Cerebral aneurysm treatment in India: Results of a national survey regarding practice patterns in India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.178044
Source of Support: None, Conflict of Interest: None
Background: The management of intracranial aneurysms (IAs) varies widely depending upon a number of factors.
Keywords: Aneurysm; clipping; coiling; India; subarachnoid hemorrhage
Aneurysmal subarachnoid hemorrhage (SAH) remains a challenging condition with a high rate of morbidity and mortality.  Prognosis following the occurrence of SAH is affected by multiple patient factors as well as by the therapeutic interventions instituted to prevent rebleeding and delayed cerebral ischemia following SAH.  These factors are, in turn, also influenced by the social trends existing in a specific geographical area. The International Subarachnoid Aneurysm Trial (ISAT) showed that in patients with SAH due to ruptured cerebral aneurysms that are amenable to both surgical clipping and endovascular coiling, the latter was associated with a significantly higher rate of independent survival at 1 year. 
Despite the existence of international guidelines, no specific guidelines exist for the management of cerebral aneurysms in India. In this study, we report the results of a survey of practice patterns in the management of cerebral aneurysms in India.
All active members (neurosurgeons, neurologists and neuro-radiologists) of the Neurological Society of India and the Neurological Surgeons Society of India were selected for the study. A total of 2088 participants were contacted through email. A reminder email was sent 2 weeks after the first. The study was conducted between February 16, 2015 and March 15, 2015.
The survey consisted of 23 questions and was set up using Google forms [Table 1]. All participants received the same set of questions. The main focus of the survey was on the management of vasospasm and the treatment modality of choice to secure the aneurysm. Participants were also asked to indicate the size of their community (rural, semi-urban, or urban), hospital setting (government-owned or private; teaching or nonteaching), average number of patients with intracranial aneurysms (IAs) treated each year, and availability of a neurointerventionist.
Statistical analyses were performed using SPSS version 21 (SPSS Institute, Chicago, IL, USA). The categorical variables were presented as percentages. To report continuous data, mean and standard deviation were calculated. To assess differences between categorical variables, Fisher's exact test was used. A P < 0.05 was considered statistically significant. Binary logistic regression analysis was performed to identify independent variables.
A total of 2088 physicians were contacted through email. Out of these, 604 emails were returned due to incorrect addresses. Additionally, four physicians replied indicating that they no longer practiced in India. Of the remaining 1480 participants to whom the email was delivered, 150 completed surveys were received (10.13% response rate).
Characteristics of the participant sample and the hospital setting
Not all participants answered all the questions. [Table 2] and [Table 3] show the summary of response characteristics. A majority of physicians worked in an urban setting (82%). Of the respondents, more than half (60.9%) worked in private owned hospitals and almost two-third in teaching hospitals. Notably, 36.8% of the surgeons worked at a hospital where neurointerventional service was not available. Majority (86%) of the physicians treated 50 or less patients with cerebral aneurysms in a year [Figure 1].
Medical management of subarachnoid hemorrhage
A number of questions were asked regarding the medical management of SAH. Notably, 50% of the respondents used steroids, at least in some cases. All the respondents used anti-epileptic drugs (AEDs) in patients with SAH except only one physician who never prescribed AEDs in SAH. Phenytoin was the anticonvulsant of first choice for two-thirds of the respondents. The participants were asked if they preferred to initiate triple-H therapy prophylactically in all the patients with SAH or only when vasospasm was suspected. Sixty-four percent always initiated triple-H therapy regardless of the presence of vasospasm. The target systolic blood pressure (SBP) during triple-H therapy was 140-160 mmHg in responses of 57.2% and 160-180 mmHg in responses of 29% of the participants. In patients with vasospasm resistant to medical management, intra-arterial infusion of vasodilators may be performed. Nimodipine was the drug of choice for intra-arterial infusion among 75.7% of the respondents, followed by papaverine in 18.6%.
