Abstract
Aneurysmal subarachnoid hemorrhage (aSAH) is a serious and debilitating condition that leads to the development of many complications, which are followed by mortality and morbidity. As anesthesiologists, we may require to manage aSAH at various settings such as in the perioperative period or in a nonoperative setting such as the neuroradiology suite for diagnostic and therapeutic interventions. Therefore, it is important to understand the pathophysiology of aSAH and anesthetic management for operations and interventions. For decades, early brain injury and cerebral vasospasm have played major roles in the outcome following aSAH. The purpose of this article is to review recent advances and future perspectives in the treatment of aSAH, early brain injury, and cerebral vasospasm.
Keywords
Anesthesia; Brain injuries; Intracranial Aneurysm; Neurosurgical Procedures. Radiology, interventional; Subarachnoid Hemorrhage; Vasospasm, intracranial;
1. Introduction
Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease and leads to the development of poor outcome and high mortality.1 Endovascular or early surgical securing of aneurysm is the standard treatment procedure, and anesthetic management of these patients is precarious due to their unstable physiology and severe systemic medical complications such as neurogenic cardiac injury, neurogenic pulmonary edema (NPE), electrolyte disturbances, arrhythmia, cerebral edema, and cerebral vasospasm (CVS).
Endovascular management of intracranial aneurysms is likely to progress rapidly and has emerged as the first-line intervention for medical treatment failure patients. With the increasing use of interventional radiology techniques, familiarization with anesthetic care and procedure-related complications becomes more important. If interventional procedures fail, emergent craniotomy and clipping of aneurysm may be required. Anesthesiologists should be familiar with specific monitoring, strategies to relax the brain and maintain adequate cerebral perfusion, specific request for deliberate hyper-/hypotension, blood glucose control, and management of surgical crises of aneurysm rupture during clipping.
Delayed cerebral ischemia (DCI) as a result of CVS is the most common cause of death and disability after aSAH. Nimodipine has been shown to improve CVS in controlled trials. In addition, patients with CVS who did not response to early triple-H therapy (hypertension, hypervolemia, and hemodilution) should be considered for urgent angioplasty with intra-arterial injection of vasodilators. Finally, future perspectives on the reduction of CVS by attenuating glutamate toxicity, inflammation, oxidative stress, and early brain injury (EBI) may improve the outcome of aSAH.
2. Systemic effects of aSAH
Physiologic derangements of the cardiac, respiratory, and endocrine systems can be caused by aSAH. Here, we list some important derangements that require further evaluation and management.
2.1. Neurogenic cardiac injury and NPE
These abnormalities may due to the excessive release of catecholamines from sympathetic nerve terminals triggered by aSAH.2, 3, 4 Marked systemic and pulmonary hypertension, cardiac arrhythmias, myocardial dysfunction, and NPE were easily found in these patients. Additionally, among patients suffering from cardiac events following aSAH, those with myocardial infarction and, in particular, those with a troponin level greater than 1.0 μg/L had a 10-time increased risk of death.5 Moreover, uncontrolled prolonged heart rate elevation is associated with major adverse cardiopulmonary events and poor outcome after aSAH.6 Myocardial dysfunction, particularly when combined with hypervolemic therapy for CVS, may exacerbate pulmonary edema.7, 8
Pulmonary complications such as NEP, pneumonia, and acute lung injury are commonly associated with aSAH, occurring in up to 80% of patients, and a high mortality rate.9, 10
2.2. Electrolyte disturbances
Hyponatremia is the most common metabolic derangement among aSAH patients as a result of either cerebral salt wasting syndrome or syndrome of inappropriate secretion of antidiuretic hormone and associated with poor outcome.11, 12 Etiology and treatment of hyponatremia vary in the presence of hypervolemia/euvolemia or hypovolemia.13 Other common electrolyte disturbances include hypokalemia, hypocalcemia, and hypomagnesemia, which should be corrected carefully.9 At the same time, hypothyroidism, cortisol deficit, and inappropriate fluid management (overload or hypovolemia) should also be considered.
2.3. Cerebral edema and CVS
Cerebral perfusion pressure (CPP) is defined as the difference between mean arterial pressure and intracranial pressure (ICP) or central venous pressure, whichever is higher. Maintenance of an adequate CPP is a major goal in managing aSAH, but often complicated in the setting of dysfunction of blood–brain barrier (BBB) and cerebral blood flow autoregulation. The combination of cerebral edema, increased ICP (IICP), and hypovolemia increases the likelihood of CVS, which may per se increase ICP as a vicious cycle.
