4.5 Hypertensive disorders in pregnancy

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    Gestational hypertension and chronic hypertension may be complicated by pre-eclampsia. Pre-eclampsia carries a significant risk of complications:

    • Placental abruption, HELLP syndrome a Citation a. The HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) is a potential lifethreatening complication for both the mother and foetus). , eclampsia, stroke, maternal death;
    • Foetal growth restriction, foetal distress, foetal death. 

     

    The goal of antihypertensive treatment is to prevent maternal complications of severe hypertension. Treatment is administered if systolic blood pressure is ≥ 160 mmHg or if diastolic blood pressure is ≥ 110 mmHg. The objective of treatment is to lower blood pressure to around 140/90 mmHg. Antihypertensive treatment does not improve foetal prognosis. It should be carried out with caution. It is essential to preserve placental perfusion and to avoid excessive fall in maternal blood pressure.

    4.5.1 Diagnosis 

     

    Pathologies Definitions [1] Citation 1. Society for the Study of Hypertension in Pregnancy. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens. 2014 Apr;4(2):97 104.

    Hypertension

    In a pregnant woman, seated and at rest, measured twice:
    Systolic blood pressure (SBP) ≥ 140 mmHg
    and/or
    Diastolic blood pressure (DBP) ≥ 90 mmHg
    Severe hypertension SBP ≥ 160 mmHg and/or DBP ≥ 110 mmHg

    Gestational hypertension

    Hypertension isolated (with no proteinuria or other signs of pre-eclampsia) develops after 20 weeks LMP.
    Pre-eclampsia without severe features Hypertension after 20 weeks LMP
    and
    proteinuria on dipstick urinalysis (1+ or more) with no signs of end-organ damage (see below) or severe hypertension.

    Pre-eclampsia with severe features

    Hypertension after 20 weeks LMP with or without proteinuria on dipstick urinalysis
    and
    One or more signs of end-organ damage:

    • severe headache, tinnitus
    • visual disturbances
    • epigastric pain, nausea, vomiting
    • hyperreflexia (overactive knee-jerk response, twitching and spasms)
    • oliguria (urine output < 400 ml/day or < 30 ml/hour)
    • pulmonary oedema
    • thrombocytopenia (platelet count < 100 000/mm³)
    • renal impairment (serum creatinine level > 1.1 mg/dl)
    • altered hepatic function (elevated transaminases over twice the normal value)

     

    OR


    Hypertension after 20 weeks LMP
    and
    Proteinuria on dipstick urinalysis
    and
    Severe hypertension, persistent despite treatment

    Chronic hypertension

    Hypertension predating the pregnancy or develops before 20 weeks LMP

     

    Notes:

    • In pre-eclampsia, other symptoms may be observed: dark urine, low urine output, sudden onset or increase in oedema of the legs and hands. These symptoms alone do not confirm the diagnosis of pre-eclampsia, but call for monitoring of blood pressure and proteinuria.
    • Abnormally high proteinuria is no longer considered a severe feature in pre-eclampsia. Nevertheless, if it is not possible to perform regular and reliable monitioring of blood creatinine levels, heavy proteinuria (3+ or more on dipstick urinalysis) should be considered as a criteria for referral to a CEmONC facility.
    • In women with proteinuria and no hypertension, consider urinary tract infection, contamination of urine with blood or vaginal secretions, nephropathy. In these cases, monitor to ensure early detection of pre-eclampsia.

    4.5.2 Management of gestational and chronic hypertension

    • Rest; monitoring once weekly: BP, proteinuria.
    • Assess the risk of foetal growth restriction (fundal height).
    • Normal sodium and caloric intake.
    • Inform the patient about the warning signs that require urgent medical attention (severe headache, tinnitus, visual disturbances, epigastric pain, nausea, vomiting, dyspnea). In the event of proteinuria or other warning signs developing, treat as for pre-eclampsia.
    • If SBP ≥ 160 mmHg or DBP ≥ 110 mmHg, administer an antihypertensive treatment:

    labetalol PO: 100 mg 2 times daily then increase if necessary in 100 to 200 mg increments until an effective dose is reached, usually 200 to 400 mg 2 times daily. If higher daily doses are required, divide in 3 doses (max. 2.4 g daily)
    or
    methyldopa PO: 250 mg 2 or 3 times daily for 2 days, then increase if necessary, in 250 mg increments every 2 to 3 days, until an effective dose is reached, usually around 1.5 g daily (max. 3 g daily)

