Diagnosis of Subarachnoid Hemorrhage: Avoiding Pitfalls and Expediting Assessmen
Diagnosis of Subarachnoid Hemorrhage: Avoiding Pitfalls and Expediting Assessment
Author: Jonathan A. Edlow, MD, Acting Chief, Division of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA; Instructor, Harvard Medical School.
Peer Reviewers: Gail D'Onofrio, MD, Research Director, Section of Emergency Medicine, Assistant Professor, Yale University School of Medicine. Andrew Ulrick, MD, Assistant Professor, Department of Emergency Medicine, Boston University School of Medicine.
One of the primary goals of emergency medicine is prompt diagnosis and treatment of treatable, life-threatening conditions. Although emergency physicians are constantly on the alert for these so-called "cannot miss diagnoses," clinical vigilance may be hindered by a variety of factors, among them, time constrains of a busy emergency department (ED), the financial pressures of managed care, the relative infrequency of these conditions, and variations in clinical presentation.
Severe headache is among the most worrisome of symptoms suggesting catastrophic intracranial pathology. As far as headache,1 SAH is not the only "cannot miss diagnosis," and the physician is well-served to keep in mind the entire list of conditions that present with this chief complaint. (See Table 1.) In fact, studies show that about 3-5% of patients presenting to an ED with headache will harbor serious neurologic pathology, and about 1% will have SAH.2,3 Differentiating these patients from those whose headache is associated with more benign etiology is critical, but difficult. Unfortunately, patients who are misdiagnosed often present with mild symptoms and are the most likely to benefit from current therapies.4,5 In this regard, two recent studies suggest that patients who are initially misdiagnosed are more likely to clinically deteriorate than those in whom the diagnosis is established at the time of presentation.5,6
Early diagnosis is essential in order to improve morbidity and mortality in subarachnoid hemorrhage (SAH). Overall, 40-50% of patients with SAH die within one month of their hemorrhage, and one-third of survivors develop major neurologic disability.7 Although the incidence of other causes of stroke have declined over the last few decades, the incidence of SAH has remained constant.8 Moreover, there is evidence that new treatments and more aggressive surgical intervention have led to a decline in the mortality rate over this period.8,9
Given the importance of prompt and precise diagnosis, it is essential that physicians understand the myriad, atypical presentations of SAH, as well as the limitations of diagnostic tests, in order to avoid misdiagnosis and improve patient outcomes. Although this review will discuss many clinical issues related to SAH, it will focus on the diagnostic strategies, clinical presentations, and implications for outcome-effective management.
-The Editor
Clinical Anatomy and Epidemiology
SAH is defined as extravasation of blood into the subarachnoid space of the central nervous system (CNS). Excluding head trauma, which is the most common cause of SAH, ruptured intracerebral aneurysm accounts for about 80% of cases of SAH. Other causes include mycotic aneurysms,10,11 arteriovenous malformations (AMV),12-14 dissection of intracranial arteries,15,16 Moyamoya disease,17 and idiopathic cases.12,14 Aneurysms can also occur but as rare, late complication of head injury.18,19
Unless otherwise specified, the term SAH, as it is used in this review, refers only to those cases caused by intracerebral aneurysm. Most of these aneurysms arise from arteries at the base of the brain, located in the circle of Willis and its branches. Eighty-five percent of aneurysms are derived from the anterior circulation,7 most often at its sites of vessel bifurcation. The most common sites are the junction of the internal carotid artery (ICA) and posterior communicating artery (PCoA), the anterior cerebral-anterior communicating artery (ACoA) complex, and the bifurcation of the middle cerebral artery (MCA).
