Introduction

Anesthesia for UIA obliteration differs from routine craniotomies because of specific physiological challenges associated with the underlying neurovascular disease and the planned procedure. The margin of safety between high blood pressure leading to rupture and a low blood pressure provoking ischemia is narrow in these patients; hence, immediate management of hypertensive or hypotensive events is critical. Moreover, the anesthesiologist must balance the need to maintain cerebral perfusion pressure (CPP) to promote brain oxygenation with the risk of increasing the transmural pressure gradient that can promote aneurysm rupture [1, 2] (Fig. 1). Respiratory parameters must be carefully titrated to optimize oxygenation and carbon dioxide tension; coagulation and electrolyte balance, maintained; and intraoperative events and complications, rapidly managed to prevent risk for devastating neurological injuries (Fig. 2). Procedure-related challenges such as temporary occlusion of the parent vessel require special anesthetic consideration. Temporary clipping of the parent vessel may be needed to rescue or preempt IA rupture or to facilitate a surgical step in elective IA surgeries. However, temporary clipping can lead to ischemic stroke, dissection of the vessel, or rupture of the aneurysm [3,4,5]. Prolonged occlusion of the parent vessel leads to extended hypoperfusion in its corresponding territory; therefore, proper anesthetic management such as careful blood pressure augmentation and neuroprotection may be warranted. Various anesthetic agents reduce cerebral metabolism—as listed in this review—and, therefore, could be considered. However, it is essential to choose an anesthetic approach that preserves or ideally even augments cerebral blood flow (CBF)—in particular collateral flow to the ischemic territory—while reducing cerebral metabolic rate of oxygen (CMRO2) (Table 1). Since temporary clipping during IA surgery may provoke cerebral vasospasm, cerebral function monitoring may be employed to guide blood pressure management and removal or reapplication of the temporary clip.

Fig. 1
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Systemic blood pressure should be monitored closely and controlled to minimize risk of aneurysm rupture due to hypertension while avoiding low blood pressure that can provoke cerebral ischemia. BP blood pressure, CPP cerebral perfusion pressure, ICP intracranial pressure, CBF cerebral blood flow

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Fig. 2
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Anesthetic considerations during obliteration of UIA (unruptured intracranial aneurysms)

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Table 1 Effects of common anesthetic agents
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In some patients, it may become necessary to induce a transient circulatory arrest or severe hypotension in case of an aneurysm rupture or for decompression of the aneurysm to facilitate clip application. With appropriate safety precautions, adenosine boluses of up to 30 mg have been successfully used to induce a transient asystole in these patients [5]. Adenosine may also be considered when temporary clipping of proximal vessels is not desirable or possible. Although some recent reviews provide general guidelines on the anesthetic management of cerebral aneurysm surgery [1, 2, 8], there are no rigorously conducted studies or reviews to assess the intraoperative anesthetic risks and outcome effects for UIA obliteration. Therefore, we conducted a systematic review of the literature examining the hemodynamic, physiological and pharmacological effects of common anesthetic agents and regimens during endovascular and open procedures to obliterate UIA.

Methods

Study selection

All articles in English language, including adult patients, and published in indexed scientific journals were considered. Randomized controlled trials (RCT), prospective and retrospective cohorts, case series, and case reports, as well as cross-sectional studies involving patients with unruptured cerebral aneurysm or those who had undergone aneurysm obliteration or neurosurgical procedures were eligible for inclusion. Given the scarcity of studies on unruptured cerebral aneurysms, we also discuss relevant findings from selective studies on neurological effects of anesthetics and patients with aneurysmal subarachnoid hemorrhage.

