Nontraumatic subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke most commonly due to the rupture of saccular (berry) aneurysms and comprises 3% of all stroke types. While a 17% to 50% decrease in the worldwide case fatality rate has been reported in the last 2 to 3 decades, thought to be due to more rapid recognition and improved treatment strategies, the prehospital and 30-day mortality rates remain high (15% and 35%, respectively). The annual incidence of aneurysmal SAH has not declined, affecting 9/100,000 people in the United States and with approximately 600,000 cases worldwide.
Despite a decline in the mortality, SAH remains a highly morbid disease. Survivors are commonly left with permanent disability, cognitive deficits (particularly executive functioning and short-term memory), and mental health symptoms (eg, depression, anxiety), resulting in a significant reduction in health-related quality of life, which has been reported to occur in 35% of patients 1 year after SAH. The average age at aneurysm rupture is 53 years; SAH onset at this young age results in a high societal cost and a number of years of lost productivity.
The most common cause for SAH is a ruptured cerebral aneurysm (85%); however, despite modern neuroimaging techniques, 10% of SAHs may not reveal a bleeding source, while the minority of cases (5%) may be due to other vascular causes (eg, arteriovenous malformation, arteriovenous fistula, reversible cerebral vasoconstriction syndrome [RCVS]). Particularly in RCVS, the presence of high-convexity SAH, rather than SAH in the basal cisterns, in addition to the typical “sausage shape” areas of constriction/vasodilation on vessel imaging has been described.
Several epidemiologic and genetic risk factors for SAH have been identified. Notably, SAH is predominant in women (female to male ratio of 1.6:1), African Americans, and Hispanics. Hypertension, smoking, and excess alcohol intake are modifiable risk factors that individually double the risk of SAH. Several other nonmodifiable and genetic risk factors have emerged (TABLE 3-1). Patient counseling on the modifiable risk factors is recommended to reduce the risk of SAH.
Current guidelines recommend screening for aneurysms if the patient has two or more first-degree relatives with aneurysms or SAH. This is based on several long-term cohort screening studies from the Familial Intracranial Aneurysm study and the International Study of Unruptured Intracranial Aneurysms. Notably, siblings are more likely than children of patients with SAH to have an unruptured intracranial aneurysm detected.
A plethora of genetic studies have emerged for unruptured and ruptured intracranial aneurysms using linkage and genome-wide association approaches. The American Heart Association’s “Guidelines for the Management of Patients With Unruptured Intracranial Aneurysms” provides a brief overview of the current state of genetics in intracranial aneurysms and SAH. While a meta-analysis of both unruptured and ruptured intracranial aneurysms identified the interleukin-6 (IL6) gene polymorphism G572C (chromosome 7) to have an elevated risk for aneurysm formation, no predominant genetic risk factor has been identified. Several other single-nucleotide polymorphisms have been associated with aneurysm formation, with the strongest associations on chromosome 9 (near CDKN2B antisense inhibitor gene), chromosome 8 (near the SOX17 transcription regulator gene), and chromosome 4 (near the EDNRA gene).
Controversy surrounds the heritability of aneurysms and SAH, and several studies, including a twin study, have suggested that environmental risk factors (many of which are modifiable) are far more important than genetic or familial inheritance. A recent review suggests that familial does not equal genetic because of the familial aggregation of risk factors (such as smoking and hypertension). Currently, routine genetic screening is not performed.
SAH remains one of the top neurologic emergencies treated in a neurocritical care unit. Neurologists should familiarize themselves with this highly morbid disease, particularly in light of the emerging science on acute brain injury after SAH and changes in the classic teaching of the etiology of cerebral vasospasm and delayed cerebral ischemia.
The acute phase of SAH can be divided into two disease phases (TABLE 3-2): (1) prompt evaluation, recognition, and diagnosis; immediate transfer to appropriate SAH centers; and rapid treatment of the bleeding source and (2) close monitoring in a neurocritical care unit with expertise in SAH and overall good neurocritical care that adheres to existing management guidelines to prevent or ameliorate secondary neurologic and medical complications.
SAH typically presents with a sudden and severe headache (often described as the “worst headache of life”), which is distinctly different from usual headaches and is often accompanied by loss of consciousness, nausea, vomiting, photophobia, and neck pain (CASE 3-1). A small proportion of patients may experience a headache without many or any of the associated symptoms (sentinel headache) and may either not seek medical attention or are misdiagnosed, thereby remaining unrecognized, with a high risk for major life-threatening rebleeding within a short period of time (hours to days). Other less typical presenting signs may be seizures, acute encephalopathy, and concomitant subdural hematoma with or without associated head trauma (due to the SAH-related syncope), which may make a diagnosis of aneurysmal SAH more difficult.
The physical examination should include determination of the level of consciousness and the patient’s score on the Glasgow Coma Scale, evaluation for meningeal signs, and presence of focal neurologic deficits. In cases with unusual presentation or uncertainty, funduscopic evaluation may be helpful. Intraocular hemorrhage associated with SAH (Terson syndrome) is associated with increased mortality and may be seen in 40% of patients with SAH.
A 43-year-old woman with a past medical history of smoking and depression presented to a community hospital with sudden onset of severe headache, brief loss of consciousness, nausea, and vomiting while using the bathroom. She reported a moderate, persistent, sudden-onset headache that had continued for 36 hours.
In the emergency department, her blood pressure was 185/100 mm Hg, pulse was 105 beats/min, arterial oxygen saturation was 95% on room air, and temperature was 36.8°C (98.2°F).
On examination, she reported neck pain, was disoriented (Glasgow Coma Scale score of 13), but had no focal deficits. Her World Federation of Neurological Surgeons Scale (WFNSS) score was 2, Hunt and Hess Scale score was 3, and modified Fisher Scale score was 4. Bolus injections of 10 mg IV labetalol and 4 mg IV morphine resulted in a partial blood pressure reduction to 170/90 mm Hg. She was started on a nicardipine infusion to achieve and maintain a systolic blood pressure of less than 160 mm Hg.
A noncontrast head CT revealed subarachnoid hemorrhage (SAH) in multiple cisterns, intraventricular hemorrhage, and mild hydrocephalus (FIGURE 3-1A). She received a loading dose of IV levetiracetam.
The patient was immediately transferred to a comprehensive stroke center and was admitted to the neurocritical care unit. Since her Glasgow Coma Scale had worsened to a score of 10 because of hydrocephalus, she had an external ventricular drain (EVD) placed, which was kept clamped prior to aneurysm coiling with intermittent opening to drain 5 mL to 10 mL of CSF hourly.
After discussion among the interventional neuroradiologist, cerebrovascular neurosurgeon, and neurointensivist, the patient underwent digital subtraction angiography (DSA) and coiling of her unsecured aneurysm (FIGURE 3-1B–D). Following the coiling, the patient was transferred back to the neurocritical care unit, where she received enteral nimodipine, pain control, IV normal saline to maintain euvolemia, intermittent compression devices, and subcutaneous enoxaparin for chemoprophylaxis for deep vein thrombosis, and IV dexamethasone (for 2 days only) for refractory headaches. The levetiracetam was discontinued based on guideline recommendations, as further discussed in the section on seizures and seizure prophylaxis in this article. Nicardipine was discontinued, and she maintained a systolic blood pressure between 140 mm Hg and 165 mm Hg spontaneously, with a goal systolic blood pressure of 100 mm Hg to 200 mm Hg with the secured aneurysm. Her EVD was leveled at 10 mm Hg and open, and 5 mL to 12 mL of CSF was drained hourly. Her neurologic examination improved to a Glasgow Coma Scale score of 15 with no focal deficits, and she was mobilized out of bed.
