subjected to the delivery process.

    In severe pre eclampsia, delivery must always be preceded by:

    • Control of severe hypertension
    • Attention to fluid status
    • Correction of coagulopathy (usually thrombocytopenia)
    • Control of eclampsia, or prophylaxis against eclampsia if indicated (see below)

    Drug Therapy

    • Intravenous fluids (Hartmann's solution) at 100 - 125 mL/hour
    • 20mg (4mL) Labetalol injection given IV slowly over 2 minutes. This dose may be repeated every ten (10) minutes until optional blood pressure levels are reached or a maximum dose of 300mg is delivered.

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    • 20mg/hour Labetalol IV infusion, titrate dose (20 – 160mg/hr) until optimal blood pressures are achieved or a maximum dose of 300mg is delivered.
    • Hydralazine remains the drug of choice for women with asthma or congestive cardiac failure.

    5-10mg Hydralazine, given intravenously as a bolus over 5-10 minutes, then by continuous infusion at 5mg/hr, with adjustment of rate to maintain BP <160/100 every 30 minutes until BP 140/90 to 160/100. Reactive tachycardia with Hydralazine may necessitate use of IV beta blockers. Note: Blood pressure should not be allowed to fall below a level of 140/80.

    • The third agent of choice for the acute treatment of hypertension is Oral Nifedipine. This is administered as a 10mg oral dose initially with a repeat dose of 10mg if there is an inadequate response after 30 minutes. Side effect of headache is frequent. Occasionally hypertension resistant to Hydralazine and Nifedipine requires other drugs eg. Nitroprusside or GTN.

    Prevention of Seizures

    Level I evidence indicates that magnesium sulphate is the superior drug to use in the prevention and the treatment of eclamptic seizures.9-12  The Magpie Trial found the risk of eclampsia was halved and the risk of placental abruption and overall maternal deaths were reduced (although not significantly) in women treated with magnesium sulphate compared to a control group. However, subgroup analysis suggests that these benefits are primarily seen in countries with high perinatal mortality rates, where blood pressure control and accurate fluid balance management is difficult.13  In addition, adverse effects were more common in the magnesium group.

    In the patient with known renal disease or myasthenia gravis, however, phenytoin sodium is the anti-seizure medication of choice. Phenytoin sodium is administered in a total dose of 15mg/kg at an infusion rate of 40mg/min with continuous cardiac and blood pressure monitoring.

    Administration of magnesium sulphate

    Magnesium sulphate therapy is recommended for severe pre eclampsia when the following factors are present:

    • persistently elevated blood pressure despite adequate hypotensive therapy and appropriate fluid management
    • evidence of CNS dysfunction, thrombocytopenia or liver disease
    • antepartum, intrapartum or within the first 24 hours postpartum

    Loading Dose

    Administer intravenous loading bolus dose of 4g of magnesium sulphate over 20 minutes. Magnesium sulphate should be administered via a controlled infusion device.

    Monitor the patient to detect magnesium sulphate toxicity - viz:

    • assessment of deep tendon reflexes (use upper limb if epidural in situ)
    • assessment of respiratory rate
    • observation of maternal urinary output
    • assay of serum magnesium levels (therapeutic range is 2 - 2.8 mmol/L).

    The magnesium infusion should be stopped and the serum levels re-evaluated if the urinary output is <30 mL/hour, in the absence of previously detected deep tendon reflexes, decreased respiratory rate (12 breaths/min.) or there is evidence of CNS or cardiac depression.

    Recurrent seizures:

    If recurrent seizures occur a further 2 - 4g of MgSO4 is given over 5 minutes. Dose depends on the woman's weight, 2g if <70kg and 4g if >70kg.

    Maintenance dose:

    The loading dose is followed by a maintenance infusion of 1 g of MgSO4 / hour for at least 24 hours after the last seizure or after birth of the infant. Use 1g per hour as maintenance therapy.

    Before discontinuation:

    • the blood pressure should be stable (consistently below 150/100)
    • the patient should have adequate diuresis the patient should be clinically improved (absence of headache, epigastric pain).

    Management of magnesium toxicity

    If magnesium toxicity (ie respiratory depression, absent deep tendon reflexes, or altered state of consciousness) is suspected:

    • Cease the infusion
    • Summon emergency medical/obstetric assistance
    • If respiratory arrest occurs, initiate respiratory support via expired air respiration (EAR) or bag and mask until the woman is intubated and ventilated.
    • Give IV calcium gluconate 1g in 10mL of a 10% solution over 3 minutes.