CVS usually develops 3–12 days after aSAH and lasts for 2 weeks on average; it affects 60–70% of patients. It frequently results in cerebral ischemia, and is the major cause of morbidity and mortality after aSAH.14 Diagnostic modalities and treatment of CVS have been reviewed in our previous article15 and updated in the section “Prophylaxis and therapy of CVS”.
2.4. Notices for anesthesia
Hypotension and hypoxia are two of the most important insults that influence outcomes. Patients who were suffering from the two conditions should be well prepared, and the anesthesiologists explained to the family and surgeons prior to operation. In addition, postponement of the operation should be considered until the condition is improved. In view of the adverse effects, therapy of cardiac insufficiency with inotropic agents should be considered.16, 17, 18 In the event of cardiorespiratory compromise, a full investigation, attentive monitoring, and appropriate interventions are required immediately to optimize cardiorespiratory function and allow subsequent management of aSAH. The use of prophylactic α- and β-blockade to reduce the effect of catecholamines has been a matter of debate. However, this strategy needs to be balanced against the need to maintain cerebral perfusion.19 Patients with severe cardiovascular failure and CVS were reported to benefit from temporary intra-aortic balloon pump counterpulsation.20, 21Patients with NPE should be treated with ventilator support having a high post end-expiratory pressure and furosemide.
3. Interventional treatment and anesthesia for ruptured cerebral aneurysms
The choice of interventional treatment following a ruptured aneurysm is either endovascularly coiling or surgically clipping. The optimal choice may not be clear and depends on the physician’s judgment about age, World Federation of Neurological Surgeons grade,22 comorbidity, aSAH onset time, and the anatomy of the aneurysm.23
According to the 2012 “Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals from the AHA/ASA”,24 some important recommendations are as follows: (1) surgical clipping or endovascular coiling of the ruptured aneurysm should be performed as early as feasible in the majority of patients to reduce the rate of rebleeding after aSAH (Class I; Level of Evidence B); (2) complete obliteration of the aneurysm is recommended whenever possible (Class I; Level of Evidence B); (3) for patients with ruptured aneurysms judged to be technically amenable to both endovascular coiling and neurosurgical clipping, endovascular coiling should be considered (Class I; Level of Evidence B); and (4) microsurgical clipping may receive increased consideration in patients presenting with large (>50 mL) intraparenchymal hematomas and middle cerebral artery aneurysms. A new recommendation is that endovascular coiling may receive increased consideration in the elderly (>70 years of age), particularly in those presenting with poor-grade aSAH (World Federation of Neurological Surgeons classification IV/V) and those with aneurysms of the basilar apex (Class IIb; Level of Evidence C).
3.1. Endovascular management of cerebral aneurysms
Emerging evidence suggests that endovascular intervention may reduce the morbidity associated with surgery.25 For poor-grade patients with brain swelling and CVS, which may deter surgeons from performing a surgery, an endovascular intervention may be preferable.26 However, limitations of coiling exist in approximately 5–15% of cases due to morphological characteristics or location of the aneurysm.27, 28, 29, 30
3.2. Radiation safety
Ionizing radiation follows the inverse square law, and the radiation exposure drops off at a rate proportional to the square of the distance from the source; therefore, activities near the patient’s head should be minimized. The use of extended infusion and monitoring lines is required in patients with a difficult access to intravenous (i.v.) lines in the upper limbs once the procedure is underway.
Throughout the whole procedure, all personnel in the room should wear protective lead aprons with thyroid shields and stay as far away from the radiation source as possible. In some hospitals, there is more radiation safety with facilities for the anesthesia team to monitor the patient from a distance.
3.3. Preoperative planning and patient preparation
For i.v. sedation cases, careful padding of pressure points to obtain comfortable positioning can assist patients in tolerating a long lying motionless time. In addition to standard monitors, end tidal CO2 sampling via nostrils by sampling line is useful for evaluation of airway pattern. Early signs of femoral artery obstruction or thromboembolism can be detected by placing a pulse oximeter probe on the side of great toe, which has femoral introducer sheath.
