Spontaneous Subarachnoid Hemorrhage

• Aneurysmal subarachnoid hemorrhage is both rare in ED patients with headache and potentially fatal.
• The fourth-generation multislice CT scans are very sensitive to blood in the subarachnoid space during the first 6 hours after symptom onset.
• The choice to perform a lumbar puncture in a low-risk patient with a normal CT scan is best approached via a shared decision-making process.
• Once diagnosed, supportive measures are important to control complications and minimize further brain damage.

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Case Example

On the third day of a long weekend, a 64-year-old female experienced the sudden onset of severe occipital headache associated with nausea, vomiting, photophobia, and chest discomfort while moving furniture. Her past medical history was significant for hypertension, depression, and smoking. She was promptly taken to the local emergency department (ED) and seen immediately by the emergency physician. Notable physical exam findings included blood pressure (BP) 170/110, tenderness of the upper cervical muscles, and a reduced cervical range of motion. A detailed neurological exam was normal. An electrocardiogram (ECG) was interpreted as showing nonspecific inverted T waves. A non-contrast computed tomography (CT) scan of the head was performed and read as negative by the radiologist. The patient was admitted and observed overnight with spontaneous resolution of both her headache and chest discomfort. She was discharged home the next day with a diagnosis of cervical sprain, non-ischemic chest pain, and hypertensive urgency and prescribed nonsterioidal anti-inflammatory and antihypertensive drugs. Six days later, the patient was found dead as the result of a ruptured cerebral aneurysm.

Introduction

Non-traumatic subarachnoid hemorrhage (SAH) is one of those concerning disorders in ED patients; it is both a rare and potentially life-threatening disease. While about half of patients with non-traumatic SAH present with the “classic” thunderclap headache, those who do not present a challenge in diagnosis.¹ Early recognition and treatment has been shown to improve patient outcomes. In addition, from a medico-legal perspective, misdiagnosed SAH represents one of the largest sources of ED litigation claims and malpractice settlement payments in the United States. In fact, of the 57% of malpractice claims related to misdiagnosis, SAH-related claims were among the top 12 diagnoses cited as having successful litigation in favor of the plaintiff. Even though SAH is a relatively uncommon event compared to other causes of headache in the ED patient, it has become a “can’t miss” diagnosis. The dilemma often presents itself as to whether extensive testing, with all its inherent complications, is necessary to exclude an SAH. The situation is similar to the scenario seen with excluding a pulmonary embolism in a patient who presents with chest pain or shortness of breath.

The purpose of this paper is to review some significant clinical questions regarding ED management of SAH, including: Does a response to medical treatment in the ED exclude SAH? Which ED patients with headache require neuroimaging? Does lumbar puncture need to be performed routinely to exclude non-traumatic SAH after a normal non-contrast brain CT study? What is the need for additional ED imaging in patients with thunderclap headache and negative CT and lumbar puncture?

Epidemiology

The incidence of aneurysmal SAH in the United States is estimated to be between 10 and 15 people per 100,000 population. The international incidence varies widely, with lower rates in South and Central America (2-4 cases/100,000) and higher rates in Finland and Japan (19-23 cases/100,000), likely due to variations in diagnostic testing. Females have a slightly higher incidence than males, possibly due to estrogen deficiency, and African Americans have a higher risk than Caucasians, possibly due to certain genetic predispositions or perhaps due to variability in reporting methods. The prevalence of intracranial saccular aneurysms in the United States based on radiographic and autopsy findings is approximately 5% (or about 15 million people), of which about 30,000 people every year will suffer SAH secondary to rupture of the aneurysm. Aneurysmal rupture can occur at any age from childhood to advanced age. However, the mean age of rupture is 55 years, with the highest incidence between the ages of 40 and 60 years. About half of all SAHs result in death, with 15% of these casualties dying before ever reaching a hospital.^2,3

There are both modifiable and genetic risk factors that predispose patients to the formation of aneurysms and subsequent rupture of aneurysms.⁴ The most important preventable risk factor appears to be cigarette smoking, with a relative risk of 2 to 7. Heavy smokers have a higher risk than light smokers, and those who stop smoking can decrease their risk of SAH over time.⁵ Hypertension is also a major risk factor and when combined with smoking appears to significantly increase the risk of SAH. Other modifiable risk factors include alcohol consumption and use of sympathomimetic drugs such as caffeine-containing medications, methamphetamine, and cocaine. In addition to increasing the risk of SAH, cocaine also is associated with higher mortality and higher rates of complications following SAH.⁶

