Discussion

Here, we present the results of an international survey of the management of cerebral vasospasm. Respondents included staff physicians and fellows, all representing a range of experience, with the majority being endovascular staff highly comfortable with aneurysm and vasospasm management. Different practices were found between conscious and unconscious patients concerning vasospasm screening and nimodipine intake.

Respondents showed a range of opinions regarding the initiation of intra-arterial treatment. However, most report a low threshold for initiating endovascular intervention in the setting of newly found clinical deterioration despite appropriate medical management.

We found a wide range of practice patterns in technique selection for the first-line endovascular therapy modality and even variation within selection of first-line chemical agents and angioplasty devices. Opinions on the effectiveness of each technique also varied.

These real-life data are of great interest especially if they are interpreted in light of the recently updated AHA/ASA guidelines published in 2012,14 Korean guidelines published in 2018,13 and new AHA/ASA guidelines15 published in 2023.

It is worth noting that the patterns of practice mostly met the annual volume requirements of the 2012 guidelines, with fewer than 17% of centers treating endovascularl less than the recommended 25 ruptured aneurysms. Indeed, the need for experienced cerebrovascular surgeons, neurointerventionalists, and multidisciplinary neuro-intensive care services are highly emphasized by experts and recommendations, stating that “low-volume hospitals (<10 aSAH cases per year) should consider early transfer of patients with aSAH to high-volume centers (>35 aSAH cases per year, Class I, Level B)”.14 Determination of the aneurysmal treatment modality between the endovascular option and neurosurgical clipping has to be made by experienced neurointerventionalists depending on the aneurysmal characteristics. When both techniques are feasible, the guidelines state “endovascular coiling should be considered” (Class I, Level B).14 International adherence to this recommendation, driven by results from the International Subarachnoid Aneurysm Trial (ISAT),16 is reflected by data from our survey, whereby only 30% of centers reported treating 25 or more ruptured aneurysms per year surgically compared with 82% percent of centers reporting treating >25 aneurysms endovascularly per year. In large volume centers, of course, > 25 aneurysms can be done with either technique.

As the aim of the initial management of patients with aSAH is to “prevent rebleeding, stabilization of neurologic states and prevent further deterioration”13; most of the patients were adequately monitored in an ICU or a stroke unit as required by Korean guidelines. In rare cases of a lack of ICU access, “early transfer to a specialized center is recommended” (Class III; Level B).13

Timing of the aneurysmal treatment is debated. We lack data comparing typical timelines for aneurysmal treatment including, day 0, night time of the first 24 hours and day 1. It is generally recommended to secure a ruptured aneurysms “within 72 hours from the initial bleeding to prevent rebleeding” (Class IIa; Level B).13 In our sample only 5% typically performed the aneurysmal treatment at day 2 or later, 11% intervened at day 0 whatever the time, 71% at day 0 during the day or day 1 otherwise, and 13% on day 1.

Screening and monitoring of arterial vasospasm is a standard of care. According to our respondents, mainstays of detection included daily transcranial Doppler in up to 79% of unconscious patients as recommended (Class IIa, Level B) when the neurologic examination is challenging to follow. Other modalities of screening are possible, for instance, CT perfusion was routinely performed in 32% of unconscious patients and AHA/ASA state it “may be useful to identify regions of potential brain ischemia” (Class IIa, Level B).14 Recent Korean guidelines recommend CT angiography and DSA, as well as perfusion CT (Class III; Level B). Daily transcranial Doppler remains the most frequently performed non-invasive screening method for any patient with an optimal sonographic window.

To prevent DCI, oral nimodipine should be administered to all patients with aSAH (Class I; Level A).14 This was also reflected as a standard of care across our respondents’ practices with 72% administering it orally and 23% by IV for conscious patients. In our survey, 5% of operators did not use any formulation of nimodipine. Nimodipine usage differed for unconscious patients where 45% received it by IV and 5% did not receive it. While nimodipine usage is evidenced based as described here, we did not explore the reasons why it is not routinely used in that 5% of centers. Intravenous nimodipine is a reasonable alternative for unconscious patients where the oral form cannot be given directly or by a nasogastric access (Class IIa; Level B).13 Other treatment modalities such as prophylactic hypervolemia and balloon angioplasty before the development of angiographic spasm is not recommended (Class III, Level B) and was not explored in our survey.

With respect to maximizing medical prevention and management of vasospasm and DCI, induction of elevated mean arterial pressures and systolic blood pressures are recommended (Class I, Level B).13 Cerebral angioplasty and/or selective intra-arterial vasodilator therapy “is reasonable in patients with symptomatic cerebral vasospasm”, particularly those who are “not rapidly responding to hypertensive therapy” (Class IIa; Level B). Physicians should first maximize medical therapy to alleviate symptoms, then consider the endovascular option in case of medical management failure. While this approach was common years ago as reported by a previous survey where physicians agreed that maximal critical care management should be attempted as a first-line therapy,10 our data suggest a change in practice with a majority (58%), now considering the endovascular option before maximizing the medical treatment.

