CONTENTS
- Rapid Reference 🚀
- Diagnosis
- Treatment
- Podcast
- Questions & discussion
- Pitfalls
lab panel
- Glucose, electrolytes including Ca/Mg/Phos.
- Complete blood count.
- Liver function tests & ammonia.
- INR, PTT, fibrinogen, LDH, haptoglobin (note that normally, fibrinogen is elevated in pregnancy).
- Urinalysis.
- TSH (thyroid stimulating hormone).
- Spot urine protein/creatinine ratio.
- If febrile/hypotensive: Blood cultures.
- (Reference on normal lab values in pregnancy: Perinatology.com)
imaging
- Chest X-ray (e.g., if respiratory failure, or concern for possible pneumonia).
- OB ultrasound (e.g., if abruption possible).
- Neuro/visual changes: may consider CT/MRI brain (r/o ICH) or retinal exam (r/o detachment).
- Right upper-quadrant pain: US to exclude subcapsular liver hematoma.
key therapies
obstetric consultation
- Fetal monitoring.
- ? Steroid for lung maturation.
- ? Expedited delivery.
when to suspect pre-eclampsia?
- Preeclampsia is common among critically ill pregnant women, so this possibility should be strongly considered any time a pregnant or postpartum woman is admitted to the ICU.
- Preeclampsia usually occurs between 20 weeks of gestation and about 6 weeks postpartum.
- Rarely can occur earlier than 20 weeks in patients with molar pregnancies.
- A key clue is hypertension, but patients may not be impressively hypertensive in an absolute sense.
- Common risk factors for preeclampsia: (RR = relative risk)(32487899)
- History of preeclampsia (RR ~7; risk of recurrence is ~20%).
- Chronic hypertension (incidence of ~20%).(Vincent 2023)
- Diabetes (RR ~3.5); Renal disease.
- Body mass index >35 (RR ~1.5).
- Thrombophilia; lupus; antiphospholipid antibody syndrome (RR ~10).
- Age >40 (RR ~1.7).
- Multifetal pregnancy (RR ~3); first pregnancy (RR ~2.9).
clinical findings of preeclampsia may include:
- Cardiopulmonary:
- Hypertension.
- Pulmonary edema.
- Rapid weight gain.
- 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.
- Neurologic:
- Altered mental status ranging from confusion to coma.
- Visual disturbance.
- Headache.
- Intracranial hemorrhage.
- Hyperreflexia (sometimes with clonus).
- Seizures.
diagnostic criteria for preeclampsia
Diagnosis requires three components. Patients who have end-organ dysfunction (not including proteinuria) have “preeclampsia with severe features.”
[1] HTN developing or worsening >20 weeks after gestation, including either:
- SBP >160 or DBP >110 (persistent over >15 minutes).
- SBP >140 and/or DBP >90 (persistent over >4 hours).
[2] Plus ANY of the following:
- Proteinuria >0.3 g/day, spot urine protein/creatinine ratio >0.3 mg/mg, or urine dipstick testing of 2+ or more.
- Urine dipstick showing proteinuria is nonspecific, but a negative dipstick can usually be accepted as excluding significant proteinuria.(29803330) Alternatively, 2+ or greater proteinuria strongly suggests clinically significant proteinuria.(34051884)
- Proteinuria is NO LONGER required for the diagnosis of preeclampsia.
- Acute kidney injury (Cr >1.1 mg/dL).
- Note that creatinine is normally <0.8 mg/dL in pregnancy.
- Cerebral/visual disturbance including:
- Seizure (eclampsia).
- Altered mental status.
- Persistent visual scotomata or blindness.
- Stroke.
- Hyperreflexia with clonus.
- Severe headaches refractory to acetaminophen.
- Pulmonary edema (in the absence of another etiology).
- Hepatic involvement:
- Transaminitis above twice normal.
- Severe, persistent abdominal pain in the right upper quadrant or epigastrium that is otherwise unexplained.
- Hematological complications:
- Thrombocytopenia <150,000/mm3.
- Disseminated intravascular coagulation.
- Hemolysis.
- Uteroplacental dysfunction, including:
[3] Exclusion of alternative diagnoses, for example:
- Toxicologic, e.g.:
- Medication side-effects.
- Cocaine or methamphetamine use.
- EtOH withdrawal.
- Thyroid storm.