Invasive BP monitoring using an arterial line is suggested. Urine output measurement assists in fluid management. A significant volume of heparinized flush solution and radiographic contrast may be used.
3.4. Important considerations for anesthesia care
According to the American Society of Anesthesiologists’ refresher suggestions,31 the important considerations for endovascular neurosurgery included the following: (1) maintaining immobility during the procedure; (2) rapid emergence to allow neurological examination and monitoring, or intermittent evaluation of neurological function; (3) managing anticoagulation; and (4) treating and managing sudden, unexpected procedure-specific complications (e.g., hemorrhage or vascular occlusion), which may involve manipulating systemic or regional blood pressure (BP) during the procedure.32, 33 Here, we list some specific considerations of anesthetic management during endovascular neurosurgery.
3.5. Anesthetic technique
3.5.1. Intravenous sedation
The goals are to alleviate pain and anxiety, provide patient immobilization, and allow rapid and smooth emergence.31 The major benefit of the technique is no endotracheal intubation. In addition, it provides rapid assessment of neurological functions during or after the procedure. Continuous propofol infusion with opioids is commonly used in this technique. The alternative is dexmedetomidine, but it should be used with care in case of hypotension in the postanesthesia recovery period.34
Discomfort resulted from sheath introduction, contrast injection, traction on vessels, and long period of lying. Upper airway obstruction is common in i.v. sedated patients. Nasopharyngeal airway may be helpful, but should be placed gently in these anticoagulated patients.
3.5.2. General anesthesia
Most centers prefer general anesthesia (GA) as opposed to sedation for optimal imaging, as this provides patient immobilization with better image quality, patient comfort, and control of the respiratory and hemodynamic profile. Disadvantages of GA are the inability to perform neurological assessment immediately and the consequences of endotracheal intubation and extubation that can lead to IICP.
The laryngeal mask airway may be used as an alternative to endotracheal intubation for the airway management. It allows airway control with less hemodynamic stress, with a smoother emergence. However, the security and protection of the airway by a laryngeal mask are not as complete as that by endotracheal intubation during this long procedure. Nevertheless, compared to i.v. sedation, we prefer GA with endotracheal intubation or laryngeal mask airway for endovascular management of aSAH.
3.6. Anticoagulation
To prevent thromboembolic complications, i.v. heparin (70 IU/kg) is given to prolong activated clotting time two to three times above the baseline level.
The sustained reduction in morbidity and mortality by antiplatelet agents in coronary thrombosis patients undergoing angioplasty or stenting has drawn interest for their use in endovascular intervention of the central nervous system (CNS).35, 36 Rapid reversal of antiplatelet activity can be achieved by platelet transfusion. However, it is not clear whether use of these agents along with heparin results in increased hemorrhage.37
3.7. Complications
Complications during the endovascular procedures can be rapid and catastrophic, which may include hematoma, non-CNS (contrast reactions or contrast nephropathy), and more serious CNS (hemorrhagic or occlusive) complications.38 The primary responsibility of the anesthesia team is to protect the airway and determine whether the complication is thrombotic or hemorrhagic.
3.7.1. Contrast reactions
These may be caused by hypertonicity, direct cardiac depression, or idiosyncratic anaphylactoid reactions. Pretreatment with steroids and antihistamines is recommended for those with the aforementioned reactions.39 Nonionic agents have a lower incidence of anaphylactoid reactions, although the incidence of fatal reactions was as high as that of ionic agents (1:10,000 exposures).40, 41, 42, 43
3.7.2. Contrast nephropathy
Perioperative fluid management should be aimed at maintaining normovolemia to prevent nephropathy. Prophylactic oral administration of N-acetylcysteine along with hydration has been shown to prevent the reduction in renal function induced by iopromide in patients with chronic renal insufficiency.44 Isotonic bicarbonate infusion 1 hour immediately prior to radiocontrast injection, during the contrast exposure, and for 6 hours after the procedure may also reduce the incidence by alkalizing renal tubular fluid.45 As anesthesiologists, we should keep in mind to constant infusion of bicarbonate for renal protection. Other agents such as vasodilators (dopamine/fenoldopam), theophylline, calcium channel blockers (CCBs), and antioxidants (ascorbic acid) have been tried without conclusions.