Preoperative imaging and choice of therapy for aneurysm repair
Fifty-seven percent of the participants preferred digital subtraction angiography prior to aneurysmal repair whereas 41% preferred computed tomography angiography. Physicians were asked separate questions on their choice of treatment of ruptured and unruptured anterior circulation aneurysms other than those on the middle cerebral artery (MCA) aneurysms and posterior circulation aneurysms. Most physicians chose surgical clipping over endovascular coiling of anterior circulation aneurysms, and the difference was more pronounced in ruptured aneurysms and those located on the MCA. Most physicians preferred the pterional approach for clipping, with only 7% clipping aneurysms using the supraorbital approach. Endovascular therapy (EVT) was the first choice in the treatment of posterior circulation aneurysms in the responses of 82.9% of the physicians. Only 31.65% used additional tools for an intraoperative assessment of aneurysmal clipping, intraoperative near-infrared indocyanine green angiography being the most preferred method in 20.14% of the participants [Table 4]. The physicians were also asked questions on the timing of aneurysmal repair in patients with aneurysmal SAH in good grade (World Federation of Neurosurgical Societies [WFNS] Grades I, II, and III) and bad grade (WFNS Grade IV and V). Notably, 97.9% physicians preferred aneurysmal repair in the 1 st week after rupture in patients in a good grade, whereas 41% preferred to wait for a week before repairing the aneurysm in patients presenting with a bad grade. A majority of physicians (64.5%) performed postoperative angiography to assess for adequate aneurysmal clipping when deemed necessary; 9.3% never performed an angiography following aneurysmal clipping [Figure 2] and [Figure 3].
Comparison was made between preferences of physicians working at teaching and nonteaching hospitals. Physicians at teaching hospitals were more likely to perform > 50 cases in a year (P = 0.03). There was no significant difference in the use of steroids, antifibrinolytics, and mannitol or hypertonic saline for edema between physicians working at teaching and nonteaching hospitals. There was no difference in the choice of therapeutic intervention (clipping or coiling) for anterior circulation aneurysms. However, in general, for all aneurysms, physicians at nonteaching hospitals were more likely to choose EVT as the first line of treatment than those at teaching hospitals (P = 0.017). Physicians working at government-owned hospitals were more likely to not have neurointerventional facilities than those working in private-owned hospitals, although the difference was not statistically significant (P = 0.77) [Table 4].
On multivariate binary logistic regression analysis after adjusting for other factors, the only significant differences between the preferences of physicians in teaching and nonteaching hospitals were the choice of therapeutic intervention for posterior circulation aneurysms, the former preferring surgical clipping to EVT (P < 0.001) and that physicians at teaching hospitals were more likely to perform >50 cases each year. Comparing physician preferences at government- and private-owned hospitals, the only significant differences were the higher number of cases in government hospitals and the preference towards coiling of MCA aneurysms in private hospitals.
Our study shows that there are significant variations in the management of IAs in India. India is a vast country and studies to accurately predict the outcome of IAs are lacking. Apart from the patient and aneurysm-specific factors and institutional preferences that govern the decision to clip or coil aneurysms, other factors such as resource availability and utilization also guide treatment.
The role of corticosteroids in the management of SAH is debatable. Through their anti-inflammatory effect, they stabilize cell membranes, reduce free radical-induced cell damage and Ca 2+ influx in endothelial cells, smooth muscle cells, neurons and glial cells mediated by phospholipase A2. A Cochrane review of the role of corticosteroids in SAH and primary intracerebral hemorrhage revealed that there is no evidence of a beneficial or adverse effect of corticosteroids in these patients.  A randomized clinical trial of the role of high-dose methylprednisolone in patients with aneurysmal SAH, revealed that there was a significant decrease in the functional outcome at 1 year in the steroid group, although there was no reduction in the incidence of symptomatic vasospasm.  In our study, half of the respondents indicated that they used corticosteroids in patients with SAH. Other studies have reported their use in other countries between 35% and 78%. As such, the recent guidelines from the European Stroke Organization and the American Heart Association/American Stroke Association (AHA/ASA) do not recommend the routine use of steroids. , The role of AEDs in patients with SAH is also controversial. Some studies have reported no impact of seizures on the functional outcome , whereas others have found seizures to be independently associated with a worse outcome. ,, As such, the prophylactic use of AEDs is either not recommended; or, recommended only in the immediate posthemorrhage period. ,
Administration of prophylactic triple-H therapy (hypertension, hypervolemia, and hemodilution) is another area lacking consensus. A recent systematic review of the different triple-H therapy components suggested that induction of hypertension is more effective in increasing cerebral blood flow than hemodilution or hypervolemia alone.  Lack of evidence-based standards with regard to hemodynamic endpoints or utilization of specific therapeutic agents has led to substantial practice variations. A recent survey of neurocritical care providers revealed that 27% still induced prophylactic hypervolemia. The reported level of SBP aimed to be achieved ranged from 140 to 240 mmHg, with an associated mean arterial pressure ranging from 70-210 mmHg.  The American Heart Association/American Stroke Association (AHA/ASA) recommends maintenance of euvolemia for vasospasm prevention and induced hypertension for patients with active cerebral vasospasm. Furthermore, recommendations advised against the induction of hypervolemia prior to radiographic evidence of vasospasm.  As such, the focus of treatment has shifted to euvolemia and induced hypertension.  In our study, 64% of the respondents indicated that they routinely started triple-H therapy even when vasospasm was not suspected and 86.2% recommended a SBP between 140 and 180 mmHg.