Data extraction

We performed a systematic search on MEDLINE to identify studies. We used the participants, interventions, comparisons, and outcomes (PICO) search tool [9] to determine the following medical subject heading terms: “Aneurysm OR Aneurysm Surgery” AND “Nitrous Oxide OR Isoflurane OR Desflurane OR Sevoflurane OR Ketamine OR Propofol OR Barbiturate OR Thiopental OR Dexmedetomidine OR Opioids” AND “brain OR intracranial OR cerebral OR cranium” AND “Surgery OR Neurosurgery OR craniotomy OR endovascular OR Vascular Surgical Procedures” AND “Neuroprotection OR mortality OR morbidity” AND “anesthetics OR anesthesia.” Additional reports were identified from reference lists of retrieved reports and Google Scholar searches.

Method of synthesis

Two reviewers independently extracted the data from trial reports, with adherence to the PRISMA guideline [10]. Details of the patient population, type of surgery, anesthetic regimen, and outcomes were recorded. The data were extracted only from studies published in English.

Results of the review

The initial search strategy captured a total of 287 studies. From these, 28 studies were included in this study (Table 2 and Fig. 3) [10].

Table 2 Clinical studies of the effects of anesthetic agents on neurological outcomes following unruptured intracranial aneurysm surgery
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Fig. 3
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PRISMA flow diagram showing the process of study inclusion

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Anesthesia for cerebral aneurysms: intravenous or inhalational agents?

There is currently no clear consensus whether intravenous anesthesia, inhalational anesthesia, or a combination thereof should primarily be used for surgical or endovascular management of UIA. Inhalational agents commonly used for these procedures include volatile anesthetic agents such as isoflurane, desflurane, and sevoflurane, as well as nitrous oxide. Commonly used intravenous agents include propofol, ketamine, and dexmedetomidine, which are typically administered in combination with a short- or long-acting opioids. Thiopental sodium and other barbiturates are still used in certain countries, and benzodiazepines are also occasionally administered as perioperative anxiolytics or anesthetic adjuncts.

There are conflicting data on not only the perioperative risks and benefits of these agents, including direct neurotoxic effects or physiological side effects that can alter the outcome of the procedure, but also their neuroprotective properties, which become essential in cerebral aneurysm surgery due to the potential neurological insults associated with these complex procedures.

Inhalational anesthesia

Nitrous oxide

While nitrous oxide (N2O) has been used continuously in clinical anesthesia for about 180 years, discussions about its neurological effects are still ongoing [39]. In 1992, Lam et al. described the important physiological effects of N2O on cerebral metabolism and intracerebral steal [40]. Although little research has been carried out on the neurophysiological properties of N2O, it is now generally accepted that N2O lacks neuroprotective effects in anesthetic doses [41]. Furthermore, N2O is known to increase cerebral metabolism, CBF, and intracranial pressure (ICP) and can potentially exacerbate an ischemic insult, all undesirable effects in the setting of intracranial surgery [42].

The debate on N2O safety has continued to simmer, mainly without any clinical neurological outcome data [42, 43]. In 2008, McGregor et al. assessed the clinical outcomes associated with N2O by analyzing the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) data [11]. They evaluated neurological outcomes at two weeks (i.e., delayed ischemic neurologic deficit (DIND)) and three months after aneurysm surgery and found that in a population of patients potentially at risk for ischemic injury, the use of N2O had no overall impact on neurological outcome [11]. A subgroup analysis of patients with temporary occlusion of a major cerebral artery for permanent clipping of the aneurysm provided a more granular analysis to capture patients who experienced ischemic events intraoperatively during exposure to N2O. In this subgroup, intraoperative N2O administration was associated with an increased risk of DIND. The long-term neurological outcome was, nevertheless, not affected [12].

To our knowledge, data from more recent studies assessing the effects of N2O on neurological outcome after UIA surgery are lacking [8]. Although intraoperative use of N2O is primarily based on the anesthetist’s preference and differs between institutions, most experts agree that it is best avoided during endovascular procedures. In addition to its effects on CBF and ICP, it is well known that N2O increases the risk of expansion of micro air bubbles in enclosed spaces. This expansion is due to N2O’s low potency, which results in high blood concentrations, and its low blood/gas partition coefficient, which causes N2O to move into an air compartment faster than air moves out. Air embolization is rare during aneurysm obliteration but can happen during contrast injection or fluid irrigation; expansion of these air bubbles with N2O can augment the risk for tissue ischemia and neurological injury [44]. Furthermore, it may be reasonable to avoid N2O during open craniotomy for UIA clipping if it is difficult to achieve sufficient brain relaxation, or in patients with disrupted autoregulation, such as those with cerebral edema, ischemia, or vasospasm [45].

