The term subarachnoid hemorrhage (SAH) refers to extravasation of blood into the subarachnoid space between the pial and arachnoid membranes (see the image below). It occurs in various clinical contexts, the most common being head trauma. However, the familiar use of the term SAH refers to nontraumatic (or spontaneous) hemorrhage, which usually occurs in the setting of a ruptured cerebral aneurysm or arteriovenous malformation (AVM).
View Image | A 47-year-old woman presented with headache and vomiting; her CT scan in the emergency department revealed subarachnoid hemorrhage. |
Signs and symptoms of SAH range from subtle prodromal events to the classic presentation. The most common premonitory symptoms are as follows:
Signs present before SAH include the following:
Prodromal signs and symptoms usually are the result of sentinel leaks, mass effect of aneurysm expansion, emboli, or some combination thereof.
The classic presentation can include the following:
Physical examination findings may be normal or may include the following:
Complications of SAH include the following:
See Clinical Presentation for more detail.
Diagnosis of SAH usually depends on a high index of clinical suspicion combined with radiologic confirmation via urgent noncontrast CT, followed by lumbar puncture or CT angiography of the brain. After the diagnosis is established, further imaging should be performed to characterize the source of the hemorrhage.
Laboratory studies should include the following:
Imaging studies that may be helpful include the following:
Other diagnostic studies that may be warranted are as follows:
See Workup for more detail.
Current treatment recommendations include the following:
Other interventions for increased ICP are as follows:
Additional medical management is directed toward the following common complications:
Surgical treatment to prevent rebleeding includes the following options:
The choice between coiling and clipping usually depends on the location of the lesion, the neck of the aneurysm, and the availability and experience of hospital staff.
Screening is not recommended in the general population. However, it can lower cost and improve quality of life in patients at relatively high risk for aneurysm formation and rupture.
See Treatment and Medication for more detail.
The term subarachnoid hemorrhage (SAH) refers to extravasation of blood into the subarachnoid space between the pial and arachnoid membranes. SAH constitutes half of all spontaneous atraumatic intracranial hemorrhages; the other half consists of bleeding that occurs within the brain parenchyma.
Subarachnoid hemorrhage (see the image below) occurs in various clinical contexts, the most common being head trauma. However, the familiar use of the term SAH refers to nontraumatic (or spontaneous) hemorrhage, which usually occurs in the setting of a ruptured cerebral aneurysm or arteriovenous malformation (AVM).
View Image | CT scan reveals subarachnoid hemorrhage in the right sylvian fissure; no evidence of hydrocephalus is apparent. |
Intracranial saccular aneurysms (“berry aneurysms”) represent the most common etiology of nontraumatic SAH; about 80% of cases of SAH result from ruptured aneurysms. SAH is responsible for the death and/or disability of 18,000 persons each year in North America alone. In the United States, it is associated with an annual cost of $1.75 billion. Unfortunately, the difficulties in detecting unruptured aneurysms in asymptomatic patients practically preclude the possibility of preventing most instances of SAH.
About 6-8% of all strokes are caused by SAH from ruptured berry aneurysms. Over the past several decades, the incidence of other types of strokes has decreased; however, the incidence of SAH has not decreased.
The history and physical examination, especially the neurologic examination, are essential components in the diagnosis and clinical staging of SAH (see Presentation). The diagnosis is confirmed radiologically via urgent computed tomography (CT) scan without contrast. Traditionally, a negative CT scan is followed with lumbar puncture. However, noncontrast CT followed by CT angiography (CTA) of the brain can rule out SAH with greater than 99% sensitivity.[2] (See Workup.)
Current treatment recommendations involve management in an intensive care unit setting. The blood pressure is maintained with consideration of the patient’s neurologic status, and additional medical management is directed toward the prevention and treatment of complications. Surgical treatment to prevent rebleeding consists of clipping the ruptured berry aneurysm. Endovascular treatment[1] (ie, coiling) is an increasingly practiced alternative to surgical clipping (see Treatment).
Aneurysms are acquired lesions related to hemodynamic stress on the arterial walls at bifurcation points and bends. Saccular or berry aneurysms are specific to the intracranial arteries because their walls lack an external elastic lamina and contain a very thin adventitia—factors that may predispose to the formation of aneurysms. An additional feature is that they lie unsupported in the subarachnoid space.
Aneurysms usually occur in the terminal portion of the internal carotid artery and the branching sites on the large cerebral arteries in the anterior portion of the circle of Willis. The early precursors of aneurysms are small outpouchings through defects in the media of the arteries.
These defects are thought to expand as a result of hydrostatic pressure from pulsatile blood flow and blood turbulence, which is greatest at the arterial bifurcations. A mature aneurysm has a paucity of media, replaced by connective tissue, and has diminished or absent elastic lamina.
The probability of rupture is related to the tension on the aneurysm wall. The law of La Place states that tension is determined by the radius of the aneurysm and the pressure gradient across the wall of the aneurysm. Thus, the rate of rupture is directly related to the size of the aneurysm. Aneurysms with a diameter of 5 mm or less have a 2% risk of rupture, whereas 40% of those with a diameter of 6-10 mm have already ruptured upon diagnosis.
Although hypertension has been identified as a risk factor for aneurysm formation, the data with respect to rupture are conflicting. However, certain hypertensive states, such as those induced by use of cocaine and other stimulants, clearly promote aneurysm growth and rupture earlier than would be predicted by the available data.
Brain injury from cerebral aneurysm formation can occur in the absence of rupture. Compressive forces can cause injury to local tissues and/or compromise of distal blood supply (mass effect).
When an aneurysm ruptures, blood extravasates under arterial pressure into the subarachnoid space and quickly spreads through the cerebrospinal fluid around the brain and spinal cord. Blood released under high pressure may directly cause damage to local tissues. Blood extravasation causes a global increase in intracranial pressure (ICP). Meningeal irritation occurs.
Rupture of AVMs can result in both intracerebral hemorrhage and SAH. Currently, no explanation can be provided for the observation that small AVMs (< 2.5 cm) rupture more frequently than large AVMs (>5 cm).
In a 25-year autopsy study of 125 patients with ruptured or unruptured aneurysms conducted at Johns Hopkins, the following conditions correlated positively with the formation of saccular aneurysms:
The occurrence of aneurysms in children indicates the role of intrinsic vascular factors. A number of disease states resulting in weakness of the arterial wall are associated with an increased incidence of berry aneurysms.
Mechanisms and disease states associated with higher incidence of berry aneurysms include the following:
Complications of SAH include the following:
Hydrocephalus
SAH can cause hydrocephalus by 2 mechanisms: obstruction of CSF pathways (ie, acute, obstructive, noncommunicating type) and blockage of arachnoid granulations by scarring (ie, delayed, nonobstructive, communicating type). Acute hydrocephalus is caused by compromise of CSF circulation pathways by interfering with CSF outflow through the sylvian aqueduct, fourth ventricular outlet, basal cisterns, and subarachnoid space. CSF production and absorption rates are unaltered.
Intraventricular blood is the strongest determinant for the development of acute hydrocephalus. Other risk factors include the following:
Rebleeding
Rebleeding of SAH occurs in 20% of patients in the first 2 weeks. The rebleeds in the first days ("blow out" hemorrhages) are thought to be related to the unstable nature of the aneurysmal thrombus, as opposed to lysis of the clot sitting over the rupture site. Clinical factors that increase the likelihood of rebleeding include hypertension, anxiety,[5] agitation, and seizures.
Cerebral ischemia
Delayed cerebral ischemia from arterial smooth muscle contraction is the most common cause of death and disability following aneurysmal SAH. Vasospasm can lead to impaired cerebral autoregulation and may progress to cerebral ischemia and infarction.[6] Most often, the terminal internal carotid artery or the proximal portions of the anterior and middle cerebral arteries are involved. The arterial territory involved is not related to the location of the ruptured aneurysm.
Vasospasm is believed to be induced in areas of thick subarachnoid clot. The putative agent responsible for vasospasm is oxyhemoglobin, but its true etiology and pathogenesis remain to be elucidated.
Intracerebral hemorrhage
The mechanism of intracerebal hemorrhage (ICH) is direct rupture of aneurysm into the brain. ICH commonly results from internal cerebral artery (ICA), pericallosal, and anterior cerebral artery (ACA) aneurysms. Secondary rupture of a subarachnoid hematoma into the brain parenchyma most commonly arises from middle cerebral artery aneurysms.
