202410271921

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Tags: Obstetrics

Preeclampsia

Preeclampsia is a pregnancy-specific disorder characterized by

• new onset hypertension
• proteinuria
• after 20 weeks of pregnancy

2nd most common cause of maternal mortality after postpartum haemorrhage

More common in

• low / middle income countries
• racial / ethnic minorities

Diagnosis

Preeclampsia is a complex and heterogeneous disease, classified based on clinical symptoms and gestational age at onset

Part of Hypertensive Disorders of Pregnancy:

• PET
• gestational HT
• chronic HT

Classification from ACOG practice bulletin 222

ACOG definition of PET

Blood pressure

• Two readings >4h apart
  • SBP >/= 140 mmHg
  • DBP >/= 90 mmHg
  • after 20 weeks of gestation
  • in a woman with a previously normal BP.
• Single reading
  • SBP >/= 160 mmHg
  • DBP >/= 110 mmHg
  • (Severe HT can be confirmed w/i a short interval (minutes) to facilitate timely anti-HT therapy)
    Proteinuria

• /= 300 mg per 24-hour urine collection

  • (or this amount extrapolated from a timed collection) or
• PCR of 0.3 mg/dL or more or
• Dipstick reading of 2+
  • (used only if other quantitative methods are not available).
    Or, in the absence of proteinuria, new-onset hypertension with the new onset of any of the following:
• Thrombocytopenia
  • plt < 100x10^9/L.
• Renal insufficiency
  • serum creatinine >1.1 mg/dL
  • or a doubling of the serum creatinine in the absence of other renal disease
• Impaired liver function
  • ↑ liver transaminases to twice the normal concentration.
• Pulmonary edema.
• New-onset headache
  • unresponsive to medication
  • not accounted for by alternative diagnoses
• presence of visual symptoms.

Classification of PET

preeclampsia without severe features if

• no end-organ dysfunction
• BP > 140/90 mmHg but < 160/110 mmHg
  PET with severe features if
• any of these symptoms are present, OR
• BP >160/110 mmHg

Some guidelines classify Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome and eclampsia as severe forms of preeclampsia with predominantly hepatic or neurologic dysfunction

HELLP syndrome is characterized by

• severe thrombocytopenia
  • platelet < 100x10^9/L
• ↑ liver enzymes > twice the normal range
  It may be associated with
• ↑BP
• proteinuria
• other signs of organ damage.

Eclampsia is a severe, life-threatening form of preeclampsia in which the patient develops generalized tonic-clonic seizures

Classification based on gestational age at onset

Only a small portion of the cases present at early gestational age; however, those are associated with high maternal and neonatal morbidity and mortality.

The majority of preeclampsia cases present at term gestation and have a milder course. Thus, preeclampsia can be classified as

• preterm
  • a/w delivery at <37 gestational weeks
• term
  • a/w delivery at 37 weeks or later
• postpartum preeclampsia
  • onset after delivery.

Risk factors

clinical high risk factors

• chronic renal disease
• chronic HT
• DM
• autoimmune disease
• Hx of PET
• multifetal gestation
  Moderate risk factors
• nulliparity
• maternal age >40
• interpregnancy interval >10y
• FHx of PET

Pathophysiology

In preeclampsia, trophoblasts fail to differentiate into endothelial-like cells, resulting in poor trophoblast invasion and incomplete spiral artery remodeling.
This leads to placental ischemia and the release of ==inflammatory and vasoactive mediators ==into the maternal circulation, triggering downstream effects such as angiogenic imbalance and endothelial dysfunction.
These changes result in a vasoconstrictive state, oxidative stress, and microemboli, contributing to the involvement of multiple organ systems and manifesting as the clinical features of preeclampsia

Mx

Antepartum Mx

most interventions have been unsuccessful, secondary to the multifactorial pathogenesis of the disease

Aspirin

Low-dose aspirin is the most useful approach currently available to prevent severe preeclampsia and delay the onset of preeclampsia in individuals at increased risk

The beneficial effect of lower doses of aspirin (60-150 mg daily) is related to a reduction in platelet thromboxane synthesis. Preeclampsia is associated with a functional imbalance between vascular prostacyclin and thromboxane A2 production, leading to increased platelet turnover

↓ PET incidence
↓ preterm birth <37wks
no sig. ↑ in adverse outcomes related to bleeding

For patients with two moderate risk factors or one high-risk factor, ACOG recommends initiating 81 mg aspirin daily between 12 and 28 weeks of gestation, ideally prior to 16 weeks, continued until delivery

No consensus exists regarding the timing of aspirin discontinuation

strong evidence supports the recommendation of moderate-intensity exercise of at least 140 minutes per week and calcium supplementation in parturients with low baseline calcium intake (less than 900 mg per day)

BP control

Effective blood pressure control is a mainstay in the management of preeclampsia to decrease maternal and fetal complications.
In the absence of pre-existing chronic hypertension, antihypertensive therapy should be expedited when blood pressure reaches or exceeds 160/110 mmHg and persists after repeat measurement 15 minutes later.