3.7.3. Occlusive complications
BP should be raised to increase collateral blood flow and maintain normocarbia during these occlusive complications. Direct mechanical lysis with local infusion of saline may be used when thromboembolism is encountered. Otherwise, thrombolytic agents are considered for use, but without conclusive results. Local intra-arterial tissue plasminogen activators have been shown to achieve a recanalization rate of 44%.46 Administration of antiplatelet agents via i.v. or intra-arterial injection has shown promising results.35 Malpositioned coils occlusion at the parent artery can be removed by endovascular trial or craniotomy; this is a rare situation.
Vasospasm can be treated, as discussed in the section “Prophylaxis and therapy of CVS”, by medical (triple-H) therapy, pharmacological (papaverine and nimodipine) therapy, or balloon angioplasty.
3.7.4. Hemorrhagic complications
Hemorrhagic complications require prompt management. While BP is adequate, an immediate injection of 1 mg protamine is required for the reversal of each 100 units of heparin. It may be well tolerated in very small leaks. However, in clinically significant bleedings, the anesthetic technique should be shifted from i.v. sedation to GA, to secure the airway. In addition, PaCO2 should be maintained at 30–35 mmHg, and mannitol (0.25–0.5 g/kg) or hypertonic saline (HTS) may be given to reduce cerebral edema.47, 48
Management of hypertension in aSAH is a difficult issue. Aggressive management of BP surge may predispose patients to the risk of ischemia in areas with a loss of autoregulation.25 Therefore, it appears best to reserve antihypertensive drugs for patients with an extreme surge of BP as well as clinical evidence of rapidly progressive end-organ deterioration.49 A practical recommendation is to maintain BP at the same level as that prior to bleeding.25
Aneurysm rupture is usually treated by packing the defect with coils. Moreover, Santillan et al50 showed that the presence of a balloon across the aneurysm neck at the time of rupture not only allowed immediate and effective control of the hemorrhage, but also was associated with better clinical outcome than the coil alone. If all methods fail, emergent craniotomy and clipping of the aneurysm may be required, which are described in the following sections.
3.8. Surgical clipping of cerebral aneurysms
3.8.1. Routine monitoring
This includes pulse oximetry, invasive and noninvasive BP, electrocardiogram, capnography, body temperature, urinary output, and neuromuscular block.
3.8.2. Hemodynamic monitoring
An arterial line is usually necessary for continuous BP monitoring and intermittent blood sampling. Many anesthesiologists routinely insert a central venous catheter for guidance of intravascular volume management, although the accuracy is doubted. In patients with decreased intracranial compliance or IICP, cannulation of the internal jugular or subclavian veins for the central venous catheter should be restrictive, because the Trendelenburg position and head-turning during placement of the central venous catheter may increase ICP critically. The femoral region is an alternative insertion site; however, this method cannot evaluate volume status. Recently, an uncalibrated arterial pressure-based cardiac output monitor (FloTrac) has been found to be a minimally invasive and convenient alternative modality. However, data suggest that the FloTrac underestimated the reference cardiac index and was not as reliable as transpulmonary thermodilution for perioperative hemodynamic monitoring after SAH.51, 52 Although, a new-generation FloTrac has been introduced, its accuracy in measuring stroke volume variation still needs to be studied in aSAH patients. Establishment of the necessary monitoring technique (pulmonary artery catheterization or pulse-induced contour cardiac output, transesophageal echocardiography, precordial Doppler, or evoked potentials) prior to induction is suggested in elderly patients, severe comorbidity, expected difficult surgeries, and sitting position.23
3.8.3. Neurophysiological monitoring
Cortical somatosensory-evoked potential and brainstem auditory-evoked potential are most commonly used to monitor cerebral function during aneurysm clipping. However, the benefit of neurophysiological monitoring during aneurysm clipping remains to be defined and is restricted due to difficult access to the recording sites and effect of anesthetics (volatile anesthetics, especially), perioperatively.53
3.9. ICP monitoring
Pressure measurement using a ventricular catheter can be performed in severe hydrocephalus or poor-grade aSAH. It provides the guidance for BP control and drainage of excessive cerebrospinal fluid (CSF) perioperatively.
3.10. Brain relaxation
Brain relaxation is necessary to optimize surgical exposure and clipping. Rapid reductions in ICP may affect transmural pressure and increase the risk of aneurysm rupture. This should be performed cautiously prior to dural opening.
Miscellaneous interventions and pharmacological therapies are discussed in the following subsections.
