Secondary Logo

Journal Logo

Perioperative Management of Aneurysmal Subarachnoid Hemorrhage: Part 1. Operative Management

Guy, John MD, FRCP(C); McGrath, Brian J. MD; Borel, Cecil O. MD; Friedman, Allan H. MD; Warner, David S. MD

Review Article

Department of Anesthesiology (Guy, McGrath, Borel, Warner) and Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (Borel, Friedman, Warner).

Accepted for publication May 31, 1995.

Address correspondence and reprint requests to Cecil O. Borel, MD, Box 3094, Duke University Medical Center, Durham, NC 27710.

Subarachnoid hemorrhage (SAH), most commonly caused by the rupture of an intracranial aneurysm, is associated with considerable morbidity and mortality. For patients who survive to reach the hospital after aneurysmal subarachnoid bleeding, aneurysm clipping is commonly performed to ablate the aneurysm and prevent rebleeding. In addition to surgical considerations, there are unique pathophysiologic changes that occur after rupture of an intracranial aneurysm that require special anesthetic and intensive care management. A special appreciation of the pathophysiology and management strategies is required at every level of care.

Effective treatment of patients with aneurysmal SAH requires care by a coordinated team of practitioners. Anesthesiologists have traditionally provided the intraoperative anesthetic management for the patient with a cerebral aneurysm, and are increasingly involved in pre- and postoperative intensive care management.

Back to Top | Article Outline


The term SAH was first coined by Symonds in 1924 [1]. Dott described the first intracranial surgery for an aneurysm [2], while Dandy reported the first clipping 5 yr later [3]. The estimated incidence of SAH is between 10 and 28 cases per 100,000 persons per year [4], producing approximately 25,000 new cases each year in the United States, about 10% of all strokes [5]. Cerebral saccular aneurysms account for 75%-80% of spontaneous SAH when an etiology can be found [6]. Cerebral arteriovenous malformations are discovered in 4%-5% of cases [7]. Despite extensive evaluation, no discrete bleeding source can be found in 15%-20% of patients with SAH [8]. Other causes of SAH include trauma, vertebral and carotid artery dissection, dural and spinal arteriovenous malformations, mycotic aneurysms, sickle cell disease, cocaine abuse, coagulation disorders, and pituitary apoplexy.

A number of potential risk factors for the development and rupture of saccular aneurysms have been identified. Hypertension, a risk factor for aneurysm formation, is a more significant factor in aneurysm rupture [9]. As with other types of strokes, the incidence of SAH increases steadily with age; however, the influence of age on risk appears less marked than with other types of strokes [10]. SAH occurs most frequently between the ages 40 and 60 yr, with the peak frequency between 55 and 60 yr of age [11]. In most epidemiologic studies, women are affected more often than men. During pregnancy the incidence increases [12]. Vascular abnormalities (e.g., Type III collagen deficiency) and genetic factors have also been linked to the occurrence of saccular aneurysms; approximately 7% of berry aneurysms are thought to be familial [13].

SAH produces significant morbidity and mortality. Of the estimated 28,000 victims each year in the United States and Canada, 10,000 die before they can receive medical attention [14]. Of the 18,000 patients who survive to receive medical attention, about one half will die or become severely disabled. Only one third of patients with SAH will be functional survivors. The International Cooperative Study on the Timing of Aneurysm Surgery, examining 3521 patients treated for SAH, found that only 58% of patients returned to their premorbid neurologic condition [15]. The leading causes of death and disability were the direct effect of the initial bleed, cerebral vasospasm, and rebleeding. Lesser causes included complications of intracranial operation, intracerebral hemorrhage, hydrocephalus, and complications of medical therapy. The prognosis of patients with nonaneurysmal SAH is better than that of those with SAH resulting from aneurysm rupture.

In the International Cooperative Study, 78% of aneurysms that presented with SAH were rated as small (<12 mm in diameter), 20% as large (12-24 mm), and 2% as giant (>24 mm) [16]. Of the anterior circulation aneurysms (90% of the total), 39% occurred at the junction of the anterior communicating and anterior cerebral artery, 30% occurred along the internal carotid artery, 22% were derived from the middle cerebral artery, and 8% involved the posterior circulation. Patients who do not have a demonstrable aneurysm, and have hemorrhage confined to the cisterns around the midbrain (perimesencephalic hemorrhage) on computed tomography (CT) scan, usually have a good outcome [17]. However, when the CT scan in patients without an angiographically defined aneurysm demonstrates hemorrhage that is diffuse or anteriorly located in the basal cisterns, death or significant disability occurs in approximately 25% [18].

Back to Top | Article Outline

Pathophysiology of Aneurysm Rupture

With rupture of a saccular aneurysm, the sudden escape of arterial blood into the subarachnoid space causes an initial increase in intracranial pressure (ICP) toward the systemic diastolic pressure in the main trunks of the intracranial arteries. The increase in ICP produces a sudden reduction in the cerebral perfusion pressure (CPP) with a coincident decrease in cerebral blood flow (CBF) [19]. The immediate change in the level of consciousness seen after SAH may be caused by global cerebral ischemia [20]. No-flow phenomena have been demonstrated immediately after experimental SAH in an animal model [21]. The dramatic reduction of flow is a major factor halting continued subarachnoid bleeding.

Two distinct cerebral hemodynamic patterns were found immediately after experimentally induced SAH [21]. In the first, ICP rose toward arterial diastolic values and caused a reciprocal reduction of CBF approaching zero. This was followed by a gradual reduction in ICP and increase in CBF over approximately 15 min, and later by reactive hyperemia with improvement of cerebral function. This pattern may correlate clinically with patients who survive the initial bleed and present with varying levels of consciousness. In the second pattern, persistent increase in ICP resulted in failure of recovery of both CBF and functional activity. The reason for the persistent increase in ICP may be related to abnormal cerebrospinal fluid (CSF) dynamics caused by thrombi formed in the cisterns. This persistent no-flow pattern is associated with acute vasospasm and swelling of perivascular astrocytes, neuronal cells, and capillary endothelium [22]. Patients with this cerebral hemodynamic response likely represent those admitted in a persistent vegetative state and those who do not survive to receive treatment.

Hypertension, frequently seen with acute SAH, may represent autonomic hyperactivity induced by cerebral ischemia or direct trauma to cerebral autonomic control mechanisms. Transmural pressure distending the aneurysm sac is the difference between mean arterial pressure (MAP) and ICP. Sudden or sustained increases in MAP or reductions in ICP tend to distend the sac and may cause rupture and rebleeding of the aneurysm. Conversely, prolonged reductions of cerebral perfusion pressure (MAP-ICP) may produce neurologic ischemia in poorly perfused areas, impair autoregulation, and globally increase ICP through ischemic disruption of the blood-brain barrier [23].

Back to Top | Article Outline

Preoperative Management

Clinical Features

Neurologic. Headache, the most common clinical symptom of SAH, occurs in 85%-95% of patients [24]. Many patients present with a brief loss of consciousness followed by various degrees of decreased mentation. Signs and symptoms similar to those of infectious meningitis can occur as a result of an inflammatory reaction of the meninges to the extravasation of blood. Other symptoms of SAH include nausea, vomiting, altered mentation, and photophobia. Other signs of neurologic involvement may include motor or sensory deficits, visual field deficits, abnormal motor posturing, or loss of various brainstem reflexes. Oculomotor nerve palsies frequently occur with posterior communicating artery aneurysms. Abducens nerve palsy is frequently seen after SAH and is thought to be related to increased ICP and traction on the nerve during caudal brainstem herniation during the hemorrhage. Trigeminal nerve distribution pain can result from aneurysm compression or SAH, but is more commonly seen with giant aneurysms within the cavernous sinus.

In 1956, Botterell et al. [25] proposed a grading scale to allow for better assessment of surgical risk and assist prognostication of outcome Table 1. This was later modified by Hunt and Hess [26]Table 2. More recently a grading scale based on the Glasgow Coma Scale was introduced by the World Federation of Neurological Surgeons [27]Table 3. The modified Hunt and Hess grading scale remains the most commonly used grading scale, because of both familiarity and ease of application. Both the botterell and the Hunt and Hess grading scales put the patient into the next worse grade if serious systemic disease or vasospasm is present.

Table 1

Table 1

Table 2

Table 2

Table 3

Table 3

Cardiovascular. After SAH, injury to the posterior hypothalamus may stimulate release of norepinephrine from the adrenal medulla and sympathetic cardiac efferents [28]. Norepinephrine, either through direct toxicity or via significant elevation of myocardial afterload, produces ischemic changes in the subendocardium [29]. Pathologic examination of the myocardium after SAH may reveal microscopic subendocardial hemorrhages and myocytolysis [30].