Intravenous hydralazine or labetalol and oral nifedipine immediate release are the three agents most commonly used to treat severe acute hypertension

In those with pre-existing chronic hypertension, the Chronic Hypertension and Pregnancy (CHAP) trial in 2022, a large, multicenter, randomized trial, demonstrated that antihypertensive treatment for mild chronic hypertension in pregnancy (blood pressure <160/105 mm Hg) to a goal (<140/90 mm Hg), primarily with labetalol or nifedipine compared with no treatment (unless blood pressure was severe), reduced the composite risk of

• superimposed preeclampsia with severe features,
• indicated preterm birth <35 weeks,
• placental abruption,
• fetal/neonatal death

As a result of this trial, professional societies in the US have recommended treatment of patients with chronic hypertension in pregnancy to a blood pressure goal of <140/90 mm Hg.
First-line agents for long-term blood pressure control include oral beta blockers, calcium channel blockers, and alpha blockers, most commonly labetalol, nifedipine XL, and hydralazine

The benefits of antihypertensive treatment must be balanced against potential risks, as overly aggressive blood pressure reduction may compromise uteroplacental perfusion, potentially leading to fetal growth restriction or distress

some antihypertensive medications such as ACE inhibitors and angiotensin receptor blockers remain contraindicated in pregnancy due to their association with fetal renal dysfunction and other congenital anomalies

While HBPM shows promise in improving hypertension management during pregnancy, it should be used as a complement to, rather than a replacement for, regular antenatal care and clinical assessments.

At this time, there is insufficient evidence to conclude that home HBPM reduces severe maternal morbidity or mortality or reduces racial disparities in clinical outcomes

Magnesium

Intravenous magnesium sulfate is a cornerstone in the management of preeclampsia with severe features and eclampsia, primarily for

• seizure prophylaxis
• fetal neuroprotection

The landmark MAGPIE Trial (2002) demonstrated that magnesium sulfate halves the risk of eclampsia in women with preeclampsia

For seizure prophylaxis, magnesium sulfate infusion begins at the start of labor or induction, or prior to cesarean delivery and continues for 12- 24 hours postpartum

in patients with severe features undergoing expectant management, magnesium is initiated in the setting of clinical instability, usually upon initial presentation, such as for persistent severe range blood pressures, and may be discontinued with stabilization

While the exact mechanism of seizure prophylaxis is unknown, magnesium’s efficacy is postulated to result from its role as a central nervous system depressant by blocking N-methyl-D-aspartate (NMDA) receptors and calcium channels

Careful monitoring is crucial due to the narrow therapeutic index of magnesium

The therapeutic range of magnesium is 4.8-8.4 mg/dL, however data supporting these values are limited

The most common regimen for achieving a therapeutic level expeditiously while also minimizing adverse effects consists of

• IV 4-6 g loading bolus over 20-30 min,
• maintenance dose of 1-2 g/h

When IV access is not feasible, magnesium sulfate can be given intramuscularly (IM) at a dose of 10 g (5 g IM in each buttock) and then 5 g every 4 hours. In order to reduce pain with IM injection, magnesium can be mixed with 1 mL of lidocaine 2% solution

In the setting of renal insufficiency, there is a higher risk of magnesium toxicity given magnesium is almost exclusively renally excreted.
In these situations, the maintenance infusion dose may need to be reduced from 2g/h to 1g/h or may need to be discontinued altogether with the plan to administer boluses as needed based on serum magnesium levels checked every 4-6 hours.

Individuals receiving magnesium for seizure prophylaxis may experience

• nausea,
• vomiting,
• flushing,
• drowsiness,
• weakness,
• confusion

The magnesium infusion should be discontinued if a magnesium serum level exceeds 9.6 mg/dL (8 mEq/L), and the level should be checked every 2 h with reinitiation of the infusion when serum levels fall below 8.4 mg/dL (7 mEq/L).

Hypermagnesemia is treated with intravenous calcium gluconate 10% solution, 10 mL over 3 minutes

Magnesium toxicity should be suspected, ruled out, and rapidly treated in parturients who suffer cardiac arrest with ongoing or recent magnesium therapy, particularly if no other etiologies are confirmed

Important considerations for when magnesium is contraindicated include

• myasthenia gravis,
• hypocalcemia,
• moderate to severe renal failure,
• acute myocardial infarction,
• heart block,
• myocarditis.
  In these cases, benzodiazepines or levetiracetam can be used for alternative seizure prophylaxis

Timing and mode of delivery

Patients with preeclampsia without severe features may be expectantly managed until 37 weeks’ gestation when delivery is indicated

Delivery for preeclampsia with severe features is indicated at 34 weeks’ gestation

Mode of delivery is based on standard obstetric indications

Anaesthetic Mx

Diastolic dysfunction is the hallmark of cardiovascular dysfunction in preeclampsia

Neuraxial anesthesia is associated with sympathetic blockade and modest afterload reduction, both of which are beneficial for blood pressure control and diastolic dysfunction. Therefore, in the absence of contraindications, EA should be initiated wherever possible and as early as possible in women with preeclampsia in active labor

There are a number of considerations when evaluating the risk of neuraxial anesthesia. Coagulopathy associated with preeclampsia, particularly in patients with HELLP syndrome or thrombocytopenia, may increase the risk of epidural hematoma, and thus, the use of neuraxial analgesia is relatively contraindicated.
Historically, societal guidelines specify a higher risk of this complication with platelet counts of < 70 x 10^9/L. Recently amended guidelines from the Society for Obstetric Anesthesia and Perinatology propose a more liberal range

If thrombocytopenia is present, the platelet count should be checked before spinal / epidural placement, and epidural catheter removal.

The sFlt-1:PlGF ratio is used as a screening tool to predict the development of severe preeclampsia over the next two weeks

The attenuation of the hypertensive response to intubation can be achieved using one or a combination of several drugs
The first is magnesium sulfate, which can be given to obtund catecholamine release as a bolus of 30 mg/kg IV immediately after induction of anesthesia in magnesium-treated patients and 45 mg/kg if the patient is magnesium naïve

Hypoxemia in patients with hypertensive disorders of pregnancy is twice as likely compared to normotensive patients

Postpartum Mx

In patients with preeclampsia diagnosed in the ante- and intrapartum periods, the main postpartum efforts are focused on managing ↑BP

References

Chapter 9 Preeclampsia and Eclampsia Enhanced Detection and Treatment for Morbidity Reduction - BPRCA