Perioperative Management of Aneurysmal Subarachnoid Hemorrhage: A Narrative Review

Stroke is the second leading cause of death and third most common cause of disability worldwide.²  In the United States, there are about 795,000 cases of stroke annually.³  A stroke may be hemorrhagic or ischemic. Hemorrhagic strokes account for about 32% of all strokes globally⁴  and 13% of all strokes in the United States.³  Hemorrhagic strokes can be caused by subarachnoid hemorrhage or intracerebral hemorrhage. Most spontaneous (nontraumatic) subarachnoid hemorrhages are caused by ruptured saccular aneurysms. Other causes of subarachnoid hemorrhage include trauma, arteriovenous malformations, vasculitides, intracranial arterial dissections, amyloid angiopathy, bleeding diatheses, and illicit drug use (cocaine and amphetamines). Intracranial aneurysms are estimated to occur with a prevalence of 3.2% in the general population.⁵  The global incidence of aneurysmal subarachnoid hemorrhage is 2 to 16 per 100,000, with an incidence rate in low- and middle-income countries almost double that of high-income countries.⁶  According to the 2003 Nationwide Inpatient Sample, in the United States there were 14.5 discharges for aneurysmal subarachnoid hemorrhage per 100,000 adults annually.⁷  The patients with aneurysmal subarachnoid hemorrhage are significantly younger than those with other types of stroke, and women have 1.24 times greater risk of aneurysmal subarachnoid hemorrhage than men.⁸  Aneurysmal subarachnoid hemorrhage accounts for approximately 5% of strokes.⁹  Despite substantial advancements in the care of patients with aneurysmal subarachnoid hemorrhage, the mortality rates are 32% to 67%, and a third of the survivors remain dependent.¹⁰ 

Aneurysmal subarachnoid hemorrhage results from the rupture of an intracranial aneurysm, an acquired focal abnormal dilation of an arterial wall. Most often, aneurysmal subarachnoid hemorrhage results from the rupture of a saccular (“berry”) aneurysm, while fusiform and mycotic aneurysms may be responsible in some patients. A saccular aneurysm is a thin-walled outpouching of the arterial wall, composed of thin or absent tunica media and absent or fragmented internal elastic lamina. Once believed to be congenital, saccular aneurysms are now recognized as acquired lesions. Hemodynamic stress and turbulent blood flow may lead to damage of the internal elastic lamina, particularly at vascular branching points.¹¹  Patients with hyperdynamic flow patterns, therefore, seem to be more predisposed to aneurysm formation. Hypertension, smoking, and connective tissue disorders are known to exacerbate the vascular damage, thereby increasing the risk of aneurysm development.¹¹  Unruptured intracranial aneurysms occur in 8% individuals with autosomal dominant polycystic kidney disease who are approximately five times more likely than the general population to have an aneurysm.¹²  However, the risk of subarachnoid hemorrhage from the aneurysm is not any greater in these individuals.¹³  Ehlers–Danlos syndrome type IV, neurofibromatosis type 1, Marfan syndrome and coarctation of the aorta are also known to be associated with aneurysmal subarachnoid hemorrhage.⁹ 

About 7% to 20% patients with aneurysmal subarachnoid hemorrhage may have a first- or second-degree relative with intracranial aneurysm.¹⁴  In fact, familial predisposition is a risk factor for aneurysmal subarachnoid hemorrhage.^15,16  Expression of matrix metalloproteinases (MMP) is associated with a predisposition to cerebral aneurysm formation and rupture.¹⁷  Specifically, MMP-2 and MMP-9 levels in the aneurysm wall are increased,¹⁸  and a single nucleotide polymorphism leading to an increased transcription of the MMP-2 gene is associated with the development and rupture of cerebral aneurysms.¹⁹  Some of the known risk factors for aneurysmal subarachnoid hemorrhage include family history, larger aneurysm size, posterior circulation location, history of rupture, and the presence of multiple aneurysms.^20–22  Pregnancy and the peripartum period do not increase the risk of aneurysmal subarachnoid hemorrhage.^23,24 

The initial aneurysmal rupture typically leads to blood quickly traversing through the intracranial cisterns and subarachnoid space within seconds.²⁵  Real-time angiographic visualization of aneurysm rupture has demonstrated dispersion of intracranial blood filling up the ventricles within seconds.²⁵  The subarachnoid hemorrhage may lead to loss of consciousness owing to global cerebral ischemia resulting from increased intracranial pressure (ICP), decreased cerebral perfusion pressure (CPP), and reduced cerebral blood flow. Acute increase in cerebrovascular resistance results in highly pulsatile flow pattern, with much reduced diastolic blood flow velocity on transcranial Doppler ultrasonography and oscillating flow pattern (anterograde flow in systole and retrograde flow in diastole) indicating zero net flow if the ICP surpasses systemic blood pressure.²⁶  Simultaneously, the jugular venous oxygen saturation may acutely decrease.²⁷  Intraventricular bleeding can cause acute ventricular dilatation and hydrocephalus.²⁵  Timely restoration of cerebral perfusion by the placement of external ventricular drain often improves the patient’s neurologic status almost immediately. Brain tissue oxygen pressure and pH are also reduced.²⁸  A compensatory sympathetic response involving systemic hypertension ensues within minutes.²⁵  Vasoactive mediators such as thromboxane and serotonin are released within minutes to hours of subarachnoid hemorrhage, leading to microcirculatory constriction.²⁹  Blood–brain barrier disruption, cerebral edema, and a thromboinflammatory cascade ensue soon thereafter.^30,31  Within hours or days, transient ischemic events increase the cerebrospinal fluid (CSF) level of endothelin-1.²⁹  These mechanisms combined with the phosphorylation of vascular endothelial growth factor and mitogen-activation protein kinase in the intracranial arteries cause the early brain injury.³²  The delayed cerebral ischemia may be the manifestation of interplay of pathophysiologic phenomena, including loss of cerebrovascular autoregulation, cerebral vasospasm, microvascular thrombosis, neuroinflammation, and cortical spreading depolarization.³³  The elimination of blood clot within the subarachnoid space starts typically 3 days after subarachnoid hemorrhage, releasing oxyhemoglobin from the erythrocytes, leading to decreased levels of nitric oxide and contributing to delayed cerebral vasospasm.^29,30  Blood in cerebral cisterns can occlude arachnoid granulations, preventing reabsorption of CSF and thereby leading to delayed hydrocephalus a few weeks after the aneurysmal subarachnoid hemorrhage.