Ischemic electrocardiographic (ECG) changes and myocardial damage seen in SAH patients cannot be satisfactorily explained by coronary atherosclerosis or thrombosis. Myocardial injury is often scattered rather than confined to a particular coronary artery distribution [31]. Although increases in plasma creatine phosphokinase (CPK) and its cardiac specific isoenzyme CPK-MB increase in 50% of patients with SAH [32], the total CPK and the ratio of CPK-MB to total CPK are rarely consistent with transmural infarction. Ventricular wall dysfunction, seen in 27%-33% of patients after SAH [33,34], is associated with greater morbidity, including pulmonary edema, intraatrial thrombus formation, and embolic stroke. Some evidence suggests that the prophylactic administration of beta -adrenergic blockers or autonomic antagonists can improve cardiac outcome in patients with SAH [35-37], while other evidence does not [29,38].

Abnormalities in ECG tracings of rhythm and morphology are seen in 50%-80% of patients with SAH [29]. A variety of changes have been reported, including prolongation of the Q-T interval, P wave changes, U waves, and dysrythmias including ventricular tachycardia and fibrillation. The most common ECG abnormalities involve ST and T wave changes, which may mimic myocardial ischemic changes. ECG changes usually occur during the first 48 h after SAH. Their duration is variable with the ECG usually normalizing by 6 wk.

Cardiac dysrythmias, the most common being premature ventricular complexes, occur in up to 80% of patients with SAH. Virtually any form of ventricular and supraventricular rhythm abnormality can be seen, including ventricular tachycardia and ventricular fibrillation [39,40]. Life-threatening dysrythmias may occur in patients during the first 48 h after SAH [41]. The development of ventricular fibrillation is frequently preceded by torsade de pointes. In those cases where torsade de pointes was followed by lifethreatening ventricular dysrythmias, the QTc interval was significantly prolonged [41].

Some patients with SAH do sustain myocardial infarction [42], although the correlation between the ECG abnormalities and ischemia may not be very good. Although most ECG abnormalities after SAH appear to be neurogenic rather than cardiogenic in nature, a dilemma exists as to whether the cardiac injury warrants a delay of surgery [43,44]. Serial cardiac enzymes and assessment of ventricular function may be helpful in suspicious cases. Even if myocardial ischemia is present, it may have minimal impact on mortality [4]. Consequently, the decision to postpone surgery must be balanced against the course of the disease, especially with respect to the risk of rebleeding and vasospasm. Significant cardiopulmonary edema or malignant dysrythmias may warrant postponement of surgery until adequate medical management can be achieved. Clinical or diagnostic evidence of myocardial dysfunction may be helpful in assessing the need for pulmonary artery catheter monitoring.

Back to Top | Article Outline

Diagnostic Studies

CT and Magnetic Resonance Imaging. Noncontrast CT scanning of the brain is the procedure of choice to confirm the diagnosis of SAH. The CT scan demonstrates the magnitude and location of the SAH, gives clues as to the probable location of the aneurysm, and assesses ventricular size. On the day of SAH, intracranial blood is detected in about 95% of patients. This proportion declines to 90% after 48 h, 80% after 5 days, and 50% after 1 wk [45]. Blood distributed within the supratentorial ventricular system points to rupture of an anterior communicating artery aneurysm [46]. Vertebral artery aneurysm would be suspected with focal blood in the fourth ventricle. Ruptured middle cerebral or distal anterior cerebral artery aneurysms usually demonstrate intracerebral blood on CT scan. In some cases, high-resolution CT scanning with slices of 1-5 mm and contrast injection can localize the aneurysm. A grading scale based on the amount and distribution of the SAH blood on CT scan has been used to predict the probability of developing delayed ischemia secondary to vasospasm [47]. Patients who have diffuse thick blood collections in the basal cisterns have a high likelihood of developing cerebral vasospasm.

Magnetic resonance imaging is not well suited for imaging SAH in the acute stage [47]. After several days or weeks, when the CT scan has normalized, magnetic resonance imaging may detect subpial hemosiderin close to the source of the rupture. Magnetic resonance angiography may allow for visualization of the aneurysm itself, especially if its size is greater than 3 mm [48].

Lumbar Puncture. Lumbar puncture can confirm the diagnosis when the CT scan is negative. In 1901, Sicard found that yellow discoloration of CSF after centrifugation was a reliable sign of SAH [49]; the term xanthochromia was first used in the 1920s [50]. Xanthochromia can usually be detected 4 h after SAH and becomes negative at 3 wk [51]. Although traumatic lumbar puncture can produce blood-stained CSF, the presence of xanthochromia is the most sensitive method for distinguishing SAH [52]. Because the sensitivity of CT scanning to detect blood diminishes with time, lumbar puncture may be most useful when patients are evaluated more than 1 wk after their initial bleed.

Lumbar puncture carries with it the risk of brain herniation and aneurysm rebleeding. Duffy [53] described severe clinical deterioration in 7 of 55 patients with SAH who had lumbar puncture before CT scanning within 12 hr of the bleed. Intracranial hematoma with brain shift was shown at operation or upon subsequent CT scanning in 6 of the 7 patients. Therefore, a CT scan should be performed first in all patients who present within 72 h of a suspected SAH, even if this requires referral to another center.

Angiography. Once the diagnosis is established, the source of bleeding must be identified. Four-vessel cerebral angiography should be performed as soon as possible after the diagnosis of SAH. The angiographic investigation should visualize all intracranial vessels to rule out the potential occurrence of multiple aneurysms [incidence 5%-33.5% [16]]. The cerebral angiogram should be repeated if the initial angiogram is negative and the distribution of blood on the CT scan is more extensive than the perimesencephalic type [54]. A repeat angiogram also appears warranted in the patient with xanthochromic CSF who has both a negative CT scan and angiogram. Significant complications from cerebral angiography occur in 1%-3% of patients [55].

Back to Top | Article Outline

Initial Treatment Plan--Surgical Versus Medical

In a retrospective analysis comparing surgical to nonsurgical management in 624 patients with ruptured aneurysms, 55.9% of patients who underwent surgery had a mortality rate of 1.4%; among 275 patients who did not have operations, 98.5% died [56]. Therefore, nonoperative management should be confined to poor-grade patients who are not expected to tolerate a surgical procedure [57], or perhaps to patients in Hunt and Hess Grades IV and V, in whom operative mortality is as high as 75% [58]. Some centers, however, report more encouraging results with poor-grade patients [59].

Rebleeding. Rebleeding from a ruptured aneurysm is major cause of morbidity and mortality. The daily risk of rebleeding varies with time after SAH [60]Figure 1. Rebleeding peaks at 4% during the first 24 h and then levels off at 1.5% per day on subsequent days [61]. The cumulative risk of rebleeding is 19% at 2 wk and 50% at 6 mo [62,63]. After 6 mo the risk of rebleeding decreases to about 3% per year.

Figure 1

Figure 1

Due to the high incidence of rebleeding with conservative management of SAH, other strategies have been used, although the only definitive means of preventing rebleeding is obliteration of the aneurysm. The antifibrinolytic agents, tranexamic acid and epsilon-aminocaproic acid, significantly decreased the incidence of rebleeding in comparison to placebo, but did not decrease mortality [64]. Antifibrinolytic therapy may reduce the rate of rebleeding at the expense of a proportional increase in mortality from ischemic neurologic deficits. In fact, one randomized study of tranexamic acid found a higher mortality rate in patients who received antifibrinolytic therapy, despite a less frequent rebleeding rate [65]. Although antifibrinolytic therapy is associated with an increased incidence of hydrocephalus, the risks for pulmonary embolus or deep vein thrombosis are not different than with placebo [64,65].

While awaiting surgical repair of the aneurysm, therapy is aimed at avoiding increases in transmural pressure. Rebleeding rates are more frequent if systolic blood pressure exceeds 160 mm Hg [66,67]. The traditional approach consisting of bed rest in a dark, quiet room with limited emotional stimulation has never been shown to reduce rehemorrhage. Hypertension from pain and anxiety is treated with narcotic analgesics, such as codeine or intravenous morphine, and sedatives, such as midazolam and phenobarbital. Intravenous lidocaine can be used to suppress the autonomic response elicited by procedures such as endotracheal suctioning. Short-acting hypotensive drugs, such as esmolol, labetolol, or nitroprusside, are reserved for control of labile hypertension or transient hypertension provoked by therapeutic maneuvers. Stool softeners are given to reduce rebleeding caused by abdominal straining.