Aneurysms arising from the posterior circulation are most likely to occur at the bifurcation of the basilar artery and at the junctions of the basilar artery with the vertebral and the posterior inferior cerebellar vessels. At the time of initial presentation, about 25% of patients will have multiple aneurysms (usually 2-3), although as many as 13 aneurysms in the same patient have been reported.7 Generally, cerebral aneurysms form in areas that are deficient in medial layers and where the internal elastic lamina is thin or absent.7 Hemodynamic stress is thought to play a primary role in the formation of aneurysms.20,21
Once an aneurysm develops, the rules of physics govern its subsequent behavior. LaPlace's law14,22 states that the tension on the wall of a chamber is a function of the radius of that chamber and the pressure gradient across the wall. Thrombus forms in the aneurysm, usually in the dome,14 and, as the aneurysm enlarges, the medial layer becomes even more tenuous and the adventitia and intima are separated only by variable amounts of connective tissue.7,8
The reported incidence of saccular, intracranial aneurysms varies according to the epidemiological techniques used to identify this condition. For example, in autopsy series, they are found in up to 6% of the population, although many of these aneurysms are quite small.7 Based on cerebral angiographic studies, it is estimated that 0.5-1.0% of individuals have aneurysms.7 A recent expert panel sponsored by the American Heart Association estimated that approximately 2 million Americans harbor unruptured aneurysms.13
In the United States, the annual incidence of SAH is about 30,000, or roughly 10 cases per 100,000 population.7,13,14 In Japan, the rate is about three times that number.23 The variable natural history of cerebral aneurysms accounts for the difference between the estimated 2 million Americans who harbor aneurysms and the 30,000 of those who rupture. Overall, the risk of rupture is about 0.5-2.0% per year7 and, as LaPlace's law would predict, small aneurysms are less likely to rupture than large ones.
SAH can occur at any age, but it is rare in children24 and the mean age at the time of presentation is about 50 years. Overall, there is a female:male ratio of 3:2; however, below age 40, men are more often afflicted than women.7 All ethnic groups are affected. However, first degree relatives (especially siblings) of patients who have had SAH have a four-fold increased risk compared to the general population of developing SAH.7 Patients with a prior SAH are six times more likely to have a second hemorrhage later in life.7
A number of underlying conditions are associated with an increased risk of aneurysm formation, including autosomal dominant polycystic kidney disease, Ehlers-Danlos syndrome (type 4), neurofibromatosis type 1,25 Marfan's syndrome,26 pseudoxanthoma elasticum, fibromuscular dysplasia, and coarctation of the aorta.14 Other situations associated with SAH include patients with CNS angitis27 and users of cocaine28 and methamphetamine.29 Well-documented risk factors for aneurysm rupture include smoking, alcohol use (especially binge drinking), and hypertension.7,30 Although aneurysms may become symptomatic during pregnancy, 31 there is no documented association. 32
Natural History of Intracerebral Aneurysms
Prior to discussion of ruptured intracranial aneurysm, it is essential for the ED physician to understand the clinical manifestations and natural history of individuals who have intact cerebral aneurysms.
In one landmark study of 111 patients who had 132 unruptured aneurysms,33 patients were divided into three groups: Group 1 presented with acute symptoms; Group 2 presented with chronic (> 2 weeks in duration) symptoms; and Group 3 were asymptomatic and had been diagnosed either incidentally or during the course of being treated for an aneurysm that had ruptured. Typically, Group 1 patients presented with symptoms related to cerebral ischemia (TIA or stroke),34,35 which was usually the result of an aneurysmal clot that embolizes distally into the territory of the affected vessel. Other symptoms in Group 1 were acute headache, seizures, and cranial neuropathy.