This case demonstrates the first phase of SAH management: rapid diagnosis of SAH and hydrocephalus and immediate emergency treatment with blood pressure lowering, EVD placement, and obliteration of the ruptured cerebral aneurysm.
Transient elevation in intracranial pressure (ICP) is the cause of nausea, vomiting, and syncope and may be associated with additional cardiac and pulmonary complications after SAH. The intraocular hemorrhages in Terson syndrome are thought to be due to the sudden elevation in the ICP. When ICP elevations are severe and sustained, coma and rapid deterioration to brain death can result.
Several diagnostic modalities may be used for the diagnosis of SAH.
Head Computed Tomography
The most rapidly available and appropriate initial diagnostic test for patients with suspected SAH is a noncontrast head CT (CASE 3-1). It is important to correlate head CT findings to the time of headache onset, as the sensitivity of head CT changes over the first 7 days from 93% (first 6 hours), to close to 100% (first 12 hours), to 93% (first day), to less than 60% (at 7 days). The characteristic appearance of hyperdense blood in the basal cisterns or sylvian, interhemispheric, and interpeduncular fissures should immediately lead to the suspicion of an aneurysmal etiology. In fact, any SAH on head CT, especially in the absence of a trauma history, should prompt further vessel imaging. In addition to the presence of SAH, clinicians should also evaluate the head CT for presence of hydrocephalus, intraventricular hemorrhage, and intracerebral hemorrhage.
In cases of negative or equivocal head CT findings in which a high suspicion for SAH still exists, a lumbar puncture is the immediate next recommended step (FIGURE 3-2). Opening pressure should be measured routinely. To differentiate a traumatic tap from true SAH, CSF should be collected in four consecutive tubes, with red blood cell count measured in tubes one and four. CSF should be spun down and evaluated for xanthochromia by visual inspection and, if available, spectrophotometry, which is superior in diagnostic accuracy for xanthochromia than visual inspection alone.
Xanthochromia takes approximately 12 hours to develop and may not be present if a lumbar puncture is performed earlier after headache onset. Most hospitals do not offer spectrophotometry, and it is unknown what the false-negative rate for xanthochromia is at various time intervals after SAH onset.
Magnetic Resonance Imaging
Head CT and MRI are considered to be equally sensitive in detecting SAH in the first 2 days, except in the hyperacute first 6 hours after SAH, during which head CT may miss a small proportion of SAHs and MRI may be slightly superior. Because of its rapid image acquisition, its widespread availability in the emergency department, and its very high sensitivity in the first 2 days after SAH, head CT remains the diagnostic modality of choice for early SAH. However, hemosiderin-sensitive MRI sequences (gradient recalled echo [GRE] and susceptibility-weighted imaging [SWI]) or fluid-attenuated inversion recovery (FLAIR) sequences have superior sensitivity to detect subacute or chronic SAH compared to head CT. Additionally, MRI may be helpful in differentiating alternative pathologies, such as arteriovenous malformations and inflammatory, infectious, and neoplastic etiologies.
Identifying the Bleeding Source
Vessel imaging should be the next step in all patients with a diagnostic head CT, lumbar puncture, or MRI. The gold standard of vessel imaging remains cerebral digital subtraction angiography (DSA) (CASE 3-1). CT angiography (CTA) has become widely available and is now commonly performed as the first-line vascular imaging in many institutions. Depending on the technique, slice thickness, and postimaging data processing, the sensitivity and specificity of CTA can range from 90% to 97% and 93% to 100%, respectively, when compared to DSA. However, CTA may miss aneurysms as small as 4 mm or less.
In specialized stroke and aneurysm centers, DSA is readily available for diagnostic as well as treatment purposes. At the author’s institution, two-dimensional and three-dimensional DSA is pursued as standard diagnostics for aneurysm detection as soon as the diagnosis of SAH has been established; CTA is usually omitted at the author’s institution to prevent the additional exposure to radiation, iodine contrast, and its potential for anaphylactic reaction and nephrotoxicity. Patients with a negative initial DSA should have a repeat study 7 to 14 days after the initial one. In addition, in those with negative initial DSA, MRI of the brain and, depending on the location of the SAH, MRI of the cervical spine should be performed to search for a possible arteriovenous malformation of the brain, brainstem, or spinal cord.
Perimesencephalic Subarachnoid Hemorrhage
Approximately 15% of patients with SAH will have negative imaging studies for a source of bleeding, of which approximately 38% have nonaneurysmal perimesencephalic SAH, a special form of nontraumatic SAH with blood isolated to the perimesencephalic cisterns (CASE 3-2). The clinical course has been reported to be more benign, although case reports have been published demonstrating rare cases of small aneurysms in the posterior circulation, fenestration of the vertebral or basilar arteries, or anterior spinal artery abnormalities. Therefore, DSA should still be performed. At the author’s institution, a brain and cervical spine MRI, as well as a repeat DSA approximately 7 days after the initial tests, are performed in all cases of perimesencephalic SAH. Patients with perimesencephalic SAH are monitored in a step-down unit and, if no bleeding source is discovered, discharged after 8 to 10 days at the author’s institution, as long as their hospital course remains uncomplicated.
A 23-year-old man presented to the emergency department for evaluation after developing a sudden-onset headache posteriorly while lifting weights in the gym. He described the headache as the “worst headache of his life.”
A noncontrast head CT revealed blood around the perimesencephalic and prepontine cisterns (FIGURE 3-3). Six-vessel angiography did not reveal a bleeding cause. He underwent MRI of the brain and cervical spine, which also did not reveal a cause for the bleeding. He was observed in the step-down unit until 8 days posthemorrhage, when he received a repeat six-vessel angiogram, which was again negative. The patient was discharged home on day 10 post–subarachnoid hemorrhage in normal condition.
This case demonstrates a typical presentation and hospital course for a perimesencephalic subarachnoid hemorrhage, with the adequate workup for a bleeding source. The patient’s course was benign, as commonly seen in patients with perimesencephalic subarachnoid hemorrhage.
This section focuses on the emergency department evaluation and management of a patient with SAH.
Airway, Breathing, and Circulation
The emergency evaluation and management of patients with SAH should focus on the airway, breathing, and circulation (the ABCs). Those patients unable to protect their airway should be intubated immediately, which includes patients in coma, in stupor from hydrocephalus, with seizures, or patients in need of sedation for agitation.
The focus in the first few minutes to hours after SAH, until the patient can undergo treatment of the ruptured aneurysm, should be directed toward the prevention of rebleeding. This life-threatening complication, with a mortality rate of 20% to 60%, has its highest rate (8% to 23%) within the first 72 hours after SAH, with the majority of rebleeding (50% to 90%) occurring within the first 6 hours, not including patients who die before hospital arrival. After the first month, rebleeding rates are low, at 3% per year. Risk factors for rebleeding include poor-grade SAH, hypertension, a large aneurysm, and, potentially, the use of antiplatelet drugs. Particularly, blood pressure fluctuations and extreme blood pressure peaks should be avoided because of the presumed propensity to cause rebleeding.
Current guideline recommendations for blood pressure goals are to keep systolic blood pressure below 160 mm Hg. Continuous blood pressure monitoring with an arterial line is highly recommended. IV medications to control blood pressure should preferably be continuous infusions of antihypertensives (nicardipine 5 mg/h to 15 mg/h or labetalol 5 mg/h to 20 mg/h) over bolus infusions (labetalol 5 mg bolus to 20 mg bolus, captopril) to prevent wide fluctuations of blood pressure that may be as detrimental to aneurysm rebleeding as high blood pressure itself.