Intraventricular hemorrhage
Found in 13-28% of clinical cases of ruptured aneurysms and in 37-54% of autopsy cases, intraventricular hemorrhage (IVH) is a significant predictor of poor neurologic grade and outcome. Sources of IVH include the following:
Left ventricular systolic dysfunction
LV systolic dysfunction in humans with SAH is associated with normal myocardial perfusion and abnormal sympathetic innervation. These findings may be explained by excessive release of norepinephrine from myocardial sympathetic nerves, which could damage both myocytes and nerve terminals.[7]
Subdural hematoma
Subdural hematoma (SDH) is rare following aneurysmal SAH, with reported incidence of 1.3-2.8% in clinical series and as high as 20% in autopsy series. The mechanisms of SDH involve tearing of arachnoid adherent to the dome of the aneurysm at the time of rupture, direct tearing of arachnoid by a jet of blood, and disruption of arachnoid by ICH, with secondary decompression of ICH into the subdural space.
Increased intracranial pressure
Elevations in ICP are due to mass effect of blood (subarachnoid, intracranial, intraventricular, or subdural hemorrhage) or acute hydrocephalus. Once ICP reaches mean arterial pressure (MAP), cerebral perfusion pressure becomes zero and cerebral blood flow stops, resulting in loss of consciousness and death.
Of nontraumatic subarachnoid hemorrhages, approximately 80% are due to a ruptured berry aneurysm. Rupture of arteriovenous malformations (AVMs) is the second most identifiable cause of SAH, accounting for 10% of cases of SAH. Most of the remaining cases result from rupture of the following types of pathologic entities:
SAH may reflect a secondary dissection of blood from an intraparenchymal hematoma (eg, bleeding from hypertension or neoplasm).
Both congenital and acquired factors are thought to play a role in SAH. Evidence supporting the role of congenital causes in aneurysm formation includes the following:
Familial cases of AVM are rare, and the problem may result from sporadic abnormalities in embryologic development. AVMs are thought to occur in approximately 4-5% of the general population, of which 10-15% are symptomatic. Congenital defects in the muscle and elastic tissue of the arterial media in the vessels of the circle of Willis are found in approximately 80% of normal vessels at autopsy. These defects lead to microaneurysmal dilation (< 2 mm) in 20% of the population and larger dilation (>5 mm) and aneurysms in 5% of the population.
Acquired factors thought to be associated with aneurysmal formation include the following:
Less common causes of SAH include the following:
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches and reversible segmental multifocal cerebral artery narrowing, and it results in SAH in more than 30% of cases. Muehlschlegel and colleagues found that clinical and imaging findings can differentiate RCVS with SAH from other causes of SAH.[8, 9]
After analyzing clinical and imaging features of 38 patients with RCVS-SAH, 515 patients with aneurysmal SAH, and 93 patients with cryptogenic (angiogram negative) SAH, Muehlschlegel et al identified clinical characteristics and radiological findings that can differentiate RCVS-SAH from aneurysmal SAH or cryptogenic SAH. These researchers concluded that these differences may be useful for improving diagnostic accuracy, clinical management, and resource utilization.[8, 9]
Although risk factors for SAH have been evaluated extensively, little conclusive evidence has been derived. Smoking appears to be a significant risk factor, as does heavy alcohol consumption. The risk of AVM rupture is greater during pregnancy. Data regarding the relationship between hypertension and SAH are conflicting. Previously documented acute severe hypertension with diastolic pressure over 110 mm Hg has been linked to SAH.
The following do not appear to be significant risk factors for SAH:
The frequency of ruptured and unruptured aneurysms has been estimated at 1-9% in different autopsy series, with a prevalence of unruptured aneurysms of 0.3-5%. Retrospective arteriographic studies show a prevalence of less than 1% with the limitation that some cases did not receive adequate evaluation and thus some aneurysms may have been missed. Annual incidence increases with age and probably is underestimated because death is attributed to other reasons that are not confirmed by autopsies.
The annual incidence of aneurysmal SAH in the United States is 6-16 cases per 100,000 population, with approximately 30,000 episodes occurring each year. Unlike other subcategories of stroke, the incidence of SAH has not decreased over time. However, since 1970, population-based survival rates have improved.
The reported incidence of subarachnoid hemorrhage is high in the United States, Finland, and Japan, while it is low in New Zealand and the Middle East. In Finland, the estimated incidence based on different studies is 14.4-19.6 cases per 100,000 population, although numbers as high as 29.7 have been reported.
In Japan, the reported rates vary between 11 and 18.3 cases per 100,000 population, with one study showing an incidence of 96.1 cases per 100,000 population (this study included only patients aged 40 and older in the data collection, and results were not adjusted for sex and age to the same reference population). In New Zealand, age-adjusted incidence was reported as 14.3 cases per 100,000 population.
An Australian study reported an incidence of 26.4 cases per 100,000 population but only for patients older than 35 years, as age was not adjusted in the reference population. In the Netherlands, the age-specific incidence was reported as 7.8 cases per 100,000 population (this is believed to be an underestimate).
Iceland reported 8 cases per 100,000 population, but a significant portion of the affected rural population was believed to be missed. Greenland Eskimos had 9.3 cases per 100,000 population; ethnic Danes there had an incidence of 3.1 cases per 100,000 population. This latter figure is consistent with the figures in Denmark—marked differences are postulated to be related to genetic factors. On the Faeroe Islands (part of Denmark with an isolated population of the same genetic ancestry), the reported incidence is 7.4 cases per 100,000 population.
In China, the reported incidence is low, but no good studies have been published to support this statement. The incidence among Indians and Rhodesian Africans is significantly lower than in those from European nations; this can be explained partly by the low incidence of atherosclerosis in these populations. In the Middle East, the numbers are very low as well; the best available estimate is 5.1 cases per 100,000 population in Qatar.
The risk is higher in blacks than in whites; however, people of all ethnic groups develop intracranial aneurysms. The disparity in frequency of rupture has been attributed to population variance with respect to prevalence of risk factors and age distribution.
The incidence of SAH in women is higher than in men (ratio of 3 to 2). The risk of SAH is significantly higher in the third trimester of pregnancy, and SAH from aneurysmal rupture is a leading cause of maternal mortality, accounting for 6-25% of maternal deaths during pregnancy. A higher incidence of AVM rupture also has been reported during pregnancy.
Incidence increases with age and peaks at age 50 years. Approximately 80% of cases of SAH occur in people aged 40-65 years, with 15% occurring in people aged 20-40 years. Only 5% of cases of SAH occur in people younger than 20 years. SAH is rare in children younger than 10 years, accounting for only 0.5% of all cases.
Although mortality rates of SAH have decreased in the past 3 decades, it remains a devastating neurologic problem. An estimated 10-15% of patients die before reaching the hospital. Approximately 25% of patients die within 24 hours, with or without medical attention. Hospitalized patients have an average mortality rate of 40% in the first month. About half of affected individuals die in the first 6 months. Rebleeding, a major complication, carries a mortality rate of 51-80%.
Age-adjusted mortality rates are 62% greater in females than in males and 57% greater in blacks than in whites. Morbidity and mortality increase with age and are related to the overall health status of the patient.
More than one third of survivors have major neurologic deficits. Cognitive deficits are present even in many patients considered to have a good outcome.
Al-Khindi et al found that survivors of aneurysmal SAH commonly experience deficits in memory, executive function, and language that affect their day-to-day functioning, including activities of daily living, instrumental activities of daily living, return to work, and quality of life. Deficits in cognition and day-to-day functioning are further compounded by depression, anxiety, fatigue, and sleep disturbances.[10]
Factors that affect morbidity and mortality rates are as follows:
Other factors that affect the prognosis of patients who have suffered an SAH include age, Hunt and Hess grade (see below), smoking history, and location of the aneurysm. Younger patients do better. Patients with a history of cigarette smoking have a poorer prognosis. Anterior circulation aneurysms carry a more favorable prognosis.