Certain inherited conditions predispose to an increased risk of SAH. These include autosomal dominant polycystic kidney disease, glucocorticoid-remediable aldosteronism, and connective tissue disorders such as Ehlers-Danlos syndrome.⁷ A family history of SAH, especially among first-degree relatives, increases the risk of SAH three- to fivefold over that of the general population. The increased incidence among family members may be related to both genetic and environmental factors.⁸ Other associations that historically have been thought to affect the incidence of SAH that have not been validated by studies include elevated serum cholesterol levels, the use of statin therapy, and the use of antiplatelet and/or anticoagulant agents.

Anatomy and Physiology

Twenty percent of all strokes are hemorrhagic in origin, of which SAH accounts for one half. Eighty percent of SAHs are caused by ruptured saccular aneurysms. Other causes of non-aneurysmal SAH (NASAH) include traumatic SAH, perimesencephalic NASAH, arteriovenous malformations, mycotic aneurysms, vasculitides, intracranial arterial dissections, amyloid angiopathy, bleeding diatheses, and illicit drug use. This discussion will focus on aneurysmal SAH.

Blood accumulation from an SAH localizes in the area between the pia mater and arachnoid layer. The normal vasculature supply to the brain arises from the internal carotid and vertebral arteries. These two arteries enter the skull and form the basilar artery and the circle of Willis. (See Figure 1.) The arteries that arise from this unique arterial formation are meant to provide collateral blood flow to the brain and serve to compensate for any ischemia that results from an occluded vessel. Anteriorly, the left and right anterior cerebral arteries are connected by the anterior communicating artery, while the internal carotid arteries (ICA) give rise to the middle cerebral arteries. The ICA also branches into the ophthalmic artery and anterior choroidal artery. Posteriorly, the basilar artery gives rise to the superior cerebellar artery and the left and right posterior cerebral arteries. The posterior cerebral arteries connect with the posterior communicating arteries, completing the circle of Willis by attaching to the ICA. The major arteries of the brain are further divided into segments that supply blood to specific areas of the brain. The anterior cerebral arteries have five branches (A1-A5), the middle arteries have four branches (M1-M4), and the posterior cerebral arteries also have four branches (P1-P4).

There are two types of aneurysms found in the cerebral vasculature: fusiform and saccular. (See Figure 2.) A fusiform aneurysm is less common than a saccular aneurysm, is more stable, and seldom ruptures. A fusiform aneurysm is a circumferential dilation over a short arterial segment and does not have a “stem” like a saccular aneurysm does. The more common and more worrisome saccular aneurysm is a focal outpouching of the wall of an intracranial artery with a “stem” allowing for communication between the saccular aneurysm and the arterial lumen. Typically, this occurs at the site of a bifurcation. A saccular aneurysm also may occur in areas distant from the bifurcation. When this occurs, the aneurysm generally points in the direction of blood flow. This type of aneurysm is often called a “berry aneurysm” because of its berry-like morphology.

The pathogenesis of classic saccular aneurysms is not completely understood. Although historically saccular aneurysms have been thought to be congenital lesions, subsequent studies have shown that this assumption is incorrect. Instead, it is suggested that the aneurysms are acquired lesions caused by a combination of hemodynamic stresses (luminal factors) and defective vessel wall responses (abluminal factors). The fact that a preferred location of saccular aneurysms is at arterial bifurcations and that there is an increased association of these aneurysms with arterial anatomical variants (such as ICA agenesis, persistent carotid-basilar anastomoses, circle of Willis asymmetry, and fenestrations) supports a hemodynamic pathogenesis.⁹

The most common locations for saccular aneurysms are the middle cerebral arteries, the anterior communicating artery, the posterior communicating artery, the top of the basilar arteries, the ICAs including the cavernous portion, the anterior choroidal artery, the A1 and A2 segment of the anterior cerebral arteries, the P2 segment of the posterior cerebral arteries, and the vertebral arteries. The mean diameter of an aneurysm is 4-7 mm, with an increased incidence of rupture in aneurysms that are larger than 7 mm. However, aneurysm size is poorly correlated with morbidity and mortality associated with SAH secondary to aneurysm rupture.¹⁰