Timing of Aneurysm Surgery. The timing of aneurysm surgery is a long-standing controversy. In the 1950s and 1960s most neurosurgeons delayed operating at least 1-2 wk after SAH because of concern that early surgery was associated with increased risk due to technical difficulties or aggravation of vasospasm [67]. Despite reporting favorable operative results, delayed operation was associated with significant morbidity and mortality from rebleeding and vasospasm during the waiting period [68]. Because of the discrepancy between the generally excellent surgical results and the less than satisfactory overall outcome with late surgery, neurosurgeons began to reexamine early aneurysm surgery. Initial reports of early surgery were favorable [69,70].

More definitive answers were suggested with a prospective, observational clinical trial--The International Cooperative Study on the Timing of Aneurysm Surgery [16]; in all, 3521 patients were enrolled in 14 countries. A relationship between "tightness" of the brain during surgery and the interval from SAH to operation was found. In almost 50% of the patients who had surgery performed on Day 0 or 1, surgeons noted that the brains were tight. In contrast, tight brains were noted in approximately 20% of those who had surgery performed on Day 10 or later. Despite greater brain swelling with early surgery, there was not an increase in the incidence of contusions, lacerations, or the requirement for major brain resections. Aneurysm dissection was no more difficult in early than in late surgery. There was no difference in the incidence of intraoperative rupture between early and late surgery. The study showed that late surgery (>10 days after SAH) offered a better surgical outcome at 6 mo than did early surgery. However, 30% of patients admitted soon after SAH did not survive to have planned late surgery. The risk of waiting 2 wk for surgery was accompanied by a 12% risk for rebleeding and a 30% risk for focal ischemic deficits. The overall management results demonstrated a similar mortality (20%) and good outcome (60%) for patients with surgery planned for early (0-3 days) and late (11-14 days) intervals. Individuals with planned surgery for Days 7 to 10 after SAH had the least favorable outcome and highest mortality rate. Patients who were alert on admission and who underwent surgery on Days 0 to 3 had the most favorable results. When only the North American patients were analyzed, early surgery (Days 0-3) provided the best results [71]. Early surgery, moreover, did not appear to decrease the risk of vasospasm and cerebral infarction as a cause of neurologic deterioration after SAH. It is believed that outcome was worse when operation occurred between Days 7 and 10 because this interval coincides with the appearance of significant vasospasm. The timing of surgery, however, did not seem to influence cerebral vasospasm [72].

Back to Top | Article Outline

Intraoperative Management

The goals of intraoperative management for cerebral aneurysm surgery include preventing intraoperative aneurysm rupture, minimizing potential neurologic injury, facilitating surgical exposure, and providing optimal conditions for smooth emergence and stable recovery.

Back to Top | Article Outline

Anesthetic Monitoring and Management

Premedication. In patients presenting for aneurysm surgery with decreased levels of consciousness (Grades III-V), significant anxiety is unlikely. Sedative premedication is not required in these patients. Grades I and II patients may require only a reassuring preoperative visit. Heavy sedation hinders preoperative neurologic assessment and depresses ventilation. Depression of ventilation may produce hypercarbia with corresponding increases in CBF and ICP. If preoperative sedation is required to prevent potential hemodynamic perturbations associated with anxiety, a small dose of a benzodiazepine is usually sufficient. If the patient is at increased risk for aspiration due to decreased level of consciousness, prophylactic administration of drugs that reduce gastric acidity and volume should be given prior to induction.

Monitoring. Adequate monitoring should be established prior to maneuvers that are likely to alter CBF, ICP, and transmural aneurysmal pressure. Induction of anesthesia and laryngoscopy are critical events that directly influence intracranial physiology. Intraarterial blood pressure monitoring is particularly useful as an early detector of hemodynamic alterations. Many clinicians prefer to place an intraarterial catheter with local anesthesia prior to induction so that blood pressure responses can be assessed continuously. Central venous access is helpful in assessing volume replacement needs prior to aneurysm clipping and in managing hypervolemic therapy in patients at risk for vasospasm. Rapid titration of vasoactive medications can be best achieved through a central venous catheter. There is a poor correlation between central venous and left ventricular end-diastolic pressure in SAH [73]. Therefore, placement of a pulmonary artery catheter may be more helpful in assessing perioperative volume status and cardiac dysfunction than a central venous catheter. If the use of barbiturate coma is anticipated, the additional information derived from a pulmonary artery catheter may be helpful in managing the hemodynamic alterations that occur with this technique [74]. Central venous access is usually accomplished after induction of anesthesia to minimize stress to the patient.

Intraoperative neurologic monitoring may be helpful in patients undergoing aneurysm surgery. Somatosensory evoked potentials detect reversible ischemia during temporary vessel occlusion [75]. Somatosensory evoked potential monitoring for cerebral ischemia during temporary vessel occlusion is limited by its inability to detect ischemia in the motor cortex, subcortical structures, and sensory regions not topographically represented by the stimulated peripheral nerve. Studies demonstrate relatively high falsepositive (38%-60%) and false-negative (5%-34%) detection rates [74-78]. Posterior circulation aneurysms appear best suited to brainstem auditory evoked potential monitoring [79], but may also benefit from somatosensory evoked potential monitoring [80]. Intraoperative electroencephalographic (EEG) monitoring may also be helpful for detection of cerebral ischemia during aneurysm surgery. The probability of increased ICP during the first 24-48 h after SAH is high. Some groups monitor ICP intraoperatively with intraventricular catheters [81]. This allows intraoperative CSF drainage to improve operating conditions and management of elevated ICP.

Angiography is a useful diagnostic test when focal neurologic deficits evolve in the intraoperative or perioperative period. Intraoperative cerebral angiography assures complete obliteration of aneurysmal neck and helps recognize clip occlusion of the parent arterial trunk or perforating arterial branches [82]. Repositioning the clip prior to emergence may decrease the incidence of ischemic complications and reduce the need for reoperation.

Induction. Rupture of an aneurysm during induction is associated with a mortality approaching 75% [83]. Although it seems appropriate to maintain lower blood pressures during induction to prevent abrupt increases in transmural pressure, significant reductions in CPP cause focal and global neurologic deficits in animal models [84]. This is particularly relevant to the patient with SAH who may have impaired autoregulation [85] and vasospasm. Decreases in CPP for brief periods during induction are probably less detrimental than sudden increases in transmural pressure.

To avoid increases in transmural pressure, the sympathetic response to laryngoscopy and intubation must be attenuated, while preventing coughing and straining. Anesthesia is usually induced with thiopental (3-5 mg/kg), although propofol (1.5-2.5 mg/kg) and etomidate (0.1-0.2 mg/kg) are reasonable alternatives [86-88]. These drugs demonstrate similar effects on reducing transmural pressure and cerebral metabolism. Narcotics are usually added to the induction sequence to blunt the hemodynamic response to laryngoscopy and intubation. Fentanyl (5-10 micro gram/kg) or sufentanil (0.5-1.0 micro gram/kg) are commonly given 3-5 min prior to laryngoscopy to deepen anesthesia and attenuate sympathetic responses [89]. Increases in transmural pressure during intubation can be further attenuated by coincident hyperventilation with isoflurane or by addition of intravenous lidocaine (1.5-2.0 mg/kg), esmolol (0.5 mg/kg), or labetalol (10-20 mg) 90 s prior to laryngoscopy [90-92].

The indication for rapid sequence induction of the anesthesia in the patient with an unclipped cerebral aneurysm is controversial. The incidence of clinically significant aspiration is 0.05% during general anesthesia [93]. The incidence of aneurysm rupture during induction is in the range of 1%-2% [94]. Therefore, careful consideration should be given to the risks and benefits prior to choosing a classic rapid sequence technique.

Maintenance. The hemodynamic goals during maintenance are similar to those during induction. Ideally, a maintenance drug should allow rapid and reversible titration of blood pressure, protect against cerebral ischemia, minimize formation of cerebral edema, allow control of ICP, and provide for rapid emergency. Commonly, anesthesia is maintained with combinations of oxygen, nitrous oxide, narcotic, isoflurane, and nondepolarizing muscle relaxant. As with induction, choosing a particular drug is less important than matching anesthetic depth to the level of surgical stimulation. Maintaining stable hemodynamic responses to the varying level of stimulation may be particularly important in preventing aneurysm rupture. Painful stimuli (e.g., pin insertion), should be anticipated and adverse hemodynamic responses prevented by additional anesthesia and/or sympathetic blockers. Local anesthetic infiltration at the Mayfield pin sites before application can reduce the hemodynamic response [95].

