Pregnancy and the postpartum

period are associated with an increased risk of ischemic stroke and cerebral hemorrhage. Labor/delivery and postpartum appear to be the periods of highest risk, with 90% of events occurring at these times.^1,2 The incidence appears to be increasing, with stroke causing about 5% of maternal deaths in the United States.³ Appropriate prenatal and obstetric care can detect risks and decrease the incidence of most common forms of stroke. Rapid diagnosis and intervention is often critical for decreasing death and morbidity.

Risk Factors

Risk factors for stroke in pregnancy are the same as in the nonpregnant population but may be increased in pregnancy by pro-coagulation changes, hypertension, and increased vascular constrictive reactivity. These latter changes are often associated with pre-eclampsia or eclampsia.

Standard risk factors for stroke include:

• Pre-eclampsia/eclampsia.
• Aura-associated migraine headaches: Vasospasm then vasodilatation in cerebral vessels are reported to be significant problems in about 2/1,000 pregnancies. Women with these types of migraines in pregnancy may have up to 15 times increased risk for stroke.
• Increased maternal age.
• Chronic hypertension.
• Substance abuse, including cocaine, methamphetamine, and tobacco.
• Intracranial vascular abnormalities, including arteriovenous malformations (AVMs) and aneurysms.
• Congenital or acquired thrombophilias, which can promote arterial or venous thrombosis.
• Cardiac or vascular pathology, which can cause arterial embolic, injury/dissection, or occlusion.
• Other conditions that can cause vascular injury or obstruction (such as sickle cell disease, syphilis infection, polycythemia vera, vasculitis).

Differential

Always consider pre-eclampsia/eclampsia as an underlying factor in patients at more than 20 weeks gestation. Postpartum angiopathy presents with a similar clinical picture as subarachnoid hemorrhage (SAH). This most often occurs in the first week post partum and is caused by reversible cerebral vasoconstriction.⁴

Dural sinus thrombosis is related to an increase in circulating clotting factors during pregnancy and relative dehydration occurring during delivery and postpartum. A case has been reported 3 months post partum.⁵ Headache is highly variable. Associated signs and symptoms can include seizures, paresis, or focal neurologic deficits, papilledema, altered mental status, and increased isolated intracranial hypertension. Risk factors include genetic hypercoagulability, advanced maternal age, hyperemesis, cesarean delivery, infection, and maternal hypertension.⁶

Diagnostic Tests

For patients who are candidates for treatment with IV tissue plasminogen activator (TPA), the goal is to complete a head CT scan without contrast within 25 minutes of ED arrival, with the study interpreted within another 20 minutes (door-to-interpretation time of 45 minutes).⁷ Radiation from this study does not put the fetus at risk.

MRI of the brain without contrast is an alternative. The use of MRI should not delay treatment of patients who are eligible for IV TPA, with the same goal of door-to-interpretation in 45 minutes.

Other useful diagnostic tests include:

• Intracranial and extracranial vessel imaging (CTA of the brain and neck, MRA of the brain and neck, carotid ultrasound, transcranial Doppler, cerebral arteriogram).
• Echocardiogram or TEE.
• Venous Doppler ultrasound.
• Basic diagnostics, including EKG (for arrhythmias such as atrial fibrillation), CBC, chemistries, INR.
• Hypercoagulability work-up.

Management

Well-planned protocols should be in place that have been coordinated with the consulting team, including OB, vascular neurology, medicine, neurosurgery, interventional, and other appropriate services. As previously noted, rapid identification of stroke type is critical to proper management. As with most management decisions concerning pregnant patients, maternal stabilization is the priority. While the mother is being stabilized, also monitor the fetus.

A good overall reference for SAH management in all patients was published in 2011.⁸ While specifics for pregnancy were not covered, the diagnostic and therapeutic approaches should be applied to pregnant patients.

Ischemic Stroke

IV TPA and mechanical thrombectomy have been used successfully in pregnancy. As with any treatment, risks and benefits should be weighed.^9-13 Because vaso-occlusive stroke may have cardiac or systemic disease–associated etiologies, these should be evaluated and treated. Most of this will usually occur post-ED care. In some cases, chronic anticoagulation treatments should be considered to prevent recurrence.¹⁴

Intracranial and Subarachnoid Hemorrhage

SAH is the most frequent cause of intracranial bleeds during pregnancy.^15-17

Many patients may have a recent history of a warning leak (sentinel bleed) with symptoms that appear and resolve prior to a major SAH. The leak may present with any of the listed clinical findings. Early identification and treatment can prevent a subsequent fatal bleed.

A patient on anticoagulant therapy requires reversal therapy. Significant thrombocytopenia would generally require platelet transfusion.

Use of hemostatic drugs such as epsilon-aminocaproic acid (EACA) and recombinant activated factor VII have not been clearly shown to affect outcomes.¹⁸ Drugs increasing clotting tendency may put pregnant patients at risk for embolic complications and probably should be avoided.

Nimodipine may be considered after a discussion with consultants. It is category C. Nimodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Mannitol can cause fluid shifts away from the fetus, leading to fetal circulation problems. It may be considered after discussion with consultants, with active monitoring for a viable fetus.

Surgical or endovascular treatment of ruptured aneurysms during pregnancy may be associated with improved maternal-fetal outcomes. Benefits are less clear with AVMs. A decision to deliver or continue pregnancy is best coordinated with specialty team.

Blood Pressure Control

Hemorrhagic Stroke

A set of AHA/ASA guideline recommendations (Class C) have been published for nonpregnant patients with hemorrhagic stroke.¹⁹ If the patient also has pre-eclampsia/eclampsia (which should be assumed after 20 weeks of pregnancy), the exact targets may need to be coordinated with neurology, neurosurgery, and OB consultants. Also, magnesium sulfate should be used prophylactically to prevent seizures in pre-eclampsia/eclampsia, which can exacerbate the severity of hemorrhagic stroke and elevated blood pressures.