Therefore, at the author’s institution, hydralazine is avoided as it can cause rebound hypertension. Pain control is best achieved with short-acting opiates. Meningeal chemical irritation from the SAH often responds to one or several single doses of dexamethasone (2 mg to 10 mg).
While prolonged infusion of antifibrinolytics can result in deep vein thrombosis, venous thromboembolism, stroke, and myocardial infarction, and should therefore not be applied, the short-term use (up to a maximum of 72 hours until aneurysm securement) of antifibrinolytics (tranexamic acid or ε-aminocaproic acid) is recommended by guidelines based on a randomized controlled trial and several small observational studies. Recently, however, a large retrospective study including 341 patients over 12 years, of whom 146 patients received ε-aminocaproic acid before their endovascular coiling, showed that short-term antifibrinolytic therapy was safe but did not reduce preprocedural rebleeding. Therefore, institutional variation may occur in the use of short-term antifibrinolytics to prevent rebleeding until a randomized controlled trial confirms or refutes the guideline recommendations.
Disease Severity Scoring
The importance of severity scoring lies in the observation that outcome and delayed cerebral ischemia are associated with clinical and radiologic scales, respectively (TABLE 3-3). Disease severity scoring provides a common language between all providers caring for a patient with SAH. The two most commonly used clinical scales, the World Federation of Neurological Surgeons Scale (WFNSS) and the Hunt and Hess Scale, are strong predictors of outcome. Higher scores are associated with worse clinical outcome. The most reliable and validated radiologic scale is the modified Fisher Scale (TABLE 3-3), which is nearly linearly associated with worse cerebral vasospasm and delayed cerebral ischemia.
The classic Fisher Scale score holds several disadvantages and has largely been replaced by the modified Fisher Scale. For example, it was developed on 1980s head CTs and does not reflect modern multislice head CT imaging. Also, it is not linear (a Fisher Scale score of 3 has a higher vasospasm risk than a score of 4), making it more difficult to apply in regression models in research and simply making it less intuitive to apply at the bedside.
Admission to High-volume Centers
If the patient is not already at a high-volume SAH-specialized center (defined as more than 35 SAH cases per year with experienced cerebrovascular surgeons, endovascular specialists, and neurocritical care services), transfer to such a center should be initiated immediately (TABLE 3-4). Likely owing to lack of protocolized care and expertise, admission of patients with SAH to low-volume centers is associated with a higher 30-day mortality. Admission to a neurocritical care unit staffed by dedicated neurointensivists has been associated with lower in-hospital mortality in patients with stroke, including SAH.
With the publication of the ISAT (International Subarachnoid Aneurysm Trial), which compared endovascular coiling to surgical clipping after SAH, the treatment of an unsecured aneurysm has shifted from surgical clipping to mostly endovascular coiling. ISAT showed that patients in the endovascular coiling group had significantly higher odds of survival free of disability 1 year after SAH and a lower risk of epilepsy when compared to the surgical clipping group.
Even 10 years after SAH, patients who underwent endovascular coiling had better outcomes. In contrast, the risk of rebleeding and incomplete occlusion of the aneurysm was lower with surgical clipping. With the introduction of newer techniques such as stent-assisted or balloon-assisted coiling, even broad-neck aneurysms can now be treated with endovascular coiling.
Currently, endovascular coiling is preferred over surgical clipping whenever possible. However, follow-up angiograms are necessary, as the recurrence rate of aneurysms is higher when they are treated with endovascular coiling.
At the author’s institution, approximately 95% of aneurysms are treated with endovascular coiling (CASE 3-1). Many aneurysms are not equally suited for endovascular coiling or surgical clipping (TABLE 3-5 and CASE 3-3A). The choice of treatment depends on the patient’s age as well as the aneurysm location, morphology, and relationship to adjacent vessels. A multidisciplinary approach to the swift treatment decision with consensus between cerebrovascular neurosurgeons, neuroendovascular specialists, and neurointensivists is recommended given the complexity of the decision. Regardless of the treatment modality, rebleeding must be prevented, and the unsecured aneurysm must be treated as soon as possible (TABLE 3-4).
A 51-year-old man presented to the emergency department of a comprehensive stroke center for evaluation of sudden-onset severe headache with rapidly worsening left-sided hemiplegia that began while shoveling snow. Upon arrival, his blood pressure was 205/110 mm Hg, his heart rate was 98 beats/min, his oxygen saturation was 98% on room air, and his temperature was 36.5°C (97.7°F). His Glasgow Coma Scale score was 14, and he had left facial weakness and a dense left hemiplegia. His World Federation of Neurological Surgeons Scale (WFNSS) score was 3, his Hunt and Hess Scale score was 3, and his modified Fisher Scale score was 4.
A noncontrast head CT revealed a subarachnoid hemorrhage with a large right frontotemporal intraparenchymal clot and intraventricular hemorrhage (FIGURE 3-4A). He received immediate blood pressure–lowering agents. A CT angiogram confirmed a suspected right middle cerebral artery aneurysm (FIGURE 3-4B). A three-dimensional digital subtraction angiogram revealed the complicated anatomy of this middle cerebral artery aneurysm with multiple vessels coming off the aneurysm and areas of irregular outpouching (FIGURE 3-4C). The patient was taken to the operating room immediately for craniotomy, clipping of the aneurysm, and clot evacuation. He was admitted to the neurocritical care unit for routine postclipping subarachnoid hemorrhage care.
This case shows a patient with a clear indication for surgical clipping due to the more superficial location of the aneurysm at the distal middle cerebral artery and the aneurysm’s anatomy with multiple vessels coming off the aneurysm. It also shows how patients with large temporal hematomas (with or without subarachnoid hemorrhage) should always undergo vessel imaging, as a middle cerebral artery aneurysm may be the culprit.
Critical Care Management of Subarachnoid Hemorrhage
SAH is a systemic disease and is not isolated to the brain. It is commonly associated with systemic inflammatory response syndrome (SIRS) (75%), which is related to elevated levels of inflammatory cytokines. SIRS has been associated with long-term cognitive dysfunction and has been linked to nonconvulsive seizures in SAH. SIRS has been found to precede nonconvulsive seizures, and patients with in-hospital nonconvulsive seizures are almost twice as likely to have SIRS as those without nonconvulsive seizures. Therefore, it has been postulated that the negative impact of SIRS on functional outcome is mediated in part by nonconvulsive seizures.
Additionally, patients with SAH are at risk for several additional neurologic complications, including hydrocephalus, brain edema, delayed cerebral ischemia, rebleeding, seizures, and neuroendocrine disorders, the latter of which can lead to impaired regulation of sodium, volume, and glucose. Furthermore, mediated through the hypothalamus, sympathetic release can result in cardiac and pulmonary complications, including neurogenic ECG changes, arrhythmias, diminished cardiac contractility (stress Takotsubo cardiomyopathy), troponin leaks, and myocardial contraction band necrosis. The early recognition and treatment of these complications is key to achieve the best possible outcome of the patient with SAH.
Several serious neurologic complications may occur after SAH.
Rebleeding is the most immediately life-threatening neurologic complication after SAH. The best measure to reduce the risk of rebleeding is the early and rapid treatment of the unsecured, ruptured aneurysm. The prevention of rebleeding via aggressive blood pressure control should begin during the prehospital transport and in the emergency department.
Acute symptomatic hydrocephalus occurs in 20% of patients with SAH, usually within minutes to days after SAH onset (FIGURE 3-1A and FIGURE 3-4A). Clinical signs of hydrocephalus are decreased levels of consciousness, impaired upgaze, hypertension, and delirium. The diagnosis is made by repeat head CT and clinical symptoms.