Patients in Group 2 had headache, visual symptoms, long-tract dysfunction, and facial pain. The three patients with facial pain all had anterior circulation aneurysms, two of which were located within the cavernous sinus, through which the first two divisions of the trigeminal nerve traverse. Not surprisingly, the investigators also noted that the patients in Groups 1 and 2 had larger aneurysms (mean diameter, 2.1 cm) than did the asymptomatic patients in Group 3 (mean diameter, 1.1 cm). The clinical importance of aneurysmal size has been noted by other authors.36-38 As a rule, aneurysms that present with findings suggestive of a mass effect are generally larger and, therefore, carry a higher risk of rupture (estimated at 6% per year). Because surgical therapy has become relatively safe, some experts advocate more aggressive surgical treatment of unruptured aneurysms,39,40 especially those that are greater than 2.5 cm in diameter.41 It should be stressed that even very small aneurysms can bleed, which suggests that clinical vigilance is required for all individuals with unruptured aneurysm.42
The neuro-opthalmic symptoms of unruptured aneurysms fall into two broad categories: visual loss and diplopia.43 Visual loss can result from intraocular bleeding or compression of the visual pathways. Hemorrhage in the retina, sub-hyaloid space, or vitreous occurs in 25-40% of patients44,45 and may be the only clue to SAH in a comatose patient. In the setting of anterior communicating artery aneurysm, ocular bleeding is referred to as Terson's syndrome; vitreous bleeding in this setting may require a vitrectomy to restore vision.45 Bleeding is thought to occur as a result of the acute rise in intrcranial pressure (ICP), which leads to venous outflow obstruction.43
Table 1. Cannot Miss Diagnosis* Presenting as a Headache
· Bacterial meningitis
· Subarachnoid hemorrhage
· Space-occupying lesion
Brain tumor
Brain abscess
Subdural and epidural hematoma
Others including other parameningeal infections
· Pseudotumor cerebri
· Hypertensive encephalopathy
· Acute narrow angle glaucoma
· Temporal arteritis
· Cerebral venous and dural sinus thrombosis (including cavernous sinus)
· Carbon monoxide poisoning
· Stroke
· Bacterial sinusitis (can lead to complications on the list)
* Defined as medical conditions that are simultaneously life, limb, or vision threatening and treatable.
Because of their proximity to the circle of Willis and the anterior visual pathways, cerebral aneurysms can produce visual field cuts or impairments in ocular function. Symptoms often develop over months to years, but acute increases or even fluctuations in symptoms can occur secondary to periodic dilation of the aneurysms, thrombosis, or changes in ICP.43 A number of visual deficits can occur depending on the location of the aneurysm and the segment of the visual pathway involved; the most common is 3rd cranial nerve (CN) palsy. About, 30% of 3rd nerve palsies are aneurysmal, and most occur at the junction of the PCoA and the ICA.46 However, patients may not complain of diplopia because of a coexistent ptosis caused by involvement of the levator palpebrae muscle. This lesion is usually associated with a dilated pupil. Early operation is advised.46
Although many entities can produce a 3rd cranial nerve palsy (cavernous sinus syndrome, lesions of the midbrain and orbit, basilar meningitides, neuromuscular disease, and uncal herniation), the most important entity in the differential diagnosis is microvascular infarct resulting from diabetes. Typically a diabetic 3rd cranial nerve palsy spares the pupil, whereas aneurysmal 3rd cranial nerve lesions do not; however, exceptions to this rule occur in a significant percentage of cases.43,47,48
Ruptured Aneurysm. Once an aneurysm ruptures, patients may present with a wide range of signs and symptoms; they may be ambulatory and fully conscious or comatose. Several clinical grading systems are used for patients with SAH. The two most widely improved are the Hunt and Hess (H&H)49 and the World Federation of Neurologic Surgeons classifications, the latter of which is based on the Glasgow coma scale. (See Table 2.)
The classical textbook history for patients with a ruptured aneurysm includes: abrupt onset of the worst headache of life associated with exertion, transient loss of consciousness with or without nausea, vomiting, and new neurologic deficits. Physical examination may yield a number of associated findings, such as acute hypertension and low-grade fever. Level of consciousness (LOC) may be diminished. The presence of ocular hemorrhage, especially sub-hyaloid bleeding, is an important clue. Other neuro-ophthalmic findings due to a mass effect have been described above and should be actively sought since they may provide useful clues to both the diagnosis and localization. Meningismus may also be present. The presence of any focal neurologic findings mandates a detailed neurologic examination.
Diagnostic Pitfalls
Despite clues to the diagnosis of SAH, there are numerous pitfalls that can compromise prompt evaluation and subsequentmanagement. These pitfalls fall into three major categories. (See Table 3.)