Acute cocaine use was associated with higher rates of in-hospital death and a significantly increased risk for aneurysm rerepture in a retrospective study of 1134 patients with aneurysmal SAH. Compared with patients who had not used cocaine in the 72 hours preceding their event, those who had used cocaine had a nearly 3-fold increased risk for in-hospital mortality. Mortality remained higher among cocaine users after patients with rerupture were excluded from the analysis, suggesting that rerupture was not entirely responsible for the higher mortality rate in these patients.[11]
Clinical assessment of SAH severity commonly utilizes grading scales. The 2 clinical scales most often employed are the Hunt and Hess and the World Federation of Neurological Surgeons (WFNS) grading systems. A third, the Fisher scale, classifies SAH based on CT scan appearance and quantification of subarachnoid blood.
The WFNS scale is as follows:
The Fisher scale (CT scan appearance) is as follows:
The Hunt and Hess grading system is as follows:
In the Hunt and Hess system, the lower the grade, the better the prognosis. Grades I-III generally are associated with favorable outcome; these patients are candidates for early surgery. Grades IV and V carry a poor prognosis; these patients need stabilization and improvement to grade III before surgery is undertaken. Some recommend more aggressive management for patients with poor clinical grade.
Survival correlates with the grade of subarachnoid hemorrhage upon presentation. Reported figures include a 70% survival rate for Hunt and Hess grade I, 60% for grade II, 50% for grade III, 40% for grade IV, and 10% for grade V.
The Hunt and Hess and the WFNS grading systems have been shown to correlate well with patient outcome. The Fisher classification has been used successfully to predict the likelihood of symptomatic cerebral vasospasm, one of the most feared complications of SAH. All 3 grading systems are useful in determining the indications for and timing of surgical management. For an accurate assessment of SAH severity, these grading systems must be used in concert with the patient's overall general medical condition and the location and size of the ruptured aneurysm.
Complications of SAH include the following:
The incidence of rebleeding complication is greatest in the first 2 weeks. The peak is within 24-48 hours following initial SAH (approximately 6%), with a rate of 1.5% per day for the next 12-13 days. The cumulative 2-week incidence is 20-30% in unoperated patients. After the first 30 days, rebleed rate decreases to 1.5% per year for the first 10 years. In another study, rebleeding was reported at a rate of 3% per year after 6 months, with a 67% mortality rate at 20 years.
Delayed ischemia
Delayed ischemia from cerebral vasospasm is currently the most common cause of death and disability following aneurysmal SAH. It has to some degree cancelled out the improvement in morbidity and mortality from the lower rebleed rate related to early surgical clipping.
An estimated 10-20% of patients with aneurysmal SAH suffer delayed cerebral ischemia, resulting in permanent disability or death. This complication alone accounts for 14-32% of deaths and permanent disability in large studies, while the direct effect of aneurysm rupture accounts for 25% and rebleeding for 17.6%. Approximately 15-20% of patients with symptomatic vasospasm will have a poor outcome despite maximal medical therapy, including mortality in 7-10% of patients and severe morbidity in 7-10% of patients.
Intraventricular hemorrhage
Found in 13-28% of clinical cases of ruptured aneurysms and in 37-54% of autopsy cases, intraventricular hemorrhage (IVH) is a significant predictor of poor neurologic grade and outcome. Patients with IVH are at higher risk of developing hydrocephalus. In one study of 91 patients, IVH was associated with an overall mortality rate of 64%. The key prognostic indicator is the degree of ventricular dilatation.
The signs and symptoms of subarachnoid hemorrhage (SAH) range from subtle prodromal events to the classic presentation. Prodromal events often are misdiagnosed, while the classic presentation is one of the most pathognomonic pictures in all of clinical medicine.
Signs and symptoms precede ruptured cerebral aneurysm in anywhere from 10-50% of cases. Premonitory manifestations generally appear 10-20 days prior to rupture. The most common symptoms are as follows:
Signs present before SAH include the following:
Prodromal signs and symptoms usually are the result of one or more of the following:
Sentinel leaks
Sentinel, or "warning," leaks with minor loss of blood from the aneurysm are reported to occur in 30-50% of aneurysmal SAHs. Sentinel leaks produce sudden focal or generalized head pain that may be severe. Sentinel headaches precede aneurysm rupture by a few hours to a few months, with a reported mean of 2 weeks prior to discovery of the SAH.
In addition to headaches, sentinel leaks may produce nausea, vomiting, photophobia, malaise, or, less commonly, neck pain. These symptoms may be ignored by the physician. Therefore, a high index of suspicion is necessary for accurate diagnosis. Sentinel leaks usually do not generate symptoms suggestive of elevated intracranial pressure (ICP) or meningeal irritation. Sentinel leaks usually do not occur in patients with arteriovenous malformations.
Mass effect
Prodromal presentations occasionally are caused by the mass effect of an expanding aneurysm and have characteristic features based on aneurysm location, as follows:
Emboli
Emboli originating from intra-aneurysmal thrombus formation can cause transient ischemic attacks.
The central feature of classic SAH is sudden onset of severe headache (thunderclap headache), often described as the "worst headache of my life." Less severe hemorrhages may cause headache of moderate intensity, neck pain, and nonspecific symptoms. Absence of headache in the setting of a ruptured intracranial aneurysm is rare and probably represents amnesia for the event.
The headache may be accompanied by nausea and/or vomiting from increased ICP and meningeal irritation. Symptoms of meningeal irritation, including nuchal rigidity and pain, back pain, and bilateral leg pain, occur in as many as 80% of patients with SAH but may take several hours to manifest. Photophobia and visual changes are common. Focal neurologic deficits may also occur.
Sudden loss of consciousness (LOC) occurs at the ictus in as many as 45% of patients as intracranial pressure (ICP) exceeds cerebral perfusion pressure. LOC often is transient; however, approximately 10% of patients remain comatose for several days, depending on the location of the aneurysm and the amount of bleeding.
Seizures during the acute phase of SAH occur in 10-25% of patients. Seizures result from the sudden rise in ICP or direct cortical irritation by blood. No correlation exists between the seizure focus and the anatomic site of aneurysm rupture.
A proposed decision rule for diagnosis of SAH focuses on the following 7 characteristics, which are strongly associated with SAH:
Should one or more of these be present in a patient with an acute nontraumatic headache reaching maximum intensity within 1 hour, the possibility of SAH hemorrhage should be investigated.[12] On the other hand, it may be possible to consider foregoing investigation in patients with none of these characteristics.[12] This decision rule has not yet been validated. Further study is needed before this approach can be recommended.
Approximately 30-40% of patients are at rest at the time of SAH. Physical or emotional strain, defecation, coitus, and head trauma contribute to varying degrees in the remaining 60-70% of cases.
Physical examination findings may be normal. About half of patients have mild to moderate blood pressure (BP) elevation. BP may become labile as ICP increases. Temperature elevation, secondary to chemical meningitis from subarachnoid blood products, is common after the fourth day following bleeding. Tachycardia may be present for several days after the occurrence of a hemorrhage.
Funduscopy may reveal papilledema. Subhyaloid retinal hemorrhage (small round hemorrhage, perhaps with visible meniscus, near the optic nerve head) is evident in 20-30% of patients. Other retinal hemorrhages may be seen.
Global or focal neurologic abnormalities are found in more than 25% of patients. Global depression of neurologic function may be noted, including altered level of consciousness and confusional state. Motor neurologic deficits occur in 10-15% of patients, usually from middle cerebral artery aneurysms. In 40% of patients, no localizing signs are evident. Seizures may occur.
Cranial nerve palsies, along with memory loss, are present in 25% of patients. The most frequent is oculomotor nerve palsy with or without ipsilateral mydriasis, which results from rupture of a posterior communicating artery aneurysm. Abducens nerve palsy is usually due to increased ICP rather than a true localizing sign. Monocular vision loss can be caused by an ophthalmic artery aneurysm compressing the ipsilateral optic nerve.
Hemiparesis results from middle cerebral artery (MCA) aneurysm, ischemia or hypoperfusion in the vascular territory, or intracerebral clot. Patients may also have aphasia, hemineglect, or both. Leg monoparesis or paraparesis with or without akinetic mutism/abulia points to anterior communicating aneurysm rupture.
Clinical assessment of SAH severity commonly utilizes grading scales. The 2 clinical scales most often employed are the Hunt and Hess and the World Federation of Neurological Surgeons (WFNS) grading systems. A third, the Fisher scale, classifies SAH based on CT scan appearance and quantification of subarachnoid blood.