Intraoperative fluid administration is governed by the patient's maintenance requirements, urine volume, blood loss, and measured cardiac filling pressures if central venous access has been established. Profound hypovolemia should be avoided in patients with SAH, as it can be associated with cerebral ischemia and perioperative neurologic deficits, especially if associated with vasospasm [96]. In fact, several authors recommend prophylactic hypervolemic therapy prior to and during aneurysm clipping to maximize CBF and minimize the detrimental effects of perioperative cerebral vasospasm [97,98]. Dextrosecontaining solutions should probably be avoided as there is an increased incidence of neurologic deficits associated with hyperglycemia and focal cerebral ischemia in experimental models [99]. Hypoosmolar solutions may induce hyponatremia, which is associated with increased incidence of delayed ischemic neurologic deficits [100].

Maintenance of adequate cerebral perfusion is imperative intraoperatively. Although increases in CPP increase transmural pressure and may predispose to aneurysm rupture, this concern is much less important after the aneurysm has been secured. The acceptable upper limit of arterial blood pressure that is safe after the aneurysm has been clipped has not been systematically evaluated. Arterial blood pressure tends to increase spontaneously when anesthetic levels are decreased after clip placement in volume-replete patients. This increase in pressure may be beneficial by increasing CPP and CBF [101], especially in patients with potential vasospasm. Reasonable outcomes were observed when systolic blood pressures of 160-200 mm Hg were maintained after aneurysm clipping in one study that included 42 patients with suspected vasospasm [94]. Before aneurysm clipping, the systolic blood pressure was kept between 120 and 150 mm Hg. In some patients, however, the elevation in blood pressure can be considerable and may damage the blood-brain barrier leading to the formation of vasogenic edema. Systolic pressure above 240 mm Hg; or a mean pressure greater than 150 mm Hg, may warrant pharmacologic reduction to prevent formation of vasogenic edema due to breakthrough of autoregulation [40,102]. Mitigating factors that should be considered in the management of blood pressure once an aneurysm is secured include evidence of ischemic coronary disease and the possibility of multiple cerebral aneurysms [103].

Emergence. The primary goals during emergence are to avoid coughing, straining, hypercarbia, and wide fluctuations in blood pressure. All anesthetic drugs should be discontinued, the patient should be well oxygenated, and residual neuromuscular blockade should be reversed. Intravenous administration of 1.5 mg/kg of lidocaine a few minutes prior to extubation may minimize coughing. Blood pressure should be reduced pharmacologically if there is evidence of cardiac ischemia, pulmonary edema, or excessive prolonged blood pressure elevation. In patients with multiple or unclippable aneurysms, blood pressure should be kept within 20% (120-160 mm Hg) of normal.

SAH Grade I or II patients usually do not require postoperative ventilation or airway support. It may not be possible to extubate Grade III patients after surgery, depending on their level of consciousness at emergence and preoperative ventilatory status. Grade IV and V patients often require postoperative ventilation. Patients with surgical clipping of vertebral-basilar aneurysms may require postoperative airway support because of injury to swallowing or airway protective reflexes.

If the patient does not return to preoperative neurologic status, any residual effects of anesthetics should be reversed, including neuromuscular blocking agents, narcotics, and sedative drugs. After elimination of anesthetics as a cause for poor emergence, a thorough diagnostic evaluation should be undertaken. Metabolic causes of poor emergence include hypoxia, hypercarbia, and hyponatremia. Although epileptic seizure activity is usually obvious from clinical examination, subclinical status epilepticus is a possible cause of delayed emergence and should be evaluated by diagnostic electroencephalography (EEG). A CT scan is imperative to rule out subdural hematoma, hydrocephalus, pneumocephalus, and intracranial hemorrhage. A cerebral angiogram may be helpful in ruling out the possibility of vascular occlusion.

Back to Top | Article Outline

Special Problems and Techniques

Hyperventilation, Dehydration, and CSF Drainage. Reduction of cerebral blood volume may be needed to decrease ICP to facilitate dural opening. Hyperventilation can be used to decrease cerebral blood volume and improve brain relaxation. The rapid reductions in ICP that occur with hyperventilation should be avoided prior to opening the dura because of the risk imposed by suddenly decreasing transmural pressure. After dural opening, PaCO2 can be adjusted to produce optimal brain compliance for surgical exposure. In patients with suspected vasospasm, the risk of ischemic injury associated with profound hyperventilation is unknown, but theoretically may be increased. Mild hypocarbia (PaCO2 30-35 mm Hg) can be instituted prior to dural opening, with moderate hypocarbia (PaCO2 25-30 mm Hg) introduced after the dura is opened. Normocarbia may be appropriate during induced hypotension, especially in patients with vasospasm, and once the aneurysm has been secured [104].

The osmotic diuretic mannitol, commonly administered intraoperatively to reduce brain tissue water, causes an immediate and transient increase in intravascular volume and CBF. The onset of action is within 10-15 min, with the peak decrease in ICP and cerebral blood volume at 60-90 min [105]. The dose varies between 0.25 and 1.0 g/kg depending on the urgency of decreasing ICP and the estimated duration of requirement for this reduction. Timing of administration should target onset of action to coincide with dural opening so that increases in transmural pressure can be avoided [106]. Rapid infusion of mannitol may cause transient but significant reductions in systemic vascular resistance that can be detrimental [107]. Because mannitol can produce acute volume overload in patients with impaired cardiac function, furosemide, which does not lead to increases of either ICP or intravascular volume, can be substituted in a dose of 0.25-0.5 mg/kg intravenously. Furosemide is often included in the dehydration regimen to potentiate the action of mannitol [108]. When diuretics are used, significant fluid and electrolyte abnormalities can occur. Volume status and electrolyte values must therefore be closely monitored and managed appropriately.

CSF drainage through a lumbar subarachnoid or ventricular catheter rapidly and effectively reduces brain bulk and facilitates surgical exposure. During placement of CSF drains, it is important to avoid significant CSF leakage to prevent sudden decreases in ICP with resulting elevation of transmural pressure. The rate of CSF drainage should be reduced if significant hemodynamic changes occur during free flow from the catheter. CSF should not be drained prior to dural opening.

Controlled Hypotension. Controlled hypotension is used to decrease transmural aneurysmal wall tension, thereby making the aneurysm neck more malleable for clip placement. The most common drugs used are isoflurane and sodium nitroprusside [109]; other drugs that have been used successfully include adenosine, labetolol, esmolol, trimetaphan, nitroglycerin, and prostaglandin E1[110-113]. The safe limit of controlled hypotension is unknown. The autoregulation of CBF is maintained to a perfusion pressure of 50 mm Hg in normotensive individuals. However, several studies have demonstrated favorable outcomes even when MAP was maintained at levels below 50 mm Hg [114]. Neurologic function monitoring, such as EEG or somatosensory evoked potentials, may be necessary to avoid decreases in CBF leading to ischemia in chronically hypertensive patients who have increased lower limits of CBF autoregulation.

Patients with SAH may be at increased risk of focal cerebral ischemia during induced hypotension due to perioperative cerebral vasospasm and impaired autoregulation [115,116]. In patients with preoperative angiographic evidence of vasospasm, a significant decrease in CBF can be demonstrated during controlled hypotension [117]. Detrimental effects of hypotension and brain retraction have been observed in humans [118]. Other sequelae of controlled hypotension include coronary ischemia, inhibition of hypoxic pulmonary vasoconstriction, reduced hepatic and renal blood flow, and hyperglycemia [119-123].

Despite its relatively common use, the ability of induced hypotension to prevent intraoperative rupture has not been systematically evaluated. One retrospective investigation failed to show any reduction in the incidence of intraoperative rerupture with the use of deliberate hypotension [124]. Therefore, the indications for profound deliberate hypotension (less than 50 mm Hg) are less clear. Perhaps a more pragmatic approach would be to reserve profound hypotension for control of intraoperative rupture or for brief periods at the time of clip application [125].

