Pre-eclampsia and Eclampsia
This hypertensive disorder of pregnancy is defined as a new onset of hypertension and proteinuria after 20 weeks of gestation. In Australia, we don't need proteinuria; we are happy to make the diagnosis with any sort of organ dysfunction. The definition of eclampsia is the presence of otherwise unexplainable seizures in a patient with preeclampsia.
This comes up fairly frequently in the SAQs. In broader terms, the pregnancy-related SAQs which are not about the jaundiced comatose woman are usually about the hypertensive seizure lady. These two variants between them seem to cover about 75% of the total spectrum of past paper questions. So, knowing these topics well sets you up to pass the majority of O&G material in the Part II exam. Here is a list of previous preeclampsia related questions:
- Question 19 from the second paper of 2014 (diagnostic approach)
- Question 20 from the first paper of 2012 (diagnostic approach and causes of seizures)
- Question 23 from the first paper of 2011 (management of severe preeclampsia)
- Question 1 from the second paper of 2008 (identical to Question 23)
Of these, several are not specifically about preeclampsia. Rather, it is the most sensible differential from a list of differentials which the candidates are expected to generate. For instance, Question 19 from the second paper of 2014 offers a scenario where a medically complex pregnant patient presents in such a manner as to bring up serotonin syndrome and PRES as sensible differentials, and preeclampsia is merely one of the possibilities.
Risk factors for preeclampsia:
There are certain features, identifiable at antenatal booking, which are associated with an increased risk of preeclampsia:
Risk factors for pre-eclampsia and eclampsia
- First pregnancy
- Multiple gestation
- African-American descent
- Molar pregnancy
- Pre-existing hypertension
- Family history
- Previous pre-eclampsia
Others have held forth extensively on the pathogenesis of this condition; suffice to say it is thought to be a systemic response to placental hypoperfusion, with increased activation of the potent vasoconstrictor endothelin-1, as well as an increased sensitivity to vasoconstrictors in general, and a down-regulation of vasodilatory mechanisms such as nitric oxide synthase.
In order to be labelled as a pregnant woman with preeclampsia, one must have a certain set f features:
Diagnostic criteria for preeclampsia:
- Hypertension: 140/90 mmHg
- Proteinuria: Over 0.3g of protein in a 24 hr collection;
- a random urine protein./creatinine ratio over 30mg/mmol
Furthermore, there are several features which suggest that the condition is severe, and worth worrying about:
Features of severe preeclampsia:
- Severe Hypertension: 160/110 mmHg
- Intracranial haemorrhage or stroke can occur
- Cardiovascular collapse:
- Normal contractility but massively increased afterload
- This progresses to pulmonary oedema
- Massive Proteinuria: Over 2g of protein in a 24 hr collection;
- Renal failure with oliguria
- Uric acid levels may rise
- Deranged LFTs
- There may be hepatic oedema and rupture
- Visual disturbance, clonus, headaches
- this progresses to seizures, cerebral oedema and stroke
- There may be a posterior reversible encephalopathy
- Thrombocytopenia, DIC, haemolysis
A standard panel of tests should be requested:
- Uric acid levels
Continuous ECG monitoring of the mother, and continuous foetal heart monitoring should commence.
Workup of the non-specific preeclampsia-like presentation in the pregnant patient
Question 19 from the second paper of 2014 presented a scenario with numerous possible causes for fever and decreased level of consciousness; the question from the college was mainly about generating differentials and doing a diagnostic workup. The list of differentials was enormous, made more so by the following features of the presenting history:
- Low-grade fever
- Hypertension, on labetalol
- Recent delivery of a stillborn foetus at 32 weeks
- DIC as a complication of vaginal delivery
- On paraetamol, tramadol and an SSRI
- Background history of Hep C
With this, you could do just about any sort of differential diagnosis list. Here is a sample, adopted from the chapter on approaching the unconscious ICU patient.