     

    Notes:

    • In case of treatment failure, these drugs can be combined.
    • Do not stop antihypertensive treatment abruptly.
    • Diuretics and angiotensin-converting-enzyme inhibitors (enalapril, etc.) are contra-indicated.
    • If the mother is taking labetalol, monitor the neonate for at least 72 hours after birth (risk of hypoglycaemia, bradycardia and respiratory distress).

    4.5.3 Management of pre-eclampsia without severe features

    Before 37 weeks LMP

    • Admit as inpatient; rest; monitoring: BP, proteinuria.
    • Assess the risk of foetal growth restriction (fundal height).
    • Normal sodium and caloric intake.
    • Do not stop uterine contractions if they occur; let the woman deliver.
    • If SBP ≥ 160 mmHg or DBP ≥ 110 mmHg, administer an antihypertensive treatment (Section 4.5.2).

     

    Pre-eclampsia is an evolving condition, always deteriorating. As soon as even a single sign of severe pre-eclampsia appears or in case of heavy proteinuria (3+ or more on dipstick urinalysis), transfer to a CEmONC facility.

    After 37 weeks LMP

    • Admit as inpatient; rest; same monitoring and antihypertensive treatment.
    • Induce labour as soon as the cervix is favourable (or before if the mother's condition deteriorates or in case of true intrauterine growth restriction).

    4.5.4 Management of pre-eclampsia with severe features

    Care is best organized with a multi-disciplinary team comprising obstetrician, anaesthesiologist and midwife.

    Delivery

    Delivery should take place within 24 hours, either vaginally or by caesarean section, depending on the state of the cervix, gestational age and condition of the foetus.

    Magnesium sulfate treatment

    To reduce the risk of eclampsia, administer magnesium sulfate. One of the following regimens may be used:

     

    magnesium sulfate
    5 g ampoule
    (500 mg/ml, 10 ml)
    IV/IM protocol

    Loading dose: 4 g by IV infusion in 100 ml of 0.9% sodium chloride over 15 to 20 minutes
    Then
    Maintenance dose: 10 g IM (5 g in each buttock), followed by 5 g IM every 4 hours (change sides with each injection)
    Continue this treatment for 24 hours after delivery.
    or

    magnesium sulfate
    5 g ampoule
    (500 mg/ml, 10 ml)
    IV protocol

    Loading dose: 4 g by IV infusion in 100 ml of 0.9% sodium chloride over 15 to 20 minutes
    Then
    Maintenance dose: 1 g per hour by continuous infusion.
    Continue this treatment for 24 hours after delivery.

     

     
    • Verify the dosage written on the ampoules (there are different dosages).
    • There is a risk of potentially lethal overdose of magnesium sulfate. Have calcium gluconate, the antidote of magnesium sulfate, immediately available (1 g ampoule).

     

    During administration, monitor:

    • Patellar reflex (knee-jerk), BP, heart rate and respiratory rate every 15 minutes for the first hour of treatment. If there are no signs of overdose, continue monitoring every hour.
    • Urine output every hour (insert Foley catheter).

     

    Manifestations of magnesium sulfate overdose start with disappearance of the patellar reflex then hypotension, arrhythmia, respiratory depression (< 12 breaths/minute). If the patellar reflex disappears, stop magnesium sulfate immediately and administer calcium gluconate (1 g IV).

     

    If urine output drops (< 30 ml/hour or 100 ml/4 hours): stop magnesium sulfate and deliver as quickly as possible.

    Antihypertensive treatment

    • If SBP ≥ 160 mmHg or DBP ≥ 110 mmHg, administer an antihypertensive treatment (Section 4.5.2).
    • If the oral route is impossible, use parenteral labetalol or hydralazine. When administering, monitor the mother’s BP and heart rate and the foetal heart rate.