Temporary Vessel Occlusion. Local decreases in transmural pressure can be achieved by occlusion of the aneurysm's feeding vessels with temporary clips. The advantages include more effective reduction of transmural pressure, reduced intraoperative rupture, technically easier clipping, and reduced requirement for controlled hypotension [126]. There is considerable controversy concerning the techniques and duration of temporary arterial occlusion. The critical threshold for conversion of temporary cerebral ischemia to permanent focal cerebral infarction is unknown. A recent study concluded that 15-20 min of temporary occlusion is a critical threshold for the development of postoperative cerebral infarctions [127]. In contrast, other series have reported safe time limits of up to 120 min [126,128-130]. If temporary occlusion involves ischemia to major deep nuclei or the brainstem, temporary clip application times of less than 10 min may be more appropriate [131]. Several risk factors that predispose patients to new neurologic deficits after temporary vessel occlusion include age >61 yr, poor neurologic condition before surgery (Hunt and Hess Grades 3-4), and distributions of the perforating arteries of the distal basilar and horizontal segment of the middle cerebral artery [127]. Controlled trials using hypothermia, cerebral protectants, or induced hypertension have not been performed during temporary feeding vessel occlusion.

Intraoperative Cerebral Protection. Barbiturates have been widely investigated to provide intraoperative protection during aneurysm surgery [132]. Barbiturates decrease CBF, ICP, and metabolic rate. Although animal investigations have shown that barbiturates can protect against focal ischemia, the few uncontrolled human series in aneurysm surgery have not demonstrated improvement in morbidity or mortality [133]. In addition, the large doses required to suppress EEG activity and significantly reduce the cerebral metabolic rate can produce profound cardiovascular depression [134]. Etomidate has a more stable hemodynamic profile and has been used during aneurysm surgery to provide a similar cerebral hemodynamic profile [135]. Like barbiturates, etomidate decreases cerebral metabolic rate electrical activity leading to EEG burst suppression [136]. Etomidate has also been shown to prevent increases in excitatory neurotrans-mitters during cerebral ischemia [137]; its protective role compared to other anesthetics is unclear [138]. One report concluded that etomidate provided significant cerebral protection during aneurysm surgery when temporary clips were used [135], but the reported incidence of good outcome (71%) was not appreciably different from that reported by the Cooperative Study on the Timing of Aneurysm Surgery [15]. Propofol's cerebral hemodynamic profile is similar to that of both barbiturates and etomidate. Like these drugs, it can cause burst suppression. Animal studies have been equivocal in demonstrating cerebral protective effects [139,140]. A uncontrolled human study that included 42 patients who received propofol during temporary clip occlusion and aneurysm clipping had favorable outcomes [87]. In primates, isoflurane has been shown to possess inferior cerebral protective effects compared to the barbiturates [141].

Intentional hypothermia has been proposed as a means of providing cerebral protection during cerebral aneurysm surgery. Hypothermia causes a reduction in cerebral metabolism by decreasing all cell functions, both those related to neuronal electrical activity and those responsible for the maintenance of cellular integrity. In contrast, barbiturates decrease cerebral metabolism only by reducing or eliminating electric activity. In addition, mild hypothermia has been shown to decrease the release of substrates associated with tissue injury like glutamate and aspartate [142]. Profound hypothermia (<22 degrees C) and circulatory arrest with cardiopulmonary bypass has been used successfully in the surgical treatment of giant intracranial aneurysms [143]. Despite some encouraging results in the repair of complex giant aneurysms, the complicated methodology and potentially harmful sequelae of deep hypothermia and systemic anticoagulation inhibit widespread application. More recently, a significant protective effect has been demonstrated using mild hypothermia (33-35 degrees C) in animals subjected to both global and focal ischemia [142,144-150]. Whether milder levels of hypothermia are beneficial during aneurysm surgery is unknown. An increased incidence of myocardial ischemia has been demonstrated in peripheral vascular surgery patients subjected to unintentional mild hypothermia [151]. Controlled studies in aneurysm surgery patients exposed to intentional mild or moderate hypothermic conditions are needed before the routine use of hypothermia can be recommended.

Intraoperative Rupture. Aneurysmal rupture may occur during induction of anesthesia or during the operative procedure. The incidence of intraoperative rupture is 2%-19% [152]. The stage in the operative procedure at which the rupture occurs influences the severity of the outcome. Sudden sustained increases in blood pressure, with or without bradycardia, suggest the possibility of aneurysm rupture. Alterations in hemodynamic variables may be subtle when the patient is anesthetized. One report used transcranial Doppler ultrasound to detect aneurysm rupture immediately after induction [153]; this information was used clinically to manage intracranial hypertension. In most circumstances when aneurysmal rupture is suspected during induction, the surgery is postponed to allow reassessment of the neurologic status and prognosis. Therapy should be instituted to control ICP and maintain cerebral perfusion. Some centers have demonstrated good results with "rescue clipping" of an aneurysm that ruptures at the time of induction [94].

Rupture occurring during aneurysm dissection usually has a lower mortality than that occurring during induction. The immediate anesthetic goals after rupture are to maintain adequate systemic perfusion and facilitate prompt surgical control of bleeding. Bleeding during repair of the aneurysm does not change morbidity if it is quickly controlled [103]. However, if significant amounts of blood enter the subarachnoid space, intraoperative rupture has resulted in marked brain swelling, which tends to be refractory to steroids and diuretics. Rapid induction of hypotension to achieve a MAP of 40-50 mm Hg may reduce bleeding enough to clip the aneurysm. If this method does not reduce bleeding enough, brief periods of manual compression of the ipsilateral carotid may be considered for an anterior circulation aneurysm. The induction of hypotension to control bleeding may be associated with a worsened neurologic outcome compared to maintaining CPP and controlling bleeding with the placement of temporary clips [154].

Back to Top | Article Outline


SAH is a complex illness embodying more than the simple rupture of an intracranial aneurysm. Operative planning should involve understanding of the unique impact of SAH on the cardiovascular system. The primary goals of intraoperative management are to prevent sudden changes in transmural aneurysmal pressure and significant reductions in CBF. Special techniques may be necessary to monitor and minimize neurologic injury intraoperatively. Insightful operative management by the anesthesiologist facilitates successful postoperative care by intensivists and neurosurgeons.