The classic clinical presentation of aneurysmal subarachnoid hemorrhage involves sudden onset of “worst headache of life.” Half of the patients lose consciousness. Some patients report an unusual headache several weeks before the acute presentation, representing a minor leak of blood into the wall of an aneurysm or the subarachnoid space.⁹  Such sentinel bleeds can worsen delayed cerebral ischemia. The patients also often have nausea and/or vomiting, nuchal rigidity, or photophobia.^9,34  Seizures occur in 6% to 16% patients, especially those with greater clot burden and subdural hematoma.^35–38  A posterior communicating artery aneurysm may present as isolated third cranial nerve palsy with pupillary dysfunction. Patients may be comatose and hypertensive at presentation.

The severity of aneurysmal subarachnoid hemorrhage is clinically categorized using Hunt and Hess Score³⁹  or World Federation of Neurological Surgeons (WFNS) grading systems.⁴⁰  The Hunt and Hess grading system (table 1) is most commonly used.³⁹  Originally proposed as an index of surgical risk with the risk increasing from grades 1 to V, the clinical grade correlates with the severity of hemorrhage. A subsequent modification added grade 0 for unruptured aneurysms and grade 1a for a fixed neurologic deficit without other signs of subarachnoid hemorrhage.⁴¹  Anesthesiologists should familiarize themselves with these grading systems because the severity of aneurysmal subarachnoid hemorrhage classified by these systems is also associated with the extent of impairment of cerebrovascular homeostasis and the severity of extracranial manifestations impacting other organ systems.

The Fisher scale (table 2) is a useful index of vasospasm risk after aneurysmal subarachnoid hemorrhage, although it does not necessarily correlate with clinical outcome.⁴²  It is based on the distribution and amount of blood on the initial computed tomography scan. The modified Fisher scale (Claassen grading system, table 2) accounts for the separate and additive risk of subarachnoid hemorrhage and intraventricular hemorrhage and involves evaluation of 10 cisterns or fissures.⁴³  A higher grade typically predicts delayed cerebral ischemia. Other less popular grading systems include the VASOGRADE scale (based on the WFNS scale and modified Fisher scale) and the Ogilvy and Carter system (based on the patient’s age, Hunt and Hess and Fisher grades, and the aneurysm size).^44,45 

A computed tomography scan can identify the extravasated blood in the basal cisterns. Lumbar puncture is useful in confirming the diagnosis when the computed tomography scan is unremarkable. Xanthochromia resulting from breakdown of hemoglobin in the CSF is typically detectable 12 h after the clinical presentation. A computed tomography angiogram is needed to identify the aneurysm and guide therapeutic intervention. Digital subtraction angiography with three-dimensional reconstructions provides detailed assessment of anatomy of the aneurysm, which informs treatment decision and provides information about collateral channels. The anesthesiologists may be called upon to assist in these diagnostic procedures if the patient has poor neurologic status or associated complications.

Early management after aneurysmal subarachnoid hemorrhage is directed at stabilizing life-threatening conditions, minimizing neurologic injury, optimizing physiology and planning definitive care. Broad goals of early management include (1) maintenance of oxygenation and ventilation; (2) rapid restoration of cerebral perfusion; (3) prevention of rebleeding; (4) seizure prophylaxis; (5) initiation of nimodipine, and; (6) planning timely definitive care.⁴⁶ 

Hypoxia worsens brain injury and is avoidable.⁴⁷  Lower brain tissue oxygen tension and longer periods of cerebral oxygen desaturation are associated with mortality after aneurysmal subarachnoid hemorrhage.⁴⁸  Both hypo and hypercarbia are associated with unfavorable neurologic outcomes.⁴⁹  Hypocarbia-induced cerebral vasoconstriction may worsen cerebral ischemia, particularly in the presence of elevated ICP. Hypercarbia contributes to poor outcomes owing to cerebral vasodilation leading to intracranial hypertension and reduced cerebral perfusion. It is essential to ensure a patent airway and adequate oxygenation and ventilation. Patients who regain consciousness after the aneurysmal subarachnoid hemorrhage may not require interventions beyond administration of supplemental oxygen. Tracheal intubation and mechanical intubation is required if (1) the patient remains comatose and is unable to protect his/her airway; (2) there is hypoxia or hypoventilation; (3) patient is hemodynamically unstable, or; (4) there is need for heavy sedation and/or pharmacologic paralysis to keep the patient safe (e.g., owing to excessive agitation during imaging or external ventricular drain placement).

Patients with aneurysmal subarachnoid hemorrhage may be obtunded on presentation because of acutely increased ICP. Early placement of an external ventricular drain to treat aneurysmal subarachnoid hemorrhage–related hydrocephalus to restore cerebral perfusion is often the first step in early management.⁵⁰  External ventricular drain–guided management of ICP also facilitates surgical exposure during aneurysm clipping.^51,52  Ventriculomegaly in patients with Glasgow Coma Scale less than or equal to 12 or Hunt and Hess grade greater than or equal to 2 has been recommended as a threshold for external ventricular drain placement,^52–54  although some institutions routinely place external ventricular drain in all symptomatic patients. The absence of neurologic improvement after external ventricular drain placement and normalization of ICP may indicate other treatable factors such as seizures. Excessive or rapid loss of CSF during external ventricular drain placement can acutely increase the transmural pressure leading to rebleeding, and must be avoided.^55,56 

Anesthesiologists are expected to manage the external ventricular drains during perioperative and peri-intervention period, including during transport. Yet, it appears that anesthesiologists are often neither trained in managing external ventricular drains nor aware of standard guidelines for their management.⁵⁷  Careful management of external ventricular drain is essential to ensure adequate management of the ICP and the CPP, preventing over- or under-drainage of CSF and to prevent infective complications. The Society for Neuroscience in Anesthesiology and Critical Care has published guidelines for the perioperative management of patients with external ventricular drains and lumbar drains.⁵⁸  The readers should familiarize themselves with these guidelines (https://www.snacc.org/wp-content/uploads/2017/03/MARCH_27_2017_EVD_LD_SNACC_Education_Document.pdf; accessed August 11, 2020).

Aneurysm rebleeding has high mortality and must be avoided. The risk of rebleeding during the first 24 h is 4% to 13.6%.^59–61  Factors associated with rebleeding include initial loss of consciousness, delayed treatment, worse neurologic status on admission, history of sentinel headaches, larger aneurysm size, and systolic blood pressure greater than 160 mmHg.^60,62  While prioritizing early definitive treatment by surgery or endovascular intervention, it is important that acute hypertension be promptly controlled. Control of headache with analgesics, anxiolysis and bed rest is important. According to the American Heart Association/American Stroke Association guidelines, strict control of blood pressure is necessary after aneurysmal subarachnoid hemorrhage.⁶³  Although the data clearly delineating a blood pressure threshold are lacking, the systolic blood pressure should be maintained at less than 160 mmHg.⁶³  Some suitable pharmacologic choices include nicardipine, esmolol, and clevidipine, although there are no data comparing their relative effectiveness. While treating acute increases in blood pressure, it is critical to avoid hypotension because the benefit of reduced rebleeding with antihypertensive therapy may be potentially offset by increased risk of cerebral infarction.⁶⁴  Brain tissue hypoxia may occur in patients with poor-grade subarachnoid hemorrhage at CPP less than 70 mmHg.⁶⁵ 

Some patients may be on anticoagulants before aneurysmal subarachnoid hemorrhage, which should be stopped and reversed to avoid rebleeding.⁶⁶  Warfarin should be reversed with prothrombin complex concentrate (PCC) and vitamin K. Fresh frozen plasma can be used in the absence of PCC. Idarucizumab, a monoclonal antibody fragment, is the specific reversal agent for dabigatran.⁶⁶  When Idarucizumab is not available, four-factor PCC or activated PCC may be used.⁶⁶  No specific reversal agent is currently available for the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban.

