The Brain of the Critically Ill Pregnant Woman

The Brain of the Critically Ill Pregnant Woman is a volume in the Critical Care in Obstetrics series. This novel reference educates physicians, nurses, and all allied healthcare personnel on updates for caring for pregnant women with neurological compromise. The book's authors have gathered the best evidence-based material that is explicitly focused on severe neurological complications in pregnant patients and postpartum. Among the chapters, the book covers medical-surgical complications that any patient can present, such as head trauma and complications specific to pregnancy.

• Includes obstetric concepts with updated knowledge of pathophysiology
• Offers best practice approaches and interventions regarding the fetus
• Explores the use and effects of drugs in the pregnant patient and during nursing
• Written by authors with extensive clinical experience in neurocritical care and critical obstetric care

• Language: English
• Publisher: Academic Press
• Release date: Nov 28, 2023
• ISBN: 9780443152047

Book preview

Section 1

Critical care

Outline

Chapter 1. Neurologic complications in the obstetric patient

Chapter 1: Neurologic complications in the obstetric patient

Christa O'Hana S. Nobleza¹,²     ¹Neurocritical Care Service, Department of Neurology, Baptist Memorial Hospital/Baptist Medical Group, Memphis, TN, United States     ²Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, United States

Abstract

Several physiologic and hemodynamic changes occur in an obstetric patient. The nervous system also undergoes adaptation in this setting. More important, physiologic and hemodynamic changes may lead to neurologic disease states if left uncontrolled. Certain conditions that are stable can also worsen in the pregnant state. This chapter discusses a general approach to neurologic complications in an obstetric patient and considers specific disease states.

Keywords

Intrapartum; Neurologic adaptation; Neurologic complications; Neurology in pregnancy; Neuro-obstetric

General approach to neurologic complications in obstetric patient

History taking

Taking the history of an obstetric patient during a possible neurologic complication is similar to that of a nonobstetric patient. However, knowledge of possible neurologic complications can guide in-depth questions that need to be asked in the setting of critical care. One of the first main consideration is whether the patient is alert and awake to give details of the history; if not, there may be a reliable companion or witness to the event to give the history. Table 1.1 shows considerations in taking the history for common neurologic complications of pregnancy that one may be encountered in the critical care setting. The age of gestation of the patient should be considered in the history because some management interventions can be affected, such as the decision to take the patient to a neurosurgergical procedure for patients presenting with an intracerebral hemorrhage due to an arteriovenous malformation. After developing the differential diagnosis from the history, the physical examination should follow, which includes a detailed neurologic examination. Although the neurologic condition may dictate the type of focused neurologic examination that can be done, basic components of the neurologic examination should be included for all pregnant patients with a neurologic complication (Table 1.2). Depending on the acuity and urgency of the situation, the history and physical examination may need to be performed while diagnostic tests are being done. In addition, as the diagnosis of neurologic complication ensues, primary steps in managing the pregnant patient begin with an assessment and management of her airway, breathing, and circulation. This allows the disability to be quickly assessed. These foundational processes in the initial approach to assessing a pregnant patient with neurologic complications enables a systematic consideration specifically for pregnant patients with neurologic complications.