1. Failure to consider the diagnosis of SAH.
2. Failure to understand the limitations of a computerized tomographic (CT) scan.
3. Failure to understand the limitations of the lumbar puncture (LP).
Failure to consider diagnosis. From a diagnostic perspective, it is important to discuss the warning bleed, a concept introduced in the medical literature in 1958 by a Scottish neurosurgeon, F. John Gillingham,50 who wrote: "It would appear from the fresh appraisal of many case histories, that a patient's first episode of SAH is commonly of minor severity; a mere leak of blood from the sac." He is also given credit for coining the term "warning leak" nine years later.51 Since then, there have been numerous references in the literature about warning bleed, warning leak, sentinel bleed, and sentinel leak.52-61 This symptom usually is also associated with a thunderclap headache, described as an abrupt (develops in seconds), very intense (like a thunderclap, reaching maximal intensity in minutes) headache that is new for the patient and lasts for hours to days. Typically, it is focal (bifrontal, bioccipital, vertex, or unilateral),55,62 and differs from the very brief "jabs and jolts" headache whose intensity, but not duration (seconds), rivals that of the thunderclap headache.63
Retrospective reviews of hospitalized patients with SAH estimate that "warning bleeds" occur in 20-60% of patients with SAH a mean of 14 days before the major bleed (range, 1 day to 4 months). A neurologic examination performed at the time is usually normal. Since the mechanism of warning headaches is thought to be a very small leak in the aneurysm, an LP will almost always demonstrate abnormal cerebrospinal fluid (CSF). There is one fatal case on record where this mechanism was documented pathologically.64 An alternative hypothesis is that the warning headache represents bleeding into the wall of the aneurysm; however, this would not account for the bloody CSF.
If the latter hypothesis were true, then one would expect some patients presenting with thunderclap headache to have a negative CT and LP and go on to develop a SAH within the next several weeks. Indeed, one such patient has been reported,65 arguing the notion that patients presenting with thunderclap headache and negative CT and LP should undergo cerebral angiography. Subsequent retrospective66 and prospective62,67-69 studies have investigated this problem and concluded that a more tempered approach is both safe and effective. The largest of these studies66 evaluated 71 patients with thunderclap headache for an average of 3.3 years. All patients had negative CT and CSF. Four patients had six angiograms (2 for recurrences) that were also negative. They concluded that cerebral angiography is not necessary for patients presenting with thunderclap headache who have a negative CT and normal CSF. It is important to stress, however, that both the CT and LP are necessary to exclude a SAH, inasmuch as these patients are clinically indistinguishable from those with SAH on presentation.62,67
From an emergency diagnostic perspective, the thunderclap headache has a differential diagnosis. Upon evaluation with CT and LP, a substantial proportion of patients will have documented SAH. For patients in whom CT and LP are negative, the diagnosis of aneurysm is essentially excluded. There may be an occasional patient with a very high, pre-test likelihood of SAH (e.g., strong family history or polycystic kidney disease with a good story) for whom additional neurologic or neurosurgical consultation is appropriate. Other explanations for this symptom include migraine,67 benign exertional cephalgia,70 and benign sexual headache,70 but these diagnoses should be considered only if the CT and LP are negative.22,71 Also in the differential is cortical vein thrombosis.72 Identifying this condition is one reason to always measure the CSF pressure when performing an LP; the pressure is often high in this "cannot miss" condition.73
The natural history of the warning bleed is unpredictable. A recent publication of a prospective, community-based study investigated whether general practitioners could accurately identify these warning bleeds and whether early identification would alter patient outcomes.74 Investigators followed 148 patients with "thunderclap headache" seen by 252 general practitioners in the Netherlands over a five-year period. One quarter of these patients had SAH and another 12% had other serious neurologic problems. The remainder of patients, who were followed for at least a year, had either a negative angiogram or a benign outcome.
Despite this study, there is no doubt that early diagnosis leads to better outcomes. This hypothesis was recently tested by Mayer and colleagues, who retrospectively examined 217 patients with symptomatic cerebral aneurysms.5 Their principle conclusions were: 1) 25% of patients were initially misdiagnosed by a physician; 2) misdiagnosed patients were more likely to be of lower grade (38% of patients with a modified H & H grade 1 or 2 were misdiagnosed); and 3) those who were correctly diagnosed on initial presentation had better clinical outcomes. These investigators also found that patients presenting with a seizure or mass effect were more likely to be misdiagnosed.