The WFNS scale is as follows:
The Fisher scale (CT scan appearance) is as follows:
The Hunt and Hess grading system is as follows:
In the Hunt and Hess system, the lower the grade, the better the prognosis. Grades 1-3 generally are associated with favorable outcome; these patients are candidates for early surgery. Grades IV and V carry a poor prognosis; these patients need stabilization and improvement to grade III before surgery is undertaken. Some recommend more aggressive management for patients with poor clinical grade.
Survival correlates with the grade of subarachnoid hemorrhage upon presentation. Reported figures include a 70% survival rate for Hunt and Hess grade I, 60% for grade II, 50% for grade III, 40% for grade IV, and 10% for grade V.
The Hunt and Hess and the WFNS grading systems have been shown to correlate well with patient outcome. The Fisher classification has been used successfully to predict the likelihood of symptomatic cerebral vasospasm, one of the most feared complications of SAH. All 3 grading systems are useful in determining the indications for and timing of surgical management. For an accurate assessment of SAH severity, these grading systems must be used in concert with the patient's overall general medical condition and the location and size of the ruptured aneurysm.
Some complications of SAH include the following:
Hydrocephalus can be an acute or a delayed complication of SAH. Acute obstructive hydrocephalus complicates 20% of SAH cases. Clinical risk factors for the development of hydrocephalus include increased patient age, use of antifibrinolytic drugs, left ventricular systolic dysfunction, and seizures.
Acute hydrocephalus usually occurs within the first 24 hours after hemorrhage but may occur as late as 7 days afterward. It presents as a relatively abrupt mental status change, including lethargy, stupor, or coma. CT scan differentiates hydrocephalus from rebleeding.
Acute hydrocephalus can precipitate life-threatening brainstem compression and occlusion of blood vessels. It is associated with lower preoperative Hunt and Hess grade and poorer prognosis. Consequently, any change in the level of consciousness requires an emergent CT scan to evaluate ventricular size. An obtunded patient with dilated ventricles deserves an immediate ventriculostomy.
Late or chronic hydrocephalus, caused by scarring of the arachnoid granulations and alterations in CSF absorption, occurs in 10-15% of patients with SAH. Typically, late hydrocephalus is of the communicating type and develops 10 or more days after SAH. Patients may present with incontinence, gait instability, and cognitive deterioration. It may be impossible to distinguish late hydrocephalus from vasospasm clinically.
The incidence of the complication of rebleeding is greatest in the first 2 weeks. The peak is within 24-48 hours following initial SAH (approximately 6%), with a rate of 1.5% per day for the next 12-13 days. Clinical factors that increase the likelihood of rebleeding include the following:
Currently, delayed ischemia from arterial smooth muscle contraction of the large capacitance vessels at the base of the brain is the leading cause of death and disability following aneurysmal SAH. Vasospasm is symptomatic in 36% of patients. The incidence of angiographic vasospasm is 30-70%; of these patients, 20-36% become symptomatic.
Risk factors for vasospasm include the following:
Vasospasm may be clinically indistinguishable from rebleeding. Symptoms vary with the arterial territory involved, but patients typically present with a new-onset general decrease in consciousness or focal neurologic deficit. Lethargy, with or without focal neurologic deficit, is a manifestation of vasospasm, until proven otherwise.
Overall, vasospasm typically has its onset on day 3 after SAH, is maximal at about days 6-8, and usually resolves around day 12. However, the time of clinical onset differs according to whether the patient has had a prior SAH. In patients with previous SAH, the incidence of vasospasm is 38.7% in the first 3 days and only 20% between days 10 and 17. In patients with no prior SAH, most frequent time of onset is between days 10 and 17, with only a 4.2% incidence on day 3.
Overall, close to 50% of patients develop vasospasm in the peak period. Correlation between the initial CT scan and the incidence of vasospasm is well established. When the CT scan fails to demonstrate blood or shows only a thin layer, vasospasm is unlikely. If the CT scan shows a significant blood clot of 5 X 3 mm or larger, severe angiographic spasm and clinical deficits follow in nearly all cases.
Conventional angiography is the definitive imaging study for vasospasm. The diagnosis of vasospasm can be made reliably at the bedside in a noninvasive fashion with transcranial Doppler.
Other tests, such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), xenon CT scan, and radioactive xenon clearance, can be useful for evaluation of regional cerebral blood flow in patients with vasospasm. However, these tests often are difficult to perform on critically ill patients.
Seizures occur in 13-24% of patients with SAH, commonly in the first 24 hours after the bleed.[13] They are most common after rupture of middle cerebral artery aneurysms. Generalized, partial, and complex-partial seizures are observed after SAH. Seizures can lead to increased cerebral blood flow, hypertension, and elevated ICP, thereby escalating the risk of rebleeding and neurologic deterioration.
Cardiac dysfunction occurs in a significant number of people with SAH. Neurogenic sympathetic hyperactivity, as well as increased levels of systemic catecholamines, has been implicated in SAH-associated cardiac dysfunction. Arrhythmias occur in as many as 90% of patients and most commonly include the following:
Arrhythmias are most prevalent in the first 48 hours following SAH. Only a small percentage of arrhythmias (usually those associated with hypokalemia) are life-threatening.
The diagnosis of subarachnoid hemorrhage (SAH) usually depends on a high index of clinical suspicion combined with radiologic confirmation via urgent computed tomography (CT) scan without contrast. Traditionally, a negative CT scan is followed with lumbar puncture (LP). However, noncontrast CT followed by CT angiography (CTA) of the brain can rule out SAH with greater than 99% sensitivity.[2]
Compared with the traditional recommendation of CT followed by LP, CT/CTA may offer a less invasive and more informative diagnostic approach for emergency department patients complaining of acute-onset headache and with no significant risk factors for SAH. A disadvantage of foregoing LP is that spinal fluid analysis may point toward an alternative diagnosis.
After the diagnosis of SAH is established, further imaging should be performed to characterize the source of the hemorrhage. This effort can include standard angiography, CT angiography, and magnetic resonance (MR) angiography.
Laboratory studies for SAH should include the following:
Serum cardiac troponin measurement is important in patients with subarachnoid hemorrhage, even in those without underlying cardiac conditions. It was initially thought to be useful only as a predictor for the occurrence of pulmonary and cardiac complications.[15] However, correlation was subsequently found between troponin levels and neurologic complications and outcome.[16]
All patients with SAH should have a baseline chest radiograph to serve as a reference point for evaluation of possible pulmonary complications. All patients with SAH should also have an electrocardiogram (ECG) on admission. Patients with SAH can have myocardial ischemia due to the increased level of circulating catecholamines or to autonomic stimulation from the brain. Myocardial infarction is a rare complication. However, suspicion of SAH is a contraindication to thrombolytic and anticoagulant therapy.
Because most of the ECG abnormalities that occur with SAH are benign and reversible, differentiating true myocardial ischemia from benign changes is important. Two-dimensional echocardiography often is more sensitive in detecting myocardial ischemia than is ECG and thus is useful in the setting of SAH.
Other imaging studies may be indicated. MRI is performed if no lesion is found on angiography, and transcranial Doppler studies are useful in the detection and monitoring of arterial vasospasm.
CT without contrast is the most sensitive imaging study in SAH (see the images below). When carried out within 6 hours of headache onset, CT has 100% sensitivity and specificity. Sensitivity is 93% within 24 hours of onset,[17] 80% at 3 days, and 50% at 1 week.[18] Sensitivity is less on older second- or first-generation scanners, but most North American hospitals have been using third-generation scanners since the mid 1980s. Thin (3 mm) cuts are necessary to properly identify the presence of smaller hemorrhages.
View Image | CT scan reveals subarachnoid hemorrhage in the right sylvian fissure; no evidence of hydrocephalus is apparent. |
View Image | CT scan reveals subarachnoid hemorrhage in the sylvian fissure, right more than left. |
View Image | A 47-year-old woman presented with headache and vomiting; her CT scan in the emergency department revealed subarachnoid hemorrhage. |
View Image | Brain CT scan showing subtle finding of blood at the area of the circle of Willis consistent with acute subarachnoid hemorrhage. Image courtesy of Dan.... |
Findings may be negative in 10-15% of patients with SAH. A falsely negative CT scan can result from severe anemia or small-volume subarachnoid hemorrhage.
