Anesthetics
Inhaled Anesthetics and Propofol:
Sevoflurane has been shown to vasodilate cerebral vessels in patients with aSAH as compared to propofol [12]. In another clinical trial, where in jugular venous oxygen saturation (SjVO2) was used as a surrogate marker of cerebral blood flow, desflurane was associated with increase in SjVO2 values when compared to propofol [13]. These initial physiological findings are promising and form the basis of use of inhaled anesthetics in patients with aSAH for limiting the incidence of DCI.
In a retrospective series of 102 patients, vasospasm as measured by transcranial doppler was significantly less with the use of desflurane than with propofol [14]. However, the authors reported no difference in the incidence of angiographic vasospasm, new onset cerebral infarction, or neurological outcome. Incidentally, in the same year, a randomized controlled trial (RCT) comparing propofol and desflurane didn’t report any difference in the incidence of clinical vasospasm, ischemia, and neurological outcome [13]. Another RCT from the same center also reported similar results with no difference in clinical vasospasm and neurological outcome [15].
This contrasted an earlier retrospective cohort study in 290 patients and which that the use of inhaled anesthetics in patients with aSAH was associated with significant reduction in angiographic vasospasm and DCI [16]. The same group analyzed retrospective data from two centers in the United States and found that the use of inhaled anesthetics was associated with angiographic vasospasm in 32% of patients versus 52% in those who received intravenous anesthetics. Similarly, the rates of DCI were 21% with inhaled anesthetics while those who received IV anesthetics had DCI rates of 40% [17].
Ketamine:
After an initial guarded relationship of ketamine and neurosurgery, recent studies have reintroduced it into the clinical scenarios. Multiple studies have demonstrated its ability to suppress the cortical spreading depolarizations and hence potentially providing neuroprotection [18–21]. Ischemia induces an excitotoxic process involving the release of large amounts of glutamate. Glutamate stimulates NMDA receptor activation, that in turn induces neuronal injury by causing excessive influx of Ca++ and decreases Ca++ efflux, augmenting apoptosis [22, 23]. This Ca++ also activates neuronal nitric oxide synthase which produces nitric oxide (NO) and damages the mitochondria. Ketamine is a NMDA antagonist, and hence exerts its neuroprotective effect by blocking the above pathway.
Benzodiazepines:
Midazolam by infusion has been in use for sedation in neurosurgical patients for decades. A study by Hertle et al described the effect of various analgesics and sedatives on cortical spreading depolarizations in patients with acute brain injury and found that Midazolam infusion was associated with an increased number of spreading depolarizations [23].
We summarize these and other findings of anesthestics in DCI in Table 1.
Table 1
Summary of literature for anesthetics noting year, author, study design methodology, sample size, and outcomes.
Year | Authors | Study Design | Methodology | Sample Size | Outcome |
2009 | Sakowitz et al 20 | Case series | Electrocorticographic recordings of patients of acute brain injury were studied | 2 patients/ 1 patient of SAH | Ketamine inhibited cortical spreading depolarizations |
2012 | Hertle et al23 | Multicentric observational study | Electrocorticographic recordings of patients under different sedatives | 115 patients/ 31 patients of SAH/ICH | Ketamine decreases and Midazolam increases cortical spreading depolarizations |
2017 | Brelie et al 18 | Retrospective, observational study | Effect of ketamine sedation on intracranial pressure (ICP), vasopressor use, occurrence of delayed cerebral ischemia (DCI) induced cerebral infarctions | 65 patients of SAH / 41 patients sedated with ketamine | -DCI- related cerebral infarctions, ICP and vasopressor use was significantly decreased in the patients sedated with ketamine -No effect on the outcome |
2018 | Carlson et al19 | Prospective controlled trial | 6 hours alternating sedation with ketamine and other sedative in patients with traumatic brain injury (TBI) /SAH | 8 patients with SAH | Less spreading depolarizations on ketamine infusions |
2018 | Bhardwaj et al13 | Randomized controlled trial | WFNS I-II aSAH patients undergoing surgical clipping. Received either propofol or desflurane anesthesia | 70 patients | Intraoperative SjVO2 values were higher in the desflurane group. No effect on incidence of clinical vasospasm and neurological outcome. |