Isoflurane

Isoflurane is commonly used in neuroanesthesia due to its modest effects on CBF and cerebral autoregulation [46]. The neuroprotective effects of isoflurane have been studied widely in animal models. Isoflurane administration in rats during reperfusion after ischemia reduces brain injury, improves neurological outcome, and decreases neuronal apoptosis [47].

Isoflurane is generally associated with good blood pressure control without significant change in cardiac output or reflex tachycardia when administered in anesthetic concentrations to normovolemic patients [48]. To further evaluate the cerebral effects of isoflurane, Madsen et al. measured CBF and CMRO2 during isoflurane-induced controlled hypotension in ten patients undergoing craniotomy for clipping of a ruptured aneurysm. CBF and CMRO2 were measured 5–13 days after aSAH. Controlled hypotension to an average mean arterial pressure (MAP) of 50–55 mmHg was induced by increasing the inspired concentration of isoflurane, which resulted in a significant decrease in CMRO2 but no change in CBF. After clipping, the isoflurane concentration was reduced, and there was a significant increase in CBF. While CMRO2 returned to baseline, CBF increased above its pre-hypotensive value. It was suggested that this advantageous supply-demand ratio can offer protection to the brain tissue during periods of induced hypotension [49]. Following prior clinical studies that emphasized the use of high concentrations of isoflurane to induce hypotension, decrease CMRO2, and stabilize CBF, Meyer et al. used end-tidal isoflurane concentrations of 2.0 to 2.5 × minimum alveolar concentration (MAC) to induce electroencephalographic (EEG) ISO electricity (see below). At these high isoflurane concentrations, hypotension can occur due to myocardial depression and vasodilatation; therefore, a vasopressor agent was used to maintain blood pressure. The study included six patients with aSAH and extended temporary vessel occlusion time. Five of six patients made a good recovery despite prolonged occlusion of major cerebral arteries. Their findings supported the use of high dose isoflurane in selective patients to suppress cerebral metabolism during aneurysm surgery, as long as it is hemodynamically tolerated and when intraoperative EEG monitoring is used to carefully titrate the anesthetic concentration [15]. However, it should be noted that prolonged inhalation of isoflurane may reverse its protective effects, as was demonstrated by an aggravated brain injury in a rat model of transient focal ischemia [50].

Although more recent clinical studies looking at isoflurane for UIA surgeries are lacking, in 2019, a retrospective analysis of seven aSAH patients who underwent decompressive craniectomy due to a critically elevated ICP showed that deep sedation could rapidly be achieved after induction of general anesthesia with isoflurane, without a critical increase in ICP. Adequate CPP was also achieved without a need for extended vasopressor treatment [51].