Short-term (less than 72 h) use of antifibrinolytic aminocaproic acid or tranexamic acid is allowable to reduce the risk of rebleeding if a delay in the definitive treatment of the aneurysm is unavoidable.^63,67  Although this does not increase the risk of delayed cerebral ischemia, the risk of deep venous thrombosis may be increased.⁶⁷ 

Although seizures are likely to worsen the neurologic injury after aneurysmal subarachnoid hemorrhage and may precipitate rebleeding, there is lack of consensus around the use of prophylactic anticonvulsant therapy after aneurysmal subarachnoid hemorrhage.^68,69  Initiation of seizure prophylaxis is reasonable in the immediate posthemorrhage period in patients with poor neurologic grade, unsecured aneurysm, and associated intracerebral hemorrhage.⁶³ 

Nimodipine has been convincingly shown to improve outcomes of aneurysmal subarachnoid hemorrhage despite any favorable effect on angiographic or symptomatic vasospasm.^70–75  Possible mechanisms responsible for the effectiveness of nimodipine may include dilation of smaller arteries not visible on angiograms, reduction of calcium-dependent excitotoxicity, and reduced platelet aggregation. Administration of 60 mg nimodipine orally or by nasogastric tube every 4 h, starting within 48 h of aneurysmal subarachnoid hemorrhage and continued for 21 days, is considered a standard of care.⁶³  The dose may have to be reduced or it may have to be discontinued because of the hypotension, especially in patients with higher grades of subarachnoid hemorrhage.^76–78  Because the incidence of delayed cerebral ischemia is increased when nimodipine is interrupted,^77,78  it is recommended to first use vasopressors to treat hypotension. If this is ineffective, dose may be reduced to half and, in cases of refractory hypotension, nimodipine may have to be stopped.

It is imperative that obliteration of the ruptured aneurysm by surgery or endovascular intervention be performed at the earliest possible time.⁶³  However, not all hospitals may be equipped or best suited to achieve the best outcomes. Teaching status, larger patient volumes, and availability of neuro-endovascular and neuro-intensive care facilities are associated with better outcomes in patients undergoing aneurysm clipping.^79–82  Consequently, the current guidelines recommend that to improve the outcomes, the patients with aneurysmal subarachnoid hemorrhage should be transferred early to experienced high-volume centers with the availability of multidisciplinary teams.⁶³ 

A Cochrane review compared endovascular coiling with surgical clipping in patients with aneurysmal subarachnoid hemorrhage to examine the effect on rebleeding, neurologic outcomes, and treatment complications.⁸³  The review included four randomized trials involving 2,458 participants, with the majority of the participants in good clinical condition and having an aneurysm of the anterior circulation. After 1 yr, 24% and 32% of the participants who received endovascular treatment and surgical clipping, respectively, had poor functional outcome (death or dependence in daily activities). The risk ratio of poor outcome for endovascular coiling versus neurosurgical clipping was 0.77 (95% CI, 0.67 to 0.87). Importantly, most patients in this review were from one trial (International Subarachnoid Aneurysm Trial), and long-term (10-yr) follow-up information was not available for all participants.⁸⁴  The risk ratio of delayed cerebral ischemia for endovascular coiling was 0.84 (95% CI, 0.74 to 0.96) in comparison with neurosurgical clipping, risk ratio of rebleeding after 1 yr was 1.83 (95% CI, 1.04 to 3.23), and at 10 yr was 2.69 (95% CI, 1.50 to 4.81).⁸³  Overall, the outcome was better with endovascular coiling in patients in good clinical condition with ruptured anterior or posterior circulation aneurysm amenable to both clipping and coiling.⁸³  Data on higher grade aneurysmal subarachnoid hemorrhage are limited. A prospective, multicenter, observational registry of 366 consecutive patients with WFNS grades IV or V aneurysmal subarachnoid hemorrhage found similar long-term outcome between endovascular coiling and clipping, although the risk of radiologic hydrocephalus was greater after endovascular treatment.⁸⁵ 

With the ongoing rapid advancements in both microsurgical and endovascular approaches, the criteria for patient and aneurysm characteristics for suitability of one approach versus the other are constantly being refined. This partially adds to the difficulty of comparing the relative effectiveness of treatment options. In general, surgical clipping is preferred in patients with large intraparenchymal hematomas, aneurysm of the middle cerebral artery, and in those not likely to be compliant with long-term follow-up. Endovascular treatment is usually preferred in the geriatric patients, particularly those presenting with high-grade aneurysmal subarachnoid hemorrhage from the rupture of basilar apex aneurysm.⁶³  Occasionally, complex aneurysms may have to be treated with trapping and intracerebral bypass surgery using vascular grafts.^86,87 

Given the relative urgency of definitive treatment, the preanesthesia evaluation should be succinct and targeted with the approach to facilitate early, definitive treatment. Table 3 lists major pathophysiological consequences of aneurysmal subarachnoid hemorrhage to guide preanesthesia assessment and to anticipate perioperative course. The evaluation should incorporate clinical grading of aneurysmal subarachnoid hemorrhage using the modified Hunt and Hess or the WFNS grading system (table 1).^39,40  Patients with worse neurologic status and higher-grade aneurysmal subarachnoid hemorrhage are more likely to have raised intracranial hypertension, intraoperative brain swelling, impaired cerebral autoregulation, and impaired cerebrovascular reactivity to carbon dioxide.^88–94  This implies a greater predisposition to cerebral ischemia and hence, the need for strict hemodynamic control, as well as aggressive interventions to reduce intraoperative brain swelling.