Intra-arterial vasodilator therapy/angioplasty is considered for patients with symptomatic cerebral vasospasm not responding to hypertensive therapy.  Many vasodilator agents have been used, namely, calcium channel blockers (nimodipine, nicardipine, and verapamil), papaverine and milrinone. There is no definite evidence of benefit of one over the other; however, papaverine has been reported to be associated with significant neurotoxicity.  In our study, 3/4 th of the participants preferred nimodipine as the first choice for intra-arterial vasodilator therapy. In contrast, in another study, verapamil was the most common vasodilator for intra-arterial treatment followed by nicardipine and milrinone. Papaverine was used only by 7.3% of the responders.  In another international survey, nimodipine was the drug of choice among physicians in countries other than the United States. 
The choice of therapy for aneurysmal repair depends upon a number of factors related to the patient, aneurysmal morphology, and institutional experience. In addition, in developing countries, additional factors such as the cost of treatment and the need for follow-up also play a significant role. The advantages of surgical clipping include durability, lack of need for frequent follow-up and a lower cost. Also, the use of anti-platelet agents is obviated. However, the disadvantages include a slightly higher incidence of complications, especially in patients presenting with ruptured aneurysms. The advantages of EVT, on the other hand, include a short hospital stay and lower risk of complications when compared with clipping. , However, this comes at a higher cost, the need for frequent follow-up and the use of anti-platelet agents in some patients. Also, neurointerventional facilities are not available in all centers. This is supported by the fact that about a third of the physicians that participated in the survey worked at a hospital without neurointerventional facilities. During the long-term follow-up of patients in the ISAT trial, patients in the endovascular group were more likely to be alive and independent at 10 years compared to patients in the neurosurgery group. The cumulative risk of a rebleed from the target aneurysm was 0.0216 for patients in the endovascular group and 0.0064 for patients in the neurosurgery group. Although the rebleed risk was small, the probability of disability-free survival was significantly greater in the endovascular group than in the neurosurgical group at 10 years.  In our results, the physicians in teaching hospitals more often treated >50 patients/year and were more likely to recommend clipping for posterior circulation aneurysms than those at nonteaching hospitals. Although the reason is not known, higher volumes and thus greater experience in treating aneurysms among physicians in teaching hospitals may account for the latter observation.
In our study, the difference in the choice of treatment between physicians working at government-owned and private hospitals might be related to the fact that EVT is more resource intensive and expensive. In a global survey of neurosurgeons and interventional neuro-radiologists across 46 countries, coiling was more prevalent in North America and Europe as compared to clipping in rest of the world. The authors also predicted a trend towards coiling all across the globe in future along with an increase in flow diversion treatment and stenting in North America and Europe. 
The International Cooperative Study on the Timing of Aneurysm Surgery demonstrated that SAH patients who underwent surgery on posthemorrhage days 4-10 had worse outcomes than patients treated on days 0-3 and days 11-14. Based on these findings, it was concluded that patients who present with SAH on days 4-10 should have aneurysm surgery delayed until after day 10.  In contrast to the results from the trials which found no difference between early and delayed surgery, results were best in North American centers when surgery was planned between days 0 and 3 after the occurrence of SAH. These findings emphasized the need for an early diagnosis and referral for surgical intervention of North American patients suspected of having a ruptured cerebral aneurysm.  In our study, 41% of the physicians preferred treating the ruptured aneurysm after the 1 st week of rupture. Gupta et al., in a review of 99 patients with SAH presenting in poor clinical grade, argue that with an aggressive approach aimed at early clipping, the chances of rebleed are reduced and vasospasm can be managed more aggressively, thus improving the final outcome. 
The survey represents the perception of participant physicians about their daily practice in managing IAs and SAH. Despite the fact that the survey provides valuable information about the prevailing practices, it has inherent limitations such as recall bias in which the participants cannot remember numerical values accurately (e.g., number of cases per year). Response bias, in which the participant attempts to conceal some of the local practices, can also alter the results of the study. Adjustment for years in training, the location of the surgeons, and whether or not the physician was subspecialty trained, was also not done.
The survey described the prevailing patterns of management of IAs and SAH in India. Surgical clipping is the preferred treatment of choice for anterior circulation aneurysms and EVT for aneurysms along the posterior circulation. Corticosteroids and prophylactic triple-H therapy are still used by a large proportion of physicians.
We are thankful to all the physicians who took part in the survey.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]