2018 | Lee et al14 | Retrospective study | Patients with aSAH undergoing emergent aneurysm clipping. Received either propofol or desflurane anesthesia | 102 patients | Incidence of TCD evident vasospasm was higher in the propofol group |
2019 | Santos et al21 | Retrospective study | Patients with aSAH receiving s-ketamine | 66 patients/33 on ketamine infusions | Significant reduction in the SDs after starting ketamine |
2021 | Bhagat et al15 | Randomized controlled trial | WFNS I-II aSAH patients undergoing surgical clipping. Received either propofol or desflurane anesthesia | 106 patients | No effect on the incidence of clinical vasospasm and neurological outcome. |
2021 | Athiraman et al16 | Retrospective study | aSAH patients undergoing aneurysm repair. Inhalational anesthetics only. | 390 patients | Inhalational anesthetics conditioning is protective against angiographic vasospasm and DCI. No impact on neurological outcome. |
2022 | Athiraman et al17 | Retrospective Study. Data of two centers. | aSAH patients undergoing aneurysm repair. Inhalational versus intravenous anesthesia. | 179 patients | Inhalational agent provided protection against angiographic vasospasm and DCI. No effect on neurological outcome |
2023 | Joys et al12 | Randomized controlled trial: Preliminary study | Good-grade aSAH scheduled for endovascular coil embolization. Received either propofol or sevoflurane anesthesia | 18 patients | Sevoflurane has cerebral vasodilating properties as compared to propofol. Effect on DCI and neurological outcome not studied |
Anti-thrombotics
Pre-hemorrhage use
Antiplatelets:
It is interesting to understand the role of antiplatelet use prior to hemorrhage in patients with aSAH. The pre-haemorrhage use of Aspirin in patients with aSAH has been found to be associated with lower risk of cerebral ischemia and infarction suggesting the protective role of antiplatelet drugs on DCI [24]. On the contrary, the observations from prospective databases of multiple centers found that the antiplatelet use was associated with increased in-hospital mortality and poor outcome at six months [25]. In a retrospective study of 305 patients with aneurysmal SAH, though the incidence of symptomatic vasospasm was similar in both aspirin users and non-users, the incidence of permanent disability was less amongst the aspirin users [26].
Anticoagulants:
A two-center study assessed the effect of pre-SAH anticoagulant and Vitamin K antagonist (VKA) use in patients with SAH [27]. The study observed that the incidence of DCI was similar in patients using either oral anticoagulants or VKA as compared to their age or sex matched controls without any effect on SAH score and neurological outcome [27].
Post-hemorrhage use
The use of anti-platelet (AP) and anticoagulant (AC) in patients following aneurysmal SAH seems perilous. Their initiation in a post-SAH patient, without robust evidence of its protection against DCI, is a matter of debate. However, since their use is mandated in patients undergoing stent assisted coiling or flow diverter placement, this population allows for indirect study.
Antiplatelets:
A retrospective study of 166 patients following endovascular embolization (either simple/ balloon assisted or stent assisted coiling who were on either single or dual antiplatelets {DAPT} respectively) reported that the incidence of symptomatic vasospasm and DCI was significantly lower in the group receiving DAPT [28]. Another retrospective study of 580 patients with aSAH who underwent endovascular coiling concluded that use of aspirin was associated with reduced risk of developing DCI with a subsequent favorable outcome [29]. Ditz et al studied patients with aSAH treated with endovascular coiling who were given either single and dual antiplatelet agents. Although antiplatelet use didn’t reduce the incidence of angiographic or DCI- related infarctions (DCIRI), the lesion volume of DCIRI was significantly lower in the dual antiplatelet group and the use of antiplatelet was independently associated with a lower incidence of unfavorable outcome at 3 months [30]. A similar study comparing the incidence of clinical vasospasm and DCI in patients on DAPT and those not on DAPT following endovascular coiling, found that the risk of clinical vasospasm and DCI was significantly lower in the group with DAPT use with no difference in the rates of haemorrhagic complications [31].