Sevoflurane

The general neurological profile of sevoflurane is largely comparable to isoflurane but with relatively smaller vasodilatory effects. At concentrations of 1 MAC or less, sevoflurane maintains global CBF (if MAP is unchanged), reduces CMRO2, and minimally increases ICP, which can be blunted by mild hyperventilation [52]. Supported by animal studies, it is argued that sevoflurane may induce neuroprotection when administered during traumatic or ischemic events [53, 54]. In 2018, Xu et al. reported that early exposure to 3.4% sevoflurane for 5 h induced not only autophagy in rat hippocampal cells but also apoptosis of neurons, potentially leading to spatial learning deficits [55], raising questions about the neuroprotective role of sevoflurane. The fact that this high concentration of sevoflurane is seldom used in clinical practice, particularly without other medications such as opioid analgesics or intravenous anesthetics, makes it impossible to determine the clinical relevance of their findings. In fact, it is more likely that the co-administration of intraoperative anesthetics influences their effects on cerebral metabolism, inflammation, and injury, as was demonstrated by Bo et al. in 2018. They showed that the addition of dexmedetomidine to sevoflurane anesthesia could suppress the sevoflurane-induced cell cycle arrest, inhibition of brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) expression and concluded that dexmedetomidine could be used to prevent or mitigate sevoflurane-induced neurotoxicity [56]. The use of dexmedetomidine during sevoflurane anesthesia was also studied in a randomized clinical trial of 120 patients undergoing intracranial aneurysm embolization, and the addition of dexmedetomidine resulted in better neuroprotection, decreased incidence of postoperative delirium, faster recovery, and more stable hemodynamics [22].

Due to its bronchodilatory effects and relatively short duration of action (low blood-gas solubility coefficient), sevoflurane may be the ideal volatile agent for patients with underlying chronic obstructive pulmonary disease (COPD, Table 3). Conversely, it may not be the agent of choice in patients with kidney disease, although clinical trials have failed to confirm clinically relevant effects on renal function when higher fresh gas flows are maintained. There is currently no consensus on the neuroprotective or neurotoxic effects of sevoflurane. Specific clinical studies of the use of sevoflurane in open clipping or endovascular repair of UIA are lacking, and further investigation is warranted.

Table 3 Anesthetic relevance of common coexisting diseases in UIA surgery
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Desflurane

With its low blood-gas solubility coefficient, desflurane has favorable pharmacokinetic properties relative to isoflurane, including a more rapid emergence from anesthesia and postoperative recovery of cortical functions that have been noted in several in vitro, animal, and human studies. [57]

Several clinical and animal studies have looked at the effects of desflurane on cerebral hemodynamics. The effects of desflurane on ICP were assessed in a porcine model of intracranial hypertension, and at 0.5 to 1 MAC, desflurane was associated with cerebral vasodilatation and higher ICP levels compared to isoflurane and sevoflurane [58]. In humans, the same vasodilatory effect was observed in patients given desflurane, but the ICP did not increase significantly [59]. Although desflurane’s cerebrovascular effects in patients with intracranial hypertension have not been thoroughly investigated, it is reasonable to avoid it in these patients to minimize the risk for significant vasodilation that could lead to ICP elevation [52, 60].

Evidence regarding the use of desflurane in aneurysm clipping is limited. In 2017, Lee et al. reported that the incidence of TCD-evident vasospasm in patients who underwent emergent clipping of cerebral aneurysms was higher with propofol as compared to desflurane, but the incidence of angiographic vasospasm, cerebral infarction, and interventions to treat vasospasm were similar between the groups [61]. Another study found that in patients undergoing intracranial aneurysm clipping, the plasma concentration of endothelin was lower when desflurane was used, suggesting a potential benefit in preventing acute cerebral vasospasm during aneurysm clipping [16].

The risks and benefits of desflurane should be considered carefully for each neurosurgical patients and procedure. As an example, given its association with adverse respiratory events, it may not be the ideal anesthetic agent in patients with severe asthma or COPD. While it has advantageous pharmacokinetic features, its physiological and neuroprotective properties are not superior to other common anesthetics, including sevoflurane and propofol. Although the associated side effects of desflurane remain theoretical or experimental, its physiological properties must be carefully considered during perioperative management of patients with UIA, especially those with poor brain relaxation or intracranial hypertension [62].

Intravenous anesthetic agents

Ketamine

The use of ketamine in neuroanesthesia, including UIA obliteration, is controversial. There is evidence that it may increase ICP, CBF, and CMRO2 [63]; however, more recent animal and human studies suggest that ketamine may actually be beneficial to brain-injured patients due to its effects on NMDA receptors [64, 65].