Back to Top | Article Outline


1. Symonds CP. Spontaneous subarachnoid hemorrhage. Q J Med 1924;18:93-123.
2. Dott NW. Intracranial aneurysms: cerebral arterio-radiography: surgical treatment. Edinburgh Med J 1933;40:219-34.
3. Dandy WE. Intracranial aneurysms of the internal carotid artery. Ann Surg 1938;107:654-9.
4. Sacco RL, Wolf PA, Bharucha NE, et al. Subarachnoid hemorrhage: natural history, prognosis and precursive factors in the Framingham study. Neurology 1984;34:847-54.
5. Kassell NF, Torner JC. Epidemiology of intracranial aneurysms. Int Anesthesiol Clin 1982;20:13-7.
6. Inagawa T, Hirano A. Autopsy study of unruptured incidental intracranial aneurysms. Surg Neurol 1990;34:361-5.
7. Phillips LH, Whisnant JP, O'Fallon WM, Sundt TM. The unchanging pattern of subarachnoid hemorrhage in a community. Neurology 1980;30:1034-40.
8. Ishii R, Kuroki M, Tanaka R, et al. Subarachnoid hemorrhage of unknown cause: clinical study. Neurol Med Chir 1983;23:262-6.
9. Hashimoto N, Choegon K, Kikuchi H, et al. Experimental induction of cerebral aneurysms in monkeys. J Neurosurg 1987;67:903-5.
10. Acheson RM, Williams DRR. Epidemiology of cerebrovascular disease: some unanswered questions. In: Rose FC, ed. Clinical neuroepidemiology. Bath, UK: Pitman Press, 1980:84-104.
11. Locksley HB. Report on the cooperative study of intracranial aneurysms and subarachnoid hemorrhage, Sect 5, p 1. Natural history of subarachnoid hemorrhage, intracranial aneurysms, and arteriovenous malformations. J Neurosurg 1966;25:219-39.
12. Tuttleman RM, Gleicher N. Central nervous system hemorrhage complicating pregnancy. Obstet Gynecol 1981;58:651-6.
13. Norrgaard O, Angqvist KA, Fodstad H, et al. Intracranial aneurysms and heredity. Neurosurgery 1987;20:236-9.
14. Garnaway WM, Whisnant WP, Dury I. The continuing decline in the incidence of stroke. Mayo Clin Proc 1983;58:520-3.
15. Kassell NF, Torner JC, Haley C, et al. The International Cooperative Study on the timing of aneurysm surgery: part 1: overall management results. J Neurosurg 1990;73:18-32.
16. Kassell NF, Torner JC, Jane JA, et al. The international cooperative study on the timing of aneurysm surgery, II: surgical results. J Neurosurg 1990;73:37-47.
17. Rinkel GJE, Wijdicks EFM, Ramos LMP, Van Gijn J. Outcome in perimesencephalic (nonaneurysmal) subarachnoid hemorrhage: a follow up study in 37 patients. Neurology 1990;40:1130-2.
18. Rinkel GJE, Wijdicks EFM, Hasan D, et al. Outcome in patients with subarachnoid hemorrhage and a negative angiography according to pattern of hemorrhage on computed tomography. Lancet 1991;338:964-8.
19. Jackobsen M, Enevoldsen E, Bjerre P. Cerebral blood flow and metabolism following subarachnoid hemorrhage: cerebral oxygen uptake and global blood flow during the acute period in patients with subarachnoid hemorrhage. Acta Neurol Scand 1980;82:174-83.
20. Grubb RL, Raichle ME, Eichling JO, Godo MH. Effects of subarachnoid hemorrhage on cerebral blood volume, blood flow, and oxygen utilization in humans. J Neurosurg 1977;46:446-53.
21. Asano T, Sano K. Pathogenetic role of no-reflow phenomenon in experimental subarachnoid hemorrhage in dogs. J Neurosurg 1977;46:454-66.
22. Ames A. Incidence and significance of vascular occlusion in focal and diffuse ischemia. In: Langfitt TW, McHenry LC, Reivich M, eds. Cerebral circulation and metabolism. New York: Springer-Verlag, 1975:551-4.
23. Volby B, Enevoldsen EM, Jensen FT. Cerebrovascular reactivity in patients with ruptured intracranial aneurysms. J Neurosurg 1985;62:59-63.
24. Jennett B, Bond M. Assessment of outcome after severe brain damage: a practical scale. Lancet 1975;1:480-4.
25. Botternell EH, Lougheed WM, Scott JW, Vandewater SL. Hypothermia and interruption of the carotid or carotid and vertebral circulation in the surgical management in intracranial aneurysms. J Neurosurg 1956;13:1-43.
26. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968;28:14-20.
27. Anonymous. Report of World Federation of Neurological Surgeons Committee on a universal subarachnoid hemorrhage grading scale. J Neurosurg 1988;68:985-6.
28. Cruickshank JM, Neil-Dwyer G, Stott AW. Possible role of catecholamines, corticosteroids, and potassium in the production of electrocardiographic abnormalities associated with subarachnoid hemorrhage. Br Heart J 1974;36:697-706.
29. Marion DW, Segal R, Thompson ME. Subarachnoid hemorrhage and the heart. Neurosurgery 1986;18:101-6.
30. Doshi R, Neil-Dwyer G. A clinicopathologic study of patients following a subarachnoid hemorrhage. J Neurosurg 1980;52:295-301.
31. Geenhoot JH, Reichenbach DD. Cardiac injury and subarachnoid hemorrhage. J Neurosurg 1969;30:521-31.
32. Kaste M, Somer H, Konittiner A. Heart type creatinine kinase isoenzyme (CKMB) in acute cerebral disorders. Br Heart J 1978;40:802-5.
33. Davies KR, Gelb AW, Manninen PH, et al. Cardiac function in aneurysmal subarachnoid hemorrhage: a study of electrographic and echocardiographic abnormalities. Br J Anaesth 1991;67:58-63.
34. Pollick C, Bibiana C, Parker S, Tator C. Left ventricular wall motion abnormalities in subarachnoid hemorrhage: an echocardiographic study. J Am Coll Cardiol 1988;12:600-5.
35. Cruickshank JM, Niel-Dwyer G, Degaute JP, et al. Reduction of stress catecholamine-induced cardiac necrosis by beta-selective blockade. Lancet 1987;2:585-9.
36. Neil-Dwyer G, Walter P, Cruickshank JM. Beta-blockage benefits patients following a subarachnoid hemorrhage. Eur J Clin Pharmacol 1984;28(Suppl):25-9.
37. Neil-Dwyer G, Crickshank J, Stastton C. Beta-blockers, plasma total creatinine kinase and creatinine kinase myocardial isoenzymes and prognosis in subarachnoid hemorrhage. Surg Neurol 1986;25:163-8.
38. Grad A, Kiauta T, Osredkar J. Effect of elevated plasma norepinephrine on electrocardiographic changes in subarachnoid hemorrhage. Stroke 1991;22:746-9.
39. Awad IA, Carter LP, Spetzler RF, et al. Clinical vasospasm after subarachnoid hemorrhage: response to hypervolemic hemodilution and arterial hypertension. Stroke 1987;18:365-72.
40. Dernbach PD, Little JR, Jones SC, Ebrahim ZY. Altered cerebral autoregulation and CO2 reactivity after aneurysmal subarachnoid hemorrhage. Neurosurgery 1988;22:822-6.
41. Andreoli A, Dipasquale G, Pinelli G, et al. Subarachnoid hemorrhage: frequency and severity of cardiac arrythmias. A survey of 70 cases studied in the acute phase. Stroke 1987;18:558-64.
42. Koselko P, Punsar S, Sipila W. Subendocardial hemorrhage and ECG changes in intracranial bleeding. BMJ 1964;1:1479-80.
43. Rudehill A, Gordon E, Sundqvist K, et al. A study of ECG abnormalities and myocardial specific enzymes in patients with subarachnoid hemorrhage. Acta Anaesth Scand 1982;26:344-50.
44. Samra SK, Kroll DA. Subarachnoid hemorrhage and intraoperative electrocardiographic changessimulating myocardial ischemia: anesthetist's dilemma. Anesth Analg 1985;64:86-9.
45. Van Gijn J, Van Dongen KJ. The time course of aneurysmal haemorrhage on computed tomograms. Neuroradiology 1982;23:153-6.
46. Wein B, Miller J, Russell D. Intracranial aneurysms: a clinical, angiographic, and computerized tomographic study. Can J Neurol Sci 1977;4:99-105.
47. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980;6:1-19.
48. Ross J, Masaryk T, Modic M, et al. Intracranial aneurysms: evaluation by MR angiography. AJNR 1990;11:449-55.
49. Sicard J-A. Chromodiagnostic du liquide cephalorachidien dans les hemorragies du nevraxe. Valeur de la teinte juanatre. C R Soc Biol 1901;53:1050-3.
50. Symonds CP. Spontaneous subarachnoid hemorrhage. Q J Med 1924;18:93-122.
51. Barrows LJ, Hunter FT, Banker BQ. The nature and clinical significance of pigments in the cerebral spinal fluid. Brain 1955;78:59-80.
52. Vermeulen M, Hasan D, Blijenberg BG, et al. Xanthochromia after subarachnoid hemorrhage needs no revisitation. J Neurol Neurosurg Psychiatry 1989;52:826-8.
53. Duffy GP. Lumbar puncture in spontaneous subarachnoid hemorrhage. BMJ 1982;285:1163-4.
54. Rinkel GJE, Van Gijn J, Wijdicks EFM. Subarachnoid hemorrhage without detectable aneurysm: a review of causes. Stroke 1993;24:1403-9.
55. Hesselink JR. Investigation of intracranial aneurysm. New York: Springer-Verlag, 1983.