In contradiction to all the above studies, a retrospective study of 108 patients with aSAH undergoing coil embolization found that newly developed cerebral infarction rate was higher in the antiplatelet group [32]. Hop et al instituted Aspirin 100 mg in patients with aSAH after surgical clipping and found that the rate of DCI was similar in the patients receiving Aspirin and control [33].
Thromboxane synthase (TBS) is an enzyme which catalyzes the formation of Thromboxane A2 which leads to platelet aggregation and activation. Thus, by targeting TBS inhibition there may be interruption in platelet activation and a decrease in the rate of DCI. Thromboxane synthase inhibitors namely Cataclot and OKY-046 were used in patients with aSAH and were found to have protective effect against DCI [34, 35].
A systematic review including 258 patients from 3 trials studying the effect of antiplatelets on DCI reported favorable effects of antiplatelet drugs in prevention of DCI after SAH [36]. The results related to DCI obtained from the meta-analysis by Cagnazzo et al contrasted with the previous meta-analysis [36, 37]. This meta-analysis included seven studies and 2822 patients with aSAH undergoing either endovascular coiling or surgical clipping [37]. The authors concluded that though the overall incidence of DCI is not significantly reduced, the use of anti-platelet therapy was associated with reduction in the number of patients with poor outcome and mortality [37].
Anticoagulants:
Aneurysmal SAH patients started on either low-dose intravenous infusion (12U/kg/h) or through subcutaneous route (5000U, thrice daily) as pharmacological DVT prophylaxis were studied and their effect on DCI were compared. It was observed that the incidence of delayed neurological deficits and cerebral infarctions were lower in the low dose heparin infusion group [38].
Pre-hemorrhage and Post-hemorrhage use
Antiplatelets:
A meta-analysis of 22 studies by Lee et al included 4378 aSAH patients who were on pre-ictal/postictal antiplatelets [39]. DCI was reviewed in 3817 patients from 20 studies which showed that antiplatelet therapy decreases the rate of DCI, vasospasm, in-hospital mortality, and improved functional outcomes without increasing the haemorrhagic events [39]. The subgroup analysis demonstrated that this benefit on DCI was limited to the postictal use of antiplatelets. No such benefit was noted in patients with the preictal use of antiplatelets.
Table two summarizes the findings referenced regarding the effect of antiplatelets and anticoagulants on DCI and outcome (Table 2).
Table 2
Summary of the trials studying the effect of antiplatelets and anticoagulants use on DCI and outcome
Year | Authors | Study Design | Methodology | Drug(s) | Sample Size | Outcome |
1995 | Juvela et al24 | -Prospective study -Pre-haemorrhage | -aSAH patients interviewed about use of Aspirin - Urine screened for salicylates | Aspirin | 291 patients | Aspirin use associated with reduced risk of Cerebral ischemia |
1989 | Suzuki et al34 | Randomized trial | -aSAH patients were given OKY-046 in two doses: 80 mg, 400 mg and compared with a placebo | OKY-046 (Thromboxane synthetase inhibitor) | 48 patients | OKY-046 (80mg/d) prevents DCI and cerebral ischemia in patients with aSAH. |
1991 | Tokiyoshi et al35 | Randomized trial | -aSAH patients given Cataclot post-operatively after aneurysmal clipping | Cataclot (Thromboxane synthetase inhibitor) | 24 patients | Cataclot decreases symptomatic vasospasm and clinical neurological deterioration. There is risk of bleeding with use of Cataclot. |
2000 | Hop et al33 | Randomized trial | - aSAH patients were given the study drug post-operatively after aneurysmal clipping | Aspirin | 50 patients | The incidence of DCI was similar in the aspirin and control group. |
2003 | Mees et al36 | -Systematic review and meta-analysis - Post hemorrhage | -5 Trials 3 RCTs reporting DCI | Aspirin, Thromboxane A2 synthetase inhibitor | 258 patients | Antiplatelet drugs decrease the risk of DCI |
