Subarachnoid haemorrhage (SAH) is a significant cause of morbidity and mortality, with an approximate incidence of 9 per 100 000 per year.1 In the European community, it adds up to about 36 000 SAH cases per year. Despite improvements in surgical and medical treatment, rupture of an aneurysm is still associated with high incidences of fatality (one-third) and of severe disability (one-sixth).2,3 The prognosis is affected by multiple factors that can be influenced by therapeutic interventions and management procedures.4 In the last 3 years, three guidelines have been published for SAH management, with some conflicting recommendations.5–7 This lack of high-quality definitive data in some areas has led to numerous approaches to management and there is limited guidance on choosing among them. We conducted a European survey on the intensive and perioperative care of patients with SAH, working on the hypothesis that there would be significant practice variability among physicians treating SAH (anaesthesiologists and intensivists) and deficiencies in the implementation of evidence-based care.
Materials and methods
The survey questionnaire was approved by the Ethics Committee of the Hospital Clinic of Barcelona (number 8803). Completion of the questionnaire was voluntary and anonymous, and was considered as consent for participation in the survey. In accordance with the Economic and Social Research Council (ESRC) Framework for Research Ethics and Sage Publication ethical considerations, the survey software was configured to disable capturing of IP addresses, making it impossible to trace responders.
Development of questionnaire
The survey was based on an interactive web questionnaire. Thirty-one clinical determinants potentially affecting SAH management were identified through consultation with six experts in neuroanaesthesiology and neurointensive care (L.V., F.B., N.F., M.S., N.B., M.N.). The questionnaire investigated three areas: anaesthetic management of SAH during coiling and clipping procedures; the approach to the diagnosis of cerebral vasospasm in patients with confirmed ruptured cerebral aneurysms; and medical and interventional management of symptomatic cerebral vasospasm. The survey instrument was developed in English and put online using a dedicated software (Google Documents, http://docs.google.com). The following procedures were used to assess validity. We first ensured the clarity of the questionnaire, its relevance, completeness and accuracy by conducting semi-structured interviews with five physicians in one centre (Marseille, France). Some modifications were suggested and appropriate changes made. As a second step, seven physicians from another centre rated the final version for clarity, utility, content validity and redundancy. Overall, the proportion of satisfactory responses during the test phase was 90%.
Administration of the questionnaire
The link to the final questionnaire (see SDC Appendix 1) was e-mailed by the ENIG group through national societies of neuroanaesthesiology and neurointensive care in 12 European countries to anaesthesiologists and intensivists practising in centres with neurocritical care. No financial compensation was provided. The survey administration was carried out according to the principles of Dillman8 and the recommendations of Burns et al.9 The first e-mail was sent in October 2012, and two reminder mails were sent 2 and 4 weeks later. The survey remained online from early October to the end of November 2012. All responses were collected anonymously in a centralised database by L.V. and N.B. Interpretation of the assembled answers obtained through the questionnaire and exported as an Office Open XML was performed by all members of the working group.
Results for this study are reported as frequency, proportion (%) or median (interquartile range, IQR). For analysis, the χ2 multinomial test was used for categorical variables to assess the zero-order associations between countries and independent variables. A Fisher exact test was used to compare high-volume clipping and high-volume coiling treatment centres. All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 11.5 for Windows (IBM, Armonk, New York, USA). Differences were considered significant if P value was less than 0.05.
We received 268 completed surveys from 172 distinct institutions in 12 European countries during the period that the survey was online. For the purposes of this survey, responses from Great Britain and the Republic of Ireland were grouped together because there is a joint Neuroanaesthesia Society. The answers cover more than 80% of cities with over 300 000 inhabitants (SDC Figure S1) and 64% of the neurovascular centres identified as taking care of SAH in the seven most represented European countries (France, Italy, Germany, Spain, Great Britain and Ireland, Austria and Switzerland; SDC Table S1). The mean response per centre was 1.5. One hundred and ninety-seven physicians (73.5%) were working in an academic or a university-affiliated hospital. Respondents were neuroanaesthesiologists (30%), neurointensivists (25%) or both (45%). The main characteristics of the respondents and their institutions are summarised in Table 1.
Seventy-two percent of respondents admitted all patients after SAH to ICU, whereas 28% only admitted high-grade patients, World Federation of Neurosurgical Societies (WFNS) 3 to 5, to ICU. There were noticeable regional variations in this practice (χ2 38.7, df 7, P < 0.05); for example, 98% of respondents in Germany admitted all SAH patients to ICU, compared with 47% in Italy (Table 2; SDC Figure S2).