Hydrocephalus can resolve spontaneously in 30% of patients but can also rapidly worsen. Insertion of an external ventricular drain (EVD) can be lifesaving. Some centers insert a lumbar drain instead of an EVD in cases of communicating hydrocephalus, while some centers insert both. Reluctance to place an EVD includes the risks of infection, bleeding (intracerebral or intraventricular), and changes in the transmural pressure precipitating the rebleeding of an unsecured aneurysm. The bleeding and infection risk for EVD insertions are close to 8% for each.
A rapid weaning of the EVD is recommended after aneurysm obliteration or within 48 hours of insertion if the patient is neurologically stable. In those for whom weaning is unsuccessful (approximately 40%), placement of a chronic ventriculoperitoneal shunt may be required. A small retrospective study from Germany has suggested that dexamethasone dosed 12 mg/d for at least 5 days may lower the risk of hydrocephalus after SAH. Given the lack of randomized controlled studies, the routine use of corticosteroids outside its application for headache control from meningeal chemical irritation after SAH cannot be recommended.
Seizures and Seizure Prophylaxis
Determining the true incidence of seizures in patients with SAH is difficult as many patients (up to 26%) present with seizurelike episodes, but these episodes are not easy to characterize as they occur at the onset of symptoms. If seizures occur prior to aneurysm securement, they are usually a sign of early rebleeding. Long-term epilepsy develops in 2% of patients with SAH and is correlated to a higher severity of SAH. The occurrence of nonconvulsive seizures (7% to 18%) and nonconvulsive status epilepticus (3% to 13%) is more common in patients with SAH who are comatose and has been associated with delayed cerebral ischemia and worse outcomes. It is not completely understood whether nonconvulsive seizures are the cause of delayed cerebral ischemia and worse outcomes or are an epiphenomenon of poor-grade SAH with outcomes due to the severity of SAH. Because nonconvulsive seizures are treatable, continuous EEG monitoring should be considered in patients with high-grade SAH. A 2015 review summarized nonconvulsive seizures and status epilepticus in SAH. However, at some institutions, the limitations lie in the capacity of performing and interpreting prolonged continuous EEG monitoring. Furthermore, recent discoveries show that surface EEG may detect nonconvulsive seizures in only 8% of patients with SAH, while they were seen in 38% of patients when intracortical depth electrodes were placed via a burr hole. Such depth electrode recording, however, is more invasive, is limited to very few centers, and is currently not considered standard of care. The suspicion of nonconvulsive status epilepticus should be high in patients with SAH who are comatose.
Currently, in the absence of randomized controlled trials of antiepileptic drug treatment in patients with SAH, treatment with antiepileptic drugs should be limited to the preaneurysm treatment time frame only, considering the known negative effects of anticonvulsants, particularly phenytoin, on neurocognitive recovery after SAH.
Guidelines and experts recommend stopping antiepileptics in patients in whom a clinical examination can be followed reliably as soon as the aneurysm has been secured and not to extend prophylaxis beyond 3 to 7 days unless the patient presented with a seizure at the onset of SAH. At the author’s institution, only patients who are comatose and patients with poor-grade SAH are continued on antiepileptics after the aneurysm has been secured given the high risk for nonconvulsive seizures in these patients.
Levetiracetam has become a popular antiepileptic because of its high bioavailability, favorable side effect profile, and lack of drug-drug interactions. However, it should be noted that no studies have shown an advantage of levetiracetam over other antiepileptic drugs. In addition, levetiracetam has not been approved by the US Food and Drug Administration (FDA) for monotherapy in epilepsy; therefore, no specific antiepileptic drugs can be recommended for seizure prophylaxis in patients with SAH.
Delayed Cerebral Ischemia
Delayed cerebral ischemia is one of the most feared neurologic complications after SAH, as cerebral infarction from delayed cerebral ischemia is the leading cause for morbidity in patients who survive the initial SAH. Monitoring for delayed cerebral ischemia is the main reason for the recommended prolonged ICU stay for patients with SAH. Delayed cerebral ischemia is defined as any neurologic deterioration that persists for more than 1 hour and cannot be explained by any other neurologic or systemic condition, such as fever, seizures, hydrocephalus, sepsis, hypoxemia, sedation, and other metabolic causes (CASE 3-3B). Delayed cerebral ischemia is diagnosed when other causes of neurologic deterioration have been excluded or deemed insufficient to cause the neurologic deterioration and is therefore a diagnosis of exclusion.
The patient in CASE 3-3A was admitted to the neurocritical care unit. He was monitored with daily transcranial Doppler (TCD). On day 5 post–subarachnoid hemorrhage (SAH), he had an uptrend in the daily TCD mean velocities from 50 cm/s to 153 cm/s in the right middle cerebral artery (FIGURE 3-5A–B).
On day 6 post-SAH, he developed worse headaches, disorientation, neglect, dysarthria, and worse left-sided weakness. He was afebrile, had a normal glucose level, and was euvolemic. He was given a fluid bolus, and his systolic blood pressure goal was elevated to greater than 180 mm Hg with phenylephrine infusion.
An emergent EEG did not reveal nonconvulsive seizures. The blood pressure augmentation improved the disorientation and neglect but not the weakness and dysarthria. Four-vessel angiography was performed, which revealed cerebral vasospasm in the right middle cerebral artery and right anterior cerebral artery (FIGURE 3-5C–D). He was treated with intraarterial nicardipine. Postprocedure he had resolution of symptoms to his immediate post-SAH baseline, but they returned by the next morning. Repeat four-vessel angiography was performed, and he was treated with intraarterial nicardipine and angioplasty (FIGURE 3-5E).
He experienced complete resolution of his symptoms. He was maintained on hypertensive and mild hypervolemic therapy until day 15 post-SAH. His TCD velocities were downtrending, and he was slowly weaned off induced hypertension. He was eventually discharged to rehabilitation.
This case demonstrates how asymptomatic cerebral vasospasm on TCD was initially appropriately treated with just euvolemia without induced hypertension. However, given the elevated alert level of the providers, when the patient worsened and developed symptomatic cerebral vasospasm, treatment with induced hypertension and endovascular treatment was swiftly initiated.
Historically, delayed cerebral ischemia was thought to be caused by cerebral vasospasm. However, evidence now indicates that the pathophysiology of delayed cerebral ischemia includes an interaction of early brain injury, microthrombosis, cortical spreading depolarizations, related ischemia, and cerebral vasospasm (FIGURE 3-6). Increasingly, some experts believe that cerebral vasospasm is only an epiphenomenon and that the underlying biochemical and biophysical changes that lead to delayed cerebral ischemia occur as early as at SAH onset. This fundamental change in the approach to delayed cerebral ischemia is supported by the negative endothelin 1 antagonist trials in patients with SAH undergoing clipping or coiling.
Endothelin 1 has been implicated to be the strongest vasoconstriction mediator in SAH. However, the administration of clazosentan, a potent inhibitor of the endothelin 1 receptor, resulted in less angiographic cerebral vasospasm yet did not ameliorate delayed cerebral ischemia and did not lead to improvement in outcomes 3 months after SAH.
Delayed cerebral ischemia occurs on average 3 to 14 days after SAH. The risk for delayed cerebral ischemia increases with SAH thickness and intraventricular hemorrhage, as demonstrated by the modified Fisher Scale. Additional risk factors include poor clinical grade, loss of consciousness at ictus, cigarette smoking, cocaine use, SIRS, hyperglycemia, hydrocephalus, and nonconvulsive seizures. Predicting who will develop delayed cerebral ischemia has proven very difficult but is of great importance. Not only does such prediction have an impact on ICU monitoring, early recognition, and treatment, but also on resource allocation and early ICU discharge for low-grade, lower-risk patients with SAH. The best predictors for patients requiring less frequent monitoring include older age (older than 65 years of age), a low WFNSS score of 1 to 3, and a modified Fisher Scale score of less than 3 (TABLE 3-4).