2004 | Sebok et al25 | -Multicentric prospective database study -Pre-haemorrhage | - Patients divided into ‘‘antiplatelet-user’’ and ‘‘non-user’’ | Aspirin | 1033 patients | Pre-haemorrhage use of Aspirin associated with poor outcome and increased in-hospital mortality |
2004 | Toussaint et al26 | -Retrospective - Pre-haemorrhage | Medical records of patients with aSAH presenting within 7 days of ictus | Aspirin | 305 patients: 29 patients with Aspirin intake | Trend towards reduced incidence of vasospasm related disability. Aspirin use had no effect on the outcome of patients. |
2017 | Nagahama et al31 | -Retrospective - Post hemorrhage | -Patients undergoing endovascular coiling/flow diverter. -Two groups: control group and those receiving DAPT | Aspirin Clopidogrel | 161 patients | Clinical vasospasm and DCI were lower in patients receiving DAPT. No increase in risk of haemorrhagic complications. |
2019 | Cagnazzo et al37 | -Meta-analysis -Post hemorrhage | 7 studies: 2 Randomised controlled trials | Aspirin Clopidogrel | 2822 patients | Antiplatelet use did not significantly lower DCI. Lower mortality rates and higher good outcomes among antiplatelet users. |
2019 | Oppong et al29 | Retrospective -case-control study - Post hemorrhage | aSAH patients | Aspirin Clopidogrel | 580 patients: 329 with Aspirin use | Aspirin use associated with reduced DCI risk and favorable outcome |
2020 | Sun et al28 | Retrospective - Post hemorrhage | -Patients undergoing coil embolization -Two groups: Control group and DAPT group | Aspirin Clopidogrel | 166 patients | DAPT group had lower incidence of symptomatic vasospasm and DCI |
2021 | Ditz et al30 | -Retrospective - Post hemorrhage | -Patients undergoing endovascular obliteration -Two groups: control group or those receiving antiplatelets (mono or dual antiplatelets) | Aspirin Clopidogrel | 160 patients | Antiplatelet use is not associated with reduced angiographic vasospasm or DCI related infarctions. Lower incidence of unfavorable functional outcome after 3 months with antiplatelet use. Reduced lesion volume in DAPT subgroup |
2021 | Kole et al38 | -Retrospective - Post hemorrhage | -Patients undergoing clipping or coiling | Low dose intravenous heparin infusion (LDIVH) versus subcutaneous heparin for DVT prophylaxis | 556 patients | Patients receiving LDIVH are less likely to have delayed neurological deficits or cerebral infarction after aSAH |
2022 | Baek et al32 | -Retrospective - Post hemorrhage | -Patients undergoing endovascular embolization. - Two groups: Antiplatelet and non-antiplatelet group | Aspirin Clopidogrel | 108 patients | DCI, sonographic /angiographic vasospasm and neurological outcome at discharge were similar in two groups. -New cerebral infarction more frequent with antiplatelet use. |
2023 | Lee et al39 | -Meta-analysis -Pre and Post hemorrhage | -22 studies | Aspirin Clopidogrel Cilostazol | 4378 patients | Antiplatelet use was associated with lower rates of DCI and symptomatic vasospasm. |
2023 | Veldeman et al27 | -Retrospective -Two centers -Pre Hemorrhage | -Case-control study -- Patients divided into ‘‘anticoagulant user’’ and ‘‘non-user’’ | -Oral anticoagulants -Vitamin K antagonists | 964 patients | Similar rates of DCI in patients with anticoagulant use when compared to the controls. The use of oral anticoagulants or Vitamin K antagonists was not associated with unfavorable outcome. |
CSF Diversion
External Ventricular Drains:
External ventricular drainage has been the historical standard for cerebrospinal fluid (CSF) diversion due to its ability to concurrently reduce intracranial pressure (ICP) while removing blood products [40–42]. The amount of blood released during aneurysmal rupture has been directly correlated with the likelihood of developing DCI [43]. Despite its longstanding use and the theoretical benefit of blood removal, improvement of DCI rates with EVD has been questioned. Aggressive drainage has not been shown to decrease the incidence of DCI [44, 45]. Though this has been debated and some groups have shown a positive effect [46, 47]. It is theorized that blood breakdown products that may contribute to DCI settle outside of the ventricles, where EVDs exert their greatest effect [48, 49].
