Hypertensive Diseases of Pregnancy

Hypertension in pregnancy is common and associated with significant maternal and foetal harm. It is classified into four sub-groups:

Gestational hypertension
- SBP > 140mmHg or DBP > 90mmHg
- Present after 20^th week of gestation
- Resolving following delivery
  Usually within 6 weeks.
Pre-eclampsia/Eclampsia
- Pre-eclampsia is defined as gestational hypertension with organ dysfunction or proteinuria
- Pre-eclampsia with severe features is pre-eclampsia with severe end-organ dysfunction
- Eclampsia is defined as pre-eclampsia with seizures
Chronic hypertension
Pre-existing hypertension.
Chronic hypertension with super-imposed pre-eclampsia/eclampsia

This covers pregnancy induced hypertension and pre-eclampsia. Eclampsia is covered at Eclampsia.

Epidemiology and Risk Factors

Risk factors include:

Patient factors:
- Age > 35
- Pre-existing HTN
- CKD
- DM
- Anaemia
- Living at altitude
- Non-smokers
Pregnancy factors:
- Nulliparity
- Multiple gestation

Pre-eclampsia is:

A leading cause of maternal morbidity and mortality
Present in 5-8% of pregnancies
Wide variation in incidence, with ↑ rates in under-resourced environments.

Pathophysiology

Underlying processes driving placental insufficiency include:

Maternal endothelial dysfunction
- Altered endothelial function
  - ↑ Endothelial secretion
  - ↓ Nitric oxide
- Normal development of a high-flow, low-resistance placental circulation does not occur
Acute atherosclerosis and thrombosis of placental vessels
Results in ↓ placental flow and structural blood vessel damage.

These processes:

Lead to the triad of:
- Vasoconstriction
- Platelet activation and aggregation
- Loss of circulating volume
Result in other end-organ dysfunction
- A
  - Laryngeal oedema
- C
  - High cardiac output state with inappropriate SVR
  - Diastolic dysfunction
  - ↓ Venous capacitance
    Subsequently, generally normal filling pressures. Risk of acute LV failure if diastolic dysfunction present, especially if given volume.
- D
  - Retinal vasospasm
  - Cerebral
    - Oedema
    - Haemorrhage
- F
  - Oliguria
  - Uraemia
- G
  - Synthetic coagulopathy
- H
  - Consumptive coagulopathy

Clinical Manifestations

Pre-eclampsia is classified by:

Gestational age at diagnosis
- Late
  ≥37 weeks.
  - Majority of cases
- Preterm
  34-37 weeks.
- Early
  <34 weeks.

Earlier onset is associated with greater severity.

Severity
- Pre-eclampsia
  Gestational hypertension with:
  - Proteinuria
    >0.3g/24 hours.
  - Organ system involvement
    - Cardiorespiratory
      - Pulmonary oedema
    - CNS
      - New-onset, persistent headache
      - Visual disturbances
    - Renal
      - Creatinine >100mmol/L or doubling
    - GIT
      - Transaminases ↑ 2× ULN
    - Haematological
      - Platelets ⩽100/μL.
    - Uteroplacental circulation
- Pre-eclampsia with severe features
  Pre-eclampsia with any of the following features:
  - Cardiorespiratory
    - Severe hypertension
      Defined as SBP > 160mmHg or DBP > 90mmHg.
    - Hypertensive crisis
      Defined as SBP >180mmHg or DBP >110mmHg.
    - Pulmonary oedema
    - Ventricular tachycardia
  - CNS
    - Seizures/eclampsia
    - Papilloedema
    - PRES
    - Clonus/hyperreflexia
  - Renal
    - Proteinuria
      ≥5g/24 hours.
    - Protein/creatinine >0.5g/mmol.
    - Renal failure
      Including oliguria <500ml/24 hours.
  - GIT
    - Hepatic tenderness
    - Nausea/vomiting
  - Haematological
    - Haemolysis
    - DIC
  - Uteroplacental circulation
    - Placental abruption
    - IUGR
    - Abnormal umbilical/uterine blood flow
      Absent or reversed end-diastolic flow.
  - HELLP syndrome
    Haemolysis, elevated liver enzymes, thrombocytopaenia.