Delayed Cerebral Ischemia Prophylaxis
Calcium channel blockers (nimodipine) and maintenance of normal intravascular volume status have the strongest evidence of prophylactic interventions for the prevention of delayed cerebral ischemia. Nimodipine (60 mg every 4 hours for 21 days) is neuroprotective and has Class I evidence for decreasing the risk of poor functional outcome. Notably, however, it does not decrease the frequency of angiographic vasospasm. A common side effect of nimodipine is hypotension, which may lead to hypoperfusion and decreased cerebral perfusion pressure. Therefore, to prevent hypotension, a dose reduction with an increase in frequency to 30 mg every 2 hours may be necessary.
In all cases, adequate maintenance of intravascular euvolemia is recommended. Decreased intravascular volume and a negative fluid balance have been associated with a higher incidence of delayed cerebral ischemia and poor neurologic outcomes.
How to monitor for euvolemia has not been defined. Trending the central venous pressure has fallen out of favor as it has been shown to be a poor predictor of fluid responsiveness and intravascular volume. Measurements of pulse pressure variation or respiratory variability of the inferior vena cava diameter using point-of-care bedside ultrasound are easy to perform and are much more reliable monitoring techniques for fluid responsiveness of patients who are critically ill, including those with SAH. Prophylactic hypervolemia must be avoided, as this strategy has not been shown to improve cerebral blood flow or decrease the frequency of cerebral vasospasm or delayed cerebral ischemia but increases adverse cardiopulmonary complications.
Maintenance of a euvolemic state may be difficult in the presence of cerebral salt wasting, a common neuroendocrine disorder in SAH (see the following section on hyponatremia). In patients with SAH and significant diuresis and natriuresis, additional administration of fludrocortisone can be helpful in maintaining intravascular volume and normal sodium values (fludrocortisone 0.2 mg to 0.4 mg enterally every 12 hours) (TABLE 3-4).
Delayed Cerebral Ischemia Diagnosis and Monitoring
Diagnosing delayed cerebral ischemia is not easy. The combination of neurologic examination and imaging studies can enhance the early detection and proper management. Admission to the neurocritical care unit with frequent neurologic examination by experienced nurses and providers every 1 to 2 hours is necessary. Delayed cerebral ischemia should be suspected if patients with SAH develop a focal or global neurologic deficit or have a decrease of 2 or more points on the Glasgow Coma Scale that lasts for at least 1 hour and cannot be explained by another cause.
Experts have recommended that all patients with SAH undergo a head CT at 24 to 48 hours after aneurysm treatment to establish any treatment-related infarctions. Any subsequent new hypodensities not attributable to EVD insertion or intraparenchymal hematoma should be regarded as cerebral infarctions from delayed cerebral ischemia regardless of the clinical signs.
Patients with SAH should undergo physiologic or imaging monitoring routinely during the risk period for delayed cerebral ischemia. Such monitoring is usually multimodal and includes ICP, cerebral perfusion pressure, continuous EEG, and transcranial Doppler (TCD) monitoring; DSA, CTA, and CT perfusion (CTP) imaging are also used when indicated as well as brain tissue oxygenation and microdialysis monitoring, when available.
TCD has been the longest used and best studied of all the monitoring modalities. In the large vessels of the circle of Willis, TCD has adequate sensitivity and specificity to detect increased cerebral blood flow velocities secondary to cerebral vasospasm but is highly dependent on the operator and cranial bone window (CASE 3-3B).
Practitioners need to be aware that the sensitivity/specificity of TCD is good for the middle cerebral and internal carotid arteries but is much lower for the anterior cerebral arteries and posterior circulation arteries. Thresholds for the diagnosis of cerebral vasospasm have been summarized.
In addition, cerebral blood flow velocities can be elevated for other reasons (hyperemia due to fever, induced hypertension, anemia), and therefore a diagnosis of cerebral vasospasm should only be made when the ratio of mean cerebral blood flow velocity of the intracranial vessel to mean cerebral blood flow velocity of the extracranial internal carotid artery is elevated. Therefore, for the diagnosis of middle cerebral artery vasospasm, routine measurement of the Lindegaard ratio (mean velocity in the middle cerebral artery/mean velocity in ipsilateral extracranial internal carotid artery) is prudent. A Lindegaard ratio of >3 indicates cerebral vasospasm. Similar ratios exist for the other main intracranial vessels.
DSA remains the gold standard for the detection of large- and middle-sized artery vasospasm. CTA is now widely available and is often applied for vasospasm screening before DSA given its high degree of specificity and lack of invasiveness. CTA, however, can overestimate cerebral vasospasm. CTP imaging with elevated mean transit time may be of additional value to CTA to assess for decreased cerebral perfusion, but further investigations on the application of CTP in SAH are needed.
Brain tissue oxygenation, cerebral blood flow, and microdialysis monitoring can provide additional information when used in the context of multimodality monitoring and may be able to detect early cerebral vasospasm before it becomes symptomatic and before delayed cerebral ischemia occurs. Clinicians must bear in mind the limitations of such monitoring, including the restriction to monitoring local rather than global brain areas.
Continuous scalp EEG offers the advantage of monitoring broader regions of the brain. Quantitative continuous EEG, if available, may offer easier interpretation of bedside data even by providers not trained or certified to interpret EEG. The cost, and thereby lack of widespread availability, is currently limiting quantitative continuous EEG from becoming standard of care.
It is very important to differentiate between angiographic/TCD vasospasm and clinical symptomatic vasospasm (CASE 3-3B). The former occurs in the majority of patients with SAH (70%) but has not been associated with outcome after SAH. Only symptomatic vasospasm, occurring in 30% of patients with SAH, has been associated with delayed cerebral ischemia and poor outcome after SAH. Given the risks of endovascular cerebral vasospasm treatment, experts recommend such treatment only for patients with symptomatic vasospasm, while angiographic/TCD vasospasm should be managed with a careful watch and wait approach with a very low threshold to trigger DSA and endovascular treatment.
Some variability exists regarding the timing and frequency of the application of the various monitoring modalities. At a minimum, the care for patients with SAH should be protocolized using a written protocol and an algorithm. Patients with SAH should be admitted to a neurocritical care unit and have their aneurysm secured as quickly as possible, preferably within the first 6 to 12 hours after presentation.
Monitoring in the neurocritical care unit includes daily TCD monitoring, although in low-risk patients it may be sufficient to monitor every other day as long as neurologic monitoring can be performed every 1 to 2 hours. Some centers perform CTA/CTP or DSA routinely for all patients 5 to 7 days after admission to screen for cerebral vasospasm. Most centers, however, perform these tests only if concern arises for symptomatic vasospasm.
In patients who are comatose or obtunded, it may be difficult to obtain a reliable examination, and therefore TCD examination and, in addition, CTA/CTP or DSA for vasospasm screening may be required. Particularly in patients with high-grade SAH with poor examination findings, diagnosis and treatment initiation of delayed cerebral ischemia may be difficult, somewhat subjective, and mostly based on neuromonitoring findings.