Table 1.1

Table 1.2

Neurologic complications in obstetric patient

Hypertensive disorders of pregnancy and cerebral dysautoregulation syndromes

Hypertensive disorders of pregnancy (HDP) complicate up to 8% of pregnancies [1] and can account for up to 7.4%–25% of maternal mortality globally owing to multisystemic involvement [2–4]. These disorders encompass chronic hypertension (CHN), gestational hypertension (GHN), preeclampsia (PEC), eclampsia (EC), and superimposed PC (SPEC). Hypertension is defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg [5–7]. The timing and other associated signs or symptoms vary. For CHN and SPEC, hypertension should have occurred before pregnancy or before 20 weeks of gestation, whereas GHN, PEC, and EC occur after 20 weeks of gestation [1,4,7]. GHN should resolve after delivery within 6 weeks or 3 months [7,8]. PEC, the most dangerous HDP, is generally defined as hypertension with proteinuria (300 mg in 24 hours) or other signs of end-organ involvement, which include proteinuria under renal dysfunction; liver dysfunction; and hematologic, pulmonary, and nervous system involvement, compared with the prior historical classic triad of hypertension, proteinuria, and edema [7–9]. Hemolysis elevated enzyme liver and low platelet (HELLP) syndrome is encompassed under PEC and is not a separate entity [8,9]. Neurologic dysfunction can manifest as hyperreflexia, the presence of clonus, headache, encephalopathy, visual disturbance, seizures, and stroke. When generalized, tonic-clonic seizures occur in a patient with PEC. In the absence of other possible etiologies, this is termed EC, which can further complicate about 1% of pregnancies [9,10]. It commonly occurs during or after the 20th week of gestation and up to 6 weeks postpartum [4], whereas kidney disease and multiple pregnancies can increase the risk for early EC [10–12]. Although EC commonly occurs as a spectrum of PEC, one-third of cases can present as the initial manifestation without the classic signs and symptoms of PEC [13]. To rule out a structural cause of the seizure such as a hemorrhagic stroke, noncontrast computed tomography (CT) head (NCCTH) imaging should immediately be done. Centers are able to perform CT angiography immediately after an NCCTH. The advantage of this is immediately to rule out a large arterial occlusion, a vascular malformation, an aneurysm, diffuse multifocal arterial narrowing, as well as venous thrombosis (if the venous phase is appropriately captured).

Initially reported in 1996, posterior reversible encephalopathy syndrome (PRES) has frequently been reported in hypertensive patients who present with a distinct neuroradiologic finding of posterior leukoencephalopathy and seizures [14]. It manifests typically with encephalopathy, visual deficits or blindness, and seizures with corresponding imaging revealing bilateral white matter changes owing to vasogenic edema [15–20]. The most common distribution of vasogenic edema involves the occipital and parietal lobes. Atypical distribution may involve the bifrontal and cerebellar lobes, the whole brain, and the brain stem [19,21,22]. The occipital and parietal areas are usually involved because sympathetic regulation is better developed in the anterior compared with posterior circulation [14,23,24]. Among pregnant patients, this syndrome has been commonly associated with PEC and EC [14,25,26] and can be seen in up to 98% of patients with EC [27]. Risk factors reported specifically among obstetric patients included more than 36 weeks of gestation, patients with EC and recurrent seizures, postpartum EC, cesarean delivery, and hypertension [25]. Mortality among those with EC and PRES was 4% [25]. Although commonly reversible, delayed diagnosis or misdiagnosis may lead to permanent brain changes. Rapid increases in blood pressure, resultant cerebral dysautoregulation and cerebral arteriolar dilatation, blood–brain barrier disruption, and an eventual vasogenic edema pattern are the proposed pathophysiology of PRES [26,27]. Upon vascular imaging, patients with PRES can develop vasoconstriction, vascular beading, and even hemorrhage in response to accelerated hypertension. These findings suggest that reversible cerebral vasoconstriction syndrome (RCVS) may have pathophysiologic features that overlap with PRES [27–29]. The postpartum state is one of the most common causes of RCVS [28]. In addition, RCVS can occur along the PEC-EC continuum and concomitantly with PRES [27,28,30]. Common names for RCVS include Call-Fleming syndrome [31,32], postpartum angiopathy [29,33,34], thunderclap headache with reversible vasospasm [35–37], migraine vasospasm or migraine angiitis [38,39] and drug-induced cerebral arteritis or angiopathy [40,41]. The names mostly depend on the setting for the patient presents in Chen and Wang [28]. The hallmark clinical features of RCVS include a thunderclap headache that can be recurrent and precipitated by strenuous activity, emotional stressors, coughing, urination, sexual activity, and common daily activities such as bathing and can be intermittent for 2–3 weeks before presentation, in which attacks are associated with hypertension up to a third of cases [28,42–46]. In addition to headache, patients can present with stroke-like symptoms, vision issues, confusion, and seizures similar to PRES [33,34,47,48]. Radiographic findings distinctly seen in RCVS compared with PRES include CT angiography (CTA) or magnetic resonance angiography (MRA) showing smooth, tapered narrowing and dilatation of cerebral blood vessels [47,49,50]. In addition, optical coherence tomography angiography may show evidence of relative retinal vasoconstriction [51]. Transcranial Doppler imagery may reveal increased flow velocities in the middle, anterior, posterior, vertebral, and basilar arteries. Because it is noninvasive, it may be used to monitor improving vasospasm, especially in the setting of pregnancy when invasive procedures and intravenous (IV) contrast use is ideally minimized [52,53]. RCVS can also have imaging findings of stroke, cortical hemorrhage, and subarachnoid hemorrhage in addition to vascular changes [38,47,50,54] The pathophysiology of PEC, EC, PRES, and RCVS have been reported to overlap [29,47,49,50,55–57]. Rapid and uncontrolled systemic hypertension is the unifying contributor for all of these syndromes that lead to blood–brain-barrier breakdown and eventual imaging and clinical changes associated with endothelial involvement and cerebral edema [47,50]. With RCVS, the hypothesis is that the neurovascular bundle can be involved via the trigeminovascular or serotonergic pathways, leading to the hallmark vasoconstriction seen in imaging as a response to cerebral dysautoregulation [47,50]. If triggers are not controlled or removed, it can progress to the development of cytotoxic edema and cerebral infarction if there is progression [50].