Certain triggers have been shown to increase the likelihood of an aneurysm rupture. Physical exertion, acute elevation in blood pressure, increased caffeine consumption, acute anger or startling, and sexual exertion seem to be the most significant precipitating factors. However, it should be noted that some aneurysmal ruptures occur during sleep without any apparent trigger.¹¹

Once an aneurysm ruptures, it can exert its effects by allowing blood to flow into the cerebrospinal fluid (CSF) and invading the intraventricular space, the brain parenchyma, and, rarely, extending into the subdural space. The initial bleeding lasts only a few seconds but re-bleeding is common and most often occurs within the first 24 hours.¹² Secondary effects of rupture include hydrocephalus due to obstruction of CSF flow, as well as increased intracranial pressure (ICP) due to hemorrhage volume, reactive hyperemia, distal cerebral vasodilation, and vasospasm.

Classification of SAH

For decades physicians have recognized that a patient’s clinical presentation at or near the time of arrival to the ED with SAH has prognostic value. As such, numerous scales exist to help describe the severity and outcome of an SAH. Grading scales are most applicable for prognostication but have limited utility in the ED assessment and treatment of SAH patients.¹³ It is important for emergency providers to be familiar with the particular grading scale used at their institution to properly communicate with the appropriate consultants, including interventional radiologists, intensivists, and neurosurgeons. Grading scales also can be a useful tool in discussing aggressive or invasive therapies with patients and their families by giving them context with regard to likely outcome.

Currently, data regarding the validity of these scoring systems are conflicting, as most grading scales were derived retrospectively. The intra- and inter-observer variability has seldom been assessed; therefore, there is no one universally adopted standard. As a result, the use of any particular SAH grading scale is largely dependent on the institutional preference. Commonly used systems include the Hunt and Hess grading system, the Fisher scale, Glasgow Coma Scale (GCS) score, Claassen CT rating scale, Ogilvy and Carter grading system, and the World Federation of Neurological Surgeons Grading Scale.¹⁴

The Hunt and Hess grading system is a prognostic indicator. (See Table 1.) The higher the grade assigned to the patient, the lower the anticipated survival rate. This grading system evaluates a patient’s mental status, symptoms, and neurological function. In addition to the outlined symptoms, the grade is increased by one level for any significant comorbidities such as diabetes, cardiac disease, or chronic obstructive pulmonary disease. A major drawback of the Hunt and Hess scale is the subjectivity of grading and multiple features that can be applicable to more than one grade.¹⁵ As an example, a patient may present with drowsiness and confusion along with a severe hemiparesis. This would place the patient in two distinct categories, grade 3 and grade 4, respectively. Assigning a grade then is left to the physician’s judgment. This is especially problematic when deciding between grades 3 and 4 because mortality changes drastically between these two categories. Despite these limitations, the Hunt and Hess scale remains the most widely used SAH grading scale.

The World Federation of Neurological Surgeons Grading Scale is a more objective scale using the GCS paired with an assessment of motor function. (See Table 2.) Higher grades are associated with worse anticipated outcomes.¹⁶

The Fisher scale is a grading system based on hemorrhage size as measured on CT of the brain and is not used for clinical prognostication. Rather, it is used to predict the risk of developing vasospasm. (See Table 3.)

The Claassen scale (see Table 4) is also used for assessing the risk of vasospasm, but unlike the Fisher scale, it uses the additive risk of SAH and intraventricular hemorrhage.

The Ogilvy and Carter grading system (see Table 5) is the most comprehensive classification scheme, incorporating both the Hunt and Hess classification as well as the Fisher scale. The score is based on a scale of 0 to 5, with one point given for each criterion.¹⁷

Clinical Presentation

Approximately 1-2% of all ED visits are for the chief complaint of headache.^18,19 When evaluating these patients, ask questions regarding the onset, severity, quality, and associated symptoms to help guide the level of clinical suspicion for SAH.

The classic description of patients presenting with SAH to the ED is characterized as a thunderclap headache that is described as the worst headache of the patient’s life.²⁰ Studies have shown that 11-25% of patients presenting with a true thunderclap headache have an SAH.^1,21 The headache typically is sudden in onset, occurs during exertion, and is most severe at onset with unilateral pain that is predominantly found to be on the side of the aneurysm.²² It is further described as pulsating toward the occiput. Other common findings include focal neurological deficits, decreased level of consciousness or loss of consciousness, neck stiffness, and vomiting.²³ Seizures develop in one of every 14 patients with SAH.²⁴ Less commonly, vitreous hemorrhages are seen, which suggest an abrupt rise in ICP.

