- Presentation & diagnosis
- Checklist & tables
- Questions & discussion
- PDF of this chapter (or create customized PDF)
presentation & diagnosis
- Very common among critically ill pregnant women.
- Consider any pregnant woman admitted to ICU as having preeclampsia until proven otherwise.
- Usually occurs between 20 weeks of gestation and about 6 weeks postpartum.
- Rarely can occur earlier than 20 weeks in patients with molar pregnancies.
- Main clue is hypertension, but patients aren't always profoundly hypertensive.
- Common risk factors for preeclampsia:
- Age >35
- Obesity, obstructive sleep apnea
- History of preeclampsia, renal disease, hypertension, or diabetes
- Thrombophilia, lupus, antiphospholipid antibody syndrome
@kat__evans “1/3 all eclampsia cases occur in the postpartum stage. If a pt of child bearing age presents with a first time seizure, could this be preeclampsia? Think, could this pt be postpartum? Investigate, is the pt lactating, is there a recent C-section scar?” #SMACC #badEM
— Amy Craike (@AmesCraike) March 27, 2019
clinical findings of preeclampsia
- Pulmonary edema
- Pitting edema – especially involving hands and face (non-dependent edema, suggesting endothelial dysfunction)
- Renal: acute kidney injury, oliguria
- GI: epigastric or right upper-quadrant discomfort
- Hypertensive encephalopathy with vision changes & headache
- Intracranial hemorrhage
- Hyper-reflexia (sometimes with clonus), seizures
- Electrolytes including Ca/Mg/Phos
- Complete blood count
- Liver function tests & ammonia
- Coags, D-dimer, and fibrinogen (note that normally, fibrinogen is elevated in pregnancy).
- LDH and haptoglobin
- Urinalysis and spot urine protein/creatinine ratio
- If febrile/hypotensive: lactate, blood cultures, procalcitonin
- Useful reference on normal lab values in pregnancy: Perinatology.com.
definition of preeclampsia?
-  HTN developing or worsening >20 weeks after gestation:
- SBP >160 or DBP >110 (persistent over >15 minutes)
- SBP >140 or DBP >90 (persistent over >4 hours)
-  Plus ANY of the following (proteinuria isn't required for the diagnosis)
- Proteinuria >0.3 g/d
- Reasonable surrogate measure is a spot urine protein/creatinine ratio >0.3 mg/mg.1
- Urine dipstick showing proteinuria is nonspecific, but a negative dipstick can usually be accepted as excluding significant proteinuria.2
- Acute kidney injury (Cr > 1.1 mg/dL or doubling of baseline value; note that normally Cr <0.8 mg/dL in pregnancy)
- Cerebral or visual disturbance (including severe headache, seizure, delirium, clonus)
- Note that the presence of seizures technically defines this as “eclampsia” (rather than preeclampsia).
- Pulmonary edema
- Transaminases above twice normal
- Platelets <100,000/mm3
- Proteinuria >0.3 g/d
-  Exclusion of alternative diagnoses, for example:
- Alternative cause of renal failure (e.g. glomerulonephritis)
- Alternative cause of hypertensive emergency (e.g. thyroid storm, cocaine)
- Primary CNS disease (e.g. meningitis, CVA)
- EtOH withdrawal
- Other types of microangiopathic hemolytic anemia (e.g., thrombotic thrombocytopenic purpura, hemolytic uremic syndrome)
diagnosis of HELLP syndrome (Hemolysis, Elevated LFTs, Low Platelets)
- HELLP is a manifestation of pre-eclampsia (not a separate disorder).2 It's a thrombotic microangiopathy which may be closely related to atypical hemolytic uremic syndrome.
- Clinical symptoms may include nausea/vomiting and right upper-quadrant pain.
- Laboratory findings:
- Microangiopathic hemolytic anemia (e.g. high LDH, low haptoglobin, schistocytes on blood smear)
- Elevated AST and ALT (above twice the upper limit of normal).
- Platelets <100,000/mm3.
- May cause hepatic hematoma that ruptures, leading to hemoperitoneum.
- Differential diagnosis includes pregnancy-induced thrombotic thrombocytopenic purpura (TTP) and acute fatty liver of pregnancy.
- Treatment of HELLP is discussed below.
HTN & volume management
blood pressure targets
- General strategy
- Antihypertensives generally indicated if SBP>160 or DBP>105 (MAP >120).
- Initial goal is decreasing MAP by ~20%.
- Eventually, the blood pressure should be gradually decreased to a target MAP of roughly ~100-115 mm. This target should be individualized to a certain extent, depending on the baseline blood pressure.
- Balance is required:
- Lowering blood pressure prevents end-organ hypertensive damage (e.g., intracranial hemorrhage).
- Excessive blood pressure drop may cause hypoperfusion (including the placenta). Placental hypoperfusion may stimulate the release of vasoconstrictive/inflammatory factors, which aggravate the underlying disease process.