Management of HDP, especially PEC, EC, PRES and RCVS, involves similar approaches. For HDP, several guidelines from different societies are available, including, but not limited to the National Institute for Health and Care Excellence, International Society of Hypertension, International Society for the Study of Hypertension in Pregnancy, American College of Obstetricians and Gynecologists, World Health Organization, US Preventative Services Task Force on Gestational Hypertension and Preeclampsia, Society of Obstetric Medicine of Australia and New Zealand, and Society of Obstetricians and Gynecologists of Canada. These can vary in specific recommendations on diagnosis and management [5,8,9,58]. However, a summary of the overall approach is presented in Table 1.3. All of these conditions can rapidly progress into acute deterioration of the obstetric patient. The basic approach to the management in the setting of acute deterioration should be the initial assessment and stabilization of the airway, breathing, and circulation, keeping in mind that fetal assessment should also ensue. A high-risk maternal fetal medicine and obstetric consultation should immediately be done if the patient is in the neurocritical care unit. If the patient is admitted to a general critical care unit, neurology consultation should be done and the patient should be seen urgently to establish an assessment of impending neurologic deterioration. The role of acquiring angiogenic markers and its association with neurologic and maternal outcomes are not consistently reported by guidelines and have not been part of routine testing. There have been recommendation to consider the determining ratio of soluble fms-like tyrosine kinase 1 to placental growth factor because of its predictive value for the development of PEC [9,59–61]. However, its use in predicting a poor outcome for the obstetric population has not been established. For PEC, after the initial stabilization, the mainstay of management is supportive care, blood pressure control, and magnesium sulfate infusion. Multiorgan dysfunction should be addressed appropriately. Coagulopathy resulting from HELLP should be managed by appropriate transfusion of blood products, especially in the setting of intracranial hemorrhage (ICH). Drugs administered should be renally dosed, and medications that can predispose patients for seizures, such as cefepime in the setting of renal dysfunction, should be avoided. Benzodiazepine such as lorazepam should be administered if the patient continues to have seizures, and appropriate antiseizure medication such as levetiracetam can be administered in addition to magnesium sulfate while a diagnostic assessment is being done (Table 1.4). The patient should be monitored with continuous electroencephalography (cEEG) even when clinical seizures are controlled, to assess for nonconvulsive seizures. At times, EC as the primary etiology of the seizures cannot be immediately established but is highly suspected. This should not preclude appropriate seizure management. Table 1.4 shows describes a stepwise approach to patients with seizures and status epilepticus with considerations for obstetric patients. In PRES and RCVS associated with pregnancy or the postpartum state, blood pressure control, magnesium sulfate, and supportive care remain the mainstay of management [47,50]. Patients should be admitted to the intensive care unit for close blood pressure monitoring. In patients with RCVS, there is a preference for calcium channel blocker (nimodipine and verapamil) use for both headache and blood pressure control [47,50,62,63]. However, caution should be exercised with rapid lowering of blood pressure because it may affect placental perfusion [47,56,57]. In severe or refractory cases, invasive approaches, including cerebral angioplasty and intraarterial calcium channel blockers, have been reported [64–67]. Those that have severe PEC and those with EC, complicating PRES, or RCVS should be considered for delivery in coordination with the obstetric, maternofetal medicine, and pediatric intensive care unit teams.