Patients often report the onset of a sudden, intense headache from 6 to 20 days prior to presenting symptoms.^20,25,26 This is referred to as a sentinel bleed, an initial warning headache that is considered to be secondary to a small leak in the aneurysm that temporarily resolves. A history of a sentinel bleed or headache is said to occur in 20% of patients who have an SAH, with a range from 11% to 53% reported from various sources.²⁷

Sudden death is the initial presentation for SAH in 10-15% of patients, resulting in a fatal outcome prior to receiving ED evaluation.

Approximately 10% of patients with spontaneous SAH present to the ED in cardiac arrest.²⁸ The patient may have experienced some of the initial aforementioned symptoms, but by the time emergency medical services arrives or the patient presents to the ED, this history is challenging to elicit. With SAH, the most common initial rhythm is pulseless electrical activity seen in 44% of cases. For those patients who are successfully resuscitated, approximately 27% have ECG changes that mimic cardiac disease.^29,30 Commonly, the post-arrest ECG will show ST elevations, reciprocal depressions, and T wave inversions. The classic “cerebral” T wave is described as a large, inverted T wave associated with a prolonged QT interval. (See Figure 3.) These ECG changes are thought to be secondary to the massive catecholamine release from the cardiopulmonary arrest that results from the sudden rise in ICP in response to the SAH. When patients are successfully resuscitated from cardiac arrest, consider SAH as an underlying cause if any of the aforementioned clinical findings exist and urgently obtain appropriate diagnostic imaging.

Many patients do not present with the classic history of a thunderclap headache and, thus, the diagnosis of SAH frequently is elusive. Up to 20% of SAH patients are initially misdiagnosed with a variety of conditions such as migraine headache, tension headache, cluster headache, transient ischemic attack, or pseudotumor cerebri.

Diagnosis

A non-contrast head CT is the mainstay of diagnosis for SAH. Clotted blood or hemorrhage is visualized in the subarachnoid space in 92% of cases when the CT is performed within 24 hours of an acute bleed. The sensitivity of a non-contrast head CT performed by a fourth- or fifth-generation scanner is nearly 100% when performed within the first 6 hours of symptom onset; however, the sensitivity of this modality declines with time. The sensitivity decreases to less than 60% by the fifth day following the acute event.^31,32

If the non-contrast head CT is negative for blood, the next step is a lumbar puncture (LP). An LP finds approximately 3% of SAHs when the initial head CT is negative.

There is debate about performing an LP following negative CT. Newer research employing fourth- and fifth-generation scanners in academic institutions with dedicated neuroradiologists has demonstrated 100% sensitivity and specificity for non-contrast CT scanning alone in the diagnosis of SAH if patients present with an isolated acute severe headache, a normal level of consciousness, and no neurological features.³³ More recent studies conducted at nonacademic institutions with staff radiologists reviewing the scans showed that sensitivity of CT alone within 6 hours remained at 100%.^25,34-37 Most studies performed up to this point have been retrospective in design. Thus, until good prospective data exist, our recommendation would be to continue discussing with patients the risks and benefits of performing an LP after a negative CT.

An LP is considered positive in diagnosing SAH based on an elevated opening pressure and high red blood cell count that is equivalent in both the first and fourth specimen collection tubes.³⁸ For the procedure, the patient must be placed in the lateral recumbent position to obtain an accurate opening pressure. Although the standard interpretation of an LP requires that tubes 1 and 4 have equivalent red blood cell counts, a declining red blood cell count from the first and fourth tube is not sufficient to exclude an SAH. A traumatic tap, defined as one contaminated by entering the rich venous plexus within the spinal canal, is classified as more than 63% reduction in red blood cell count between tube 1 and tube 4.³⁹

The CSF also should be evaluated for xanthochromia, which is defined as the yellowish tint to the CSF fluid resulting from the breakdown of hemoglobin, typically after two hours of exposure to the CSF. Xanthochromia can be assessed by visual inspection comparing the collected CSF to a tube of water. Alternatively, one can use spectrophotometry.⁴⁰ Spectrophotometry is more sensitive than visual inspection for diagnosis of SAH, but the procedure has a low specificity and is not routinely recommended for diagnostic confirmation.