Aneurysm treatment and anaesthetic management
In our sample, 82% of respondents replied that aneurysm repair was conducted early (< 24 h after the initial SAH), 15% within 48 h after admission and 3% within 72 h (Table 1). A significant proportion of the institutions (66%) treated more than 60% of aneurysms by coiling (92% in Great Britain and Ireland vs. 39% in Italy; Fig. 1), only 18% clipped more than 60% of aneurysms and 16% used both methods equally, with striking variations among countries (χ2 53.9, df 7, P < 0.05; Fig. 1).
Less than half of respondents had an anaesthetic protocol in their institution (Table 2; SDC Figure S2). More than 70% of respondents used total intravenous anaesthesia for both clipping and coiling procedures. The most commonly used opioid was remifentanil (70%), whereas sufentanil was used by less than 20% of respondents (46% in France, none in Italy, Spain, Great Britain and Ireland, or Austria; Table 2). One-third of respondents used burst suppression for neuroprotection during temporary clipping (50% in Spain and Austria; Table 2), and 4% used perioperative hypothermia. No clear blood pressure target was identified for use during coiling, temporary clipping (SDC Figure S2) or in patients without vasospasm after the aneurysm was secured (data not shown). During the procedure, the most commonly used vasoconstrictor was norepinephrine (> 50%); metaraminol was used only in Great Britain and Ireland (Table 2).
Nineteen percent of respondents delayed recovery and tracheal extubation after uncomplicated clipping surgery in the postanaesthesia care unit (PACU) (6%) or the ICU (13%). Antiepileptic agents were administered only to patients with a history of seizures by 51% of respondents; only 20% used systematic prophylaxis, with a striking variation between countries (χ2 42.7, df 14, P < 0.05; e.g. 36% in Spain vs. 0% in Germany; Fig. 2).
Vasospasm prevention and neuromonitoring
For prevention of vasospasm (Table 3; SDC Figure S3A), nearly all respondents (97%) used nimodipine, 21% statins (44% in France; less than 10% in Spain, Great Britain and Ireland, and Germany) and 20% used magnesium (44% in Austria, 6% in Spain). Regarding neuromonitoring, most respondents (78%) routinely used transcranial Doppler (TCD) ultrasound to monitor vasospasm; computed tomography (CT) perfusion and CT angiography were used by 27 and 41%, respectively.
Management of symptomatic cerebral vasospasm
Nearly every respondent used induced hypertension (95%), with norepinephrine (90%) as the most commonly used agent in patients with symptomatic vasospasm (Table 3; SDC Figure S3B). Only 30% used hypertension alone; most respondents (66%) used it with hypervolaemia (44% used ‘triple-H’ therapy and 22% used ‘double-H’ therapy). No clear threshold for fluid volume in addition to standard fluid replacement was reported by respondents using ‘triple-H’ or ‘double-H’ therapy. Only a minority of respondents (22%) initiated hyperdynamic therapy to increase cardiac output in the presence of severe cerebral vasospasm. When it was used, 78% used dobutamine, 15% used milrinone and 7% used epinephrine.
When endovascular techniques were used to treat symptomatic vasospasm, 25% of respondents used an intra-arterial vasodilatator alone, 5% cerebral angioplasty alone and 50% both methods (Table 3; SDC Figure S3C). In high-volume clipping treatment centres (>60% of aneurysms clipped), 58% of respondents used endovascular methods to manage vasospasm compared with 86% at high-volume coiling treatment centres (P < 0.05). The most commonly used intra-arterial vasodilator was nimodipine (82%), but milrinone was used by 23% (58% in France; none in Italy, Spain, Great Britain and Ireland) and papaverine by 19%.
This large-scale European survey offers insights into the current practices and beliefs of anaesthesiologists and intensivists regarding SAH management. It was important to reassess the European practices because three guidelines have been published for SAH management since the last large survey.10 We found wide variability in the organisation of SAH care, the proportion of aneurysm repair procedures, the diagnostic approach to vasospasm and in the treatment goals of patients with symptomatic vasospasm following repair of the aneurysm.