56. Yasargil MG. Unoperated cases. In: Microneurosurgery. Stuttgart, Germany: Georg Thieme Verlag, 1984:329-30.
57. Hernesniemi J, Valalahti M, Niskanen M, et al. One-year outcome in early aneurysm surgery: a 14 years experience. Acta Neurochir (Wien) 1993;122:1-10.
58. Hunt WE. Grading of patients with aneurysms [letter]. J Neurosurg 1977;47:13.
59. Bailes JE, Spetzler RF, Hadley MN, Baldwin H. Management morbidity and mortality of poor-grade aneurysm patients. J Neurosurg 1990;72:559-66.
60. Rosenorn J, Eskesen V, Schmidt K, Ronde F. The risk of rebleeding from ruptured intracranial aneurysms. J Neurosurg 1987;67:329-32.
61. Kassell NF, Torner JC. Aneurysmal rebleeding: a preliminary report from the Cooperative Aneurysm Study. Neurosurgery 1983;13:479-81.
62. Nibbelink DW, Torner J, Henderson WP. Intracranial aneurysms and subarachnoid hemorrhage--report of a randomized treatment study: IV. A regulated bed rest. Stroke 1977;8:202-18.
63. Jane JA, Kassell NF, Torner JC, Winn HR. The natural history of aneurysms and arteriovenous malformations. J Neurosurg 1985;62:321-3.
64. Kassell NF, Haley EC, Torner JC. Antifibrinolytic therapy in the treatment of subarachnoid hemorrhage. Clin Neurosurg 1986;33:137-45.
65. Fodstad H, Forssell A, Liliequist B, et al. Antifibrinolysis with tranexamic acid in aneurysmal subarachnoid hemorrhage: a consecutive controlled clinical trial. Neurosurgery 1981;28:21-3.
66. Nibbelink DW, Torner JC, Henderson WG. Randomized treatment study: drug induced hypotension. In: Sahs AL, Nibbelink DW, Torner JC, eds. Aneurysmal subarachnoid hemorrhage: report of the cooperative study. Baltimore: Urban and Schwarzenberg, 1981:77-106.
67. Brown MF, Benzel EC. Morbidity and mortality associated with rapid control of systemic hypertension in patients with intracranial hemorrhage. J Neurosurg 1990;2:53-5.
68. Jane JA, Winn HR, Richardson AE. The natural history of intracranial aneurysms. Rebleeding rates during the acute and long-term period and implications for surgical management. Clin Neurosurg 1977;24:176-84.
69. Ohman J, Heiskanen O. Timing of operation for ruptured supratentorial aneurysms: a prospective randomized study. J Neurosurg 1989;70:55-60.
70. Yoshimoto T, Uchida K, Kaneko U, et al. Analysis of follow-up results of 1000 intracranial saccular aneurysms with definitive surgical treatment. J Neurosurg 1979;50:152-7.
71. Haley EC Jr, Kassell NF, Torner JC, Participants. The International Cooperative Study on the Timing of Aneurysm Surgery: the North American experience. Stroke 1992;23:205-14.
72. Macdonald RL, Wallace MC, Coyne TJ. The effect of surgery on the severity of vasospasm. J Neurosurg 1994;80:433-9.
73. Haley EC, Kassell NF, Torner JC, et al. A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage. J Neurosurg 1993;78:537-47.
74. Todd MM, Drummond JC, Hoi SU. Hemodynamic effects of high dose pentobarbital: studies in elective neurosurgical patients. Neurosurgery 1987;20:559-63.
75. Momma F, Wang AD, Symon L. Effects of temporary arterial occlusion on somatosensory evoked responses in aneurysm surgery. Surg Neurol 1989;27:343-52.
76. Manninen PH, Lam AM, Nantau WE. Monitoring of somatosensory evoked potentials during temporary arterial occlusion in cerebral aneurysm surgery. J Neurosurg Anesthesiol 1990;2:97-104.
77. Schramm J, Antou K, Gerhard S, et al. Surgical and electrophysiological observations during clipping of 134 aneurysms with evoked potential monitoring. Neurosurgery 1990;26:61-70.
78. Kidooka M, Nakasu Y, Watanabe K, et al. Monitoring somatosensory evoked potentials during aneurysm surgery. Surg Neurol 1987;27:69-76.
79. Lam AM, Keane JF, Manninen PH. Monitoring of brainstem auditory evoked potentials during basilar artery occlusion in man. Br J Anaesth 1985;57:924-8.
80. Manninen PH, Gelb AW, Lam AM, et al. Perioperative monitoring of the electrocardiogram during cerebral aneurysm surgery. J Neurosurg Anesthesiol 1990;2:16-22.
81. Auer LM, Mokry M. Disturbed cerebrospinal fluid circulation after subarachnoid hemorrhage and acute aneurysm surgery. Neurosurgery 1990;26:804-8.
82. Martin N, Doberstein C, Bentson J, et al. Intraoperative angiography in cerebrovascular surgery. Clin Neurosurg 1991;37:312-31.
83. Mendleson CL. The aspiration of stomach contents into the lungs during obstetric anesthesia. Am J Obstet Gynecol 1946;52:191-205.
84. Cole DJ, Drummond JC, Shapiro HM, Zorrow MH. Influence of hypotension and hypotensive technique on the area of profound reduction in cerebral blood flow during focal ischemia in the rat. Br J Anaesth 1990;69:498-502.
85. Farrar JK, Gamache FW, Ferguson GG, et al. Effects of profound hypotension on cerebral blood flow during surgery for intracranial aneurysms. J Neurosurg 1981;55:857-64.
86. Ravassin P, Templehoff R, Modica PA, Bayer-Berger MM. Propofol, thiopental and isoflurane for neurosurgical anesthesia: comparison of hemodynamics, CSF, pressure, and recovery. J Neurosurg Anesthesiol 1991;3:85-95.
87. Ravussin P, Detribulet N, Gianott SL, et al. Total intravenous anesthesia with propofol for burst suppression in cerebral aneurysm surgery--preliminary report of 42 patients. Neurosurgery 1993;32:236-40.
88. Frizzell RT, Meyer YJ, Borchers J, et al. The effects of etomidate on cerebral metabolism and blood flow in a canine model for hypoperfusion. J Neurosurg 1991;74:263-9.
89. Kautto UM. Attenuation of the circulatory response to laryngoscopy and intubation by fentanyl. Acta Anaesth Scand 1982;26:217-20.
90. Hamill JF, Bedford RF, Weaver DC, et al. Lidocaine before endotracheal intubation: intravenous or laryngeal? Anesthesiology 1981;55:578-81.
91. Payne KA, Murray WB, Oosthvizen JHC. Obtunding the sympathetic response to intubation. S Afr Med J 1988;73:584-6.
92. Parnass SM, Rothenburg DM, Kerchberger JP, Ivankovich AD. A single bolus dose of esmolol in the prevention of intubation-induced tachycardia and hypertension in an ambulatory surgery unit. J Clin Anesth 1990;2:215-20.
93. Olsson GL, Hullen B, Hambraeus-Jonzonk K. Aspiration during anesthesia: a computer-aided study of 185,358 anesthetics. Acta Anaesthesiol Scand 1986;30:84-92.
94. Tsementzis SA, Hitchcock ER. Outcome from rescue clipping of ruptured intracranial aneurysm during induction anesthesia and endotracheal intubation. J Neurol Neurosurg Psychiatry 1985;48:160-3.
95. Colley PS, Dunn R. Prevention of the blood pressure response to skull-pin head-holder by local anesthesia. Anesth Analg 1979;58:241-3.
96. Maroon JC, Nelson PB. Hypovolemia in patients with subarachnoid hemorrhage: therapeutic implications. Neurosurgery 1979;4:223-6.
97. Origitano TC, Reichman OH, Anderson DE. Prophylactic hypervolemia without calcium channel blockers in early aneurysm surgery [letter]. Neurosurgery 1992;31:804-6.
98. Solomon RA, Fink ME, Lennichon L. Early aneurysm surgery and prophylactic hypervolemic hypertensive therapy for the treatment of aneurysmal subarachnoid hemorrhage. Neurosurgery 1988;23:669-704.
99. Sieber FE, Smith DS, Traystman RJ, Wollman H. Glucose: a reevaluation of its intraoperative use. Anesthesiology 1987;67:72-87.
100. Hasan D, Wijdicks EFM, Vermeulen M. Hyponatremia is associated with cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Ann Neurol 1990;27:106-8.
101. Origitano TC, Wascher TM, Reichman H, Anderson DE. Sustained increased cerebral blood flow with prophylactic hypertensive, hypervolemic hemodilution ("triple-H" therapy) after subarachnoid hemorrhage. Neurosurgery 1990;27:729-39.
102. Strandgaard S, Mackenzie ET, Sergupta D, et al. Upper limit of autoregulation of cerebral blood flow in the baboon. Circ Res 1974;34:435-40.
103. Sundt TM, Kobayoshi S, Fode NC, Whisnant JP. Results and complications of surgical management of 809 intracranial aneurysms in 722 cases. J Neurosurg 1982;56:753-65.
104. Sullivan HG, Keenan RL, Isrow L. The critical importance of PaCO (2) during intracranial aneurysm surgery. J Neurosurg 1980;52:426-31.
105. Rosenorn J, Westergaard L, Hansen PH. Mannitol induced rebleeding from intracranial aneurysm. J Neurosurg 1983;59:529-30.