When evaluating a non-traumatic aneurysmal SAH, a Canadian study recently concluded that no visible xanthochromia to the naked eye along with a red blood cell count < 2000 × 10⁶/L rules out an aneurysmal SAH with a sensitivity of 100% and a specificity of 91%, which may help decrease further testing via advanced imaging use.⁴¹

Angiography is another method of testing routinely employed for additional imaging in patients with suspected or confirmed SAH. Digital subtraction angiography (DSA), CT angiography (CTA), and magnetic resonance angiography (MRA) are more specific and provide better anatomic delineation of the cerebral vasculature than the non-contrast head CT.⁴² DSA requires a percutaneous approach to the cerebral vasculature and is considered the gold standard for detecting intracranial aneurysms. It is the most comprehensive imaging modality for detection of aneurysm, as it provides real-time visualization of the cerebral vasculature. However, the study also takes longer to perform, is more invasive, and is thus a riskier procedure than CTA or MRA. Therefore, these latter studies are more commonly used. It should be noted that the CTA and MRA are less sensitive than the DSA for smaller aneurysms.⁴³ Often when the diagnosis of SAH is made via a non-contrast head CT, the patient will immediately undergo a CTA to better visualize the anatomy for optimal intervention and pre-surgical planning.

In summary, there are several modalities available to assist in the diagnosis of an SAH and underlying cerebral aneurysm. The clinical presentation and physical examination are the keys to suspecting the diagnosis. When the clinical suspicion exists for spontaneous SAH, an emergent non-contrast CT of the head should be obtained. The next step typically would be an LP if the CT is negative. However, there is emerging evidence that the LP can be deferred within 6 hours of symptom onset if the non-contrast CT is interpreted as negative by an experienced radiologist.

If an SAH is found, a CTA or MRA then is commonly performed to better define the underlying anatomy. There is debate about what to do with the patient who has a “classic” thunderclap headache, a normal non-contrast head CT, and an LP without red cells or xanthochromia. Because of the potential for an aneurysm that may have triggered the headache, many experts recommend further imaging with a CTA or MRA.¹ If the CTA or MRA is normal, further imaging the brain with MRI or DSA may detect an abnormality. There are no prospective studies upon which to make recommendations for further imaging if the initial non-contrast head CT and LP are normal in patients with thunderclap headache. In this event, the emergency physician should consider appropriate consultation or transfer to another facility.

Differential Diagnosis

Due to the varied presentation of SAH, the differential also is very broad. (See Table 6.) For many causes of headache, such as tension headache or cluster headache, the patient history along with a normal CT scan may be enough to exclude SAH. In other cases, such as subdural hematoma, epidural hematoma, or intraparenchymal hemorrhage, the CT will reveal the cause. In rare instances when conditions such as metabolic encephalopathy are considered, a more comprehensive laboratory analysis is required.

A potentially misleading symptom is a reduction in pain over time. After an acute leakage of blood, the initial intense pain may resolve over time. If there is coincident pharmacologic treatment for an alternative diagnosis (e.g., migraine), the potential diagnosis of SAH may be falsely discounted.

Treatment

Prehospital Management. Prehospital care is primarily supportive, with the understanding that a sudden headache in a previously healthy individual is a high-risk presentation that requires advanced support transportation for immediate ED evaluation. The main focus of care in the prehospital setting remains on the airway, breathing, and circulation. In the case of patients complaining of headache and/or neck pain in the presence or absence of neurologic symptoms, prehospital providers should focus on pain control. In cases in which there is a high suspicion for SAH (e.g., sudden severe headache, depressed level of consciousness, motor impairment), the patient should be preferentially taken to tertiary hospitals that have the specialists and imaging capabilites to diagnose and treat these patients, i.e., comprehensive stroke centers.⁴⁴

ED Management. Once the diagnosis of spontaneous SAH is established in the ED, move the patient to an intensive care setting. Ideally, this would include a center with neurocritical care capabilities, neurovascular surgeons, and endovascular specialists. There are ample data to suggest that such care results in improved outcomes and lower mortality rates. Until such transfer can be accomplished, the emergency physician may be called upon to initiate treatment.