The location of blood within the subarachnoid space correlates directly with the location of the aneurysm in 70% of cases. In general, blood localized to the basal cisterns, the sylvian fissure, or the intrahemispheric fissure indicates rupture of a saccular aneurysm. Blood lying over the convexities or within the superficial parenchyma of the brain often is indicative of arteriovenous malformation (AVM) or mycotic aneurysm rupture.
Intraparenchymal hemorrhage may occur with middle communicating artery and posterior communicating artery aneurysms. Interhemispheric and intraventricular hemorrhages may occur with anterior communicating artery aneurysms.
A contrast-enhanced CT scan may reveal an AVM. However, this study should not be performed before a noncontrast CT scan because the contrast may interfere with the visualization of subarachnoid blood.
Degree and location of SAH are significant prognostic factors. The Fisher grading system is used to classify SAH, as follows:
CT scan allows for the detection of ventricular size and, thus, evaluation and surveillance of mass effect and hydrocephalus. On CT scan, hydrocephalus is evident as trapped temporal horns and "Mickey Mouse" appearance of the ventricular system.
Some centers have obtained good results with infusion CT scanning. This scan employs a contrast dye and can be performed immediately after a noncontrast CT scan. Reformatted image data can be viewed and rotated in 2-dimensional displays. Infusion CT scanning has been reported to detect aneurysms larger than 3 mm with a sensitivity of 97%, which may provide sufficient anatomic detail to allow for surgical management in the absence of angiography.
LP is traditionally performed as a follow-up test when a CT scan has shown no SAH and has excluded possible contraindications to LP such as significant intracranial mass effect, elevated ICP, obstructive hydrocephalus, or obvious intracranial bleed. LP should not be performed if the CT scan demonstrates an SAH because of the (small) risk of further intracranial bleeding associated with a drop in ICP.
An LP is performed to evaluate the cerebrospinal fluid for the presence of red blood cells (RBCs) and xanthochromia. LP may be negative if performed less than 2 hours after an SAH occurs; LP is most sensitive 12 hours after onset of symptoms. CSF samples taken within 24 hours of the ictus usually show a WBC-to-RBC ratio that is consistent with the normal circulating WBC-to-RBC ratio of approximately 1:1000. After 24 hours, CSF samples may demonstrate a polymorphonuclear and mononuclear polycytosis secondary to chemical meningitis caused by the degradation products of subarachnoid blood.
RBCs in the CSF can reflect a traumatic LP rather than SAH; however, SAH often can be distinguished from traumatic LP by comparing the RBC count of the first and last tubes of CSF. In traumatic LP, the RBC count in the last tube is usually lower, whereas in SAH the RBC typically remains consistently elevated. Nevertheless, cases of SAH in which the RBC count is lower have been reported.
No consensus is found in the literature on the lower limit of the RBC count in the CSF that signifies a positive tap. However, most counts range from a few hundred to a million or more cells per cubic millimeter. The most reliable method of differentiating SAH from a traumatic tap is to spin down the CSF and examine the supernatant fluid for the presence of xanthochromia, a pink or yellow coloration caused by the breakdown of RBCs and subsequent release of heme pigments.
Xanthochromia typically will not appear until 2-4 hours after the ictus. In nearly 100% of patients with an SAH, xanthochromia is present 12 hours after the bleed and remains for approximately 2 weeks. Xanthochromia is present 3 weeks after the bleed in 70% of patients, and it is still detectable at 4 weeks in 40% of patients. Spectrophotometry is much more sensitive than the naked eye in detecting xanthochromia. Nevertheless, many laboratories rely on visual inspection.
Some authors have suggested that the D-dimer assay can be used to discriminate SAH from traumatic LP. Results have been conflicting, however, and further data are needed.
Patients with negative CT and LP findings have a favorable prognosis. However, LP findings can be negative in approximately 10-15% of patients with SAH. In the past, LP findings were thought to be positive in 5-15% of all SAH presentations that are not evident on the CT scan. This number may be no longer valid with the advent of newer generations of CT scans. A small retrospective review of patients who presented to the ED and underwent fifth-generation CT scans and LP showed no cases of a positive LIP after a negative CT scan.[19]
Digital-subtraction cerebral angiography has been the criterion standard for the detection of cerebral aneurysms (see the images below). It is particularly useful in cases of diagnostic uncertainty (after CT scan and LP) and in patients with septic endocarditis and SAH to search for the presence of mycotic aneurysms.
In cases where the diagnosis of SAH has been determined, the timing of cerebral angiography will depend on surgical considerations. Cerebral angiography can provide the following important surgical information in the setting of SAH:
A trial balloon occlusion of the parent artery can be performed and may help to guide preoperative surgical planning.
View Image | Cerebral angiogram reveals a middle cerebral artery aneurysm. |
View Image | Cerebral angiogram reveals a middle cerebral artery aneurysm. |
View Image | Cerebral angiogram (lateral view) reveals a large aneurysm arising from the left anterior choroidal artery. |
View Image | Cerebral angiogram (anteroposterior view) reveals a large aneurysm arising from the left anterior choroidal artery. |
Negative angiographic findings do not rule out aneurysm. Approximately 10-20% of patients with clinically diagnosed SAH (on CT and/or lumbar puncture) have negative angiographic findings. A repeat angiogram is usually required in 10-21 days in such cases.
A negative study finding can result from aneurysm obliteration secondary to clotting. Hemorrhage secondary to a ruptured AVM or spinal cord aneurysm may be present despite a negative finding on cerebral angiogram. Perimesencephalic venous hemorrhage also should be considered
Follow-up angiography is useful after surgical intervention. The postoperative study can confirm aneurysmal obliteration and to evaluate for possible cerebral vasospasm. The management of moribund patients with CT scan evidence of a large SAH and focal hematoma is controversial. Performing angiography may result in a life-threatening delay in treatment.
Although digital-subtraction cerebral angiography has been the criterion standard for the detection of cerebral aneurysms, multidetector CT angiography (MD-CTA) of the intracranial vessels is now routinely performed, and it is becoming fully integrated into the imaging and treatment algorithm of patients presenting with acute subarachnoid hemorrhage in many centers in the United Kingdom and Europe.[20]
The popularity of MD-CTA derives from its noninvasiveness and a sensitivity and specificity comparable to that of cerebral angiography.[21, 22] This technique is beneficial in very unstable patients who cannot undergo angiography or in emergent settings prior to operative intervention for clot evacuation.[21]
MRI is performed if no lesion is found on angiography. Its sensitivity in detecting blood is considered equal or inferior to that of CT scan. The higher cost, lower availability, and longer study time make it less optimal for detecting SAH. In addition, MRI is not sensitive for SAH within the first 48 hours.
MRI is a useful tool to diagnose AVMs that are not detected by cerebral angiography or spinal AVMs causing SAH. It can also be useful for diagnosing and monitoring unruptured cerebral aneurysms. MRI can detect aneurysms 5 mm or larger with a high sensitivity and is useful for monitoring the status of small, unruptured aneurysms. MRI can be used to evaluate the degree of intramural thrombus in giant aneurysms.
One study found that cranial MRI including the brain and craniocervical region does not provide additional benefit for the detection of bleeding sources in patients with perimesencephalic and nonperimesencephalic SAH. However, MRI should be considered on a case-by-case basis because rare bleeding sources are possible in cases of nonperimesencephalic SAH.[23]
The role of magnetic resonance angiography (MRA) in the detection of SAH currently is under investigation; however, many authors believe that MRA eventually will replace conventional transfemoral cerebral angiography. Given the current limitations of MRA, which include lower sensitivity than cerebral angiography in the detection of small aneurysms and failure to detect posterior inferior communicating artery and anterior communicating artery aneurysms in one series, most authors feel that the risk/benefit ratio still favors conventional angiography.
All patients with SAH should have a baseline chest radiograph to serve as a reference point for evaluation of possible pulmonary complications. All patients with SAH should have an electrocardiogram (ECG) on admission. Patients with SAH can have myocardial ischemia due to the increased level of circulating catecholamines or to autonomic stimulation from the brain. Myocardial infarction is a rare complication.
ECG abnormalities frequently detected in patients with SAH include the following:
The traditional treatment of subarachnoid hemorrhage (SAH) from a ruptured cerebral aneurysm included strict blood pressure control, with fluid restriction and antihypertensive therapy. This approach was associated with a high rate of morbidity and mortality from the ischemic complications of hypovolemia and hypotension.