- Nicardipine infusion
- Not traditionally a first-line agent for preeclampsia.
- However, it is an accepted option which has been shown to be safe and effective. It may be the most easily titrated strategy.3–5
- Traditionally the first-line agent.
- Given long half-life of labetalol, may be most sensible to administer as sequential boluses (see below).
- Nitroglycerine infusion
- May be useful in patients with cardiogenic pulmonary edema.
- IV hydralazine
- Not usually preferred, due to the capacity to cause unpredictable and prolonged drops in blood pressure.6
- If hydralazine is used, caution should be employed (e.g. using small doses, provided gradually over time).
- Oral nifedipine immediate release
- Although traditionally avoided in hypertensive emergencies, recent studies have shown that oral nifedipine is a potential treatment of preeclampsia.7
- If nifedipine is used, safety may be improved by spacing out doses sufficiently. Also note that the tablet must be swallowed whole (not administered sublingual or chewed or broken open).
- Pre-eclampsia causes endothelial damage, leading to third-spacing of fluids. This creates a very challenging situation, where patients are often intravascularly depleted. Unfortunately, administered fluid will generally rapidly extravasate into the tissues (causing harm rather than benefit).
- Some fluid might be reasonable to support perfusion among patients who are NPO (e.g. ~50 ml/hr of 5% dextrose in half-normal saline). However, large volumes should be avoided, as this may promote pulmonary edema.
- Avoid chasing oliguria with large volume of fluid. If oliguria doesn't respond to a small fluid bolus (300 ml), additional fluid may be inadvisable.8
Kat Evans at #SMACC discussed women presenting with eclampsia/preeclampsia in an emergency setting do not need IV crystalloids. Receiving enough with IV meds. High risk of fluid overload and Pulmonary Oedema. #INFiLL pic.twitter.com/ausPuGAMo2
— Bel Bruce (@BelRBruce) March 27, 2019
- Start oral antihypertensives once hemodynamically stabilized and improving. Unfortunately, many antihypertensives aren't suitable for pregnancy.
- Labetalol is generally the first-line agent (especially for patients who responded to IV labetalol).
- Start 200 mg PO BID
- Escalate dose gradually, until no longer requiring IV labetalol doses.
- Extended-release nifedipine is another solid option.
- Methyldopa is traditionally used; it is safe but not terribly effective.
- Other options which are safe for pregnancy include hydralazine, prazosin, or clonidine.
magnesium infusion for seizure prophylaxis
- Should be given to any critically ill, preeclamptic woman to reduce risk of seizure (unless contraindicated by myasthenia gravis, heart block, or severe hypocalcemia).
- Magnesium levels aren't routinely monitored in women with normal renal function. If levels are checked, they may be interpreted roughly as shown below.9
- Make sure to use the appropriate units! There are three different units in clinical use, so it's easy to get confused.
- If you are going to check magnesium levels, consider also checking electrolytes and calcium as well.
- The optimal duration of the magnesium infusion is unclear. Treatment is often continued until ~24 hours after delivery, when the patient is showing clinical signs of resolving preeclampsia.
- Load with 6 grams IV magnesium sulfate (24 mM).
- Infuse magnesium at 1-2 grams/hour (4-8 mM/hour)(some newer data and guidelines suggest that 1 gram/hour may be adequate).2,10
- 2 grams/hour (8 mM/hr) – may be more appropriate for higher weight & antepartum patients.
- 1 gram/hour (4 mM/hr) – may be more appropriate if mild renal insufficiency (Cr 1-2.5) and/or mild oliguria.
- Monitor carefully. Hold the infusion and check levels if signs of magnesium toxicity or renal failure:
- Signs of magnesium toxicity: loss of patellar reflexes, tachypnea due to respiratory muscle weakness
- Reduced urine output: acute kidney injury will eventually lead to magnesium accumulation
treatment with severe oliguria or creatinine >2.5 mg/dL
- Load with 4-6 grams IV magnesium sulfate (16-24 mM).
- Follow electrolytes & magnesium levels q4-6hr.
- Bolus with magnesium based on levels (don't use a maintenance infusion).
- Common side-effects include flushing, mild hypotension, and muscle weakness.
- Severe magnesium toxicity may cause respiratory depression or heart block. The treatment is IV calcium.
- Magnesium can suppress parathyroid hormone production, leading to symptomatic hypocalcemia. Treatment is cessation of the magnesium infusion and (again) administration of IV calcium.
- Most eclamptic seizures are self-limited.
- Magnesium is the front-line antiepileptic to prevent seizure recurrence.
- If patient hasn't yet received magnesium, load with 6 grams IV and infuse as above.
- If patient has received magnesium, consider re-loading with 2-4 grams IV.
- Infusion or maintenance doses as described above
- Benzodiazepine may be used for status epilepticus (e.g., ongoing generalized seizure >5 minutes).