    Postpartum Management

    • Monitor patients in a high dependency situation until the patient begins to recover.
    • Continue magnesium sulphate until stabilisation and adequate diuresis is achieved.

    Hypotensive therapy should be commenced if the BP is >150 mmHg systolic or >100 mmHg diastolic in the first four postpartum days.  Options for hypotensive therapy include:14

    • Atenolol 50mg daily. On rare occasions, may need increasing to 100mg/day.
    • Nifedipine 10mg BD increasing to 20mg TDS.
    • Enalapril 5-10mg daily.

    Non-acute Hypotensive Therapy

    Evidence suggests that hypotensive drug therapy confers no clear benefit to women with mild pre eclampsia.8,15 Randomised control trials of women with mild pre eclampsia remote from term, which compared hypotensive drug therapy with no medication or a placebo, have been reported. In some of these trials, the frequency of proteinuria, progression to severe disease, and neonatal respiratory distress syndrome were higher in the women not treated.16-19  These observations however have not been confirmed in other trials.20-22

    In women with severe pre eclampsia, or those who have received treatment for hypertensive crisis, maintenance control of BP is essential for maternal safety to reduce the risk of cerebral events, and prolongation of pregnancy if it is contemplated for fetal benefit. However, the maternal blood pressure must not be lowered too drastically because of the impact on a placental circulation that has adapted to a higher blood pressure. With a lowered blood pressure there may not be adequate placental perfusion.

    Management of HELLP syndrome

    Antenatal management

    If the platelet count is sufficiently low to preclude epidural anaesthesia (consult with Consultant Anaesthetist) or to present a hazard for operative delivery, a platelet transfusion should be administered (consult with Consultant Haematologist or Obstetric Physician). Steroid treatment (see Dexamethasone therapy below) is not useful for the acute management of thrombocytopenia, such as in preparation for surgery.

    Post-natal management

    If there is significant bleeding attributed to pre-eclamptic thrombocytopenia at any time in the puerperium a platelet transfusion be given (consult with Consultant Haematologist or Obstetric Physician).

    In the absence of bleeding, platelet transfusion be considered in the first 72 hours only if count falls below 40,000 and there is concern at possible bleeding (eg after caesarean section).

    If the count remains below 40,000 after 72 hours from delivery without significant bleeding and without sign of impending recovery, consultation with Consultant Haematologist or Obstetric Physician is indicated. In addition, consideration should be given to steroid therapy in view of the possibility of undiagnosed ITP or SLE, or prolonged pre-eclamptic thrombocytopenia. Usual therapy is prednisolone, 40-60mg daily, but dexamethasone may be used (equivalent dose is 6-8mg per day). Such therapy is expected to lead to a gradual rise in the platelet count beginning after 24-48 hours.

    In rare cases where severe thrombocytopenia persists, with evidence of microangiopathic haemolysis, consideration should be given to differential diagnosis in addition to the above, including postpartum thrombotic thrombocytopenic purpura and postpartum antiphospholipid syndrome. These disorders may respond to high dose steroids, or may need treatment by apheresis.

    High dose Dexamethasone therapy

    Women with severe HELLP syndrome may be treated with a high dose regime of Dexamethasone at a dose of 10mg IV every 12 hours until delivery (consult with Consultant Haematologist or Obstetric Physician). Postpartum 10mg every 12 hours is administered until the maternal platelet count is >100,000uL and the LDH is falling. When these conditions are met, two additional doses of dexamethasone 5mg IV are administered - 12 hours apart.23-24

    The administration of Ranitidine 150mg BD with a sip of water should be considered when dexamethasone therapy is used.

    Women first diagnosed with HELLP syndrome postpartum (1/3 of the women will be first diagnosed postpartum) may be treated with this regimen postpartum.