Current recommendations advocate the use of antihypertensive agents when the mean arterial pressure (MAP) exceeds 130 mm Hg. Intravenous beta-blockers, which have a relatively short half-life, can be titrated easily and do not increase intracranial pressure (ICP). Beta-blockers are the agents of choice in patients without contraindications.
Most clinicians avoid the use of nitrates, such as nitroprusside or nitroglycerin, which elevate ICP. Hydralazine and calcium channel blockers have a fast onset and lead to a relatively lower increase in ICP than do nitrates. Angiotensin-converting enzyme inhibitors have a relatively slow onset and are not first-line agents in the setting of acute SAH.
Patients with signs of increased ICP or herniation should be intubated and hyperventilated. Minute ventilation should be titrated to achieve a PCO2 of 30-35 mm Hg. Avoid excessive hyperventilation, which may potentiate vasospasm and ischemia.
Other interventions for increased ICP include the following:
Patients must be admitted to the intensive care unit (ICU) with strict bed rest until the etiology of hemorrhage is determined. Patients should not be allowed out of bed for any reason. All patients should receive frequent neurologic evaluation. Use sedatives and analgesics cautiously to avoid masking the neurologic examination findings.
Additional medical management is directed to prevent and treat the following common complications of SAH:
Ideally, management of the complications of SAH should take place in a neurologic ICU or in an ICU similarly equipped. To minimize stimuli that may lead to an elevation of ICP, have the patient placed in a darkened, quiet, private room and given mild sedation if agitated. The head of the bed should be kept elevated at 30° to ensure optimal venous drainage.
Blood pressure must be maintained with consideration of the patient's neurologic status. Optimally, systolic blood pressure (SBP) of no more than 130-140 mm Hg should be the goal, unless clinical evidence of vasospasm is noted.
Indwelling catheters include an arterial line, central venous access, and Foley catheter. Seizure prophylaxis and calcium channel blockade are standard medical measures. Some centers favor volume expansion to treat vasospasm that develops days after the initial bleeding episode.
Surgical treatment to prevent rebleeding consists of clipping the ruptured berry aneurysm. Endovascular treatment[1] (ie, coiling) is an increasingly practiced alternative to surgical clipping. The neurosurgeon/neurointerventionalist must be involved early in the care of the patient with an aneurysmal SAH.
The initial management of patients with SAH is directed at patient stabilization. Assess the level of consciousness and airway, breathing, and circulation (ABCs).
Endotracheal intubation should be performed for patients presenting with coma, depressed level of consciousness, inability to protect their airway, or increased intracranial pressure (ICP). Rapid-sequence intubation should be employed, if possible, including the use of sedation, defasciculation, short-acting neuromuscular blockade, and agents to blunt an increase in ICP.
Intravenous access should be obtained, including central and arterial lines. A short-acting benzodiazepine, such as midazolam, should be administered prior to all procedures. Monitoring should include the following:
For more information, see the Medscape Reference article Emergent Management of Subarachnoid Hemorrhage.
Rebleeding is the most dreaded early complication of SAH. The greatest risk of rebleeding occurs within the first 24 hours of rupture (4.1%). The cumulative risk of rebleeding is 19% at 14 days. The overall mortality rate from rebleeding is reported to be as high as 78%. Measures to prevent rebleeding include bed rest in a quiet room, analgesia, and sedation. Stool softeners are given to prevent Valsalva maneuvers with resultant peaks in SBP and ICP. Clipping or coiling aneurysms is the surgical approach to prevent rebleeding (see below).
Pain is associated with a transient elevation in blood pressure and increased risk of rebleeding. Analgesia is preferably achieved with a short-acting and reversible agent such as fentanyl. Sedation is used with caution to avoid distorting subsequent neurologic evaluation. The preferred agent is a short-acting benzodiazepine such as midazolam. Antifibrinolytics have been shown to reduce the occurrence of rebleeding. However, outcome likely does not improve because of a concurrent increase in the incidence of cerebral ischemia.
Surgical treatment to prevent rebleeding is by clipping the ruptured berry aneurysm. Endovascular treatment[1] (ie, coiling) is an increasingly practiced alternative to surgical clipping. For more information, see the Medscape Reference article Subarachnoid Hemorrhage Surgery.
The choice between coiling and clipping usually depends on the location of the lesion, the neck of the aneurysm, and the availability and experience of hospital staff. At many institutions, higher-grade patients and those with significant medical comorbidities tend to be treated by coiling rather than clipping. Posterior circulation aneurysms are preferentially treated by coiling because of the significant morbidity and mortality associated with surgical clipping.
Koivisto et al did not show any difference between the 2 techniques at 1 year.[24] In contrast, the randomized prospective International Subarachnoid Aneurysm Trial (ISAT) found coiling to be significantly safer for the treatment of ruptured aneurysms that were deemed equally suitable candidates for either surgical or endovascular treatment.[25, 26, 27] The incidence of rebleeding was slightly higher in the coiled group, but the endovascularly treated group did so much better overall that the study was stopped after reviewing the 1-year outcome data.
Partially because of the ISAT study, endovascular treatment is becoming the first-line treatment for many aneurysms. However, a 2009 study expresses concerns regarding the generalizability of the ISAT and suggests that further analyses are needed.[28]
The data to establish long-term results of endovascular treatment are insufficient. In general, the incidence of recanalization is higher with coiling. Significant advances have been made with the introduction of new coated coils that either swell within the aneurysm or promote fibrous tissue formation and organization of the intra-arterial clot.
Other advances include the use of intracranial stents to promote coiling (especially in aneurysms with wide necks) and decrease inflow into the aneurysm in certain instances. The stents have also provided a novel approach to treating certain types of aneurysms that have historically been untreatable. At the moment, no long-term follow-up data exist to assess the efficacy of these new treatment modalities.
In a retrospective study, Chitale et al compared the safety and efficacy of stent-assisted coiling (SAC) and balloon-assisted coiling (BAC) in 84 patients with ruptured complex and wide-necked aneurysms in the setting of acute SAH. They concluded from their findings that SAC may be an acceptable alternative to BAC for the management of these types of aneurysms in the acute phase of SAH. According to the authors, the rates of hemorrhagic, thromboembolic, and overall procedural complications were not significantly different in the SAC and BAC groups: 6.8% vs 2.5% (P = .5), 11.4% vs 7.5% (P = .6), and 18.2% vs 10% (P = .3), respectively. In addition, they found that the rate of favorable outcomes did not differ significantly: 61% vs 77% (P = .1).[29]
The timing of surgery has been the subject of controversy for more than 40 years. Initially, the high complication rate related to early clipping of the aneurysm was thought to outweigh the risk of rebleeding, and a philosophy of delayed surgery was generally accepted. With the improvement of surgical technique, especially the routine adoption of microneurosurgical techniques, a major shift has occurred in favor of early surgery for patients with aneurysms of favorable grade.
Early surgery or coiling is generally recommended in patients with straightforward aneurysms of a favorable clinical grade. Evidence from clinical trials suggests that patients who undergo surgery within 72 hours have a lower rate of rebleeding and tend to fare better than those treated later.[30]
Poor-grade patients who fail to improve after stabilizing measures (including ventriculostomy placement) may not get treated in the acute period or may be preferentially treated by coiling. Delayed intervention is also recommended in patients with giant or complicated aneurysms.
A cost-utility analysis from the Netherlands reports that at age 80 years, the risks and benefits of aneurysm occlusion sway toward not performing the procedure. The authors suggest that in patients 80 years or older, aneurysm occlusion should be performed only if the predicted life expectancy of the patient leaves a margin for benefit.[31]
For prevention of vasospasm, maintenance of normovolemia, normothermia, and normal oxygenation are paramount. Volume status should be monitored closely, with avoidance of volume contraction, which can predispose to vasospasm.
Oral nimodipine is the most studied calcium channel blocker for prevention of vasospasm after SAH. An American Heart Association/American Stroke Association guideline recommends its use for this purpose (class I, level of evidence A).[32] Calcium channel blockers have been shown to reduce the incidence of ischemic neurologic deficits, and nimodipine has been shown to improve overall outcome within 3 months of aneurysmal SAH. Calcium channel blockers and other antihypertensives should be used cautiously to avoid the deleterious effects of hypotension.[33, 34]
The mechanisms of nimodipine’s protective effect in vasospasm is unproved. However, it appears that nimodipine may prevent the ischemic complications of vasospasm by the neuroprotective effect of blockading the influx of calcium into damaged neurons.