Haemolysis screen consists of:

Reticulocyte count
↑ Due to ↑ marrow turnover.
Blood film
- Schistocytes
  Mechanically fragmented erythrocyte, favours intravascular mechanical haemolysis.
LDH
Present in many cells and so not specific for haemolysis (as opoposed to other cellular destruction). Substantial ↑ (4-5× ULN) favours intravascular over extravascular haemolysis.
Haptoglobin
Binds free haemoglobin, and is non-specific for intravascular vs. extravascular haemolysis. Acute phase reactant and so result may be equivocal in inflammatory states.
Free Hb
↑ Due to cellular destruction.
Bilirubin
↑ Due to haemoglobin metabolism. Classically ↑ conjugated bilirubin, although unconjugated may ↑ in concurrent hepatic impairment.

Investigations

Management

For severe pre-eclampsia or hypertensive crisis:

Give magnesium for seizure prophylaxis
Aim to lower BP by 10-20mmHg every 10-20 minutes to ↓ incidence of intracerebral haemorrhage

Preventative:

Limit intravenous fluid
IV fluid ↑ risk of APO.
- Avoid if:
  - Euvolaemic
  - Renal function normal
Avoid NSAIDs
Reduce APO risk.
Aspirin
Indicated in pregnancy with major risk factors for pre-eclampsia, including:
- Pre-disposing medical conditions
  - SLE
  - Scleroderma
  - Anti-phospholipid syndrome
- Chronic hypertension
- Diabetes
- CKD
- Oocyte donation
- Family history of pre-eclampsia
  Mother or sister.

Resuscitation:

C
- Control of blood pressure
  - Target SBP 140-150mmHg and DBP 90-100mmHg
  - Strategy depends on severity of hypertension
    - Hypertensive crisis:
      - Labetalol
        
        20-80mg IV over 2 minutes
        Can repeat every 10 minutes.
      - Nifedipine
        
        10-20mg PO IR
      - Hydralazine
        
        10mg IV Q20 minutes
      - GTN
        For hypertension and APO
D
- Seizure treatment and prophylaxis
  - Magnesium Sulphate
    - Prophylaxis and treatment for eclampsia in women with severe pre-eclampsia
      Not recommended for use as an antihypertensive agent.
    - Multifactorial mechanism of action:
      - ↑ Prostacyclin synthesis
      - ↓ Calcium influx
        Thereby ↓ ATP-consuming Ca²⁺-dependent processes.
      - NMDA antagonism
    - Give 4g over 20 minutes, and then 1g/hr thereafter
    - Target level is 1.7-3.5mmol/L
    - Blood levels should be performed:
      - Q6H in women with renal impairment
      - If any of:
        
        RR < 12
        
        UO < 100ml over 4 hours
        
        Loss of patella reflexes
        
        Seizures
        Including repeat seizures.
    - Magnesium toxicity
      - Associated with muscular weakness, rarely respiratory arrest
      - Unlikely if deep tendon reflexes present
      - Treated with:
        
        Calcium
        
        RRT
  - Anticonvulsants
    - Conventional anticonvulsants are only indicated for:
      - Persistent seizures (>5 minutes) with therapeutic magnesium levels
      - Magnesium contraindication
    - Benzodiazepines
      - Lorazepam 4mg IV
      - Midazolam 1-2mg IV

Specific therapy:

Pharmacological
- For non-severe hypertension:
  - Labetalol
    Drug of choice.
    - 100-400mg PO BD-TDS
  - Nifedipine
    - 20-60mg PO SR
  - Methyldopa
    - 250-750mg PO TDS
  - Clonidine
    - 75-300μg PO TDS
  - Hydralazine
    - 25-50mg PO Q8H
  - Metoprolol
  - Propranolol
Procedural
- Delivery
  - Only curative option
    Note that pre-eclampsia can continue to worsen after delivery and may persist until after the puerperium.
  - Neuraxial techniques preferred in absence of coagulopathy
    No clear advantage of any (CSE, epidural, single-shot spinal) technique.