At the author’s institution, the SAH treatment protocol dictates induced hypertension, CT/CTA, and DSA when these patients have elevated TCD mean velocities and elevated Lindegaard (or other) ratios (CASE 3-3B). Other centers use information from multimodality monitoring (continuous EEG or even intracortical depth EEG, brain tissue oxygenation, microdialysis, cerebral blood flow monitoring) to decide if hypoperfusion or vasospasm may be occurring and when to send the patient for DSA. While randomized controlled data are lacking on the value of multimodality monitoring on short-term and long-term outcomes in the treatment of patients with SAH, resources at the various institutions may dictate, at least in part, how much advanced multimodality monitoring can be employed.
At the author’s institution, all patients are treated with nimodipine and euvolemia. Low-risk patients whose neurologic examination, TCD, and, if performed, CTA remain unchanged are transferred to the neuro step-down unit under the care of neurointensivists between days 8 and 10 and receive neurologic examinations less frequently (every 2 hours instead of hourly) than in the ICU. Patients are then discharged to the floor or home by day 14. High-risk patients whose neurologic examination, TCD, and, if performed, CTA remain unchanged will transfer to the floor or other lower level of care 14 days after SAH. If at any time the patient develops elevated TCD mean cerebral blood flow velocities and abnormal CTA findings, the intensity of neurologic monitoring is escalated (CASE 3-3B).
If patients experience a neurologic deterioration suggestive of delayed cerebral ischemia, certain rescue therapies are initiated. In the case of symptomatic cerebral vasospasm and delayed cerebral ischemia, induced hypertension is indicated per current guidelines (TABLE 3-4 and FIGURE 3-6). Hypervolemic, hypertensive, and hemodilutional (Triple H) therapy is no longer supported by guidelines because of the existing evidence of adverse associations with outcomes after the use of hemodilution, and the standard treatment is now hypertensive and mild hypervolemic therapy (HHT). Many institutions initiate an IV fluid bolus (1 L to 2 L of 0.9% saline) and maintain fluids for euvolemia or mild hypervolemia. Hypertension is preferably induced using α1 receptor agonists by a continuous infusion (norepinephrine or phenylephrine). This group of drugs are the vasopressors of choice in SAH, as the brain vessels lack α1 receptors, and therefore only systemic but not brain vasoconstriction is achieved. Blood pressure augmentation should progress in a stepwise fashion with frequent neurologic assessments at each step.
At the author’s institution, a mean arterial pressure (MAP) about 20 mm Hg above the baseline MAP is set as the first goal (often MAP >90 mm Hg). Some institutions use systolic blood pressure goals instead of MAP goals, and no evidence exists to guide clinicians regarding whether one parameter is better than the other. In institutions where systolic blood pressure goals are set for induced hypertension, the initial goal for induced hypertension should be approximately 20 mm Hg to 40 mm Hg above the baseline systolic blood pressure. This commonly results in a systolic blood pressure goal of >180 mm Hg or >200 mm Hg.
If the clinical examination has returned to the prior baseline examination, no further blood pressure elevations are necessary, unless the clinical examination deteriorates further at this blood pressure goal. In the latter case, further increases in the blood pressure goal should be attempted. While no optimal or maximum blood pressure goal is known, adverse effects on the cardiac and pulmonary systems and the brain (for example, autoregulatory side effects with elevated ICP with increasing MAP or posterior reversible encephalopathy syndrome [PRES]) should be considered for each patient.
At the author’s institution, inotropic agents (milrinone, dobutamine) are reserved for those patients with known poor cardiac output from acute or chronic cardiomyopathy. If neurologic deficits persist despite induced hypertension, the patient is sent for CT/CTA followed by DSA with endovascular therapy if cerebral vasospasm is confirmed. A noncontrast head CT prior to DSA is useful in ruling out hydrocephalus and determining preexisting stroke prior to endovascular treatment. If other causes for the neurologic deterioration have already been ruled out, and TCDs suggest cerebral vasospasm, the CTA may be skipped to spare the patient radiation, iodine contrast, and to save time and allow the patient to go to DSA immediately for treatment. Endovascular therapy using intraarterial vasodilators (nicardipine, milrinone, verapamil) or angioplasty is supported by prospective and retrospective observational data and is recommended by guidelines (TABLE 3-4 and CASE 3-3B). At the author’s institution, prophylactic angioplasty is not performed if cerebral vasospasm is detected during TCD or CTA without neurologic deterioration because this practice is associated with higher complication rates.
SAH is a systemic disease, and patients commonly experience additional medical complications. Anticipation of these complications leads to rapid recognition and treatment.
Cardiopulmonary dysfunction is a well-known complication of SAH and can range from minor ECG changes to severe stress cardiomyopathy and neurogenic pulmonary edema. The incidence of left ventricular dysfunction in the first week after SAH ranges from 9% to 30% and can include regional wall motion abnormalities not correlating with coronary artery territories or severe systolic left ventricular dysfunction with an ejection fraction of less than 30%. ECG changes can include T-wave inversions and prolonged QTc intervals and may be the culprit for arrhythmias such as bradycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation. The severity of SAH is an independent predictor of cardiopulmonary injury, suggesting that the cardiopulmonary injury is neurally mediated. Troponin elevation can be seen in up to 30% of patients, but its significance is unclear. Certain ECG changes, such as prolonged QTc intervals, have been reported to predict death.
Similarities have been observed between pheochromocytoma crisis and SAH, linking the observed cardiac changes to a catecholamine surge. Patients with SAH can have a threefold increase in norepinephrine levels for 10 days or longer after ictus, which normalize after this time period. Myocardial cell necrosis, also known as contraction band necrosis, is the hallmark of a catecholamine surge and can be found in patients with pheochromocytoma and SAH. The central catecholamine release has been localized to the posterior hypothalamus based on postmortem pathologic studies, which found microscopic hypothalamic lesions including small hemorrhages and infarctions in patients with contraction band necrosis.
Clinically, the catecholamine surge during aneurysm rupture results in direct myocardial injury, leading to decreased inotropy and an increase in cardiac preload due to venous constriction, as well as increased cardiac afterload due to peripheral arterial constriction (FIGURE 3-7 ). Consequently, stroke volume diminishes, which cannot be compensated by reflex tachycardia, resulting in decreased cardiac output and neurocardiogenic shock. Because of loss of myocardial compliance (“stunning” of the heart), the cardiac silhouette on a ventriculogram and on chest radiograph has the characteristic shape of a Japanese octopus fishing pot (tako-tsubo), which is why this disease has also been named Takotsubo cardiomyopathy. Neurogenic cardiomyopathy in SAH is associated with higher mortality and worse long-term outcomes.
Pulmonary edema leading to hypoxia is also frequently encountered and may occur either as a result from the acute left ventricular dysfunction or independently as neurogenic pulmonary edema from substantial increases in pulmonary capillary pressures from the sympathetic surge. FIGURE 3-7 summarizes the pathophysiology of cardiopulmonary complications mediated by alpha and beta receptors. Cardiopulmonary complications after SAH are usually transient and resolve within several days to 2 weeks. However, during this period, the patient must be maximally supported to prevent secondary brain injury from hypoxia and decreased cerebral perfusion. In extreme cases, the insertion of an intraaortic balloon pump may be required to support the patient until resolution of the transient symptoms.
At the author’s institution, every patient with SAH receives a baseline ECG, echocardiogram, and chest x-ray on admission. Excessive fluid intake is avoided with a goal of euvolemia and not hypervolemia. Lung-protective mechanical ventilation with tidal volumes of less than 7 cc/kg of ideal body weight without permissive hypercarbia is performed routinely. If delayed cerebral ischemia is present and induced hypertension is initiated, inotropic agents may be used in addition to vasopressors to increase cardiac contractility. Hypervolemia is restricted to avoid or prevent worsening of pulmonary edema. A repeat follow-up echocardiogram is performed 10 to 14 days after ictus to evaluate for resolution of Takotsubo cardiomyopathy.