Basilar Cisternal Drainage:
To address the limitations of EVDs, neurosurgeons have attempted drainage from more inferior locations to capitalize on the gravity dependent accumulation of blood. Some studies have had difficulty displaying the benefits of cisternal lavage placements [50, 51]. However, some have found that cisternal basilar drainage placement can reduce the incidence of vasospasm [52, 53]. Nevertheless, cisternal drainage is still being analyzed in a clinical setting with the SPLASH trial in Southern Germany looking to use stereotactic catheter ventriculocisternostomy and is actively enrolling [54].
Lumbar Drainage:
In pursuit of more dependent areas of CSF drainage, lumbar drains have been hypothesized to remove blood from the subarachnoid space much more effectively, thereby reducing symptomatic vasospasm, cerebral infarction, and mortality [55, 56]. One study found that LD may reduce incidence of vasospasm, shorten hospital stay, and possibly improve patient outcomes following aSAH [57]. A computational fluid dynamics model was created to simulate LD and mimic a hemorrhagic event and ultimately validated predictions of LD benefits [58]. Another computational model corroborated this finding, adding that LD accelerates clearance of blood and thereby spasmogens [59]. In different meta-analyses and systematic reviews, LD placement was found to decrease the risk of DCI related complications and severe disability as well as reduced need for angioplasty and increased incidence of favorable GOS score at six month follow ups [60–70]. LD also showed reduced markers of oxidative stress, which is correlated with clinical outcome [71]. Lumbar puncture (LP) versus LD has also been analyzed, showing that serial LP may reduce incidence of CSF infection and accelerate clearance of toxic products [72, 73]. Some have hypothesized that LP may reduce the need for EVD or LD placement entirely. In one study, ½ of the patients with LP for deterioration from acute hydrocephalus did not require any sort of drain placement [74].
Overall comparison between EVD and LD found that LD was more successful at removing blood, reducing clinical vasospasm and risk of DCI as well as more rapid clot clearance [45, 60, 75, 76]. Two randomized control trials- LUMAS and EARLY DRAIN- have also demonstrated reduction in DCI and adverse secondary outcomes by LD, however both trials did not compare EVDs head-to-head with LDs [71, 77]. There is an active clinical trial in the United States aiming to definitively answer the question of superiority of one drain over the other for DCI (NCT03065231). The concern of downward herniation in cases of obstructive hydrocephalus is an important consideration when assessing for lumbar drainage.
CSF Filtration/Plasmapheresis:
Due to the success of early LD trials in comparison to EVD, CSF filtration has been a hypothesized avenue of innovation. One device, Neurapheresis, has been developed that offers the benefit of CSF clearance by filtration while also returning CSF back to the body [78]. CSF is removed, cleaned above physiological production rates, and returned to the lumbar spine. This method may reduce blood burden following aSAH more promptly compared to EVD or LD [79]. There is an active human trial of this novel CSF filtration device with primary evidence (N = 13) showing 59.2% reduction in RBC count and 71% protein reduced (NCT0287263). Since the causative factor(s) linking subarachnoid hemorrhage and DCI are not yet known, it has yet to be proven if filtration/lavage specifically eliminates the factors as done by and EVD or LD where CSF and all dissolved products are removed [80].