Conditions most likely to be confused with SAH included viral meningitis, migraine, headache of unknown etiology, stroke, sinus headache, hypertension, tension headache, and depression. These results are similar to those of another study examining pitfalls in the diagnosis of SAH.4 In this trial, 41 of 181 (23%) patients were misdiagnosed with conditions nearly identical to that in Mayer's study.5 Still another study showed a remarkable 51% (69 of 131 patients) rate of delayed diagnosis; two-thirds of the patients suffered recurrent bleeding leading to worse outcomes prior to correct diagnosis.6 Other investigators have examined the rate of late diagnosis in the same geographical area over time and found no change in the rate of delayed referral over the last 15 years.75
Why is this diagnosis missed? One reason the diagnosis of SAH is missed is over-reliance on the classic teaching. For example, the classic teaching that the leak occurs at time of stress or Valsalva was supported in only 43% of patients in one series of 500 consecutive patients.22 In 12% of patients, the hemorrhage occurred during rest or sleep. Moreover, some patients did not have abrupt onset of symptoms.4,69 New-onset headache or a distinct change in a patient's prior headache pattern requires diagnostic evaluation. At the very least, this should include a very detailed history and physical examination, with the goal being to exclude "cannot miss" possibilities. Furthermore, the headache of SAH can be relieved with non-narcotic analgesics76 and may improve spontaneously during observation in the ED.69
It should be stressed that there is a wide range of atypical symptoms, or symptom complexes, that may confuse the clinician. One common presentation is primary neck pain and/or stiffness. The erroneous diagnosis of neck arthritis or musculoskeletal neck pain (in the absence of trauma) is identified with some regularity in studies on misdiagnosis.4,9,77 Similarly, viral meningitis, which can be mimicked by chemical irritation from blood, is another common misdiagnosis.4-6 Hypertension, which frequently accompanies SAH, also can confuse physicians. Headache caused by hypertensive encephalopathy should resolve promptly after lowering the blood pressure.
Another potential source of confusion is head injury that results from a fall or injury secondary to the transient syncopal episode sometimes associated with SAH.29 Sakas reported on four patients in whom mild to moderate head injury followed a fall that resulted from a spontaneous SAH.78 On initial presentation, there was confusion as to cause and effect between the subarachnoid blood and the trauma. Some unusual presentations include shock,79 cardio-respiratory arrest,80 and psychosis from a frontal aneurysm.81
ECG abnormalities can also lead to diagnostic confusion.82,83 The ECG changes in SAH range from T-wave flattening and inversions to prolonged QTc intervals, to life-threatening brady-and-tachyarrhythmias. An ECG pattern simulating acute myocardial infarction has also been reported. These changes may be related to subendocardial ischemia.84 One prospective study identified arrhythmia in 91% of patients and a potentially dangerous arrhythmia in 41%.85 The vast majority of patients with SAH have headache, a symptom that is uncommon in acute MI, unless it is accompanied by administration of nitrates. Reversible pump dysfunction may also occur.86
Limitations of CT. Once the diagnosis of SAH is considered, a systematic diagnostic strategy is mandatory. The non-contrast CT scan is the first step in evaluation.87, 88 The advantage of CT is that it is non-invasive, relatively inexpensive, readily available, and has high sensitivity in the first 24 hours.87-89 Another advantage is that it can yield other important information and identify other diagnostics such as intraventricular or intracerebral hemorrhage87,88 and subdural hematoma, which can occur secondary to SAH.87,88,90,91
Moreover, the pattern of blood identified on CT can sometimes predict the bleeding site. For example, interhemispheric blood between the frontal lobes suggests aneurysm of the ACA or ACoA, whereas blood localized to the Sylvian fissure suggests a lesion in the MCA. This can be useful information if the angiogram shows multiple aneurysms. Furthermore, there is a syndrome characterized by isolated perimesencephalic blood which, if no aneurysm is found on initial angiography, carries an extremely benign prognosis and obviates the need for repeat angiography (assuming the first test is negative).92,93 Using a protocol of very thin cuts (3 mm) through the region of the circle of Willis helps pick up small bleeds.88
Sensitivity with CT is high during the first hours of SAH.87-89,94,95 In two studies that specifically evaluated CT scans performed within the first 12 hours using a third generation scanner, one demonstrated 98% sensitivity (2 of 119 false negatives) 94 and the other 100% sensitivity (0 of 80 false negatives).95 Therefore, although the CT is an excellent test, especially during the first 12 hours, it is not infallible. If one extends the time window to the first 24 hours, however, sensitivity drops to 93-95%.87,89 Overall, SAH is detected in about 90% of patients after one day, 58-80% after five days, and roughly 50% after seven days.87,88
In addition to timing, other important factors affecting sensitivity of CT for detection of SAH are density and quantity of blood.88 Blood with a hemoglobin count of less than 10 g/dL may not show up on CT scanning; likewise, small amounts of blood can be missed. False positives can also occur from calcification of dural and vascular structures at the base of the brain, as well as from artifact caused by patient movement and partial volume averaging.