Pulmonary complications including neurogenic pulmonary edema, pulmonary embolism, and aspiration pneumonia occur in up to 22% patients.⁹⁵  Neurogenic pulmonary edema occurs more often in patients with ruptured aneurysms of the posterior circulation and is believed to result from the sympathetic surge after severe aneurysmal subarachnoid hemorrhage and the associated inflammatory response.^96–99  Elevated plasma norepinephrine may be primarily contributory to aneurysmal subarachnoid hemorrhage–induced pulmonary edema, although both epinephrine and norepinephrine appear to be involved.¹⁰⁰  Direct irritation of the brainstem, causing a direct neurogenic stimulation of the lungs, has also been suggested as a possible mechanism of neurogenic pulmonary edema.

The risk of stress cardiomyopathy and cardiac arrhythmias is higher in patients with higher-grade aneurysmal subarachnoid hemorrhage.^101,102  In patients with high-grade aneurysmal subarachnoid hemorrhage, myocardial dysfunction resulting from sympathetic hyperactivity should be suspected.¹⁰³  A variety of electrocardiographic abnormalities such as sinus bradycardia, sinus tachycardia, ST segment depression, T-wave inversion, U-waves, and prolonged QT interval occur commonly after aneurysmal subarachnoid hemorrhage.^104,105  Most often, the electrocardiographic abnormalities are neurogenic rather than cardiogenic.^101,106  Myocardial dysfunction with regional wall motion abnormality and Takotsubo cardiomyopathy (“neurogenic stunned myocardium,” transient cardiac syndrome involving left ventricular apical akinesis mimicking acute coronary syndrome) are relatively uncommon.^107–110  In fact, the electrocardiogram abnormalities in patients with aneurysmal subarachnoid hemorrhage are usually not related to left ventricular dysfunction.¹¹¹  Nevertheless, elevated Troponin I and brain natriuretic peptide levels reflect myocardial stunning.^112,113  Possible pathophysiological mechanisms for neurogenic stunned myocardium include hypothalamic and myocardial perivascular/microvascular lesions associated with a catecholamine surge.^106,114,115 , The management of cardiac dysfunction remains largely supportive with judicious use of inotropes. Electrocardiographic changes, especially in hemodynamically stable patients, should not delay urgent surgery for further investigations. Interestingly, QTc prolongation, bradycardia, conduction abnormality, and echocardiographic changes recover postoperatively.¹¹⁶  Troponin I levels should be serially monitored in patients with electrocardiogram changes suggestive of myocardial ischemia such as Q-waves and ST elevations, particularly in the presence of hypotension or hemodynamic instability. Urgent aneurysm clipping can proceed safely even in patients with Takotsubo cardiomyopathy although more vigilant perioperative monitoring is needed.¹¹⁰  Although it has not been specifically studied in aneurysmal subarachnoid hemorrhage, there may be a role for point of care echocardiography to guide the choice of vasopressors and inotropes in the perioperative period.

Severe aneurysmal subarachnoid hemorrhage is often associated with hyperglycemia requiring insulin administration.^117–119  In addition, the patients may be hypovolemic.^120,121  Cerebral salt wasting is typically responsible for hyponatremia owing to increased secretion of brain natriuretic peptide with subsequent suppression of aldosterone synthesis.^122–124  However, in aneurysmal subarachnoid hemorrhage with anterior circulation aneurysms, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) may be more common.^125,126  Hypopituitarism-related diabetes insipidus can present as hypernatremia in some patients.¹²⁷  Hypokalemia is also commonly present.¹²⁸  Although the surgery may not be delayed in patients with ruptured aneurysms, the anesthesiologists should initiate the correction of fluid, electrolyte, and glucose derangements. The management of electrolyte abnormalities may be complicated by administration of mannitol or hypertonic saline. Therefore, electrolytes and osmolality of blood and urine may need to be serially monitored. The computed tomography scan should be reviewed for hematoma volume, sulcal effacement, midline shift, and hydrocephalus, which may predict intraoperative brain swelling. The cerebral angiogram should be reviewed to examine the aneurysm as well as to assess collateral cerebral circulation.

Table 4 summarizes recommendations relevant to perioperative management of aneurysmal subarachnoid hemorrhage based on American Heart Association/American Stroke Association guidelines.⁶³ 

Following are the main goals of anesthetic management of craniotomy in aneurysmal subarachnoid hemorrhage:

1. facilitate timely definitive treatment

2. prevention of rebleeding

3. maintain cerebral perfusion

4. prevent/manage intraoperative brain swelling to facilitate surgical exposure

5. facilitate neurophysiological monitoring

6. facilitate temporary clipping

7. optimize systemic physiology and manage glycemia

8. anticipate and manage crisis situations (e.g., aneurysm rupture)

9. facilitate timely, smooth emergence and neurologic assessment

10. prevent postoperative pain and other complications

The anesthetic goals for endovascular intervention are the same as above with the following exceptions: (1) interventions for brain relaxation are not required; (2) the use of neurophysiological monitoring is uncommon; (3) patient immobility, especially during deployment of coils and stents, is critical, and; (4) anticoagulant (heparin) is needed and should be managed safely with preparedness for emergent reversal with protamine if needed.

For complex aneurysms requiring trapping coupled with high-flow arterial or venous grafts and reconstruction surgery, anesthesiologists should be prepared for prolonged temporary occlusion times and potential for major blood loss requiring transfusion.

The primary goal for induction of anesthesia is to prevent hypertension in response to laryngoscopy and tracheal intubation, which can potentially cause rebleeding because of an increase in the aneurysmal transmural pressure (fig. 1). Standard measures to prevent hemodynamic responses should be used. These include increasing the depth of anesthesia, use of antinociceptive strategies (e.g., boluses of fentanyl, remifentanil) and short-acting antihypertensive agents (e.g., esmolol, nicardipine). Rapid sequence induction may be desirable in patients who are actively vomiting or are nauseous. Succinylcholine may be used safely without concerns for increased ICP after ensuring adequate anesthetic depth.^129,130  Although hypertension is detrimental, hypotension is also undesirable given the risk of cerebral ischemia, especially in patients experiencing elevated ICP. Presence of myocardial dysfunction or Takotsubo cardiomyopathy may make patients particularly susceptible to hypotension during induction of anesthesia. Hence, both antihypertensive and vasopressor agents should be readily available. Placement of an arterial line before anesthetic induction allows continuous monitoring of blood pressure and prompt intervention. However, placement of an arterial line itself can cause pain and anxiety with resulting hypertension. In the author’s experience, a preinduction arterial line may not be necessary in all patients with aneurysmal subarachnoid hemorrhage. Blood pressure may be monitored noninvasively every minute and specifically checked after induction of anesthesia, before laryngoscopy and immediately after tracheal intubation. A preinduction arterial line should be placed in patients with concerning cardiac dysfunction, particularly those with elevated troponin values and hemodynamic instability.