Hemodynamic and endovascular management
Hemodynamic:
The description of using fluids and pressors to augment cardiac output and increase cerebral blood flow for the treatment of vasospasm in SAH patients dates to the early seventies [81]. In addition, the detrimental effect of permissive hypertension in SAH patients suffering vasospasm has been documented [82]. The actual term triple-H was first coined in the early nineties and constituted the mainstay of treatment for angiographic vasospasm during the following two decades [81, 83, 84]. However, despite lacking evidence, the treatment was applied by the lion’s share of responders to a 2011 survey [85]. The biggest leap in DCI prevention came about after randomized testing of oral nimodipine as a primary prophylactic drug able to improve functional outcome, but without affecting the rate of angiographic vasospasm [86, 87].
Although triple-H treatment as such has never been tested in a randomized trial, but single components of the triad have been. In a randomized trial including 82 SAH patients, half were treated with prophylactic hypervolemia [88]. Patients receiving an additional 5% albumin solution on top of crystalloid baseline infusion, did not present with higher Xenon-CT measured cerebral blood flow (CBF) compared to the control group. In a Norwegian randomized study, prophylactic hypervolemic hypertension did not result in improved regional CBF on day 12 or clinical outcome after one year [89]. Ribdeau et al. randomized 41 SAH patients, to either receive moderate induced hypertension via norepinephrine or dobutamine infusion. The rate of angiographic vasospasm was equal in both groups, however, the dobutamine groups presented with a shortened ventilation time and intensive care length of stay [90]. Bulters at al. compared intra-aortic balloon counter pulsation with induced hypervolemia as a prophylactic measure against DCI [91]. In this randomized study, no differences were noted at 6 months clinical outcome as measured by the Glasgow outcome scale.
The IMPROVES trial compared prophylactic normovolemia versus hypervolemia and normotension versus induced hypertension. This small pilot trial included 20 SAH patients and demonstrated no differences in patients’ modified Rankin scales after 6 months [92]. In this study, preventive volume expansion was associated with a four-fold increased likelihood of suffering adverse events such as pulmonary edema or DCI. In a post-hoc matched case-control analysis of data gathered in the Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1) trial, colloid administration and hypervolemia were associated with poor clinical outcome [93]. More elaborate hemodynamic monitoring might be beneficial in severe SAH patients. So-called early goal-directed fluid therapy using pulse contour monitoring, proved advantageous in poor-grade SAH patients in relation to DCI occurrence and mRS after 3 months [94]. The Albumin in Subarachnoid Hemorrhage (ALISAH) Pilot Clinical Trial demonstrated promising results in patients receiving the lower tier albumin doses in respect to mRS after 3 months [95]. This dose-escalation study was, however, not powered to demonstrate a significant effect on DCI incidence and clinical outcome. No further information on the thereafter scheduled randomized ALISAH II trial has been published so far.
In a 2010 systematic review by Dankbaar et al. 11 studies including one RCT were analyzed applying one or more components of triple-H treatment. The authors rated the overall quality of studies as poor and concluded that there exists no good evidence from controlled studies in favor of any positive effect of triple-H or its separate components on CBF in SAH patients. In uncontrolled studies, hypertension seems to be more effective in increasing CBF than hemodilution or hypervolemia [96]. In the context of contemporary clinical evidence, the application of prophylactic hypertension, or hypervolemia has been abandoned. Hypervolemia carries the risk of systemic complications, mainly cardiac problems, pulmonary edema and hyponatremia whereas prophylactic induced hypertension, though increasing cerebral blood flow [97], does not prevent DCI or improve clinical outcome [84].
Endovascular:
Interventional neuroradiological treatment options can consist of transluminal balloon angioplasty to address proximal vasospasm or intra-arterial spasmolysis in case of more diffuse vasospasm. Due to the invasive nature of these treatments, the number of trials assessing prophylactic properties is limited. Prophylactic spasmolysis in case of asymptomatic angiographic vasospasm carries not only the risks associated with vessel catheterization but might even induce symptoms by disturbing compensatory mechanisms on a microcirculatory level [98]. To the best of our knowledge, there exist no clinical studies assessing the prophylactic properties of intra-arterial spasmolysis. This could be explained by the major drawback of vasopressor dependency when intra-arterial vasodilatory agents such as nimodipine or milrinone are used [99]. A pilot trial of prophylactic balloon angioplasty, with presumably rupture of the tunica medial of arterial vessels, disabling arterial constriction, demonstrated promising results [100]. In the subsequent randomized trial, Hunt Hess grade 3 SAH patients either received prophylactic balloon angioplasty or not [101]. This study revealed no significant differences between groups, in terms of clinical outcome after three months. With four iatrogenic vessels ruptures out of 85 treated patients, the rate of this potentially deadly complication (in this series, three out of four patients died) is high for a prophylactic procedure.