Accordingly, the majority of patients with suspected SAH whose CT scans are negative should undergo LP.87-89,94,95 In making this decision, the clinician should consider the pre-test likelihood of the disease before deciding whether or not to proceed with an LP after a negative CT. There are two major factors to be considered. The first is the likelihood of the disease based on purely clinical parameters, and the second is the timing of the CT, since the sensitivity is highly dependent upon temporal factors. Generally, if the pre-test probability is low, and the CT has been done during the first 12 hours on a third generation scanner, and it is negative, then the likelihood of SAH approaches zero.96 Magnetic resonance imaging (MRI) is not as sensitive in diagnosis of acute SAH, although MR angiography may play some role in defining the aneurysms.
Limitations of the Lumbar Puncture (LP). There are several pitfalls in diagnosis of SAH related to the LP. The first is failure to recognize that it may take up to 12 hours post-ictus for the CSF sampled from the lumbar theca to reflect the pressure bleed,94,97,98 which can take the form of frank blood or xanthochromia. Xanthochromia is a yellow-golden discoloration of CSF caused by the enzyme-dependent breakdown of hemoglobin into oxyhemoglobin and bilirubin; this may account for the delay.99 There are two ways of detecting xanthochromia: 1) visual inspection of the CSF with the naked eye; and 2) examination of the fluid by spectrophotometry. Depending on the quantity of breakdown products, xanthochromia may or may not be visible to the naked eye. Only about 50% of specimens that are positive by spectrophotometry are also positive visually.100 Although it is well established that it may take up to 12 hours for xanthochromia to be visible, some investigators have reported it to be visible with the naked eye as early as four hours after symptoms.101
This had led to some controversy about the significance of bloody CSF without xanthochromia in a patient suspected of having SAH. If an LP yields bloody fluid, it should immediately be centrifuged and the supernatant should be examined for xanthochromia. It should be compared to water, and both specimens should be examined against a white background. If xanthochromia is present visually, SAH is strongly suggested. If it is negative to the naked eye, the specimen should be examined for optical density by spectrophotometry. If it is negative by spectrophotometry and the fluid was obtained between 12 hours and two weeks after the onset of headache, this suggests a traumatic LP rather than SAH.
Although there are several methods that can help to distinguish a traumatic tap from blood associated with SAH, none is error-free. Two time-honored methods include: 1) looking for diminishing redness (and RBC counts) in sequential tubes of CSF; and 2) examining the fluid for xanthochromia. The former approach is useful, but is not foolproof,102 and absence of xanthochromia (as measured by spectrophotometry) strongly suggests a traumatic tap.
In one study of 12 patients with sudden onset of headache, normal CT, bloody CSF, and no xanthochromia by spectrophotometry, none had subsequent SAH diagnosed during a mean follow-up of four years. This suggests that absence of xanthochromia is strong evidence in favor of a SAH. Another technique is to re-tap one interspace higher, which should yield non-bloody or less bloody fluid if the first tap was traumatic. One other method to distinguish traumatic tap from acute bleed that has proved to be without value is looking for crenated red cells in the CSF.101 These data should always be interpreted in the clinical context.
The best strategy is to avoid a traumatic tap. Proper attention to procedural detail is imperative. The most important factor is patient preparation-both physical and mental. The plane of the patient's back must be perpendicular to the floor, with hips and shoulders directly on top of their counterparts. Sometimes having the patient push his back out toward the operator "like a cat arching its back" will help spread the spinous processes. Taking time to feel the landmarks and identify the midline are keys for success. Advancing the needle so that one's finger (or thumb) tip is applying the pressure to the hub of the needle assists the operator to feel the decrease in resistance on dural entry.