It is also necessary to avoid inadvertent hypo- and hypercarbia during bag-mask ventilation. Hypercarbia-induced cerebral vasodilatation may increase ICP and compromise cerebral perfusion. On the other hand, aggressive hyperventilation leading to hypocarbia can acutely reduce ICP, which may increase the transmural pressure (fig. 1) across the aneurysm wall, potentially resulting in rebleeding. If an external ventricular drain is in place, the ICP should be monitored during induction of anesthesia. Sustained hypertension with bradycardia and new-onset pupillary asymmetry after laryngoscopy and intubation may indicate a possible rebleeding.

In addition to the standard American Society of Anesthesiologists monitors, an arterial line is essential not only for continuous hemodynamic monitoring but also to monitor blood gases and pH trends, glucose, and electrolytes. The arterial blood pressure transducer should be placed at the level of external auditory meatus. Central venous cannulation is not necessary unless the patient demonstrates hemodynamic instability and postoperative infusion of vasopressors/inotropes is anticipated. The external ventricular drain should be used to monitor ICP and CPP. It should be referenced at the level of external auditory meatus⁵⁸  and typically left open to drain CSF if the ICP exceeds 20 mmHg. Jugular venous oximetry can detect intraoperative cerebral oxygen desaturation¹³¹  and guide anesthetic interventions such as hyperventilation therapy and management of perfusion pressure, fluids, and oxygenation to optimize the cerebral physiology.^132,133  In the author’s experience, intraoperative jugular oximetry is useful to individualize physiologic parameters to target optimal cerebral oxygenation in patients with high-grade aneurysmal subarachnoid hemorrhage. However, jugular oximetry has not been shown to improve outcomes in aneurysmal subarachnoid hemorrhage and its routine use cannot be recommended.

Monitoring of the electroencephalogram (EEG) may be needed if a decision is made to use burst suppression during temporary clipping. Anesthesiologists can also use raw and processed EEG to titrate the anesthetic dose. Surgical clipping often involves temporary clip placement on the parent vessel for proximal control of the aneurysm. Temporary clipping may cause cerebral ischemia and symptomatic strokes in up to 10% to 12% patients.^134–136  Intraoperative neurophysiologic monitoring involving somatosensory-evoked potentials (SSEPs) and motor-evoked potentials can help in timely detection of cerebral ischemia. Prolongation of central conduction time on SSEPs to greater than 10 ms or a reduction in the amplitude of cortical N20 component of SSEP by greater than 50% is considered clinically significant and indicative of ongoing cerebral ischemia.^134,137,138  These changes allow corrective measures, such as removing/manipulating the clip to restore blood flow to ischemic territory, adjusting the retractor and/or blood pressure augmentation to prevent postoperative neurologic deficits (fig. 2). SSEP monitoring has significant utility in clipping anterior circulation aneurysms because the amplitude of SSEPs reflects perfusion to the middle and anterior cerebral artery territories. A review analyzing data from 14 studies involving more than 2,000 patients reported SSEP monitoring to have a specificity of 84.5% (95% CI, 76.3 to 90.3) and sensitivity of 56.8% (95% CI, 44.1 to 68.6) for predicting stroke.¹³⁸  Additionally, motor-evoked potentials can quickly detect subcortical ischemia during surgery, especially pure motor deficits caused by perforating arteries or large branches.^139,140  For ischemia of short duration, the motor-evoked potential signals typically recover with reposition of the clip. Importantly, the motor-evoked potential amplitude is decreased, and latency is increased during deep anesthesia. In fact, during EEG burst suppression, motor-evoked potentials may not be reliably recorded, limiting their diagnostic accuracy.^141,142 

The ideal anesthetic agent for aneurysmal subarachnoid hemorrhage should (1) reduce the cerebral metabolic rate; (2) avoid intracranial hypertension; (3) maintain adequate cerebral blood flow; (4) maintain hemodynamic stability; (5) provide neuroprotection; (6) not interfere with neurophysiological monitoring, and; (7) be easily titrated to the required anesthetic depth allowing rapid emergence. Obviously, a single agent with all these properties does not exist. Intravenous and inhaled anesthetic agents differ substantially in their pharmacodynamic and pharmacokinetic properties, but both can be judiciously used in aneurysmal subarachnoid hemorrhage. The choice is based on the patient’s neurologic status, proposed procedure (craniotomy or endovascular treatment), coexisting diseases, and the need for neurophysiological monitoring.

It is important to avoid any increase in cerebral metabolic demand in case of possible cerebral ischemia resulting from increased ICP (global ischemia) or temporary artery occlusion (focal ischemia). A reduction in cerebral blood flow coupled with reduction in cerebral metabolic rate is also beneficial is preventing intraoperative brain swelling. Propofol maintains the coupling between cerebral metabolic rate and cerebral blood flow while inhaled anesthetics have a dose-dependent effect on the cerebral blood flow, with higher doses increasing cerebral blood flow despite reducing cerebral metabolic rate.¹⁴³  Inhaled anesthetics typically decrease cerebral blood flow when used in less than 1.0 MAC (minimum alveolar concentration) doses but tend to cause cerebral vasodilation at higher concentrations leading to uncoupling between cerebral blood flow and metabolism.¹⁴³  This may be both advantageous and disadvantageous. High-dose desflurane has been shown to increase brain tissue oxygenation in patients with aneurysmal subarachnoid hemorrhage and to improve brain tissue acidosis in patients with high-grade aneurysmal subarachnoid hemorrhage during temporary clipping.²⁸  Conversely, in patients with increased intracranial elastance (reduced compliance), this “luxury perfusion” can worsen brain swelling.¹⁴⁴  Isoflurane has been shown to cause more cerebral vasodilation than sevoflurane at similar anesthetic concentration.¹⁴⁵  However, the cerebral vasodilatory effect of inhalational agents can be minimized by hyperventilation. On the other hand, institution of hypocapnia in patients under propofol anesthesia may lead to excessive cerebral vasoconstriction and cerebral ischemia.¹⁴⁶  In patients with supratentorial tumors, the ICP has been shown to be lower and CPP higher in patients who received propofol as opposed to sevoflurane or isoflurane anesthesia,¹⁴⁴  although another study reported similar intracranial conditions with intravenous and inhaled anesthetics.¹⁴⁷  A study comparing propofol and desflurane for aneurysm clipping in patients with WFNS grades 1–2 aneurysmal subarachnoid hemorrhage reported no difference in intraoperative hemodynamics, brain relaxation, or time to emergence or extubation, although intraoperative jugular venous oxygen saturation values were greater in patients who received desflurane.¹⁴⁸  Essentially, both intravenous and inhaled anesthesia as part of balanced anesthetic technique can effectively provide optimal operative conditions, particularly in patients with good-grade aneurysmal subarachnoid hemorrhage. Data on long-term impact of anesthetic agents on neurologic outcomes of aneurysmal subarachnoid hemorrhage are lacking. However, given the physiologic rationale and the potential to offset brain swelling by avoidance of cerebral vasodilatation, it may be advantageous to prefer propofol anesthesia in patients with high-grade aneurysmal subarachnoid hemorrhage with raised ICP.