Based on data from relevant randomized trials between 1994 and 2004, a systematic review suggested that with controlled ventilation and co-administration of a GABA receptor agonist, ketamine can be safely administered without raising the ICP [66]. In another study of 20 patients who underwent craniotomy for either brain tumor resection or cerebral aneurysm clipping, ketamine did not increase ICP during isoflurane or N2O anesthesia. The same study also showed that middle cerebral artery blood flow velocity, mean arterial blood pressure (MAP), and bilateral fronto-occipital processed EEG remained stable after the administration of ketamine, suggesting it can be used safely during neurosurgical procedures [17].

Although clinical studies of ketamine use in the anesthetic management of UIA surgery are lacking, one retrospective, observational study published in 2016 found that among 65 patients with SAH, administration of ketamine decreased ICP and was not associated with a higher rate of neurological complications. This study also found that the rate of delayed cerebral ischemia (DCI)-associated cerebral infarction and the use of vasopressors for induced hypertension were lower when ketamine was administered [18]. Currently, ketamine is avoided in patients with elevated ICP, but based on available animal and human data, it may prove to be a valuable agent for UIA obliteration in the near future. A re-evaluation of its role in these patients is suggested, particularly in those who may benefit from its systemic effects (e.g., bronchodilation in patients with COPD).

Dexmedetomidine

Based on its favorable hemodynamic properties and an ability to attenuate the cardiovascular responses to intubation, pinning, and extubation, the introduction of dexmedetomidine was met with enthusiasm among clinicians. It significantly decreases both CBF and ICP [67, 68]. As an anesthetic adjunct, it decreases the amount of intravenous or volatile anesthetic agents required for induction and the need for opioid analgesics intraoperatively [69].

Dexmedetomidine is commonly used for intracranial procedures and cerebral aneurysm surgery. A retrospective analysis of 12 patients undergoing endovascular procedures for intracranial aneurysm management confirmed a stable hemodynamic profile when dexmedetomidine was used as an anesthetic adjunct. Vital signs and the Ramsey sedation scale for depth of sedation were analyzed every 10 min and showed no statistically significant differences between time points [21]. Another retrospective analysis of 49 patients admitted to the ICU after cerebral aneurysm surgery revealed a higher sedation level in the dexmedetomidine group, with only one patient requiring physical restriction as compared to ten controls [70]. Dexmedetomidine is effectively used in combination with other anesthetics such as sevoflurane to reduce the stress response during surgical clipping of intracranial aneurysms and has also been used in selected patients as the sole sedative agent during monitored anesthesia care for coil embolization of unruptured cerebral aneurysms [22]. Randomized trials with outcome data is, nevertheless, missing in this population.

Barbiturates

The neuroprotective properties of barbiturates have been well documented in many clinical settings, including status epilepticus and traumatic brain injury. Shapiro et al. described its effects on ICP reduction in 1973 [71]. Subsequent animal studies demonstrated its neuroprotective effects by reducing CBF, ICP, and CMRO2 [72, 73]. In humans, however, these effects have not consistently resulted in improved neurological outcomes. An RCT of 300 patients undergoing coronary artery bypass grafting (CABG) did not find a reduction in the incidence of postoperative neurological deficits with thiopental [74]. Another study of 182 CABG patients found that even though thiopental was associated with a significantly lower incidence of persistent neuropsychiatric complications, hemodynamic instability was more frequent, resulting in prolonged use of inotropic support [75].

Clinical studies of barbiturate usage in the UIA population are scarce. A study of 92 patients with cerebral aneurysms in which 23 received pentobarbitone during clipping showed that the complication rate was lower in the pentobarbital group (17%) than the non-barbiturate group (21%) [76]. A case report also documented how multiple thiopental boluses were used in a patient undergoing a combined procedure involving clipping of an intracerebral aneurysm and carotid endarterectomy with an encouraging clinical outcome and a rapid recovery with no postoperative neurological deficits reported [24].