It is important to avoid post-LP headache in patients being evaluated for SAH for two reasons. First, minimizing pain and discomfort will be in the patient's best interest. Second, to the extent that the mechanism of post-LP headache involves persistent leakage of CSF through the dural rent, this would also decrease the pressure gradient across the aneurysm wall (see LaPlace's law, above). Proven factors that reduce the likelihood of this event are needle size (smaller is better), design (pencil point, non-cutting needle may be better), and orientation (bevel should split rather than transect dural fibers).103 Reinsertion of the stylet on needle removal may also help.104
In some patients who are being evaluated for SAH, bacterial meningitis will be in the differential diagnosis. One should not delay LP in order to perform a CT105 in these patients, except in those with abnormal level of consciousness, focal neurologic findings, or papilledema. If these findings are present in a patient in whom meningitis is a serious consideration, the appropriate sequence is to treat with antibiotics, scan, and then tap (if there is no contraindication by CT).106
There is a small potential for deterioration following LP in patients with SAH.107,108 In one study of 283 patients, there was a documented complication rate of 2.2%. These four cases were all initially alert prior to the LP. Others have investigated the same phenomenon and found no patients who deteriorated post-LP.109 While this is another reason that CT has been proposed as the diagnostic method of choice for patients suspected of having SAH, it should be stressed that in patients in whom meningitis is a strong possibility, one must proceed with either treatment or LP prior to CT.
Complications and Management: General Principals
Once the diagnosis is secure, prompt consultation with a neurologist and/or neurosurgeon is mandatory to arrange for angiography and definitive treatment. While this has a high priority, there are a number of urgent or emergent issues that will require prompt attention in the ED.
Attention to the ABCs is paramount. Patients with loss of protective airway reflexes should be intubated with attention to blunting reflex elevations in intracranial and systemic blood pressure. Lidocaine and short-acting barbiturates have been used. A short-acting paralytic such as succinylcholine would lead to rapid resumption of the baseline neurologic status. Succinylcholine's lack of producing hyperkalemia has been specifically studied in this setting.110
In general, ED care of the patient with SAH should be focused on prevention or treatment of major complications, among them: rebleeding, vasospasm, seizures, and obstructive hydrocephalus. Prevention of other, longer term sequelae, such as thromboembolic disease, peptic ulcer, and long-term control of hypertension, will not be discussed, but the reader is referred to excellent references.13,14
Severe, systemic hypertension should be treated with drugs such as labetalol or possibly hydralazine, but one must factor in the patient's pre-morbid pressure and not aim for any pre-set value.14
Seizures occur in 10-25% of cases.14 In these patients, phenytoin, 17 mg/kg, should be administered intravenously to prevent additional seizures, which can provoke re-bleeding.13,14 Patients undergoing painful procedures should be treated with short-acting analgesics such as fentanyl.7 Anxiety in the awake, alert patients can be treated with small doses of short-acting benzodiazepines such as midazolam to minimize the catecholamine release that pain and anxiety may provoke.14
Acute obstructive hydrocephalus can be seen within the first 24 hours and is manifested by diminished level of consciousness, stupor, and coma.13,111 In one series of 473 patients admitted within 72 hours of SAH, 91 (19%) had hydrocephalus on the initial scan.112 Diagnosis is by CT, and emergency ventriculostomy is indicated for drainage.14 Patients will often have a dramatic response to this procedure. Care should be taken not to reduce the ICP too rapidly as this will increase the pressure gradient across the wall of the aneurysm and increase the likelihood of rebleeding.14
Nimodipine, 60 mg, administered either by mouth or nasogastric tube within the first 12 hours is important for prevention of vasospasm.13,14 This can be administered in the ED. Vasospasm is a serious and common complication of SAH, and is seen by angiography in as many as 75% of patients.14 Symptoms will depend on which vessel(s) is in spasm-in the same way that stroke symptoms reflect the vascular territory supplied by the thrombosed vessel. There is a wide range of treatments for vasospasm, including calcium channel blockers, hemodynamic therapy to increase blood pressure and intravascular volume, percutaneous transluminal angioplasty and intrathecal papaverine and tissue plasminogen activator.14 These therapies fall within the province of the neurointensivist.