    Reference

    1. American College of Obstetricians and Gynecologists. 1996. Hypertension in pregnancy., Washington, DC: ACOG.
    1. Brown MA. Hague WM. Higgins J. Lowe S. McCowan L. Oats J. Peek MJ. Rowan JA. Walters BNJ. Consensus statement: The detection, investigation and management of hypertension in pregnancy: Executive summary. Aust N Z Obstet Gynaecol. 2000; 41:133-138
    1. Barton JR O'Brien JM Bergaver NK Jaxques DL Sibai BM.. Mild gestational hypertension remote from term: progression and outcome. Am J Obstet Gynecol. 2001; 184: 979-83.
    1. American College of Obstetricians and Gynecologists. 1999. Thrombocytopenia in pregnancy ACOG Practice Bulletin No 6. In ACOG 2001 Compendium of Selected Publications, Washington DC: ACOG.
    1. Douglas N. Robinson J. & Fahy K. 2001. Inquiry into obstetric and gynaecological services at King Edward Memorial Hospital 1990-2000. Government of Western Australia
    1. Brown MA. Pre-eclampsia: a lifelong disorder. Med J Aust. 2003; 179: 182-184 (Editorial review)
    1. Sibai BM Mercer BM Schiff E Reidman SA. Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial. Am J Obstet Gynecol. 1994; 171: 818-22.
    1. Sibai BM Mavie WC Shamsa F Villar MA Anderson GD. A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy. Am J Obstet Gynecol. 1990; 162: 960-5.
    1. Duley, L, Gulmezoglu, AM and Henderson-Smart, DJ. 2001. Anticonvulsants for women with pre-eclampsia (Cochrane Review). In The Cochrane Library (Vol. Issue 4.), Oxford: Update Software.
    1. Duley, L & Gulmezoglu, AM. 2001. Magnesium sulphate versus lytic cocktail for eclampsia (Cochrane Review). In The Cochrane Library (Issue 1), Oxford: Update Software.
    1. Duley, L & Henderson-Smart, DJ. 2001. Magnesium sulphate versus phenytoin for eclampsia. (Cochrane Review). In The Cochrane Library, Oxford: Update Software.
    1. The Magpie Collaborative Group. Do women with pr-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. The Lancet 2002; 359: 1877-1889.
    1. Royal College of Obstetricians and Gynaecologists. Magnesium sulphate regimens for women with eclampsia: Messages from the Collaborative Eclampsia Trial. British Journal of Obstetrics and Gynaecology 1996; 103: 103-105.
    1. Tan, LK & de Sweit, M. The management of postpartum hypertension. British Journal of Obstetrics and Gynaecology. 2002; 109: 733-736.
    1. Abalos E. Duley L. Steyn DW. Henderson-Smart DJ. 2001. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database of Systematic Reviews 3
    1. Pickles CJ. Pipkin FB. Symonds EM. A randomized placebo controlled trial of labetalol in the treatment of mild to moderate pregnancy induced hypertension. Br J Obstet Gynaecol. 1992; 99: 964-8
    1. Rubin PC. Butters L. Clark DM. Placebo-controlled trial of atenolol in treatment of pregnancy associated hypertension. Lancet. 1983; 1:8322: 431-4.
    1. Pickles CJ. Symonds EM. Pipkin FB. The fetal outcome in a randomized double blind controlled trial of labetalol versus placebo in pregnancy induced hypertension. Br J Obstet Gynaecol. 1989; 96: 38-43.
    1. Phippard AF. Fischer WE. Horvath JS. Early blood pressure control improves pregnancy outcome in primigravid women with mild hypertension. Med J Aust. 1991; 154: 378-82.
    1. Sibai BM. Gonzalez AR. Mabie WC. Moretti M. A comparison of labetalol plus hospitalization versus hospitalization alone in the management of pre eclampsia remote from term. Obstet Gynecol. 1987; 70: 323-7.
    1. Sibai BM. Barton JR. Aki S. Sarinoglu C. Mercer BM. A randomized prospective comparison of nifedipine and bed rest versus bedrest alone in the management of preeclampsia remote from term. Am J Obstet Gynecol. 1992; 167: 879-84.
    1. Wide-Swensson DH. Ingemarrsson I. Lunnell NO. Forman A. Skajaa K. Lindeberg B. Marsal K. Andersson KE. Calcium channel blockade (isradipine) in treatment of hypertension in pregnancy: a randomized placebo-controlled study. Am J Obstet Gynecol. 1995; 173: 872-8.
    1. Magann EF. Bass D. Chauhan SP. Sullivan DL. Martin RW. Martin JN Jr. Antepartum corticosteroids: Disease stabilization in patients with the syndrome of hemolysis elevated liver enzymes, and low platelets. Am J Obstet Gynecol. 1994; 171: 1148-53.
    1. Magann EF. Perry KG Jr. Meydrich EF. Harris RL. Chauhan SP. Martin JN Jr. Postpartum corticosteroids: Accelerated recovery from the syndrome of hemolysis, elevated liver enzymes, and low platelets. Am J Obstet Gynecol 1994; 171: 1154-8.

     

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