Despite their suggested neuroprotective effects, barbiturates are rarely used in the perioperative setting because of a concern for adverse effects such as cardiorespiratory depression, prolonged duration of post-infusion clinical unresponsiveness, impaired white blood cell function, hypokalemia, and hepatic and renal dysfunction [77]. While this drug class should be used cautiously during cerebral aneurysm surgeries, it can result in satisfactory intraoperative conditions and good neurological outcomes if carefully administered.

Propofol

Because of its favorable hemodynamic, pharmacological, and physiological properties, propofol remains one of the most commonly used anesthetics for neurosurgical procedures, including endovascular and open approaches to securing intracranial aneurysms. It is well tolerated by most patients [78], and its hemodynamic effects are readily managed with common vasopressors. Propofol decreases CBF, CMRO2, and ICP and has been shown to have neuroprotective effects in various models of neuronal injury. Animal models have demonstrated its direct antioxidant properties that can protect against oxidative stress as well as anti-inflammatory and antiapoptotic properties [79, 80]. Its rapid recovery profile also allows the possibility of prompt neurological examination postoperatively.

Propofol has been evaluated in aneurysm surgery in multiple studies. In 1993, Ravussin et al. evaluated 42 patients, including seven with unruptured aneurysms, who underwent cerebral aneurysm clipping using total intravenous anesthesia with propofol. The propofol infusion rate was reduced postoperatively to allow for early recovery and subsequent neurological examination, and they concluded that using a propofol infusion for maintenance of burst suppression could be a suitable alternative to isoflurane for aneurysm clipping [25]. Similarly, Guo et al. randomized 60 patients undergoing intracranial aneurysm clipping to propofol post-conditioning or sevoflurane and found improved mini mental status exam (MMSE) and Montreal Cognitive Assessment (MoCA) scores seven days after their surgery [31].

Due to its cerebral vasoconstrictive effects, propofol is generally considered to be an ideal anesthetic for effective brain relaxation during aneurysm surgery. A 2014 meta-analysis by Chui et al. showed that propofol-based anesthesia was associated with lower initial ICP values compared to maintenance with volatile anesthetics; however, this finding did not translate into better brain relaxation scores [2, 81]. A more recent study of 15 patients undergoing elective surgery for UIA found that cerebral circulation times were longer during propofol anesthesia compared to sevoflurane-based anesthesia, as were the circulation times in the internal carotid and middle cerebral arteries [30]. The presence of an unruptured intracranial aneurysm also did not affect the propofol-induced reactivity of cerebral vessels [29]. Multiple studies have compared propofol to other anesthetics for neurovascular procedures [29,30,31], but most have focused on the hemodynamic or neuroprotective effects of propofol, with only limited data regarding its effects on neurological outcomes.

Opioids

Among opioid receptors, the delta-opioid receptor (DOR) has received special attention for its proposed neuroprotective properties. Early animal studies suggested that opioid receptor agonists could increase survival rates during cerebral ischemia [82]. Zhang et al. further elucidated this concept using neuronal cultures from rat neocortex while studying glutamate-induced neuronal injury. These investigators found that activation of DORs reduced injury by half, whereas mu- or kappa-opioid receptors did not [83]. DORs are suggested to provide neuroprotection by different mechanisms such as inhibiting excitatory neurotransmitter release, increasing antioxidant capacity, and stabilizing ionic homeostasis [84].

In humans, however, mu-opioid receptor agonists are more commonly used for analgesia during surgery. Their perioperative use is limited primarily due to their respiratory depressant effects, which can lead to hypercapnia with cerebral vasodilation and increased ICP. Fentanyl can decrease CBF and CMRO2, but if ventilation is not controlled, it can lead to hypercapnia and as a result an increase in ICP. Similarly, remifentanil can reduce CBF and CMRO2, and although it is not demonstrated to directly increase the ICP, it can also cause respiratory depression and hypercapnia that can result in cerebral vasodilation [85].