3.10.1. Mannitol
The effect of mannitol on brain relaxation is to create an osmotic pressure gradient in intact BBB to move water out of the swollen tissue. It occurs about 30–45 minutes after infusion and judged by the response of the ICP or brain tissue rather than urine output.
The effectiveness of a hyperosmolar solute depends on its “reflection coefficient” (RC) determining the relative impermeability to the BBB of the solute, where 1 indicates an impermeable solute and 0 an ideally permeable solute. Because the RC of mannitol is 0.9, therefore 10% of mannitol will penetrate the intact BBB and cause rebound IICP.
3.10.2. Hypertonic saline
HTS was reported to improve outcomes in some controlled trials or experimental SAH model studies.47, 48, 54, 55, 56, 57 However, there were also detrimental results including hyperchloremic acidosis and lacks of benefit compared to normal saline solution group in rats.58 Several prospective clinical trials that compared the effects of HTS and mannitol on ICP suggested that HTS is at least as effective as, if not better than, mannitol in the treatment of IICP in patients with stroke and traumatic head injury.59, 60, 61 In addition, in our previous study, we found that 3% HTS provided better brain relaxation than mannitol during elective supratentorial brain tumor surgery, which did not affect intensive care unit stays or hospital days.62Therefore, the role of HTS in aSAH still needs further investigation.
3.10.3. Furosemide
Furosemide is administered alone at a high dose (1 mg/kg) or, if not effective, combined with mannitol (0.25–1 g/kg) at lower doses (5–20 mg) to achieve brain relaxation.63, 64 However, significant loss of free water and electrolytes can be noticed. Therefore, very close monitoring of intravascular volume, electrolytes, acid–base, and serum osmolality is required.
3.10.4. Drainage of CSF
This can be achieved by using a ventricular or lumbar subarachnoid catheter. Rapid drainage of a large volume of CSF should be prevented, because an abrupt shift of pressure may disrupt the aneurysm wall. The amount of acutely drained CSF should not exceed 20–30 mL during procedure.23
3.10.5. Miscellaneous interventions
Head-up elevation is useful for venous drainage from brain tissue. Temporary mild hyperventilation may be considered (PaCO2 at 30–35 mmHg prior to dura opening and 25–30 mmHg during dura opening) in critical situations, but without benefit during long-period use. Recent data suggest that hypothermia does not improve neurologic outcome; however, hyperthermia must be avoided perioperatively in SAH patients. Keep in mind that brain swelling refractory to any therapy may be caused by an intracerebral hematoma, which should be disclosed.
3.11. General principles of anesthesia
The goals of anesthesia include controlling the transmural pressure gradient of the aneurysm, preserving adequate CPP and oxygen delivery, avoiding large and sudden swings in ICP, providing conditions that allow optimal surgical exposure with least brain retraction, and allowing rapid emergence.23 There are also some recommendations by the American Heart Association/American Stroke Association (AHA/ASA) on anesthetic management: (1) minimization of the degree and duration of intraoperative hypotension during aneurysm surgery is probably indicated (Class IIa; Level of Evidence B); (2) there are insufficient data on pharmacological strategies and induced hypertension during temporary vessel occlusion to make specific recommendations, but there are instances when their use may be considered reasonable (Class IIb; Level of Evidence C); (3) induced hypothermia during aneurysm surgery is not routinely recommended but may be a reasonable option in selected cases (Class III; Level of Evidence B); and (4) prevention of intraoperative hyperglycemia during aneurysm surgery is probably indicated (Class IIa; Level of Evidence B).