Fever is the most common medical complication after SAH, occurring in up to 70% of patients. Fever is more likely to occur in patients with high-grade SAH and poor neurologic status. Fever has been associated with delayed cerebral ischemia and worse clinical outcomes and is likely related to SIRS and chemical meningitis rather than an infectious process. While fever is commonly treated with therapeutic temperature modulation and induced normothermia, no clear evidence currently indicates that such treatment is beneficial. Current recommendations are to monitor body temperature and to rule out or treat infectious etiologies. If fever is suppressed with induced normothermia, shivering should be strictly avoided and aggressively treated if it occurs.
Thromboembolism and Prophylaxis
Deep vein thrombosis after SAH is common, with rates between 2% and 20% depending on the screening method. Patients with high-grade SAH are at greatest risk, presumably because of limited mobility. To prevent the potential life-threatening consequences of pulmonary embolism, mechanical venous thromboembolism prophylaxis should be initiated immediately on admission with the use of pneumatic compression devices. At the author’s institution, chemoprophylaxis with subcutaneous fractionated or unfractionated heparin is usually initiated immediately after endovascular aneurysm repair and within 24 hours after craniotomy for clipping. Heparin-induced thrombocytopenia type II affects 6% of patients with SAH. The exact mechanism for this observation is not clear. However, a clinical suspicion of this syndrome should immediately be raised and diagnostic measures and treatment should be initiated when the platelet counts are decreasing rapidly and the patient has been exposed to fractionated or unfractionated heparin.
Glycemic dysfunction is very common after SAH because of stress and has been associated with delayed cerebral ischemia and poor clinical outcome. However, it remains unclear whether this is merely an association or causative. Hypoglycemia can lead to brain metabolic crisis and must be vigilantly avoided. In the absence of clinical trials of glucose control in patients with SAH, current recommendations are to maintain a blood glucose level between 80 mg/dL and 200 mg/dL (TABLE 3-4).
Hyponatremia is the most common electrolyte disorder in SAH and can occur in up to 30% of patients. Its cause is presumed to be hypothalamic dysfunction, most commonly from cerebral salt wasting due to an increase in circulating brain natriuretic peptide levels. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) should always be considered but is generally uncommon in patients with SAH. Knowledge about how to differentiate cerebral salt wasting and SIADH is a basic and very important skill of any clinician caring for patients with SAH. Reviews of the diagnoses of both syndromes have been published (FIGURE 3-8).
It is important to note that in both cerebral salt wasting and SIADH, the laboratory findings are similar: low serum sodium (<134 mEq/mL), low serum osmolality (<274 mmol/L), high urine sodium (>20 mmol/L), and high urine osmolality (>100 mmol/L). The only differentiating finding is the patient’s intravascular volume status; cerebral salt wasting is a hypovolemic state, while patients with SIADH are euvolemic or even hypervolemic. It is of utmost importance to correctly differentiate these two syndromes because treatment is opposite and an incorrect diagnosis with improper treatment can lead to detrimental effects in patients with SAH.
Cerebral salt wasting is treated with fluid administration and sometimes a continuous infusion of hypertonic saline (1.5% to 3%) and fludrocortisone if diuresis and natriuresis impede maintenance of adequate volume status. However, patients with SIADH are treated with fluid restriction and sometimes diuresis with loop diuretics. Serum sodium as well as the volume status must be followed closely.
As shown in FIGURE 3-8, it is also important to test thyroid and adrenal functions as well as serum glucose (>500 mg/dL can result in pseudohyponatremia) and triglyceride levels to adequately address other causes of hyponatremia. Pseudohyponatremia (not due to true hyponatremia but from laboratory test interference from extreme triglyceridemia) should be considered in patients on propofol.
Most patients with SAH will experience anemia during their hospitalization, which is presumably due to excessive blood draws, blood loss from other reasons, or systemic inflammation. Anemia and hemoglobin concentrations of less than 9 g/dL have been associated with delayed cerebral ischemia and poor clinical outcomes; however, optimal hemoglobin goal levels and transfusion thresholds are not known. A recent small, randomized controlled trial comparing the safety and efficacy of transfusion to higher hemoglobin levels (goal hemoglobin concentration of at least 10 g/dL or 11.5 g/dL) in patients with SAH demonstrated safety of transfusing to these high hemoglobin levels, but no differences were seen in delayed cerebral ischemia and short-term (14 days) functional outcomes.
PROGNOSTICATION AFTER SUBARACHNOID HEMORRHAGE
While established clinical scales such as the WFNSS and the Hunt and Hess Scale may be helpful in discriminating high-risk from low-risk patients, just like any prognostic scale, they were established for populations and must not be applied to individual patients.
Outcome is also influenced by many other factors, which are generally not included in prognostic scales, such as patient values and preferences, comorbidities, social networks, resilience, and time for recovery. Unless the patient presents with bilaterally dilated pupils and a head CT or DSA inconsistent with brain perfusion and life, all efforts should be made initially to salvage even patients with very high-grade SAH with treatment of high ICP and hydrocephalus, followed by securing the aneurysm. Adequate protocolized neurocritical care should be provided for the first 2 weeks or longer, at which time, after establishing preexisting patient wishes and preferences with the family, further goals of care may need to be discussed.
The Functional Recovery Expected After Subarachnoid Hemorrhage (FRESH) scale is a recently published prognostic scale for expected 12-month cognitive outcome and quality of life after SAH, and the same caution should be used with this scale as should be used with any prognostic scale. This score has excellent discrimination and calibration, has been externally validated, and may be calculated at the bedside using a free smartphone app.
SAH is a life-threatening type of hemorrhagic stroke and a neurologic emergency that carries a high risk of morbidity and mortality. This female-predominant disease should be approached in two phases: (1) expeditious and accurate recognition of SAH, transfer to an appropriate high-volume center, and identification and securement of the aneurysm and (2) observation, prevention, or swift treatment of medical and neurologic complications in a neurocritical care unit with state of the art neurocritical care adhering to established guidelines. The main neurologic complications include hydrocephalus, seizures, brain edema, and delayed cerebral ischemia. Common medical complications encompass cardiopulmonary complications, neuroendocrine disorders, and fever, which require expert care.
- Despite a decline in the mortality, subarachnoid hemorrhage remains a highly morbid disease.
- In patients with subarachnoid hemorrhage, aneurysm rupture occurs at an average age of 53 years. This young age at onset results in a high societal cost and number of years of productivity lost.
- The most common cause for subarachnoid hemorrhage is a ruptured cerebral aneurysm (85%); however, 10% of subarachnoid hemorrhages may not reveal a bleeding source, while the minority of cases (5%) may be due to other vascular causes.
- Subarachnoid hemorrhage is predominant in women, African Americans, and Hispanics. Hypertension, smoking, and excess alcohol intake are modifiable risk factors that individually double the risk of subarachnoid hemorrhage.
- Current guidelines recommend screening for aneurysms if the patient has two or more first-degree relatives with aneurysms or subarachnoid hemorrhage.
- Subarachnoid hemorrhage typically presents with a sudden and severe headache (“worst headache of life”), which is distinctly different from usual headaches.
- Physical examination of a patient with subarachnoid hemorrhage should include determination of the level of consciousness and the patient’s score on the Glasgow Coma Scale, evaluation for meningeal signs, and the presence of focal neurologic deficits.
- Transient elevation in the intracranial pressure is the cause of nausea, vomiting, and syncope and may be associated with additional cardiac and pulmonary complications after subarachnoid hemorrhage.