- Glomerulonephritis.
- Primary CNS disease (e.g., stroke, meningitis).
- Other types of microangiopathic hemolytic anemia:
- TTP (thrombotic thrombocytopenic purpura).
- HUS (hemolytic uremic syndrome).
- Acute fatty liver of pregnancy.
- Further possibilities & differential diagnoses:
diagnosis of HELLP syndrome (Hemolysis, Elevated LFts, Low Platelets)
- HELLP is a manifestation of preeclampsia (not a separate disorder).(29803330) It's a thrombotic microangiopathy which may be closely related to atypical hemolytic uremic syndrome.
- Clinical findings: 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).
- Acute fatty liver of pregnancy.
- Treatment of HELLP is discussed below.
neuroimaging
- The primary reason to perform neuroimaging is to exclude an alternative pathology (e.g., intracranial hemorrhage).
- Neuroimaging findings in (pre)eclampsia are listed below, in a rough order of decreasing frequency and increasing severity. All of these findings are largely identical to those seen in Posterior Reversible Encephalopathy Syndrome (discussed further here: 📖).
- (#1) PRES (posterior reversible encephalopathy syndrome) is the most common finding.
- Bilateral edema that is most often located in the parito-occipital regions.
- Edema may be seen as hypodense on CT scanning. MRI reveals vasogenic edema as bright on T2/FLARE sequences.
- For example, 98% of patients with eclampsia in one series had PRES on their MRI scans.(33630183)
- (#2) More severe cases may reveal diffusion restriction, which implies the presence of cytotoxic edema that may be irreversible. This may reflect the presence of superimposed vasospasm (e.g., overlap between Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome 📖).(27831835)
- (#3) In very severe cases, there may be subarachnoid hemorrhage and small cortical hemorrhages (especially in the parietooccipital and occipital regions).(Louis 2021; 27831835)
lumbar puncture
- Lumbar puncture is not generally performed, but might be persued if there is concern for alternative diagnoses (e.g., meningitis).
- In preeclampsia the CSF will often be normal. However, protein levels and opening pressure may be elevated (similar to PRES 📖).
blood pressure targets
general strategy
- Antihypertensives are urgently indicated if SBP>160 and/or DBP>110.
- (#1) The initial goal is decreasing MAP by ~20% within a few hours.
- (#2) Subsequently, the blood pressure should be gradually decreased to a target MAP of roughly ~105-115 mm. This target may be individualized, depending on the baseline blood pressure.
- Vasodilators (eg nicardipine) may be the most rational therapy (since the pathophysiology of preeclampsia centers around excessive vasoconstriction).
the optimal target is unclear:
- 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.
initial antihypertensive for rapid blood pressure control
nicardipine infusion 💉
- Nicardipine may be the preferred agent for titrated, precise blood pressure control.(35707886) It is an accepted option that has been shown to be safe and effective.(19396743, 16269975, 20591204).
- Nicardipine does require careful monitoring. Once the target blood pressure is achieved, it's generally best to reduce the infusion rate (to prevent accumulation). 💉
nitroglycerine infusion 💉
- Nitroglycerine is the preferred agent for preeclampsia plus severe cardiogenic pulmonary edema (SCAPE).
other agents that may not be preferred in the ICU
- Labetalol 💉
- Labetalol is safe and effective for preeclampsia, with an extensive track record.
- Drawbacks of labetalol:
- (1) It has a long half-life, limiting its ability to be utilized as a titratable infusion.
- (2) Negative inotropy may reduce systemic perfusion and potentially worsen cardiogenic pulmonary edema.
- (3) >800 mg/24 hours poses a risk of fetal bradycardia.(30165588)
- IV hydralazine: Not usually preferred, due to the capacity to cause unpredictable and prolonged drops in blood pressure.(14576246)
oral antihypertensives
- Start oral antihypertensives once hemodynamically stabilized and improving. Unfortunately, many antihypertensives aren't suitable for pregnancy.
- 🏆 Extended-release nifedipine 💉 is an excellent option (especially for patients who responded favorably to IV nicardipine). Shorter dosing intervals or higher doses may be needed, given accelerated hepatic metabolism during pregnancy through CYP3A4. (30704579)
- Labetalol 💉 is a good option (especially for patients who responded to IV labetalol).
- Other options include:
- Hydralazine 💉 – Caution is required regarding potential reflex tachycardia.