In May 2013, the US Food and Drug Administration (FDA) approved a new oral nimodipine solution (Nymalize) for the treatment of patients with SAH. Nimodipine had been available previously only as a liquid-filled gel capsule. Intravenous (IV) administration of nimodipine meant for oral use has been reported to cause death, cardiac arrest, severe decreases in blood pressure, and other heart-related complications. The oral formulation has the potential to decrease or eliminate inadvertent IV administration of the drug.[35]
Some evidence indicates that subarachnoid clot removal achieved via intracisternal injections of recombinant tissue plasminogen activator (rTPA) may dramatically reduce the risk of vasospasm. This is performed after the clipping of the aneurysm.
Thrombolytic therapy is associated with the theoretical risk of intracranial bleeding, and although the results of preliminary studies are favorable, rigorous clinical trials are needed to establish the safety and efficacy of this approach. Intracisternal antioxidants and anti-inflammatory agents are of uncertain value.
Aspiration and irrigation of the subarachnoid clot at the time of aneurysmal clipping usually results in suboptimal removal of the clot and is associated with a significant risk of iatrogenic trauma to pial surfaces and small vessels.
Intraoperative sodium chloride lavage to clear blood products from the subarachnoid space may be of some benefit, but its effectiveness remains unproved.
Some authors suggest that early CSF drainage via a ventricular drain may decrease the incidence of vasospasm. This intervention is performed after the aneurysm has been secured.
Use caution to prevent rapid or overly aggressive drainage of CSF, which may precipitate aneurysmal rebleeding. One author suggests draining the CSF if the intracranial pressure exceeds 20 mm Hg. The drain should be set at a height to drain at 20 mm Hg to avoid an excessive reduction in ICP.
Statin therapy has been proposed as a means of preventing vasospasm and delayed cerebral ischemia. Statins may improve cerebral vasomotor reactivity through cholesterol-dependent and cholesterol-independent mechanisms.[36, 37] The use of statins in SAH is controversial. Several small studies have shown promise. Two meta-analyses have shown contradicting results. Sillberg et al concluded that statin therapy reduces vasospasm and cerebral ischemia,[38] while Vergouwen et al found no benefit of statin therapy.[39] Until more data are available, the use of statins cannot be routinely recommended.[40]
The Simvastatin in Aneurysmal Subarachnoid Hemorrhage (STASH) study, a multicenter randomized controlled clinical trial, will be investigating the effects of 40 mg of simvastatin in patients with SAH. The trial is currently recruiting participants. The planned sample size is 1600 patients, which should be powerful enough to answer the controversy surrounding statin therapy in SAH.
Treatment for symptomatic vasospasm has traditionally involved the induction of hypertension, hypervolemia, and hemodilution, or triple H therapy. This therapy should be reserved for patients with aneurysms secured by surgical clipping or endovascular techniques in order to reduce the risk of rebleeding.
The efficacy of triple H therapy remains subject to debate. A review of controlled studies showed no positive effect of triple H therapy or its components on increasing cerebral blood flow.[41]
Aggressive hypertensive therapy with inotropes and vasopressors (eg, dobutamine) can be initiated, if warranted. Hypervolemia may be achieved by using packed erythrocytes, isotonic crystalloid, and colloid and albumin infusions in conjunction with vasopressin injection. Corticosteroids may be of some benefit; however, such treatment remains controversial. Hemodilution or transfusion is used to maintain the hematocrit at 30-35% in order to optimize blood viscosity and oxygen delivery.
Initiation of triple H therapy requires placement of a pulmonary artery catheter in order to guide volume expansion and inotropic or vasopressor therapy. Central venous pressure (CVP) should be maintained at 10-12 mm Hg. Pulmonary artery wedge pressure (PAWP) should be maintained at 14-20 mm Hg.
Transluminal balloon angioplasty is recommended for treatment of vasospasm after failure of conventional therapy. One study reported improved neurologic outcome in 70% of patients with symptomatic vasospasm after transluminal angioplasty. Case series reports have indicated that angioplasty appears to be effective in treating vasospasm of large proximal vessels.[42]
Angioplasty is not effective in direct treatment of vasospasm of more distal vessels; however, distal blood flow may be increased as a result of increased proximal vessel diameter. The potential complications of angioplasty include vessel rupture, dissection, or occlusion, as well as intracerebral hemorrhage.
Intra-arterial injection of papaverine has been reported to improve outcome, but more data are needed before its routine use can be recommended. The beneficial effects of papaverine infusion appear to be short-lived compared with those of angioplasty.
Magnesium is a neuroprotective agent that acts as an N-methyl-D-aspartate (NMDA) receptor antagonist and a calcium channel blocker. It has been used to reduce cerebral ischemic events in SAH patients. Magnesium levels should be carefully monitored. Studies of magnesium treatment in SAH have yielded disparate results. A small, randomized, placebo-controlled pilot study by Westermaier et al found that maintaining serum magnesium concentrations of 2-2.5 mmol/L reduced the occurrence of cerebral ischemic events following aneurysmal SAH.[43]
A meta-analysis showed that magnesium reduced the risk of delayed cerebral ischemia and poor outcome in aneurysmal SAH.[44] However, a larger multicenter phase III trial by Wong et al found no significant difference at 6 months between patients treated with magnesium IV or placebo.[45]
Several new agents have been investigated for the use in SAH, especially to ameliorate vasospasm. In a randomized, double-blind, placebo-controlled, pilot trial, methylprednisolone did not decrease vasospasm but improved functional outcomes.[46] Tirilazad, a nonglucocorticoid 21-aminosteroid, has not shown consistent benefit.[47] Intra-arterial colforsin is under investigation to improve vasospasm.[48]
Treatment for acute hydrocephalus includes external ventricular drainage, depending on the severity of clinical neurologic dysfunction or CT scan findings. Rapid lowering of intracranial pressure during intraventricular catheter placement is associated with a higher risk of rebleeding and should be avoided. Resolution of hydrocephalus may be assessed periodically by blocking CSF drainage while monitoring ICP.
Symptomatic cases of hydrocephalus may be managed by temporary lumbar CSF drainage, serial LPs, or placement of a permanent ventricular shunt. Ventriculostomy placement is associated with an increased risk for rebleeding, along with known infectious risk; therefore, patients with dilated ventricles but no compromise of level of consciousness should be treated conservatively, with close monitoring of mental status and prompt intervention in case their clinical status declines.
Nevertheless, ventriculostomy, when done correctly, is a relatively low-risk procedure that can result in dramatic and immediate clinical improvement in about two thirds of patients. If the patient's grade improves enough as a result of ventriculostomy, the patient may become a candidate for early surgery.
When grading patients clinically, great care must be taken to note possibly reversible deficits related to hydrocephalus, which may be contributing to the patients' poor condition. According to a study of 47 patients with poor-grade aneurysm without CT evidence of irreversible brain destruction who underwent ventriculostomy, early control of the ICP and aggressive management appeared to be the appropriate treatment in this subset of patients.
Hyponatremia following subarachnoid hemorrhage occurs in 10-34% of cases. Elevated levels of atrial natriuretic factor (ANF) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been implicated.
Administration of isotonic fluid can prevent volume contraction but not hyponatremia. Use of slightly hypertonic sodium chloride (1.5% sodium chloride) at rates above maintenance requirements usually is efficacious for SAH-induced hyponatremia. Avoid fluid restriction in patients with SAH.
Agents used for seizure prophylaxis include the following:
Some studies argue that anticonvulsant therapy can be limited safely to the immediate perioperative period in patients with no parenchymal clot, ischemic infarct, or postoperative hematoma.
Acute pulmonary edema and hypoxia are almost universal in severe subarachnoid hemorrhage. The pulmonary edema in SAH is believed to be neurogenic in origin and unrelated to triple H therapy; however, the latter is associated with an increased risk of fluid overload.
SAH-induced hypoxemia likewise is believed to be partially neurogenic in origin because it is out of proportion to what would be expected from cardiac insufficiency or fluid overload.
Treatment of acute pulmonary edema may include the use of gentle diuresis, dobutamine, and positive end-expiratory pressure.
Cardiac dysfunction is common in subarachnoid hemorrhage, particularly in the first 48 hours, but it is typically benign. The perioperative therapy to prevent secondary cerebral ischemia (hypervolemia, hypertension) may exacerbate myocardial ischemia.