Other factors such as the effect on evoked potential signal quality should be considered while selecting the anesthetic agent. Although inhalational agents cause dose-dependent increases in latency and decreases in amplitude of SSEPs, less than 1.0 MAC concentration is compatible with monitoring of cortical SSEPs although propofol anesthesia does not affect SSEPs.¹⁴⁹  Nevertheless, if motor-evoked potential monitoring is contemplated, propofol anesthesia may be preferred especially in patients with preexisting neurologic deficits, although less than 0.5 MAC desflurane is also compatible with motor-evoked potentials.¹⁵⁰  Remifentanil is a useful adjunct to provide intense analgesia and to facilitate immobility with motor-evoked potential monitoring, although most opioids have similar effects on ICP and CPP when titrated considering their pharmacokinetic differences.^151,152  Nitrous oxide is generally avoided because of its cerebral vasodilatory effects, increasing cerebral blood flow and cerebral blood volume. It should be avoided if there is evidence of intracranial air (e.g., resulting from external ventricular drain placement^153–155 ).

Dexmedetomidine, an α₂-adrenoceptor agonist, is a useful adjunct for craniotomy.¹⁵⁶  Potential advantages include reduction of anesthetic and opioid requirements, attenuation of neuroendocrine and hemodynamic responses, reduced use of antihypertensive agents, and faster emergence.¹⁵⁷  However, it may adversely affect evoked potentials. In a study involving intracranial tumor surgery, dexmedetomidine loading dose of 0.5 μg/kg over 10 min followed by infusion rate of 0.5 μg · kg⁻¹ · h⁻¹ was found to lead to more frequent false positive motor-evoked potential changes than control.¹⁵⁸  In addition, the intensity and repetition rate of transcranial electrical stimulation required were significantly greater in dexmedetomidine group, implying difficulty in acquisition of adequate responses from the recording muscles although SSEPs were unaffected.¹⁵⁸  Interestingly, in a similar study in patients undergoing thoracic spinal cord tumor resection, the addition of dexmedetomidine in same doses to propofol-remifentanil regimen did not exert any adverse effect on motor-evoked potential and SSEP monitoring.¹⁵⁹  The susceptibility of transcranial motor-evoked potentials to dexmedetomidine is dependent of targeted blood levels of the drug. As an adjunct to propofol, dexmedetomidine at target plasma concentrations of 0.6–0.8 ng/ml can significantly attenuate the amplitude of transcranial motor-evoked potentials.^160,161  It is suggested that dexmedetomidine be used cautiously as an adjunct during evoked potential monitoring, avoiding doses greater than 0.4–0.5 μg · kg⁻¹ · h⁻¹.

Ketamine is known to increase cerebral metabolic rate when administered as a sole agent and has been historically not favored in neurosurgical anesthesia. However, there is currently a renewed interest in its use in patients with acute brain injury, including aneurysmal subarachnoid hemorrhage. Sedation with ketamine in patients with aneurysmal subarachnoid hemorrhage has been deemed safe. It can also reduce ICP, vasopressor use, cerebral infarction, and spreading depolarizations.^162,163  It has also been used safely during aneurysm clipping as an adjunct to isoflurane anesthesia without adversely altering cerebral hemodynamics, including in patients with mildly increased ICP.¹⁶⁴  Adding ketamine to a background anesthetic likely blunts its property of central nervous “excitation” and increases the “depth of anesthesia” evident by a decrease in total EEG power.¹⁶⁴  Given its analgesic and neuroprotective potential, it may be used as an adjunct during surgery for aneurysmal subarachnoid hemorrhage, although bolus doses my impair transcranial motor-evoked potentials and should be avoided.¹⁶⁵ 

The goals for hemodynamic management in aneurysmal subarachnoid hemorrhage depend on the stage of the surgical procedure. Briefly, the anesthesiologists should (1) avoid hypertension before the aneurysm is secured; (2) induce brief periods of hypertension during temporary clipping of a feeding vessel; and (3) normalize blood pressure goals after the aneurysm is secured. Before the aneurysm is secured, hypertension can increase the transmural pressure (fig. 1), leading to rebleeding. Hence avoidance of hypertension during placement of skull pins, positioning, and surgical stimulation is critical and requires close communication between the neurosurgeon and the anesthesiologist. The current recommendation is to maintain systolic blood pressure less than 160 mmHg.⁶³  CPP less than 70 mmHg may increase the risk of cerebral ischemia in patients with higher-grade aneurysmal subarachnoid hemorrhage^65,166  and, hence, relative hypotension is also undesirable. Blood pressure should be controlled with an easily titratable agent to balance the risk of hypertension-related rebleeding and cerebral ischemia.⁶³  Common options for prevention/treatment of hypertension include increasing the anesthetic depth and administration of analgesics (fentanyl, remifentanil) or antihypertensive agents (esmolol, nicardipine). Local anesthetic infiltration at the skull pin insertion point is also a useful technique. Nevertheless, there appears to be considerable variability in target blood pressure thresholds among physicians.¹⁶⁷ 

Placement of a temporary clip on the parent vessel is often needed to facilitate accurate placement of a permanent clip but can cause a reduction in brain tissue oxygen tension and an increase in carbon dioxide tension.¹⁶⁶  To ensure perfusion of the “at-risk” brain during temporary clipping through collateral channels, it is recommended that the blood pressure be raised 10% to 20% above the patient’s baseline. Once the aneurysm is successfully secured, blood pressure can be normalized. A recent study examined the data from 1,099 patients who underwent surgical clipping or endovascular coiling after aneurysmal subarachnoid hemorrhage using a standardized protocol comprising intravenous anesthesia, end-tidal CO₂ 35–45 mmHg, and mean arterial pressure greater than 80 mmHg, with systolic blood pressure less than 180 mmHg before and greater than 220 mmHg after securing the aneurysm.¹⁶⁸  Interestingly, the authors did not find any association between intraoperative hypocapnia, hypotension, and hypertension (time-weighted average area under the curve thresholds of end-tidal CO₂ or mean arterial pressure) and neurologic outcome at discharge.¹⁶⁸  However, as the authors themselves clarified, the study does not support abandoning strict ventilation and blood pressure regulation because there were few patients with extremes of physiologic values in the study.¹⁶⁸  Importantly, although induced hypotension was used in the past to facilitate aneurysm clipping, it is not recommended anymore because of the risk of neurologic deficits.^169,170 