- Clonidine 💉
- May provide some anxiolysis.
- Especially useful in patients with incurrent withdrawal.
- Shorter dosing intervals may be needed in pregnancy. (30704579)
- Not ideal for long-term use, given a risk of rebound hypertension if doses are missed.
- Prazosin:
- Likely safe in pregnancy, but rarely used for preeclampsia (there may be some unproven concern regarding a risk of stillbirth).(34327714)
- Pharmacokinetics: Onset in ~2 hrs, duration of action ~12 hours.
- Dosing: Starting dose 1-2 mg q12 hours, maximal dose 10 mg q12.
fluid resuscitation
- Preeclampsia 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.
getting started: indications & loading bolus
- Magnesium should be given to any critically ill, preeclamptic woman to reduce risk of seizure, unless there are contraindications:
- ⚠️ Myasthenia gravis (discussed here: 📖).
- ⚠️ Heart block.
- ⚠️ Severe hypocalcemia.
- Load with 4-6 grams IV magnesium sulfate (16-24 mM).(34327714)
magnesium infusions (if Cr <2.5 mg/dL & adequate urine output)
- 1 gram/hour infusion (4 mM/hr): The original Magpie RCT used a dose of 1 gram/hour.📄 A 1 gram/hour dose is recommended by current guidelines and some newer data.(29803330, 26485229, 34051884, 34327714)
- 2 gram/hour infusion (8 mM/hr):
- Some practitioners prefer a dose of 2 grams/hour, to achieve therapeutic magnesium levels more rapidly.
- 2 grams/hour may be reasonable for patients with:
- Higher body weight.
- Excellent renal function.
- If 2 grams/hour is utilized initially, it may be reasonable to reduce the infusion rate to 1 gram/hour after ~6-8 hours.
monitoring & adverse effects
- Potential adverse effects:
- (1) Hypermagnesemia is the most common concern. Severe magnesium toxicity may cause respiratory depression or heart block. The treatment of hypermagnesemia is IV calcium (e.g., 1 gram of IV calcium gluconate).(32736751)
- (2) Hypocalcemia. (Magnesium can suppress parathyroid hormone production, leading to symptomatic hypocalcemia. Treatment is cessation of the magnesium infusion and administration of IV calcium.)
- Signs of magnesium toxicity:
- Loss of patellar reflexes.
- Tachypnea due to respiratory muscle weakness.
- Heart block.
- Electrolytes aren't necessarily monitored for women with normal renal function (who may be followed with serial monitoring of reflexes). However, electroltyte monitoring may be increasingly beneficial among the sickest patients.
- If electrolytes are checked, consider including both calcium and magnesium levels.
- Magnesium levels can be interpreted based on the table shown below.(30575675)
- ⚠️ If the urine output decreases, this may reflect acute kidney injury with subsequent accumulation of magnesium.
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, PRN (don't use a maintenance infusion).
duration of therapy
- 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.
immediate therapy
- 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.
- More on the management of status epilepticus here.
diagnostics & neuroimaging
- Check fingerstick glucose immediately, to exclude hypoglycemia. Obtain a full laboratory panel, if not recently performed.
- 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 overlap substantially.
- However, if a single isolated seizure occurs in the context of preeclampsia with no persistent neurological alterations, neuroimaging isn't necessarily required.(Shutter, 2019)
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
- This 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).
complement-directed therapy?
- Growing evidence indicates that HELLP could share many similarities with atypical hemolytic uremic syndrome (aHUS), which is caused by dysregulated complement activation.(29717384, 26921648)
- One case report describes successful treatment of HELLP with eculizumab (a complement inhibitor).(30159857) 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).(30575675)
fetal monitoring
- 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.
delivery
- 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.(29747734)
acute kidney injury
- Management is generally supportive (more on the management of AKI here 🚀).
- 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. However, these patients often have leaky capillaries, so large-volume fluid resuscitation is often counterproductive (merely worsening pulmonary and systemic edema).(26412014)
other complications to be aware of
- Intracranial hemorrhage.
- Retinal detachment.
DVT prophylaxis
- 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.
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- Failure to consider preeclampsia (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).
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PMID: 35659948 DOI: 10.1016/j.bpa.2022.02.003; PMID: 36122982 DOI: 10.1016/j.ogc.2022.02.016