Conversely, therapy for myocardial ischemia, such as nitrates, may increase intracranial pressure, lower cerebral perfusion pressure, and exacerbate cerebral ischemia.
Screening is generally not recommended in the general population. Even in special populations, such as patients with polycystic kidney disease, studies have failed to show any benefit to screening.[49] In patients who have had 2 or more first-degree relatives with radiographically proven intracranial aneurysms, screening with CT or MR angiography may be considered on an individual basis.[50]
In general, the screening of patients with previous SAH cannot be recommended. However, screening can save costs and increase quality-adjusted life-years (QALYs) in the subset of patients who are at relatively high risk of both aneurysm formation and rupture. In addition, in patients with fear of recurrence, screening may increase QALYs at acceptable costs.[51] Nevertheless, more data are needed to help identify patients who can benefit from screening.
The goals of treatment in patients with subarachnoid hemorrhage (SAH) are as follows:
Medications used for these purposes include analgesics, calcium channel blockers, antiepileptic drugs, stool softeners, antihypertensive agents, antiemetics, osmotic agents, diuretics, and general anesthetics. The use of aminocaproic acid for hemostasis is controversial.
Clinical Context: Fentanyl is a synthetic opioid that is 75-200 times more potent than morphine sulfate and has a much shorter half-life. It has less of a hypotensive effect and is safer in patients with hyperactive airway disease than morphine because of minimal to no associated histamine release. By itself, fentanyl causes little cardiovascular compromise, although the addition of benzodiazepines or other sedatives may result in decreased cardiac output and blood pressure.
Consider giving fentanyl by continuous infusion because of its short half-life. The parenteral form is the drug of choice for conscious sedation analgesia. It is ideal for analgesic action of short duration during anesthesia and the immediate postoperative period. It is also an excellent choice for pain management and sedation, with its short duration (30-60 min) and easy titration. After the initial parenteral dose, subsequent parenteral doses should not be titrated more frequently than every 3 or 6 hours.
The transdermal form of fentanyl is used only for chronic pain conditions in opioid-tolerant patients. When using the transdermal dosage form, most patients are controlled with 72-hour dosing intervals; however, some patients require dosing intervals of 48 hours.
The effects of fentanyl are easily and quickly reversed by naloxone. Fentanyl is highly lipophilic and protein bound. Prolonged exposure leads to accumulation in fat and delays the weaning process.
Pain control is essential to quality patient care. It ensures patient comfort and promotes pulmonary toilet. Most analgesics have sedating properties that benefit patients who experience pain.
Clinical Context: Nimodipine is indicated to reduce poor outcome related to aneurysmal subarachnoid hemorrhage.[32] While studies have shown benefit regarding severity of neurologic deficits caused by cerebral vasospasm following SAH, no evidence exists that nimodipine either prevents or relieves spasms of cerebral arteries. Thus, the actual mechanism of action is unknown.
Begin therapy within 96 hours of SAH. Nimodipine is given orally. If the patient cannot swallow the gel capsule because he or she is undergoing surgery or is unconscious, administer the oral solution (Nymalize, 60 mg/20 mL) via nasogastric or gastric tube and flush tubing before and after with normal saline. If the oral solution is not available, make holes at both ends of the gel capsule with an 18-gauge needle and extract the contents into a syringe, empty the contents into the patient's in situ nasogastric tube, and flush the tube with 30 mL of isotonic saline.
In specialized conducting and automatic cells in the heart, calcium is involved in the generation of the action potential. The calcium channel blockers inhibit movement of calcium ions across the cell membrane, depressing both impulse formation (automaticity) and conduction velocity. These agents may attenuate deleterious effects of calcium influx in patients with acute neurotrauma.
Clinical Context: Phenytoin may act in the motor cortex, where it may inhibit spread of seizure activity. The activity of brainstem centers responsible for the tonic phase of grand mal seizures also may be inhibited. The dose should be individualized. If the daily dose cannot be divided equally, administer the larger portion at bedtime.
Clinical Context: Phenobarbital elevates the seizure threshold and limits the spread of seizure activity; it also has sedative properties.
Clinical Context: Fosphenytoin is a diphosphate ester salt of phenytoin that acts as a water-soluble prodrug of phenytoin; plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin; phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.
The dose of fosphenytoin is expressed as phenytoin equivalents (PE), to avoid the need to perform molecular weight–based adjustments when converting between fosphenytoin and phenytoin sodium doses.
Fosphenytoin is intended for parenteral administration. Intravenous use is the route of choice and should be used in emergency situations.
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity. The use of antiepileptic drugs in patients with SAH who have not had seizures is controversial and depends on the individual preference of the neurosurgeon; they usually are used only in patients who have had seizures. Conventional loading doses may be used.
Clinical Context: Docusate is an anionic surfactant used for patients who should avoid straining during defecation. This agent allows incorporation of water and fat into stool, causing stool to soften. It has minimal laxative effect.
Clinical Context: Senna is an anthraquinone stimulant hydrolyzed by colonic bacteria into an active compound. It is more potent than cascara sagrada and produces considerably more abdominal pain. Senna usually produces action 8-12 hours after administration.
These agents prevent elevation of intracranial pressure from the Valsalva maneuver.
Clinical Context: Labetalol blocks alpha-, beta1-, and beta2-adrenergic receptor sites, decreasing blood pressure.
In patients who have suffered SAH from a ruptured aneurysm, these agents are used to maintain blood pressure in a range that allows for sufficient cerebral perfusion yet limits the risk of rebleeding from elevated ICP.
Clinical Context: Promethazine is an antidopaminergic agent effective in the treatment of emesis. It blocks postsynaptic mesolimbic dopaminergic receptors in the brain and reduces stimuli to the brainstem reticular system.
Clinical Context: Mannitol may reduce pressure within the subarachnoid space by creating an osmotic gradient between the CSF in the arachnoid space and the plasma. This agent is not for long-term use.
These agents are used in an attempt to lower ICP and cerebral edema by creating an osmotic gradient across an intact blood-brain barrier; as water diffuses from the brain into the intravascular compartment, ICP decreases.
Clinical Context: Furosemide is used in the acute setting for reduction of increased ICP. Doses must be individualized. The proposed mechanisms in lowering ICP include the following:
• Suppression of cerebral sodium uptake
• Inhibition of carbonic anhydrase, resulting in decreased CSF production
• Inhibition of the cellular membrane cation-chloride pump, thereby affecting transport of water into astroglial cells
These agents are used to decrease plasma volume and edema by causing diuresis.
Clinical Context: Aminocaproic acid inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. The main problems with its use are that thrombi that form during treatment are not lysed and its effectiveness is uncertain. This agent has been used to prevent recurrence of SAH.
These agents are potent inhibitors of fibrinolysis and can reverse states that are associated with excessive fibrinolysis. Their use is controversial; consultation with admitting physicians is urged prior to use.
Clinical Context: Thiopental is a short-acting barbiturate sedative-hypnotic with rapid onset and a duration of action of 5-20 minutes. Like methohexital, it is most commonly used as an induction agent for intubation.
Thiopental depresses consciousness and diminishes or terminates seizure effects; it facilitates transmission or impulses from the thalamus to the cortex of the brain, resulting in an imbalance in central inhibitory and facilitating mechanisms. To use thiopental as a sedative, titrate in dosage increments of 25 mg (adjust to lower dose in children).
Clinical Context: Amidate is a nonbarbiturate imidazole compound with sedative properties. It is short-acting and has a rapid onset of action; the duration of action is dose dependent (15-30 minutes). Its most useful feature as an induction agent is that it produces deep sedation while causing minimal cardiovascular effects.
The major application of amidate is induction for endotracheal intubation, particularly in patients with, or at risk for, hemodynamic compromise. Amidate has been shown to depress adrenal cortical function; however, this effect is not significant clinically during short-term administration. Since the drug is mixed in propylene glycol, continuous infusion not recommended.
These agents provide sedation when neuromuscular blocking agents are used for intubation.
Clinical Context: Midazolam is a shorter-acting benzodiazepine sedative-hypnotic that is useful in patients requiring acute or short-term sedation. It is also useful for its amnestic effects.
By binding to specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyrate (GABA) and to facilitate inhibitory GABA neurotransmission, as well as other inhibitory transmitters.