     

    The dose is adjusted according to changes in BP. Hypertension is controlled when DBP is between 90 and 100 mmHg and SBP between 130 and 150 mmHg.

     
    Respect dosage and administration rate. Administering too much of the drug, or administering it too quickly, can provoke a sudden, excessive fall in maternal BP, with placental hypoperfusion and foetal death. DBP should not go below 90 mmHg. In the event of hypotension, use Ringer lactate solution to bring the DBP back up to 90-100 mmHg. Proceed with caution and monitor the patient closely as there is a risk of fluid overload and pulmonary oedema.

     

    One of the following regimens may be used:

     

    labetalol
    slow IV
    (ampoule of 100 mg in 20 ml, 5 mg/ml)

    One dose of 20 mg (4 ml) over at least one minute. Check BP 5 and 10 minutes after injection. If hypertension remains uncontrolled, administer another dose of 20 mg and check BP. Administer additional doses, of 40 mg then 80 mg with 10 minutes between each dose as long as hypertension is not controlled. Do not exceed a total dose of 300 mg.
    or

    hydralazine
    slow IV
    (20 mg/1 ml vial)

    Dilute 20 mg (1 vial of hydralazine reconstituted in 1 ml of water for injection) in 9 ml of 0.9% sodium chloride to obtain 10 ml of solution containing 2 mg hydralazine/ml.
    Administer 5 mg (2.5 ml of the diluted solution) over 2 to 4 minutes. Monitor BP for 20 minutes. If hypertension remains uncontrolled, repeat injection. Continue repeating if necessary, waiting 20 minutes between each injection. Do not exceed a total dose of 20 mg.
    or

    hydralazine
    IV infusion
    (20 mg/1 ml vial)

    Dilute 100 mg (5 vials of reconstituted hydralazine) in 500 ml of 0.9% sodium chloride or Ringer lactate to obtain a 200 micrograms/ml solution.
    The initial dose is 200 to 300 micrograms/minute; the maintenance dose is 50 to 150 micrograms/minute.
    Administer by increasing the rate up to 20 drops/minute (max. 30 drops/minute), monitoring the BP every 5 minutes.
    As soon as the hypertension is controlled, gradually reduce the rate (15 drops/minute, then 10, then 5) until stopping infusion. Stopping abruptly can trigger a hypertensive crisis.

     

    Notes:

    • If the mother receives labetalol, monitor the newborn for at least 72 hours after birth (risk of hypoglycaemia, bradycardia and respiratory distress).
    • If anaesthesia is necessary, avoid ketamine. Whenever possible, use spinal anaesthesia.
    • Oxytocin may be used in pre-eclampsia, but requires BP monitoring: drops and elevations in BP have been described in rare cases.
    • Methylergometrine is contraindicated.
    • Pre-eclampsia can appear up to 7 days after delivery (and on rare occasions up to 6 weeks).

    4.5.5 Secondary prophylaxis for severe pre-eclampsia

    acetylsalicylic acid PO: 75 to 150 mg once daily starting at 12 weeks LMP and continuing until 36 weeks LMP reduces the risk of recurrence during the next pregnancy. If this prophylactic treatment is feasible, recommend that the woman comes for consultation as soon as she knows she is pregnant. There is no point in starting this treatment after 20 weeks LMP [2] Citation 2. World Health Organization. Prevention and treatment of pre-eclampsia and eclampsia. Summary of recommendations. Geneva, 2011. WHO/RHR/11.30.
    http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/rhr_11_30/en/         .

     

    During the next pregnancy, calcium supplementation is recommended [3] Citation 3. World Health Organization. Calcium supplementation in pregnant women. 2013.
    http://apps.who.int/iris/bitstream/10665/85120/1/9789241505376_eng.pdf          in women with low calcium intake (Chapter 1, Section 1.2.5).

    Footnotes
    • (a)The HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) is a potential lifethreatening complication for both the mother and foetus).
    References
    Path