Conclusions and Future Predictions
Anesthetics
Based on the preclinical data, it appears that the inhaled anesthetics have a favorable profile over intravenous anesthetics in preventing DCI following aSAH. Anesthetic agents can exert multipronged and multilevel effects targeting various pathological mechanisms of occurrence of DCI (Fig. 1).
However, the clinical data available in literature regarding the effect of anesthetic agents on DCI is sparse and most of them are retrospective. The prospective ones were not powered to study the effects of anesthetics on DCI. Based on the current literature it is difficult to recommend the use of any anesthetic agent for prevention of DCI. Consequently, there is a need for robust prospective trials to address the effect of anesthetic agents on DCI following aSAH.
Anti-thrombotics
The data on the use of antiplatelets agents in patients with aSAH appears to demonstrate some advantage in prevention of DCI and improving neurological outcome. Though the use of antiplatelets seems to be safe, there is a wavering risk of hemorrhagic complications. The data on the use of anticoagulants is meager. In the current scenarios, and with the absence of good quality data, it is difficult to propose any definite recommendation for the routine use of antiplatelet therapy for prevention of DCI in patients with aSAH. There is a need for a large multicentric prospective study to evaluate the effect of antiplatelets agents in prevention of DCI following aSAH.
CSF Diversion
In cases of aSAH with non-obstructive hydrocephalus lumbar drainage should be considered the first line for the prevention of DCI. In cases where the risk of lumbar drainage outweighs the benefits, standard ventricular drainage should be performed. Even though EVD has been the historical standard, its effectiveness in preventing DCI is questionable, leading to the use of more anatomically dependent regions, like the cisterna magna and lumbar cisterns, as potentially more effective alternatives. Figure 2 shows a diagram demonstrating the preferential blood accumulation in the lumbar spine as a result of gravity (Fig. 2).
These lower regions may outperform EVD in reducing DCI and both this and Neurapherisis are being actively explored in clinical trials.
Hemodynamic and Endovascular
The maintenance of euvolemia before and during the vasospasm phase, is recommended as it is the best strategy to prevent DCI and improve functional outcomes after SAH [1]. Vasopressor induced hypertension should be reserved for patients diagnosed with DCI and not as a prophylactic measure [102].
The Induced Hypertension for Treatment of Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage (HIMALAIA) trial randomizing SAH patients suffering DCI into either receiving induced hypertension or not, yielded negative results [103]. Recruitment was halted prematurely based on slow inclusion rates and encountered side effects of the treatment [104]. Despite anecdotal treatment response to induced hypertension, the evidence in favor of hypertension in DCI treatment remains weak. Guided by multimodal neuromonitoring, blood pressure management can now be individualized in the form of a cerebral perfusion pressure optimal for cerebral autoregulation (CPPopt). Individualized and milder blood pressure targets might overcome the side effects encountered during induced hypertension. The concept has been developed and is finding clinical application in severe traumatic brain injury [105, 106]. So far, autoregulation guided blood pressure management has only been retrospectively assessed in SAH but shows promising results [107].
There is currently no evidence in support of prophylactic spasmolysis or angioplasty for asymptomatic angiographic vasospasm. In addition, both invasive procedures have complication profiles not justifying liberal preventive use.
There is accumulating observational evidence that intra-arterial spasmolysis in patients with refractory DCI not responding to induced hypertension might be beneficial. Careful patient selection, early weaning and patient (radiological or multimodal) monitoring during treatment are mandatory for optimal results.