106. Fearnside MR, Adams CP. The treatment of raised intracranial pressure following aneurysm surgery. J Neurol Neurosurg Psychiatry 1980;43:957-61.
107. Cote CJ, Greenhow E, Marshall BE. The hypotensive response to rapid intravenous administration of hypertonic solutions in man and rabbit. Anesthesiology 1979;50:30-6.
108. Pollay M, Fullenwider C, Roberts PA, Griffin G. Effect of mannitol and furosemide on blood-brain osmotic gradient and intracranial pressure. J Neurosurg 1983;59:445-52.
109. Lagerkransen M. Controlled hypotension in neurosurgery. J Neurosurg Anesthesiol 1991;3:150-2.
110. Stange K, Lagerkransen M, Sollevi A. Nitroprusside-induced hypertension and cerebral vascular autoregulation in the anesthetized pig. Anesth Analg 1991;73:745-52.
111. Abe K, Iwanaga H, Yoshiya I. Carbon dioxide reactivity and local cerebral blood flow during prostaglandin E1 or nitroglycerin-induced hypotension. Can J Anaesth 1992;39:799-804.
112. Zall S, Eden E, Winso I, et al. Controlled hypotension with adenosine or sodium nitroprusside during cerebral aneurysm surgery: effects on renal hemodynamics, excretory function and renin release. Anesth Analg 1990;71:631-6.
113. Jordon WS, Graves CL, Boyd WA, et al. Cardiovascular effects of three techniques for inducing hypotension during anesthesia. Anesth Analg 1971;50:1059-68.
114. Pinaud M, Savron R, Lelausque JN, et al. Cerebral blood flow and cerebral oxygen consumption during nitroprusside-induced hypotension to less than 50 mmHg. Anesthesiology 1989;70:255-60.
115. Allcock JM, Drake CG. Ruptured intracranial aneurysms--the role of arterial spasm. J Neurosurg 1965;22:21-9.
116. Pickard JD, Matheson M, Patterson J, Wyper D. Prediction of late ischemic complications after cerebral aneurysm surgery by the intra-operative measurement of cerebral blood flow. J Neurosurg 1980;53:305-8.
117. Ruta TS, Mutch WAC. Controlled hypotension for cerebral aneurysm surgery: are the risks worth the benefits? J Neurosurg Anesthesiol 1991;3:153-6.
118. Lownie S, Wu X, Karlik S, Gelb AW. Brain retractor edema during induced hypotension: the effect of the rate of return of blood pressure. Neurosurgery 1990;27:901-6.
119. Yuki K, Kodama Y, Onda J, et al. Coronary vasospasm following subarachnoid hemorrhage as a cause of stunned myocardium. J Neurosurg 1991;75:308-11.
120. Lagerkransen M, Gordon E, Rudehill A. Cardiovascular effects of sodium nitroprusside in cerebral aneurysm surgery. Acta Anaesthiol Scand 1980;24:426-32.
121. Kick O. Vital organ blood flow during deliberate hypotension in dogs. Anesth Analg 1993;77:737-42.
122. Kofke A, Hawkins RA, Davis DW, Biebuyck JF. Comparison of the effects of volatile anesthetics on brain glucose metabolism in rats. Anesthesiology 1987;66:810-3.
123. Kinkor R, Warner DS. Unexpected myocardial ischemia during controlled hypotension. J Neurosurg Anesthesiol 1991;3:136-41.
124. Inomata S, Mizuyama K, Sato S, et al. The effect of deliberate hypotension anesthesia on the prognosis of patients who underwent early surgeries for ruptured cerebral aneurysms. Jap J Anesth 1992;41:207-13.
125. Drummond JC. Deliberate hypotension for intracranial aneurysm surgery: changing practices. Can J Anaesth 1991;38:935-6.
126. Charbel FT, Ausman J, Dias FG, et al. Temporary clipping in aneurysm surgery: techniques and results. Surg Neurol 1991;36:83-90.
127. Samson D, Hunt B, Bowman G, et al. A clinical study of the parameters and effects of temporary arterial occlusion in the management of intracranial aneurysms. Neurosurgery 1994;34:22-7.
128. Jabre A, Symon L. Temporary vascular occlusion during aneurysm surgery. Surg Neurol 1987;27:47-63.
129. Ljunggren B, Saneland H, Brandt L, et al. Temporary clipping during early operation for ruptured aneurysm: preliminary report. Neurosurgery 1983;12:525-30.
130. Suzuki J, Kwak R, Okudaira Y. The safety time limit of temporary clamping of cerebral arteries in the direct surgical treatment of the intracranial aneurysm under moderate hypothermia. Brain Nerve 1973;25:407-16.
131. Rosenorn J, Diemer N. The risk of cerebral damage during graded brain retractor pressure in the rat. J Neurosurg 1985;63:608-11.
132. Spetzler RF, Hadley MN. Protection against cerebral ischemia: the role of barbiturates. Cerebrovasc Brain Metab Rev 1989;1:212-29.
133. Hoff JT, Pitts LH, Spetzler R, Wilson CB. Barbiturates for protection from cerebral ischemia during aneurysm surgery. Acta Neurol Scand 1977;56:158-9.
134. Todd MM, Drummond JC, Hoi SU. Hemodynamic effects of high dose pentobarbital: studies in elective neurosurgical patients. Neurosurgery 1987;20:559-63.
135. Batjer HH, Frankfurt AI, Purdy PD, et al. Use of etomidate, temporary arterial occlusion and intraoperative angiography in surgical treatment of large and giant cerebral aneurysms. J Neurosurg 1989;25:899-903.
136. Frizzel RT, Meyer YJ, Borchers J, et al. The effects of etomidate on cerebral metabolism and blood flow in a canine model for hypoperfusion. J Neurosurg 1991;74:263-9.
137. Koorn R, Brannan TS, Martinez-Tica J, Weinberger J. Effect of etomidate on in vivo ischemic-induced dopamine release in the corpus striatum of the rat: a study using cerebral microdialysis. Anesth Analg 1994;78:73-9.
138. Sano T, Patel PM, Drummond JC, et al. A comparison of the cerebral protective effects of etomidate, thiopental, and isoflurane in a model of forebrain ischemia in the rat. Anesth Analg 1993;76:990-7.
139. Ridenour TR, Warner DS, Todd MM, Gionet TX. Comparative effects of propofol and halothane on outcome from temporary middle cerebral artery occlusion in the rat. Anesthesiology 1992;76:807-12.
140. Gelb AW, Zhang C, Henderson S. A comparison of the cerebral protective effects of propofol, thiopental and halothane in temporary feline focal cerebral ischemia [abstract]. J Neurosurg Anesthesiol 1992;4:318.
141. Nehls DG, Todd MM, Spetzler RF, et al. A comparison of the cerebral protective effects of isoflurane and thiopental during temporary focal ischemia in primates. Anesthesiology 1989;70:678-83.
142. Busto R, Globus MY, Dietrich WD, et al. Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 1989;20:904-10.
143. Solomon RA, Smith CR, Raps EC, et al. Deep hypothermic circulatory arrest for the management of complex anterior and posterior circulation aneurysms. Neurosurgery 1991;29:732-8.
144. Chopp M, Knight R, Tidwell CD, et al. The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat. J Cereb Blood Flow Metab 1989;9:141-8.
145. Minamisawa H, Nordstrom BH, Smith ML, Siesjo BK. The influence of mild body and brain hypothermia on ischemic brain damage. J Cereb Blood Flow Metab 1990;10:365-74.
146. Chopp M, Chen H, Dereski MO, Garcia JH. Mild hyperthermia intervention after graded ischemic stress in rats. Stroke 1991;22:37-43.
147. Kader A, Brisman MH, Maraine N, et al. The effect of mild hypothermia on permanent focal ischemia in the rat. Neurosurgery 1992;31:1056-61.
148. Yamashita K, Eguchi Y, Kajiwana K, Ito H. Mild hypothermia ameliorates ubiquitin synthesis and prevents delayed neuronal death in the gerbal hippocampus. Stroke 1991;22:1574-81.
149. Sano T, Drummond JC, Patel PM, et al. A comparison of the cerebral protective effects of isoflurane and mild hypothermia in a model of incomplete forebrain ischemia in the rat. Anesthesiology 1992;76:221-8.
150. Fischer CM, Roberson GH, Ojemann RG. Cerebral vasospasm with ruptured saccular aneurysms: the clinical manifestations. Neurosurgery 1977;1:245-8.
151. Frank SM, Beattie C, Christopherson R, et al. Unintentional hypothermia is associated with postoperative myocardial ischemia. Anesthesiology 1993;78:468-76.
152. Sundt TM, Whisnant JP. Subarachnoid hemorrhage from intracranial aneurysm surgical management and natural history of disease. N Engl J Med 1978;299:116-22.
153. Calvin CE, Lam AM, Byrd S, Newell DW. The diagnosis and management of a perianesthetic cerebral aneurysmal rupture aided with transcranial Doppler ultrasonography. Anesthesiology 1993;78:191-4.
154. Giannotta SL, Oppenheimer JH, Levy ML, Zelman V. Management of intraoperative rupture of aneurysms without hypotension. Neurosurgery 1991;28:531-5.
© 1995 International Anesthesia Research Society