Disposition:

Admission
ICU or HDU may be required for BP management, and after delivery.
Delivery
Timing of delivery is dependent on gestational age at time of onset of pre-eclampsia:
- Previable (< 23⁶ weeks)
  - High risk patient
  - Will likely require either:
    - Termination of pregnancy
    - Extreme preterm delivery
- 24-31⁶ weeks
  - High risk patient
  - Transfer to tertiary institution
  - Will likely require pre-term delivery
  - Aim to prolong pregnancy as able
- 32-36⁶ weeks
  - Aim to prolong pregnancy
  - Delivery where appropriate paediatric support is available
- 37⁰
  - Planned delivery

Breastfeeding and Post-Partum Management

Ongoing and new-onset hypertension occur in the post-partum period. In addition to drugs used antenatally, drugs with low milk:maternal plasma ratios include:

Enalapril
Captopril

Anaesthetic Considerations

A
- Laryngeal oedema
  - Note presence of stridor pre-induction
  - Use a smaller ETT
C
- Hypertension
  - Management is difficult
  - Hypertension with light GA/laryngoscopy may be problematic
  - Key questions:
    - What is the current BP?
    - What is the trend in the BP?
    - What antihypertensive agents is the patient taking?
- Volume state
  May have ↓ intravascular volume; ↑ hypotension with neuraxial techniques.
D
- Likelihood of eclampsia
  Evaluate presence of:
  - Headache
  - Hyperreflexia/clonus
  - Visual symptoms
  - Extreme hypertension
- Anaesthetic technique
  - Epidural
    - Reduces BP, and improves placental perfusion
    - Provides analgesia during labour
    - Slow titration may be better than spinal in severe pre-eclampsia
    - Consider inserting early, prior to thrombocytopenia developing
    - Requires normal coagulation profile prior
      - Platelet count >70,000/ml
        Higher is better. Institutional policy may differ.
      - Routine APTT/PT is not required unless:
        
        Clinical history of bleeding
        
        Other clinical condition that may contribute to coagulopathy
  - Spinal
    - Safe alternative
    - May require additional volume to compensate for the low-volume pre-eclamptic state
  - CSE
    - Preferable to spinal if surgery is long
  - GA
    - RSI associated with dangerous hypertension
      Consider:
      - Labetalol 1mg/kg pre-induction
        ↓ BP without affecting foetal blood flow.
    - Magnesium ↑ sensitivity to muscle relaxants
F
- Volume state
  - Urine output
  - Thirst
H
- Coagulation profile

Complications

Maternal complications of severe pre-eclampsia include:

Death
- 40% due to cerebral oedema/haemorrhage
- 40% due to pulmonary
  Usually iatrogenic fluid overload.
- Hepatic failure
  Including hepatic rupture.
A
- Airway obstruction
  Vocal cord oedema due to ↓ oncotic and ↑ hydrostatic pressure.
B
- Pulmonary oedema
  - Usually due to low oncotic pressure or ↑ capillary permeability
  - Rarely due to diastolic dysfunction
  - Risk ↑ following delivery
D
- Cerebral haemorrhage
- Cerebral oedema
F
- Renal failure
H
- DIC

Foetal complications of pre-eclampsia include:

IUGR
FDIU
Preterm birth

Prognosis

Significant risk for maternal mortality:

4× for pre-eclampsia
40× for eclampsia

Morbidity persists even after delivery, with ↑ risk of:

Death
IHD
CVA
Renal disease

Key Studies

MAGPIE (2002)
- ~10,00 women with pre-eclampsia, pre- or <24 hours post-partum, without contraindication to magnesium
- Multi-centre, double-blind, RCT
- Magnesium sulfate vs. placebo
- Significantly ↓ eclampsia in magnesium group (0.8% vs. 1.9%, 58% RRR, NNT 91)
- No change in maternal mortality (0.2% vs. 0.4%)
- No change in foetal mortality
  Obviously only for the pre-partum cohort.

References

Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
Dennis AT. Management of pre-eclampsia: issues for anaesthetists. Anaesthesia. 2012;67(9):1009-1020.
Dennis AT, Castro J, Carr C, Simmons S, Permezel M, Royse C. Haemodynamics in women with untreated pre-eclampsia*. Anaesthesia. 2012;67(10):1105-1118.
Dennis AT, Solnordal CB. Acute pulmonary oedema in pregnant women. Anaesthesia. 2012;67(6):646-659.
Dennis AT, Castro JM. Hypertension and haemodynamics in pregnant women - is a unified theory for pre-eclampsia possible? Anaesthesia. 2014;69(11):1183-1189.
New Zealand Committee of RANZCOG, NZCOM. Guidance regarding the use of low-dose aspirin in the prevention of pre-eclampsia in high-risk women. 2018.
Lowe SA, Bowyer L, Lust K, McMahon LP, Morton M, North RA, Paech M. Said JM. Guideline for the Management of Hypertensive Disorders of Pregnancy. 2014.
Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. The Lancet. 2002;359(9321):1877-1890. doi:10.1016/S0140-6736(02)08778-0