Table 1.3

ACR, albumin creatinine ratio; CBC, complete blood count; CMP, comprehensive metabolic profile (include liver and kidney function tests); CSF, cerebrospinal fluid; CT, computed tomography; EEG, electroencephalogram; IV, intravenous; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; PCR, protein creatinine ratio; TCD, transcranial Doppler; UDS, urine drug screen.

Table 1.4

ABG, arterial blood gas; AED, antiepileptic drug; CBC, complete blood count; cEEG, continuous EEG; CMP, complete metabolic profile; CSF, cerebrospinal fluid; CT, computed tomography; CTA, computed tomography angiography; EEG, electroencephalogram; hCG, β-human chorionic gonadotrophin; ICH, intracerebral hemorrhage; IV, intravenous; LD, loading dose; LP, lumbar puncture; MD, maintenance dose; MRI, magnetic resonance imaging; TSH, thyroid stimulating hormone; UDS, urine drug screen.

Hypercoagulable and prothrombotic state

The development of a hypercoagulable state in pregnancy is well-documented. Although the exact mechanism of the development of a hypercoagulable state in pregnancy has not been established, it has been reported to be associated with an increase in procoagulant factors such as V, VII, VIII, IX, X, and XII and von Willebrand factor, an increase in fibrinogen, an increase in placental-derived plasminogen activator inhibitor type 2, and a decrease in protein S activity as well as an acquired resistance to protein C [68–72]. Other pregnancy-related risk factors for thromboembolic events include maternal age >35 years, cesarean delivery, obesity, family or known history of thrombophilia, delivery itself, the puerperium, and immobilization with most of these contributing to the Virchow's triad of pregnancy [72,73]. Intravascular changes such as vasodilation associated with progesterone, iliac and inferior vena cava compression owing to the enlarging uterus, and venous hypertension can also lead to an increased hypercoagulable state [73].