Intrinsic neurological cause
Traumatic or environmental causes
Endocrine and metabolic causes:
Differentials specific to pregnancy:
Causes of worsening seizure control in pregnancy
So, perhaps it is not eclampsia but the consequences of normally well controlled epilepsy going haywire. Reasons an epileptic might have more seziures during pregnancy:
- Poor compliance
- Anxiety regarding teratogenicity, and cessation of drugs on those grounds
- Increased clearance of the drug
- Increased volume of distribution
- Stress and sleep deprivation
- Malabsorption of oral agents due to poor stomach emptying
Weirdly, progensterone has an antiepileptic effect, and its levels are wildly elevated in pregnancy. In fact Vajda et al (2007) did a review of this issue and found that "the epileptic process seemed to become “better” no less often than it became “worse” during pregnancy".
Consequences of seizures in terms of perinatal morbidity and mortality
Consequences to the foetus:
- maternal hypoxia = foetal hypoxia
- maternal acidosis = foetal acidosis
- Transient foetal bradycardia during the seizure
- Uterine haemorrhage and foetal loss
- Foetal intracranial haemorrhage
- Vitamin K deficiency due to antiepileptic use, leading to coagulopathy
Management of preeclampsia
The key step is to get the baby out. Everything returns to normal after delivery. Except pulmonary oedema: this may actually be exacerbated.
While you are organising the delivery, there are various supportive measures which should be taken:
Blood pressure control
On one hand, one must prevent maternal stroke, intracranial haemorrhage and cerebral oedema. On the other hand, one must perfuse the placenta. The key is to keep the systolic under 160, and the diastolic under 110.
Labetalol, hydralazine and nifedipine are used as first line agents. There is no difference between them in terms of outcomes.
Methyldopa and sodium nitroprusside are second-line agents, if the hypertension is refractory.
Magnesium sulfate is the primary agent. Both Oh's manual and the RCOG statement quote the MAGPIE study, which convincingly demonstrated a reduction in maternal morbidity with magnesium. How it works, nobody knows. It has a half-life of 4 hours and is rapidly excreted (its pharmacokentics are dealt with elsewhere). One aims for a serum level of 2.0-3.5mmol/L.
Respiratory paralysis is difficult to accomplish; you need a level over 7.5mmol/L. As long as the deep tendon reflexes are present, you are unlikely to develop that sort of toxicity.
Seizure control in eclampsia
- Give an extra dose of magnesium
- Administer IV diazepam
- Consider phenytoin
- If all else fails, its time for thiopentone and intubation.
In general, there might be many possible aetiologies for the seizures, and one must consider a CT head to exclude major structural pathology.
A template approach
- Attention to the ABCS, with management of life-threatening problems simultanous with a rapid focused examination and a brief history.
- Assess the need for airway support in context of post-ictal unconscious state
- Weigh benefits of intubation against risks in context of the known airway access problems associated with pregnancy
- Assess oxygenation and briefly examine for aspiration
- High flow oxygen via NRBM if patient is not in need of immediate intubation
- Circulatory support
- Assess cardiovascular stability
- left lateral 30° tilt if hypotensive
- Access with widebore cannula
- Assess cardiovascular stability
- Immediate investigations:
- FBC - looking for thrombocytopenia
- LFTs - looking for HELLP, hepatic encephalopathy
- EUC - looking for hyponatremia
- Antiepileptic drug levels, if relevant
- CT brain, if the patient fails to awaken
- Specific management
- labetalol, nifedipine or hydralazine are of equivalent benefit
- methyldopa and sodium nitroprusside are second line agents
- Antiepileptic therapy:
- Loading dose of magnesium sulfate, followed by an infusion, aiming at a serum level of 2.0-3.5mmol/L
- Diazepam and phenytoin can be considered if seziures are refractory
- Arrange for a consultation with the obstetrician regarding the safety and practicality of immediate delivery.