Early mortality among those patients who reach the hospital alive is caused by the common complications of SAH, which include re-bleeding, hydrocephalus, increased ICP, seizures, cardiac complications, vasospasm, and delayed cerebral ischemia. The initial treatment of SAH patients is to provide initial stabilizing care and to optimize treatment to help prevent the complications of SAH.⁴⁵

Early endotracheal intubation is recommended in those presenting with GCS of 8 or less, for those with concern for elevated ICP, poor oxygenation or hypoventilation, or hemodynamic instability, and in those who will need heavy sedation. Rapid sequence intubation is recommended, and the same medications used for most intubations would be considered safe. Pretreatment with fentanyl or lidocaine may be considered with the theoretical possibility of lowering ICP. In addition to establishing an airway, pulmonary edema and cardiac arrhythmias need to be treated appropriately, as one-third of patients with SAH will develop these cardiovascular complications. Care must be taken in treating these conditions with diuretics, nitrates, or anti-arrhythmics, as these medications may have a direct impact on the patient’s hemodynamic status. Obtain venous access and monitor fluid administration to maintain euvolemia and a normal electrolyte balance.

To prevent re-bleeding, two mainstays of treatment are proper blood pressure management and reversal of the effects of antithrombotic medications.

BP control is considered a major factor in the prevention of re-bleeding. No universally accepted target has been established. The American Stroke Association (ASA) guidelines suggest a systolic target of less than 160 mmHg is reasonable. Many experts, however, still believe a target systolic BP less than 140 mmHg is more appropriate. It should be noted that if the systolic BP drops too low, there could be an increased risk of infarction. When BP control is necessary, vasodilators should be avoided, as they may increase cerebral blood volume and potentially increase ICP. This, in turn, could lower cerebral perfusion pressure and increase the risk of infarction.^46,47 The recommended medications for BP management include labetalol at a bolus dose of 10-20 mg and enalapril given as a bolus dose of 1.25-2.5 mg. Nicardipine offers the benefit of being a titrated medication, allowing for tighter BP control. Nicardipine should be started at a dose of 5 mg/hr and can be titrated to achieve a targeted BP with a maximum infusion of 15 mg/hr.

There are not much data regarding the clinical impact of antithrombotic reversal; however, most experts agree reversal is necessary until the culprit aneurysm resulting in an SAH has been secured. According to the American Heart Association/ASA guidelines, all anticoagulant and antiplatelet agents should be discontinued after the patient has been diagnosed with an SAH. Warfarin-induced coagulopathy should be reversed immediately with vitamin K, fresh frozen plasma, and/or prothrombin complex concentrate with a goal INR of 1.4 or less.⁴⁸

To reverse dabigatran, the specific antibody-fragment reversal agent idarucizumab (Praxbind®) is recommended. For rivaroxaban and apixaban, activated prothrombin complex concentrate (Feiba®) or 4-factor prothrombin complex concentrate (Kcentra®) is recommended. For antiplatelet agents such as clopidogrel, ticagrelor, and prasugrel, reversal can be initiated by giving desmopressin (DDAVP) at a dose of 0.3 mcg/kg (with a maximum of 20 mcg) can be used. This should be followed by a transfusion of pooled platelets. These recommendations have been extrapolated from data derived from surgical patients who have been given desmopressin and platelets to control bleeding. No studies have specifically evaluated antiplatelet reversal in a patient population with intracerebral hemorrhage or SAH.

Antifibrinolytic therapy with tranexamic acid or aminocaproic acid has been studied for the prevention of re-bleeding. As noted in the 2012 ASA guidelines, antifibrinolytic therapy is a reasonable option if treatment of the aneurysm is delayed and there are no other contraindications. In these cases, treatment is recommended for less than 3 days. Subsequent data, however, show that despite the fact that the rate of re-bleeding is decreased up to five-fold, clinical outcomes, including mortality and Glasgow Outcome Score, were not affected by this treatment. The lack of benefit for antifibrinolytic agents may be explained by the increased risk of cerebral ischemia in patients treated with these agents. At this time, treatment with antifibrinolytics in patients who present with SAH is not considered standard care.^49,50

Patients with SAH often develop increased ICP due to acute hydrocephalus and reactive hyperemia. The definitive intervention to monitor and treat elevations in ICP is the placement of a ventriculostomy. In the ED, treatment of patients with elevated ICP is limited to osmotic therapy in those patients in whom there is a high index of suspicion based on presentation and clinical examination, as well as CT findings.