The hypercoagulable state in pregnancy predisposes patients to cerebrovascular events such as maternal ischemic stroke (mIS) and maternal cerebral venous thrombosis (mCVT). The incidence of mIS has been reported to be 12.2–30/100,000 (95% confidence interval, 6.7–22.2) [74–76]. The incidence was reported to be increasing in a study in Finland comparing the incidence in 1987–1991 and 2012–16 [76]. There is a five times increased odds of mIS postpartum compared with the first trimester [76,77]. Other risk factors for developing mIS include African American ethnicity, congenital or acquired cardiac disease, history of migraine, smoking after the first trimester, infection, ovarian hyperstimulation syndrome associated with in vitro fertilization, and development of HDP [76,78]. Mortality associated with mIS can range from 2.7% to 20.4% [76,78,79]. The mechanism of mIS largely involves the known hypercoagulable state in addition to the other common mechanisms of ischemic stroke (Fig. 1.1). Amniotic fluid embolism is a separate etiology of mIS, which can present as hypoxia, hypotension, and disseminated intravascular coagulation with the development of mIS via a paradoxical mechanism [78,80,81]. Prompt recognition and evaluation of acute mIS are warranted owing to its time-dependent management. A delay in diagnosis for a potentially reversible mIS syndrome may lead to significant disability. A major limitation of stroke therapy in the setting of mIS is that pregnant patients were not included in landmark trials for acute stroke therapy. However, clinically, the American Heart Association guidelines for the acute assessment and management of mIS is still recommended. For the purpose of the definition of an acute stroke, it does not differ in mIS. An acute ischemic stroke is an episode of neurologic dysfunction caused by focal cerebral, spinal, or retinal infarction along with the objective, imaging, or pathologic evidence of an ischemic injury or clinical symptoms lasting more than 24 h [82,83]. The initial approach to mIS is similar to nonpregnant acute ischemic stroke. Each hospital or institution should establish a unified code stroke system to activate several personnel and processes in a timely manner to move the patient along the acute stroke care continuum. After the recognition of a possible mIS, identification and documentation of the last known well time or witnessed symptom onset code stroke activation follows, and the patient should immediately be evaluated. Medical stability should still be the priority; in parallel, there should be an assessment of the neurologic disability using a stroke scale. The most common stroke scale used is the National Institute of Health Stroke Scale score [84]. This scale has limitations, but it gives an idea of the size of the infarction and has been used to gauge the level of disability. In the pregnant patient, considerations in this assessment phase should include noting the blood pressure, the initial symptoms, whether a headache was involved, whether the patient recently had epidural anesthesia, the age of gestation, whether the patient was in labor, the delivery method, and whether the patient was being treated for PEC or HELLP syndrome. Rapid history-taking and evaluation should account for these factors. The time window for acute stroke therapy is available for up to 24 h, depending on available neuroimaging in the hospital (Fig. 1.2). Neuroimaging is primarily needed to rule out a hemorrhage and determine an acute large vessel occlusion. In the nonpregnant patient, CT, CTA, and CT perfusion are most commonly performed; however, in the pregnant patient, there are concerns about the effects of radiation and contrast on the fetus [85]. When proceeding with neuroimaging in mIS (Fig. 1.2), magnetic resonance imaging (MRI) is the imaging of choice [85]. MRI may pose concerns for the fetus, including exposure to the magnetic field, which may lead to possible cellular changes, pulse radio-frequency that can expose the fetus to heat, gradient-echo magnetic fields that can expose the fetus to noise, and gadolinium-based contrast agents (GBCAs) [85,86]. The teratogenic effect of 1.5-3T MRIs on the fetus have not been established, thus are considered safe [85,86]. However, one has to weigh the need for GBCAs because even in the acute setting, MRI or MR vascular imaging can be performed without contrast, and decisions may be made based on these [85–87]. For mIS, an MR angiogram can be performed without contrast and may decrease the exposure of the fetus to gadolinium. If MR imaging is not readily available, CT imaging can still be an option because radiation from a head CT has been determined to be low-dose compared with other body imaging [85,88]. Iodinated contrast used for a CT angiogram can cross the placenta and can pose a risk to the fetus [85]. However, a statement from the American College of Radiology stated that there was no evidence to establish the risk of fetal harm from iodinated contrast exposure when administered through maternal IV access [85,87]. It is still recommended to perform the MR mode of imaging when readily available, but if it causes significant delay for stroke therapy, CT head, CTA, and computed tomography perfusion (CTP) may be used [85,89]. Contraindications for acute stroke therapy are [85–87] the same for a pregnant patient, but the timing of delivery has to be considered when deciding on thrombolytic or endovascular therapy (EVT). When deciding on IV alteplase, it is a level IIB recommendation that it is reasonable to consider IV alteplase administration when the benefit of it in a moderate to severe stroke is weighed against the risk for uterine bleeding [84]. EVT as an acute therapy for stroke have been reported to be safe among pregnant patients [89–91]. Pregnant patients who underwent EVT for stroke had lower ICH rates and lower rates of poor functional outcome compared with nonpregnant patients [90]. In cases of malignant cerebral edema complicating pregnancy, decompressive hemicraniectomy can potentially be life-saving, but more studies need to explore its effect on both maternal and fetal outcomes