Evidence from clinical studies on the use of opioids in UIA is scarce; however, a few have shed light on the subject. Degoute et al. found that remifentanil in combination with propofol or an inhalational agent could produce reliable hypotension when needed for certain phases of aneurysm surgery [86]. In another study, Uchida et al. conducted a propensity score-matched analysis of more than four thousand patients who underwent open intracranial aneurysm clipping and found that the group who received remifentanil had significantly lower in-hospital mortality than controls [32]. Remifentanil can be a good adjunct to the anesthetic regimen if rapid recovery and postoperative neurological evaluation are desired or if opioid-induced respiratory depression is contraindicated (e.g., patients with severe COPD), but more clinical studies are needed to determine if its administration is associated with improved outcomes after UIA.

Discussion

Obliteration of UIA can result in devastating complications despite advances in surgical and endovascular techniques, careful preoperative optimization, and enhanced anesthetic and perioperative management of the patient. A thorough understanding of the anatomical features of the aneurysm, the technical approach, physiological and metabolic challenges, and the systemic and neurological effects of the anesthetic agents is crucial for reducing the risk of neurological injury in these patients. These cases also require preparedness for perioperative complications, and implementation of resuscitative and neuroprotective measures should these complications occur [87]. Animal and human studies have documented the neurophysiological and neuroprotective properties of common anesthetics, but there is only limited data regarding their effects on neurological outcomes, particularly in patients with UIA [41, 47, 62, 72, 73, 79, 80, 82, 88, 89]. Pharmacodynamic, cardiovascular, and neurophysiological effects of common anesthetics have been extensively studied, but not in the specific context of EVT or aneurysm clipping. Endovascular aneurysm coiling can be complicated by intra-procedural perforation by the microcatheter, guidewire, or coil [87]. Thromboembolic events or vasospasm can also occur and lead to cerebral ischemia with devastating neurological injury [90]. Intra-arterial vasodilators are sometimes administered, requiring careful titration of systemic vasopressors and anesthetics to avoid hypotension and cardiovascular collapse. Blood pressure fluctuations along with respiratory and other physiological parameters such as temperature and glucose levels must be meticulously controlled, and patient movement should be avoided [1, 2, 8]. Similar to EVT, successful open clipping of UIA is critically dependent on the perioperative control of hemodynamic perturbations, optimization of cerebral perfusion and metabolism, careful fluid management, and maintenance of cellular homeostasis. Blood pressure augmentation with common vasopressors such as phenylephrine may be required to improve the collateral blood supply by increasing the CPP and should be considered especially when the duration of temporary clipping is anticipated to exceed two minutes. Increasing brain tolerance for ischemia by pharmacologically inducing electroencephalogram (EEG) silence or burst suppression is another consideration. It is important to note, nevertheless, that despite supporting evidence in patients with prolonged (> 10 min) temporary clipping [91], pharmacological burst suppression or EEG silence is currently not recommended for routine use in cases with temporary arterial occlusion. Also, available literature provides limited data to support a specific anesthetic regimen, and our understanding of their physiological and outcome effects continues to evolve. It is unlikely that smaller trials will have the required power to identify significant outcome differences following uncomplicated procedures, as long as the above perioperative goals are met (Fig. 1). It is possible, however, that outcomes in a subgroup of patients at risk for perioperative neurological injury (e.g., those with aneurysm rupture, severe vasospasm, or prolonged temporary clipping) are critically dependent on the physiological and neuroprotective properties of the anesthetic agents used, in addition to perioperative hemodynamic, metabolic, and respiratory parameters [6, 7, 77, 92, 93]. This at-risk population would be an ideal target for future randomized trials to assess the protective effects of different anesthetic agents during UIA obliteration.

Conclusion

The existing literature does not support any specific anesthetic regimen during EVT or open craniotomy for the management of UIA. Further studies are needed to compare the perioperative physiological and clinical effects of different anesthetic regimens and define their influence on neurological outcomes.