Hemorrhage as well as acute hydrocephalus can lead to intracranial hypertension and “brain swelling” in aneurysmal subarachnoid hemorrhage. To facilitate surgical exposure of the aneurysm and to avoid the risk of brain injury associated with retraction pressure applied to the brain, it is critical to provide “brain relaxation.” Standard strategies for intraoperative brain relaxation and control of ICP include the following:

1. maintenance of adequate depth of anesthesia and analgesia and optimization of hemodynamic parameters (avoid hyperemia)

2. selection of suitable anesthetic agents and doses (less than 1.0 MAC inhaled anesthetic; intravenous anesthetics if brain swelling is anticipated)

3. optimal positioning (head elevation with avoidance of excessive flexion or rotation of the neck to facilitate cerebral venous drainage)

4. controlled ventilation for normocarbia to moderate hypocarbia (PaCO₂ 30–35mmHg) with brief periods of PaCO₂ less than 30 mmHg if other ICP reduction maneuvers fail

5. intravenous mannitol

6. intravenous hypertonic saline

7. intravenous Furosemide

8. CSF drainage

9. burst suppression with intravenous bolus of propofol/thiopental

The timing of hyperventilation is important. Aggressive hyperventilation should not be instituted before opening of the dura because the resulting increase in the transmural pressure (fig. 1) can precipitate rebleeding. Hypertonic saline augments cerebral blood flow in patients with poor-grade aneurysmal subarachnoid hemorrhage and significantly improves cerebral oxygenation.¹⁷¹  Data from supratentorial tumor surgery suggest more effective ICP reduction and brain debulking with 3% hypertonic saline than 20% mannitol.^172–174  Similarly, meta-analyses of randomized studies, including craniotomy for mixed indications including aneurysmal subarachnoid hemorrhage, report more effective brain relaxation with hypertonic saline compared with mannitol.^175,176  However, in a meta-analysis of 5 small studies in patients with aneurysmal subarachnoid hemorrhage, hypertonic saline was found as effective as mannitol at reducing increased ICP.¹⁷⁷  Essentially, both mannitol and hypertonic saline are acceptable during aneurysm surgery. Finally, drainage of CSF is an effective method for rapid ICP reduction but should be used cautiously. Excessive drainage of CSF with the closed dura may lead to sudden increase in the transmural pressure with possible risk of rebleeding.

A temporary clip may be placed on the parent vessel to reduce blood flow through the aneurysm, facilitating the dissection and the accurate placement of a permanent clip around the neck of the aneurysm while avoiding aneurysm rupture. However, it exposes the downstream brain tissue to potential ischemia. A temporary clip may be applied for a duration of up to 10 min without ischemia of the middle cerebral artery territory.¹³⁶  Potential strategies to prevent ischemic damage during temporary clipping include (1) avoiding prolonged temporary clipping (typically greater than 10 min); (2) intraoperative neurophysiological monitoring to alert a signal change due to ischemia and to guide reperfusion; (3) reducing cerebral metabolic demand during temporary clipping (e.g., burst suppression, hypothermia), and; (4) induced hypertension to recruit collateral flow.

The notion that reduction in cerebral metabolic rate by pharmacologically induced burst suppression on the EEG is neuroprotective against cerebral ischemia during temporary clipping is not fully substantiated. However, if temporary occlusion is required for more than 10 min, intravenous administration of pentobarbital, propofol or etomidate titrated to achieve EEG burst suppression has been shown to reduce new infarction on postoperative imaging.^136,178  In a small study of 20 patients where temporary clipping was performed after producing burst suppression with thiopental or desflurane, cerebral oxygenation in the ischemic territory was better maintained with desflurane, likely owing to its cerebral vasodilatory effect.¹⁷⁹  However, a post hoc analysis of the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) did not find pharmacologic protection to affect short- and long-term neurologic outcomes of the patients who underwent temporary clipping. Patients with temporary clip duration of greater than 20 min had less favorable outcome despite receiving thiopental or etomidate for neuroprotection.¹⁸⁰  Although routine use of supplemental medications to induce burst suppression is not required, it may be advantageous in patients with high-grade aneurysmal subarachnoid hemorrhage with inadequate collaterals and complex aneurysm when prolonged temporary clipping is anticipated, provided hypotension from the bolus drug can be avoided. Hemodynamic stability can be maintained in patients with good ventricular function when high-dose thiopental is administered for burst suppression.¹⁸¹  Myocardial depression and 20% reduction in mean arterial pressure has been reported while inducing EEG burst suppression with propofol.^181,182  Etomidate, in burst suppression doses, can also cause hypotension.¹⁸³  Although there are no definitive data, it is reasonable to induce hypertension during anticipated prolonged temporary vessel occlusion.⁶³  Usually, blood pressure is increased to 10% to 20% above preinduction baseline value during temporary clipping to recruit collateral blood flow to the territory at risk of ischemia. Evoked potential monitoring can often alert the surgical and anesthesia teams, allowing reperfusion by releasing temporary clip or by raising systemic blood pressure.

Induced hypothermia to decrease the metabolic requirement of the brain during temporary clipping has been proposed as a neuroprotective strategy. However, the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) involving 1,001 patients with WFNS grades I–III randomized to intraoperative hypothermia (target temperature, 33°C, with surface cooling) or normothermia (target temperature, 36.5°C) observed no advantage of hypothermia on improving the neurologic outcome.¹⁸⁴  In fact, postoperative bacteremia was more common in the hypothermic patients.¹⁸⁴  A post hoc analysis did not find any advantage of hypothermia in patients requiring temporary occlusion either.¹⁸³  Hence, intraoperative hypothermia cannot be recommended for neuroprotection in patients with good grade aneurysmal subarachnoid hemorrhage but may be an option in selected cases.⁶³  Importantly, hyperthermia is detrimental and should be avoided.

Multiple other pharmacologic approaches have been proposed for cerebral protection during aneurysm surgery, although none has been shown to clearly improve outcomes.^185,186  The anesthesiologist’s focus should be physiologic optimization. Intraoperative hyperglycemia during aneurysm clipping is associated with increased risk of cognitive changes at glucose concentrations greater than 129 mg/dL and neurologic deficits at glucose concentrations greater than 152 mg/dL.¹⁸⁷  Intraoperative glucose greater than 180 mg/dL has been shown to be independently associated with postoperative new-onset composite infections in a mixed neurosurgical population undergoing craniotomy for a variety of indications.¹⁸⁸  Intensive insulin therapy after surgical clipping of aneurysms appears to decrease infection rates, although the benefit of strict glycemic control on vasospasm, neurologic outcome, and mortality is questionable.¹⁸⁹  In fact, it may cause iatrogenic hypoglycemia.¹⁹⁰  Prevention of intraoperative hyperglycemia is recommended according to the current guidelines, although no specific threshold glucose value is advised.⁶³  Periodic glucose monitoring under anesthesia with timely institution of protocolized insulin administration to maintain the blood glucose 80–180 mg/dl is recommended.