The risk of early rebleeding is high-approximately 4% during the first day and 1-2% per day for the next two weeks,14,113 and rebleeding carries a high mortality. Once a clot is formed around an aneurysm, fibrinolysis begins to occur in the CSF. For many years, antifibrinolytics were administered to reduce clot dissolution. However, they produced no improvements in mortality because what is gained by reduction of rebleeding is lost due to cerebral ischemia and thromboembolic complications.13,14
Patients with SAH should not be "run dry" (i.e., dehydrated), although data to support this approach are lacking. There is a tendency for these patients to become volume contracted and hyponatremic, possibly from SIADH. These patients should not be fluid restricted but should be given isotonic or slightly hypertonic saline.1 Ensuring that patients stay well- or even overhydrated has led some to recommend so-called triple-H therapy (hypertension-hypervolemia-hemodilution) to increase diminished cerebral blood flow seen after SAH.13,114
After the patient is stabilized, four-vessel angiography is performed by the neuroradiologist to ascertain the cause of the bleed and the location of the aneurysm. Visualization of all four cerebral arteries is important, even in those cases where the CT shows the likely source of bleeding, because of the frequency of multiple aneurysms. In 15-20% of cases, no aneurysm is demonstrated.113,115 This group of patients is heterogeneous: some have aneurysms that are not visualized because the feeder vessel is in spasm; about two-thirds have the previously described perimesencephalic pattern of bleeding that is thought to be venous in origin; some have occult aneurysm and others have an other diagnosis, such as dissection, AVM, or a bleeding disorder. Angiography is remarkably safe when carried out by qualified individuals;116 it has a mortality rate of less than 0.1%.113 Although conventional angiography is still the gold standard, magnetic resonance angiography is playing an increasingly important role.117
Timing of Surgery. Definitive therapy requires isolating the aneurysm from the general circulation. The time-honored method is surgical clipping of the aneurysm. For many years, there was controversy regarding the timing of surgery. Some felt early surgery was better because the risk of rebleeding was reduced; others thought that delaying surgery until after the acute inflammation had receded was a better method. In 1990, the results of an international cooperative trial of 3521 patients partly resolved this controversy.118,119 While there was no difference in mortality outcomes for patients with H & H grades 1-3, patients operated on early (0-3 days) did better than those operated on late (11-14 days). The international study found that predictors of mortality were decreased level of consciousness, increased age, thickness of clot on CT, elevated blood pressure, co-morbid conditions and basilar aneurysms.
As a result, the general recommendation currently is that H&H grades 1-3 undergo early surgery.29 The benefits of early surgery are reduced risk of rebleeding, opportunity to clear blood from the subarachnoid cisterns, and ability to aggressively treat vasospasm with triple-H and other therapies.29
The timing of surgery for H & H grades 4 and 5 is less clear and the results in these patients are not very encouraging. Some advocate using the endovascularly placed coil to obliterate the aneurysm at the time of initial angiography and then to consider surgical therapy if the patient improves.29 Others advocate a more aggressive approach in these high-grade patients.120 There may also be a place for surgery immediately following CT scan in the rare patient who has an aneurysm that ruptures directly into the brain parenchyma, leading to an acute mass effect.29
The most recent advance in treatment of intracranial aneurysms is endovascular placement of a variety of balloons or coils that either obliterate the fundus of the aneurysm or decrease flow to the parent vessel. This field is undergoing constant revision as technology changes, and it would seem that these non-surgical techniques will be used more rather than less in the future.111 Nevertheless, more long-term data are needed to establish the precise indications for this novel method.29 One recently published study of more than 400 patients treated with the Guglielmi detachable coil showed promising results.121 Some experts argue that endovascular treatment is indicated for aneurysms which are technically difficult to operate on and in patients with H & H grades 4 and 5 who would normally not be operated on immediately.111
These innovative treatments are more useful in patients diagnosed earlier rather than later. Therefore, emergency physicians must strive to identify patients with SAHearly in the natural history of their disease.
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