Mannitol or hypertonic saline are the primary osmotic agents. Mannitol acts as a diuretic and is recommended at a dose of 0.5 to 1 g/kg. Due to its diuretic effect, potential for hemodynamic instability, and the challenges of administering large volumes of the medication, hypertonic saline has emerged as the preferred agent for osmotic therapy. Three percent hypertonic saline is usually given as a bolus of 250 mL followed by an infusion at 30 mL/hr. The limitations in using hypertonic saline include the fact that this medication generally is not stored in the ED and requires central venous access.⁵¹ Hyperventilation with a goal of achieving a pCO₂ of 30-32 may be beneficial in the first 30-60 minutes of treatment for ICP, but studies have not demonstrated long-term benefit from continuous hyperventilation. As such, hyperventilation is not considered essential to the treatment of increased ICP but may have some utility as a temporizing measure. Hyperventilation may be initiated after consultation with a neurosurgeon or intensivist, until definitive treatment with osmotic therapy or surgical intervention can be achieved.

Patients with SAH are at higher risk for seizure; however, prophylactic treatment with anti-epileptic drugs (AED) is somewhat controversial. Many experts believe seizure prophylaxis in the setting of an unsecured aneurysm is reasonable because of the low risk of complications from AEDs compared to the potential deleterious effects of seizure activity on a brain that has lost its inherent autoregulation. On the other hand, there are several reports demonstrating worse outcomes in SAH patients treated with phenytoin.

Newer agents such as levetiracetam should be considered in high-risk patients, as they are believed to be safer than phenytoin in patients with SAH. Levetiracetam at a dose of 500-1000 mg twice daily typically is administered for 3-7 days or until the aneurysm is secured.⁵²

Vasospasm and delayed cerebral ischemia also contribute to unfavorable outcomes after SAH. Clinically significant vasospasm occurs in 20-30% of SAH patients.⁵³ Vasospasm typically occurs from 3 days to 3 weeks after initial hemorrhage. Nimodipine should be initiated in the ED to prevent this complication. Nimodipine is the only calcium channel blocker capable of crossing the blood-brain barrier. Its beneficial effects in preventing vasospasm had been thought to be due to its direct vasodilatory properties. Recent studies, however, have shown that the incidence of vasospasm is unchanged with nimodipine administration. On the other hand, meta-analyses of randomized trials consistently show benefit and improved outcomes in patients receiving nimodipine treatment. The dose of nimodipine is 60 mg every 4 hours, administered orally or via nasogastric tube.

Early Hospital Management

An extension of the care given in the ED, the goal of early hospital treatment is preventing many of the previously mentioned complications. The first and most essential therapeutic decision to be considered is the method by which the culprit aneurysm is be secured. Most experts agree that definitive securing of the aneurysm should be addressed as early as is feasible. This will prevent further re-bleeding and allow for more aggressive treatment of downstream complications, such as vasospasm and delayed cerebral ischemia.

Currently, the two main therapeutic options for securing a ruptured aneurysm are microvascular surgical clipping and endovascular coiling. Historically, surgery has been the preferred method of treatment, but during the past 15 years endovascular coiling has become more prevalent and popular as a minimally invasive method employed in selected patients. The International Subarachnoid Aneurysm Trial was a prospective trial that examined patients with ruptured aneurysm who were equally suitable for surgery or coiling. These investigators found that a favorable one-year outcome, defined as survival free of any physical disability, occurred more commonly in patients treated with coiling. However, there was a slightly higher rate of re-bleeding and higher rates of inadequate occlusion of the aneurysm. In general, patients are not equally suitable for these techniques, and coiling is the preferred therapeutic option in elderly patients, those with aneurysms in the vertebrobasilar circulation, and those with aneurysms deep in the skull base.⁵⁴

Once the aneurysm is secured, standard intensive care principles are followed to optimize patients’ recovery and functional outcome. Patients are aggressively treated with analgesia and sedation to prevent fluctuations in BP and ICP.

Metabolic parameters are closely monitored and maintained to prevent worsening of diffuse brain injury. Hypoxemia, metabolic acidosis, hyperglycemia, fever, renal insufficiency, and anemia are all monitored and addressed, as these abnormalities have been associated with poor outcomes. SAH patients are particularly prone to develop hyponatremia as the result of syndrome of inappropriate antidiuretic hormone secretion or cerebral salt wasting syndrome. Due to the potential deleterious effects of water restriction, hyponatremia is typically treated with hypertonic saline to maintain adequate sodium levels.