There are no current guidelines or recommendations that favor one particular endovascular technique over another. Our real-world survey data show major differences in practices in terms of preferred first-line endovascular therapy techniques. Indeed, only 17% of responders judged chemical intra-arterial treatment effective in more than 75% of their cases; 65% reported the most effective treatment was mechanical angioplasty and specifically 71% judged balloon angioplasty to be more effective than chemical intra-arterial treatment. A large majority (79%) used chemical intra-arterial treatment as a first-line therapy, with a huge heterogeneity of medications. Intra-arterial nimodipine was the most used (40%). This apparent reluctance to use mechanical methods as first-line despite a better perceived efficacy over intra-arterial drugs may be explained by the reported risks associated with balloon angioplasty, such as rupturing blood vessels, vasospasm exacerbation, thromboembolism, and delayed stenosis.17 This belief is held despite reports on the relative safety and high efficacy of this strategy18 especially with balloon angioplasty.19–22

No specific recommendation is given concerning patients who undergo an endovascular therapy or for those where the first-line is ineffective. In our survey, 71% of physicians would start a second-line endovascular treatment within the same procedure in this case, 74% of them would use a mechanical treatment.

Imaging after endovascular therapy is not addressed by current guidelines. In our survey, CT and CTP were mainly performed in cases of endovascular complication, while 8.5% of responders performed it systematically after the procedure. The question of CTP after the endovascular treatment remains, especially for unconscious patients as it is not possible to evaluate them clinically. One could argue that systematically evaluating the effect of mechanical angioplasty in the absence of complications could be helpful in future decisions. Indeed, as angiographic vasospasm and its radiographic improvement does not always lead to clinical and robust hemodynamic improvement, absence of improvement on post-mechanical angioplasty CTP in unconscious patients could guide immediate and future strategy and help to avoid potential future DSA and balloon angioplasty and their inherent risks.

In recent publications on clinical practice of vasospasm monitoring/treatment, De Winkel et al23 reported significant practice variability in aSAH treatment worldwide among 145 participating centers, including in endovascular management. However, the survey was sent to many different specialties such as neurointensivists, and epidemiologists and did not focus on neurointerventionalists or endovascular management. No specific questions were asked on particular endovascular therapies, techniques, decision making or perceived effect of mechanical or chemical intra-arterial treatments. US-based physicians were the most represented (44%) in their survey, while they represent only 25% in our survey respondents, furthermore the results of their survey study was based on the perspective of aSAH center practice and not on each physician’s actual clinical practice. Our survey and the information presented here, is thus arguably more appropriate for the neurointerventionalist audience.

Picetti et al24 reported variability in monitoring and management strategies for DCI related to vasospasm after aSAH among 292 members of the European Society of Intensive Care Medicine and Neurocritical Care Society. Similarly to our results, they reported that neurological examination was the most frequent diagnostic modality to detect delayed neurological deficits related to DCI caused by cerebral vasospasm (95.2%), while in unconscious patients transcranial Doppler was the most frequent modality (68.5%). However, interestingly they reported that CTA was used to confirm the presence of vasospasm in most cases, whereas we report a lower use of routine CTP and CTA, in respectively 24% and 16% of patients. Intra-arterial procedures were used in only 59.6% of cases as second-line therapy in case of first-line failure, whereas we report that 98.5% of physicians would initiate an endovascular therapy to treat cerebral vasospasm in case of maximal medical management failure. Again, their survey respondents were a more heterogenous group compared with ours which was targeted only at neurointerventionalists.

Tjerkstra et al25 reported variations in the definition, diagnosis, and treatment of DCI among 79 intensivists, neurologists, and neurosurgeons in The Netherlands who answered all questions in the survey. Interestingly, they used CTP in a high proportion of patients (32%) if DCI was suspected, to rule out differential diagnoses and increase confidence in the DCI and vasospasm diagnosis. Very few questions were asked about endovascular management.

Screening and treatment remain highly heterogeneous especially between different endovascular options. Reasons for this are centered around lack of standardized practice or highly disseminated international guidelines from an absence of appropriate trials. Additional local factors may also include resource availability, different perspectives on best practice, low volume of cases with resultant lack of experience with balloon and stent-retriever angioplasty. Nevertheless, the effect of the different endovascular options and overall management with its effect on outcomes needs to be further elucidated so optimal evidence-based and cost-effective decisions can be made in post-aSAH vasospasm.

To this end, we have initiated two prospective trials, the Chemical and Mechanical Angioplasty for Vasospasm (SAVEBRAIN, NCT05268445 on clinicaltrial.gov) and the Brain Imaging after Non-traumatic Intracranial Hemorrhage (SAVEBRAINPWI, NCT05276934 on clinicaltrial.gov). SAVEBRAIN is an ongoing, single-center randomized trial among patients with vasospasm and DCI refractory to standard hospital care for whom both Chemical and Chemical+Mechanical Angioplasty are considered safe and potentially efficient by the treating neurointerventionalist. By random assignment to Chemical or Chemical+Mechanical Angioplasty, these data will help us to understand the role of mechanical angioplasty in the neurointerventionalist’s armamentarium. Primary outcome parameters include changes in perfusion parameters on CT, secondary outcomes include changes in post-treatment vessel caliber, morbidity and mortality.

We hope these studies will improve our knowledge of such patients and help to determine an evidence-based approach to achieve a uniform standard of best practice for the endovascular management of patients with DCI and cerebral vasospasm.