Temporary clipping may sometimes not be feasible either because of the location of the aneurysm or because of difficulty visualizing the proximal artery. In such situations, temporary blood flow arrest with adenosine can allow decompression of the aneurysm facilitating optimal positioning the permanent clip.^191,192  However, unlike temporary clipping, which only reduces blood flow through the aneurysm, adenosine causes global reduction of cerebral blood flow. Hence, adenosine should be administered in close communication with the surgeon to minimize the overall duration of reduced global cerebral blood flow. Adenosine is a dromotropic and chronotropic agent with rapid onset and short duration of action that causes bradycardia progressing into a brief asystole. The duration of adenosine-induced asystole is dose dependent and is variable.^191,192  A dose of 0.29–0.44 mg/kg leads to approximately 57 (range, 26–105) seconds of moderate hypotension.^191,192  The flow arrest immediately decompresses the aneurysm and allows the surgeon to dissect and expose the aneurysm safely. In fact, the surgeon can continue to work around the aneurysm even after the return of cardiac activity while the blood pressure remains in profound-moderate hypotensive range before normalizing. After the circulation has returned to baseline, additional doses of adenosine can be given if needed, although dose escalation may be required. Adenosine is best avoided in patients with coronary artery disease or abnormalities of the cardiac conduction system as well as in patients with reactive airways disease. Recovery of cardiac rhythm after flow arrest may be preceded by transient cardiac arrhythmias including atrial fibrillation, ventricular tachycardia, or atrial flutter. Depression of the ST segment may be visible on the electrocardiogram and troponin levels may be elevated postoperatively, although echocardiography may not demonstrate cardiac dysfunction.¹⁹³  With experienced anesthesiologists, adenosine-induced temporary flow arrest is safe for aneurysm clipping in patients without preexisting coronary artery disease.^194–196  Moreover, adenosine is also useful to control bleeding in case of inadvertent aneurysm rupture during surgery. The induced flow arrest provides a clear surgical field and allows the surgeon to control the source of bleeding.^197,198 

Another emerging technique for controlling complex aneurysms during clipping is rapid ventricular pacing, which induces ventricular tachycardia, and ventricular filling is compromised because of the high rate and the absence of atrioventricular synchrony. Ventricular contractility is reduced because of the dyskinetic ventricular contraction caused by apical stimulation. It reduces stroke volume and cardiac output, leading to decreased blood pressure without causing cardiac arrest, allowing the surgeons to dissect around and clip the aneurysm. Compared with adenosine, rapid ventricular pacing allows better control of the start time, the length of pacing, and the induced flow/pressure reduction under controlled conditions.^199,200  Yet, given the global reduction of cerebral blood flow, the duration of rapid ventricular pacing should be minimized to avoid cerebral ischemia. The technique involves a bipolar pacing electrode introduced through the internal jugular vein into the right ventricle under fluoroscopy and external defibrillating pads placed. Pacing is started at 180 beats/min and titrated to the desired effect.^199,200  The majority of the experience with rapid ventricular pacing is with unruptured aneurysms.²⁰¹  It is not suitable for patients with coronary heart disease and cardiac arrhythmias, and its safety in patients with aneurysmal subarachnoid hemorrhage is undetermined.²⁰² 

Deep hypothermic circulatory arrest for aneurysm surgery is now seldom required given the complex set-up, high complication rates, and the availability of other treatment innovations including endovascular approach.²⁰² 

Cerebral vasospasm is a devastating complication of aneurysmal subarachnoid hemorrhage. It is the result of macro- and microvascular spasms typically between 3 and 14 days posthemorrhage, although it can occasionally persist up to 21 days. The majority of the aneurysms are secured early enough before the development of vasospasm, but occasionally vasospasm may have already set in at the time of presentation of aneurysmal subarachnoid hemorrhage when the patients present in a delayed manner. Angiographic vasospasm may be seen in up to 70% to 90% of patients.^203,204  However, symptomatic vasospasm affects only about a third of the patients.²⁰⁵  The most concerning complication of vasospasm is delayed cerebral ischemia leading to cerebral infarction, although delayed cerebral ischemia can also occur in the absence of vasospasm.^206–209  Cerebral vasospasm results from an imbalance in the expression of vasodilators and vasoconstrictors such as endothelin-1 along with the associated stimulation of calcium. This, along with the impairment of cerebral autoregulation and associated increase in ICP, can lead to cerebral ischemia and infarction. Despite any demonstrated benefit on improving angiographic vasospasm, oral nimodipine is the only agent currently known to reduce delayed cerebral ischemia.^70–75  The current mainstay of treatment for vasospasm is fluid resuscitation to avoid hypovolemia and the use of pressors or inotropes to induce hypertension.²¹⁰  Patients refractory to these interventions may be candidates for endovascular intervention involving supraselective intra-arterial injection of vasodilators or angioplasty and typically require anesthesia.^211–214  The primary goal of anesthetic management in these cases is to continue ongoing intensive care; specifically, continue medical management of vasospasm with hypertensive therapy and prevent any hypotension in response to the arterial administration of vasodilators.^215–217  Anesthesiologists should anticipate and should be prepared to promptly manage profound decrease in blood pressure during endovascular treatment. A detailed discussion of intensive care and therapies for delayed cerebral ischemia is beyond the scope of this review.

Aneurysmal subarachnoid hemorrhage is a neurologic emergency associated with significant extracranial sequala. After rapid stabilization, early, definitive treatment by neurosurgical clipping or endovascular coiling is required. The data on the impact of anesthetic agents on long-term outcomes of aneurysmal subarachnoid hemorrhage are very few and insufficient. The optimal anesthetic technique depends on patient characteristics, severity of aneurysmal subarachnoid hemorrhage, planned intervention, and monitoring. Successful perioperative management requires incorporation of principles of anesthetic neuropharmacology, optimizing systemic physiology and familiarity with specific techniques, including but not limited to evoked potential monitoring, burst suppression, temporary clipping, management of external ventricular drain, adenosine standstill, and rapid ventricular pacing.

The author thanks James G. Hecker, Ph.D., M.D., Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, for valuable inputs in article preparation and for proofreading.

Dr. Sharma receives support from Agency for Healthcare Research and Quality (AHRQ; Rockville, Maryland) grant No. 5 R18 HS026690-02 (Improving Patient Safety in Subarachnoid Hemorrhage Using Transcranial Doppler Simulation for Bedside Diagnosis of Cerebral Vasospasm).

Dr. Sharma is an editorial board member (Journal of Neurosurgical Anesthesiology) and President of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC; Richmond, Virginia). He also receives honorarium from Wolters Kluwer (Philadelphia, Pennsylvania) for UpToDate.