The complications that most often contribute to an unfavorable outcome after aneurysmal SAH are vasospasm and delayed cerebral ischemia. Clinically significant vasospasm occurs in 20-30% of patients with aneurysmal SAH and is believed to be caused by spasmogenic substances that are released during lysis of blood clots. The typical time course for development of vasospasm is day 3 to day 21, with the peak incidence around day 8 after aneurysm rupture. The primary approach to vasospasm is prevention with nimodipine.⁵⁵

The diagnosis of vasospasm is made using transcranial doppler studies, CTA, or, most definitively, by DSA, which can serve as both a diagnostic and therapeutic tool. Although 30-70% of patients with ruptured SAH may have some angiographic evidence of vasospasm, only 20-30% of patients have clinically significant vasospasm, and treatment should be directed toward this specific group of patients. Treatment options include hemodynamic augmentation with pressors to increase cerebral perfusion, maintenance of euvolemia using crystalloids or colloids, intra-arterial vasodilators, and, in severe cases, balloon angioplasty of the affected segment.

Outcomes

The outcome after treatment of an aneurysmal SAH is affected by several factors, including the underlying brain injury from the SAH, intensity of subsequent complications, and the risks related to neurosurgical procedures. Risk factors for poor neurosurgical outcomes include advanced age, clinical and radiographic severity of SAH on presentation, and the occurrence and severity of complications. There is direct correlation between the Hunt and Hess scores on presentation with clinical long-term outcomes. (See Table 1.) There is also a trend toward favorable outcomes with those undergoing coiling rather than surgical clipping.

Mortality from aneurysmal SAH is high. Ten percent of patients with aneurysmal SAH die prior to reaching the hospital, 25% die within the first 24 hours, and another 45% die within 30 days. Those who survive beyond 30 days continue to have an increased mortality rate compared to the general population, with cerebrovascular events representing the largest factor in this mortality risk. Due to the devastating effects of SAH, several factors should be considered by the emergency physician, the neurosurgeon, and the intensivist when offering patients and their families treatment options. The patient’s age, clinical presentation (i.e., Hunt and Hess grade, Fisher grade), underlying chronic conditions, present quality of life, and patient wishes regarding intubation, cardiac resuscitation, and surgical intervention must be considered.

Long-term complications of SAH include neurocognitive dysfunction, epilepsy, and other focal neurologic deficits. Global impairment is present in about 20% of all survivors at 3 months following an aneurysm clipping. Even when the patient appears to be making a good neurologic recovery, cognitive deficits are routinely discovered in those undergoing neurocognitive testing, with particular deficits in memory, executive functioning, and language. Only two-thirds of survivors are able to return to their previous profession, and three-fourths are able to perform activities of daily living independently. The quality of life among survivors with a good neurologic outcome can still be affected due to depression, anxiety, and sleep disturbances. About 4% of SAH patients will develop epilepsy up to one year after treatment, with those having seizures during their initial presentation for SAH treatment to be at only a slightly higher risk.^56-59

Aneurysm recurrence and late re-bleeding can occur, but the risk is generally very low; however, the risk does persist due to de novo aneurysm formation, rupture of another aneurysm, or re-bleeding from a successfully treated aneurysm.

Conclusion

Spontaneous SAH is a rare neurologic emergency that can be both life-threatening and can result in long-term disability. The current approach for this condition is a non-contrast CT scan followed by a lumbar puncture in cases in which the initial scan is negative. This latter procedure is controversial and may be influenced by the time from symptom onset to presentation. Once the diagnosis is made, careful attention should be directed to the patient’s airway patency, oxygenation, and ventilation, as well as hemodynamic status. Monitoring for complications, such as elevated ICP and vasospasm, should be done in conjunction with a specialist in neurocritical care as well as neurosurgery.

Case Conclusion

The patient’s family initiated a lawsuit naming both the emergency physician and the radiologist. It was found that the radiologist did not comment on subarachnoid blood adjacent to the right temporal lobe, which was clearly visible on the CT. An old infarction may have been a distracting factor. It was noted that an LP was not performed on this patient for whom there was a high suspicion for SAH. There were subtle ECG changes that were likely due to intracranial bleeding rather than cardiac ischemia. Expert support for the physicians was sought, but unobtainable, and a settlement was reached in favor of the plaintiff.

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