No premedication was suggested. The aim of induction is to administer drugs that abolish or blunt the hypertensive response to laryngoscopy and tracheal intubation. During induction, a moderate (approximately 20%) initial reduction or rise in baseline BP is acceptable.23
Smooth emergence and adequate CPP are needed. After surgery, the patient should respond to verbal commands as soon as possible to allow early neurological assessments. If emergence from anesthesia is unexpectedly delayed or a new neurological deficit is present upon awakening, CT or angiography may be used to rule out intracerebral hematoma or occlusion of a blood vessel. A 20–30% increase in BP above the preoperative baseline poses the risk of intracranial hemorrhage and edema. We should prevent this situation by prophylactic administration of the appropriate type and dose of analgesics, antihypertensive drugs, or lidocaine (i.v. or intratracheal). Patients with preoperative Hunt and Hess Grades III or IV65 or intraoperative complications should not be extubated after operation and require intensive postoperative care.23
3.12. Choice of anesthetics
In general, it is advisable to avoid all anesthetics with cerebrovasodilatory potentials (basically all volatile anesthetics and N2O) and use those with cerebrovasoconstrictive and cerebrodepressant characteristics (basically all i.v. anesthetics, with the exception of ketamine).23 If sensory-evoked potentials are to be recorded, a total i.v. anesthesia may be the preferred technique.66, 67
In an experimental study, isoflurane was associated with reduced mean arterial pressure, incomplete recovery of posthemorrhagic regional cerebral blood flow, and a high anesthesia-related mortality after SAH. In addition, anesthesia induced with midazolam/medetomidine/fentanyl provided stable hemodynamics, high posthemorrhagic regional cerebral blood flow values, and a high rate of rebleeding, a phenomenon often observed after SAH in humans.68 However, in SAH mice, isoflurane may suppress post-SAH brain inflammation69 or post-SAH BBB disruption.70 Therefore, more studies on the effect of volatile anesthetics after aSAH are compulsory.
3.13. Deliberate hypertension
Deliberate hypertension may be requested during temporary clipping to improve collateral blood flow to the clipped area. It is critical that hypertension is induced only after the temporary clip has been placed. Often i.v. phenylephrine or ephedrine can be used for this purpose.
3.14. Deliberate hypotension
To facilitate clipping of the aneurysm and control bleeding, a decrease of the aneurysmal wall stress may be optimized through a reduction in systemic BP. However, it is no longer used routinely, because it may impair overall cerebral perfusion critically, and has been associated with an adverse outcome and a higher incidence of severe CVS.71
3.15. Strategies of surgical crises: intraoperative aneurysm rupture
Intraoperative aneurysm rupture is associated with high morbidity and mortality. It may occur at any time during the procedure, associated mostly with an abrupt increase in the transmural pressure gradient of the aneurysm or with surgical manipulation. Emergency interventions depend on the size of the leak/rupture, completeness of the dissection of the aneurysm, surgeon's direct assessment, and feasibility of temporary occlusion of blood vessels proximal and distal to the aneurysm.23
BP management during the rupture of an aneurysm is controversial. A transient decrease in the mean arterial pressure to 40–50 mmHg will decrease the wall shear stress, reduce bleeding, and facilitate surgical orientation, exposure, and clipping. However, in the presence of clinically relevant blood loss, the combination of hypotension and hypovolemia may result in profound cerebral ischemia. Thus, temporary vessel occlusion is the preferred technique to gain control over a ruptured aneurysm—with the possible exception of when temporary occlusion is not possible.
Although blood loss during aneurysm rupture is uncontrollable and unpredictable, call for help and effective communications between surgical and anesthesia teams are necessary. An accurate estimation of blood loss is essential to guide volume supplement. Induced hypotension, adenosine planned arrest, or, occasionally, manual pressure on the ipsilateral carotid artery in the neck may be helpful during the desperate situation of a large and uncontrolled premature rupture.
If volatile anesthetics and N2O were being used, they should be discontinued and replaced by i.v. anesthetics. Some anesthesiologists administer a bolus dose or continuous infusion of thiopental for its cerebrovasoconstrictive property and brain relaxation. However, it may necessitate pharmacological vital sign support and delay awakening.23
4. Prophylaxis and therapy of CVS
CVS is a segmental or diffuse narrowing of the lumen of intracranial arteries, and the severity is apparently related to the amount and location of subarachnoid blood. There are many related studies, and we list the key points here.15, 23, 24, 72 Recommendations from the AHA/ASA are as follows: (1) oral nimodipine should be administered to all patients with aSAH (Class I; Level of Evidence A); (2) maintenance of euvolemia and normal circulating blood volume is recommended to prevent DCI (Class I; Level of Evidence B); (3) prophylactic hypervolemia or balloon angioplasty prior to the development of angiographic spasm is not recommended (Class III; Level of Evidence B); (4) transcranial Doppler is reasonable to monitor for the development of CVS (Class IIa; Level of Evidence B); (5) perfusion imaging with CT or magnetic resonance can be useful to identify regions of potential brain ischemia (Class IIa; Level of Evidence B); (6) induction of hypertension is recommended for patients with DCI, unless BP is elevated at baseline or cardiac status precludes it (Class I; Level of Evidence B); and (7) cerebral angioplasty and/or selective intra-arterial vasodilator therapy is reasonable in patients with symptomatic CVS, particularly in those who are not responding rapidly to hypertensive therapy (Class IIa; Level of Evidence B).