Drug treatment for pre-eclampsia/eclampsia is usually reserved for patients with BP greater than 160 systolic and greater than 110 diastolic. Avoid lowering blood pressure below 140/90 because of the possible untoward consequence of uterine hypoperfusion.²⁰

Ischemic Stroke

In the pregnant patient, a significantly elevated BP may be detrimental to the pregnancy, especially when associated with pre-eclampsia. This condition requires treatment with magnesium sulfate, which promotes vasodilation and prevents seizures. Symptomatic hypoxic neurologic injury associated with ischemic brain pathology caused by occlusive vasospasm of pre-eclampsia (and demonstrated on MRI) is frequently completely reversed by conservative management that includes the use of magnesium sulfate, expedited delivery of the fetus and placenta, and management of any additional complications associated with pre-eclampsia.

Blood Pressure Drugs

Optimal drugs have not been well studied in pregnant patients. Strongly consider pre-eclampsia when significant hypertension is present. A consulting team can help select the best option. Labetalol drip, commonly recommended in pre-eclampsia, is a widely used option.

Limited experience with nicardipine has shown it to be an effective antihypertensive agent in severe pre-eclampsia and in pregnant women with autonomic hyperreflexia. So far, nicardipine has not been shown to have any deleterious effect on neonatal outcomes, even when an overdose was accidentally given to one patient. To avoid undesired precipitous drops in BP, consider an initial dose of 2.5 mg/hour without a bolus and the use of an arterial line for continuous BP monitoring. Close clinical surveillance in the postpartum period is mandatory because of a possible increased risk for uterine atony after treatment with nicardipine.²¹

One study showed patients treated with nicardipine were more likely to reach a physician-specified systolic BP target range within 30 minutes versus those treated with labetalol.²²

Antiepileptics

Assume seizures are caused by eclampsia (after 20 weeks of pregnancy)²³ even if BP is not elevated. Also assume there is risk for seizures with the diagnosis of pre-eclampsia and progressive hypertension or other neurologic symptoms. In either case, initiate magnesium sulfate therapy to decrease risk of new or recurrent seizures, according to the following protocol:

• Give a 4- to 6-g IV loading dose over 15-20 minutes.
• Give a maintenance infusion at 2 g/hour.
• Check DTRs, urine output, and respiratory rate hourly. For depressed DTRs or oliguria, stop infusion and check serum magnesium level. For magnesium overdose, administer 1 g of calcium gluconate via a slow IV push.
• Treat a breakthrough seizure with a 2-g bolus over 3 minutes. If ineffective, consider sodium amobarbital 250 mg IV over 3-5 minutes, lorazepam 1-2 mg/min IV up to 10 mg, or diazepam 2 mg/min up to 20 mg. Lorazepam has a longer duration of action. These drugs, especially in combination with magnesium, may result in substantial maternal and neonatal respiratory depression.
• Consider RSI as necessary.

Benzodiazepines are used as in nonpregnant patients for terminating acute seizures. These drugs may affect fetal heart rate variability. Initial stabilization with a fosphenytoin loading dose or benzodiazepine drip are acceptable options. Refractory cases can be treated with propofol.^24,25

A 2011 published paper showed first-trimester exposure to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam was not associated with an increased risk of major birth defects, compared with no exposure.²⁶

Airway, Oxygen, and RSI

To avoid fetal hypoxia, use high-concentration oxygen. In compromised respiratory settings, pregnant women have an increased tendency for rapid hypoxemia. Anticipate a higher potential for regurgitation of gastric contents and aspiration; antiemetics (such as ondansetron) and a nasogastric tube are strong considerations. Failed intubation is more common in pregnancy because of physiologic and anatomic changes that can lead to difficult intubation.²⁷ Mask ventilation may also be difficult because of increased intra-abdominal pressure and low chest compliance.²⁸

Neuromuscular blockade (such as succinylcholine, vecuronium, or atracurium) can be used in conventional doses. Transplacental passage is insignificant at the usual dose for intubation relaxation. If a paralytic agent is used, it crosses the placenta in dose-dependent fashion and will cause fetal heart rate tracing to become nonreactive.²⁹ Longer-acting agents can mask continuing seizure activity. Consider propofol or benzodiazepine drips during the stabilization period.

Analgesia

Pain control with narcotics can be given in any trimester as required to properly provide comfort to an injured mother.³⁰ Communicate doses and times to the physician caring for the newborn at delivery so that the effect on the fetus can be anticipated.

Risks

Maternal risks include death and other complications.³¹ Intracerebral hemorrhage is associated with the highest morbidity and mortality. Neonatal outcomes are generally good, with an increased rate of preterm delivery via cesarean. If pre-eclampsia/eclampsia is present, those risks would likely be additive.

References

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Dr. Roemer is an Associate Professor in the Department of Emergency Medicine at the University of Oklahoma (OU) School of Community Medicine, Tulsa. Dr. Ogburn is a Professor of Obstetrics & Gynecology and Director of the Division of Maternal-Fetal Medicine at SUNY Stony Brook School of Medicine, New York. Dr. Katz is a Clinical Professor in the Department of Obstetrics and Gynecology at Oregon Health Sciences University and Medical Director of Women’s Services at Sacred Heart Medical Center and Center for Genetics and Maternal-Fetal Medicine in Eugene, Ore. Dr. Wanahita is a Stroke Neurologist and Co-Medical Director, St. John Stroke Center, and Director of St. John Stroke Service at St. John Medical Center in Tulsa. Dr. Crane is a Resident in the Department of Emergency Medicine at the OU School of Community Medicine.