- IV access: Lorazepam 0.1 mg/kg IV bolus
- No IV access: Midazolam 10 mg IM
seizure refractory to benzodiazepine & magnesium
- This is unusual and may suggest another process (e.g. intracranial hemorrhage).
- Consider early intubation and propofol infusion.
- Levetiracetam may be added as a second-line agent after magnesium.
diagnostics & neuroimaging
- Fingerstick glucose immediately, to exclude hypoglycemia
- Additional laboratory studies (if not already available).
- Consider imaging to exclude other pathology (e.g. intracranial hemorrhage, cerebral venous thrombosis). Patients with eclampsia will often have imaging features of PRES, as these two conditions may overlap substantially.
- More on PRES here.
treatment of HELLP syndrome
(don't forget the treatment for preeclampsia)
- HELLP is a subset of preeclampsia. Therefore, patients with HELLP also have preeclampsia
- Magnesium infusion is indicated in HELLP syndrome, as these patients are at risk for seizure.
- If hypertension is present, it should be treated in the same fashion as preeclampsia in general (see above).
subcapsular liver hematoma
- Should be suspected in any patient with preeclampsia/HELLP with RUQ pain.
- Diagnosis is based on ultrasonography.
- Treatment includes optimization of coagulation factors, large bore IV access, emergent surgery and/or angiographic embolization to treat hepatic rupture, and potentially even liver transplant.
- Get all hands on deck early (e.g. trauma surgeons with expertise in liver injury and transplant teams).
- Growing evidence indicates that HELLP could share many similarities with atypical hemolytic uremic syndrome (aHUS), which is caused by dysregulated complement activation.11 12
- One case report describes successful treatment of HELLP with eculizumab (a complement inhibitor).13 This might be considered in cases of HELLP which closely resemble atypical hemolytic uremic syndrome (e.g. prominent microangiopathic hemolytic anemia with low complement levels).
delivery & post-delivery course
- As with preeclampsia in general, severe HELLP is an indication for delivery.
- Deterioration may continue for two days after delivery, but improvement should subsequently occur. If deterioration continues for four days after delivery, consider alternative diagnostic possibilities (e.g. atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura).9
fetal monitoring & delivery
- As per Obstetrics team.
- Note that the fetus is a maternal end-organ, so fetal distress can be an early sign of systemic hypoperfusion (shock).
- If fetal stress is a symptom of maternal shock, then both delivery and maternal resuscitation may be required simultaneously.
- Definitive treatment of preeclampsia/HELLP is delivery of the fetus.
- If expedited delivery is possible and the fetus is pre-term (<37 weeks), consider steroid administration to promote fetal lung maturity.
- This decision will be made by obstetrics. Indications for delivery may include:
- Gestational age >37 weeks (term pregnancy)
- Refractory HTN despite three classes of antihypertensive agents
- Progressive thrombocytopenia
- Progressively worse renal or liver tests
- Pulmonary edema
- Worsening neurologic features (e.g. intractable headache, repeated visual scotomata, or seizures)
- Non-reassuring fetal status, suspected placental abruption, rupture of membranes.
disseminated intravascular coagulation (DIC)
- Follow coagulation studies.
- Factor replacement may be needed prior to delivery or if there is active bleeding.
- Note that fibrinogen targets in post-partum hemorrhage may be somewhat higher than in most patients (e.g. >200 mg/dL).
- Consider whether DIC may be caused by placental abruption.14
acute kidney injury
- There is no specific therapy for renal failure other than supportive care and avoidance of nephrotoxins.
- Consider other possible causes of kidney injury including glomerulonephritis, thrombotic thrombocytopenic purpura, or atypical hemolytic uremic syndrome. These may require specific treatment.
- Perfusion should be optimized as discussed above, with cautious use of fluids. Note that these patients often have leaky capillaries, so large-volume fluid resuscitation is unhelpful (may merely worsen pulmonary & systemic edema).15
other complications to be aware of
- Intracranial hemorrhage
- Retinal detachment
- Preeclampsia, immobility, and pregnancy are all risk factors for venous thromboembolism.
- DVT prophylaxis should be determined in coordination with the Obstetrics team, as this may affect spinal anesthesia & delivery.
checklist & tables
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questions & discussion
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- Failure to consider preeclampsia (may occur even in absence of proteinuria).
- IV hydrazine may cause precipitous drop in blood pressure, so try to avoid this when possible.
- Excessive volume administration in attempts to stimulate urine output.
- Failure to obtain an adequate laboratory panel (e.g. leading to a missed diagnosis of HELLP syndrome).
- ACOG Practice Bulletin 2019: Gestational HTN & preeclampsia
- Preeclampsia & eclampsia (Chris Nickson, LITFL)
- Preeclampsia & eclampsia (Anand Swaminathan and Jenny Beck-Esmay, CoreEM)