4.1. Triple-H therapy
Although some clinicians use prophylactic triple-H therapy, beneficial effects on outcome have not yet been shown.8, 73, 74 Accumulating literature has shifted the focus from this triple-H therapy to the maintenance of euvolemia and induced hypertension.75 Patients without an early response to triple-H should be considered for urgent endovascular treatment of CVS.72
4.2. Calcium channel blockers
Nimodipine, a CCB, has been demonstrated to improve outcomes and reduce the risk of death and disability due to CVS.76 Administration of other CCBs, nicardipine and nifedipine, via cerebral intra-arterial and intrathecal routes are being used with some success in major academic centers.77
4.3. Intra-arterial papaverine
When CVS affects distal vessel segments, chemical angioplasty with intra-arterial administration of papaverine may be more effective (maximally 300 mg per hemisphere).78 Although capable of dilating distant cerebral vasculature and microcirculation, not all outcomes following papaverine injection are beneficial,78 and the duration of action is extremely short.79Papaverine has neurotoxic effects and has been associated with seizures, coma, blindness, and irreversible brain injury.80
4.4. Balloon angioplasty
This intervention is often used in patients who do not improve with hemodynamic augmentation such as triple-H therapy, and in those with sudden focal neurological deficits and focal lesions on angiography referable to their symptoms.81 In general, balloon angioplasty can be used for accessible lesions and accompanies infusion of vasodilators such as CCBs (nicardipine or nifedipine) and phosphodiesterase inhibitor (milrinone) for more distal vessels.82
5. Future perspectives
Newer vasodilator therapies or experimental drugs for prophylaxis or treatment of CVS have been reported.15 These new approaches are based on robust experimental data that indicate a critical role for endothelial dysfunction, particularly at the microcirculatory level.83 Several recent clinical trials have investigated the utility of statins, endothelin-1 antagonists, and magnesium sulfate.84 However, these are all in the experiment phase, and larger randomized trials are suggested.
There are also emerging data for several novel methods to reduce the incidence and ischemic consequences of aSAH-induced CVS and DCI.24, 85Many patients survive acute phenomena, but deteriorate days later from DCI, which causes poor outcome or death in up to 30% of patients with aSAH. DCI is thought to be caused by the combined effects of angiographic CVS, arteriolar constriction and thrombosis, cortical spreading ischemia, and processes triggered by EBI.
The term EBI describes the immediate injury to the brain after aSAH, prior to the onset of CVS, in general <72 hours after SAH. During the EBI period, a ruptured aneurysm causes several physiological derangements such as IICP, decreased cerebral blood flow, and global cerebral ischemia. These events initiate secondary injuries such as BBB disruption and brain edema, and influence nitric oxide synthesis, excitotoxic amino acids, inflammation, and oxidative cascades that all ultimately lead to cell death.86, 87, 88 Given the fact that the reversal of CVS does not appear to improve patient outcome, it could be argued that the treatment of EBI may attenuate some of the devastating secondary injuries successfully and improve the outcome of patients with aSAH.88, 89, 90 Novel strategies including treatment with drugs such as statins, sodium nitrite, albumin, dantrolene, and cilostazol, and intracranial delivery of nimodipine or magnesium are also noted.85 In our previous studies, early (3 hours after SAH) and multiple administration of curcumin or baicalein was found to decrease CVS by attenuating glutamate neurotoxicity and oxidative stress.88, 90
6. Conclusion
An anesthesiologist should be familiar with the etiology, pathophysiology, treatment, and complications of aSAH. Endovascular management of intracranial aneurysms is likely to progress rapidly in the future. With the increasing use of interventional radiology techniques, familiarization with the whole procedure becomes very important. However, if this method fails, emergent craniotomy and clipping of aneurysm are required. Being familiar with the whole anesthetic care and management of surgical crises is important. Finally, future perspectives on the reduction of DCI and attenuation of CVS, glutamate toxicity, inflammation, oxidative stress, and EBI may improve the outcome of aSAH.