- The most rapidly available and appropriate initial diagnostic test for patients with suspected subarachnoid hemorrhage is a noncontrast head CT.
- In cases of negative or equivocal head CT findings in which a high suspicion still exists for subarachnoid hemorrhage, a lumbar puncture is the immediate next recommended step.
- CSF should be spun down and evaluated for xanthochromia by visual inspection and, if available, spectrophotometry. Xanthochromia takes approximately 12 hours to develop and may not be present if a lumbar puncture is performed earlier after headache onset.
- Head CT and MRI are considered equally sensitive in detecting subarachnoid hemorrhage in the first 2 days, except in the hyperacute first 6 hours after subarachnoid hemorrhage, during which head CT may miss a small proportion of subarachnoid hemorrhages and MRI may be slightly superior.
- Hemosiderin-sensitive MRI sequences (gradient recalled echo and susceptibility-weighted imaging) or fluid-attenuated inversion recovery sequences have superior sensitivity to detect subacute or chronic subarachnoid hemorrhage compared to head CT.
- The “gold standard” vessel imaging remains cerebral digital subtraction angiography.
- Approximately 15% of patients with subarachnoid hemorrhage will have negative imaging studies for a source of bleeding, of which approximately 38% have nonaneurysmal perimesencephalic subarachnoid hemorrhage.
- The focus in the first few minutes to hours after subarachnoid hemorrhage, until the patient can undergo treatment of the ruptured aneurysm, should be directed toward the prevention of rebleeding.
- Risk factors for rebleeding include poor-grade subarachnoid hemorrhage, hypertension, a large aneurysm, and, potentially, the use of antiplatelet drugs.
- The short-term use (up to a maximum of 72 hours until aneurysm securement) of antifibrinolytics (tranexamic acid or ε-aminocaproic acid) is recommended by guidelines, although there is institutional variation in their use.
- The two most commonly used clinical scales, the World Federation of Neurological Surgeons Scale and the Hunt and Hess Scale, are strong predictors of outcome in patients with subarachnoid hemorrhage. The most reliable and validated radiologic scale is the modified Fisher Scale.
- For the treatment of aneurysm, endovascular coiling is preferred over surgical clipping whenever possible, but the choice of treatment depends on the patient’s age as well as the aneurysm’s location, morphology, and relationship to adjacent vessels.
- Patients with subarachnoid hemorrhage are at risk for several additional neurologic complications, including hydrocephalus, brain edema, delayed cerebral ischemia, rebleeding, seizures, and neuroendocrine disorders, the latter of which can lead to impaired regulation of sodium, volume, and glucose.
- Acute symptomatic hydrocephalus occurs in 20% of patients with subarachnoid hemorrhage, usually within minutes to days after subarachnoid hemorrhage onset. In cases of hydrocephalus, insertion of an external ventricular drain can be lifesaving.
- If seizures occur prior to aneurysm securement, they are usually a sign of early rebleeding.
- The occurrence of nonconvulsive seizures (7% to 18%) and nonconvulsive status epilepticus (3% to 13%) is more common in patients with subarachnoid hemorrhage who are comatose and has been associated with delayed cerebral ischemia and worse outcomes.
- Continuous EEG monitoring should be considered in patients with high-grade subarachnoid hemorrhage.
- In the absence of randomized controlled trials of antiepileptic drug treatment in subarachnoid hemorrhage, but with known negative effects of anticonvulsants, particularly phenytoin, on neurocognitive recovery after subarachnoid hemorrhage, treatment with antiepileptic drugs should be limited to the preaneurysm treatment time frame only.
- Delayed cerebral ischemia after subarachnoid hemorrhage is defined as any neurologic deterioration that persists for more than 1 hour and cannot be explained by any other neurologic or systemic condition.
- Delayed cerebral ischemia occurs on average 3 to 14 days after subarachnoid hemorrhage. The risk for delayed cerebral ischemia increases with subarachnoid hemorrhage thickness and intraventricular hemorrhage, as demonstrated by the modified Fisher Scale.
- Delayed cerebral ischemia should be suspected if patients with subarachnoid hemorrhage develop a focal or global neurologic deficit or have a decrease of 2 or more points on the Glasgow Coma Scale that lasts for at least 1 hour and cannot be explained by any other cause.
- Patients with subarachnoid hemorrhage should undergo physiologic or imaging monitoring routinely during the risk period for delayed cerebral ischemia.
- Transcranial Doppler has adequate sensitivity and specificity to detect increased cerebral blood flow velocities secondary to cerebral vasospasm in the middle cerebral and basilar arteries but is highly dependent on the operator and cranial bone window.
- Digital subtraction angiography remains the gold standard for detection of large- and middle-sized artery vasospasm.
- Only symptomatic vasospasm, occurring in 30% of patients with subarachnoid hemorrhage, has been associated with delayed cerebral ischemia and poor outcome after subarachnoid hemorrhage.
- Hypervolemic, hypertensive, and hemodilutional (Triple H) therapy is no longer supported by guidelines because of the existing evidence of adverse associations with outcomes after the use of hemodilution. Standard treatment is now hypertensive and mild hypervolemic therapy (HHT).
- In the management of patients with symptomatic vasospasm, hypertension is preferably induced using α1 receptor agonists by a continuous infusion (norepinephrine or phenylephrine).
- Cardiopulmonary dysfunction is a well-known complication of subarachnoid hemorrhage and can range from minor ECG changes to severe stress cardiomyopathy and neurogenic pulmonary edema.
- The severity of subarachnoid hemorrhage is an independent predictor of cardiopulmonary injury, suggesting that the cardiopulmonary injury is neurally mediated.
- Takotsubo cardiomyopathy in subarachnoid hemorrhage is associated with higher mortality and worse long-term outcomes.
- Fever is the most common medical complication after subarachnoid hemorrhage, occurring in up to 70% of patients.
- Fever has been associated with delayed cerebral ischemia and worse clinical outcomes and is likely related to systemic inflammatory response syndrome and chemical meningitis, rather than an infectious process.
- Deep vein thrombosis after subarachnoid hemorrhage is common, with rates between 2% and 20%.
- Mechanical venous thromboembolism prophylaxis should be initiated immediately on admission with the use of pneumatic compression devices. At the author’s institution, chemoprophylaxis with subcutaneous fractionated or unfractionated heparin is usually initiated immediately after endovascular aneurysm repair and within 24 hours after craniotomy for clipping.
- In the absence of clinical trials of glucose control in patients with subarachnoid hemorrhage, current recommendations are to maintain a blood glucose level between 80 mg/dL and 200 mg/dL.
- Hyponatremia is the most common electrolyte disorder in patients with subarachnoid hemorrhage and can occur in up to 30% of patients.
- The laboratory findings are similar in both cerebral salt wasting and syndrome of inappropriate secretion of antidiuretic hormone. The only differentiating finding is the patient’s intravascular volume status; cerebral salt wasting is a hypovolemic state, while patients with syndrome of inappropriate secretion of antidiuretic hormone are euvolemic or even hypervolemic. It is of utmost importance to correctly differentiate these two syndromes because treatment is opposite.
- Cerebral salt wasting is treated with fluid administration and sometimes a continuous infusion of hypertonic saline and fludrocortisone if diuresis and natriuresis impede maintenance of adequate volume status. Patients with syndrome of inappropriate secretion of antidiuretic hormone are treated with fluid restriction and sometimes diuresis with loop diuretics.
- Anemia and hemoglobin concentrations of less than 9 g/dL have been associated with delayed cerebral ischemia and poor clinical outcomes; however, optimal hemoglobin goal levels and transfusion thresholds are not known.