According to European guidelines, patients should be monitored in an ICU or neurovascular unit.6 In this survey, SAH patients were routinely admitted to an ICU by 72% of respondents. It is interesting to note that the lowest rate (54%) was found in Great Britain and Ireland where the availability of ICU resources is scarce (3.5 beds per 100 000 population) and highest in Germany (98%) where ICU resources are large (24.6 beds per 100 000 population).11 Thus, differences in medical management may be due, in part, to differences in healthcare systems. There were also large differences among countries in the proportion of coiling vs. surgical clipping for securing the aneurysm. Despite the results of the International Subarachnoid Aneurysm Trial (ISAT)12,13 and improving experience with endovascular coiling, surgery is still used in a large proportion of patients and is still the most frequently used technique for aneurysm treatment in some centres.
Our survey shows that most clinicians maintain the mean arterial pressure (MAP) greater than 60 mmHg during aneurysm clipping or coiling. This is in agreement with data showing an increased risk of early and delayed neurological deficits with induced hypotension during aneurysm surgery.14,15 A minority of clinicians have no specific target for blood pressure, but there is no agreement on the target. This is not surprising because there is no agreement or recommendation on this matter, except minimisation of the degree and duration of intraoperative hypotension.5 Induced hypertension may be one method of brain protection during temporary clipping of a parent aneurysmal vessel to promote collateral blood flow and may explain why some respondents had a high target blood pressure (MAP >80 mmHg). The other main neuroprotective strategy used was drug-induced burst suppression, despite the absence of any prospective randomised blinded trial showing its efficacy. Perioperative hypothermia was very seldom used, most likely due to the negative Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST).16
One striking finding of this study is that the use of prophylactic anticonvulsants was noticeably variable among countries. The American Heart Association (AHA) guidelines do not recommend long-term use of anticonvulsants for prophylaxis, but advise that anticonvulsants should be considered in the immediate posthaemorrhage period.17 A 2011 conference concluded that seizure prophylaxis is controversial and, when used, 3-day treatment should be preferred over a longer term course.18 Finally, the European Stroke Organisation stated in 2013 that there is no evidence to support the prophylactic use of antiepileptic drugs and they should be administered only in patients with clinically apparent seizures.6 This controversy is reflected in the results of our survey and it seems that more European ICU physicians now consider antiepileptic prophylaxis than the findings of a previous international survey.10 Antiepileptic treatments have been associated with worse outcome in retrospective studies,19,20 but phenytoin, a drug with several side effects, was used most commonly.
Nimodipine was used by 97% of respondents for the prevention of vasospasm, in accordance with high-grade recommendations in all guidelines. Statin therapy was used by 21% of respondents to prevent vasospasm, with striking variations between countries. A recent meta-analysis reported no evidence of clinical benefit 21 and a large phase-3 trial [SimvasTatin in Aneurysmal Subarachnoid Hemorrhage (STASH)] has confirmed this result. Magnesium is used by 20% of respondents despite a recent large phase-3 trial [Magnesium for Aneurysmal Subarachnoid Haemorrhage (MASH-2)] and a meta-analysis showing no efficacy.22
Interestingly, TCD ultrasound is often used for the diagnosis of vasospasm despite its low sensitivity, especially for arteries other than the middle cerebral artery.23 Its use was variable from one country to another (e.g. 94% in France and 46% in Great Britain and Ireland). Despite its limitations, TCD was used by most respondents for detecting vasospasm in a previous international survey.10 The American Academy of Neurology (2004)24 and the latest AHA guidelines (2012)17 both support the use of TCD on the basis of high reliability in identifying severe vasospasm. In agreement with this statement, the 2011 consensus conference concluded that TCD is a useful screening tool for middle cerebral artery vasospasm, with less utility in evaluating other intracranial vessels.25
For the treatment of symptomatic vasospasm, nearly all respondents induced hypertension, in agreement with AHA guidelines.17 Again, the blood pressure target was variable, although a threshold of MAP of 90 mmHg was the commonest. This is an important issue because too low a blood pressure may not restore cerebral blood flow in poorly perfused areas and too high a blood pressure may worsen cerebral oedema and intracranial hypertension. Most respondents associated hypertension with hypervolaemia and haemodilution (‘triple-H’ therapy), despite weak evidence for the effectiveness of hypervolaemia and haemodilution in reversing delayed cerebral ischaemia. A systematic review of ‘triple-H’ therapy in 2003 concluded that there was a paucity of good quality clinical trials and inconsistencies around clinical end-points,26 and the latest AHA guidelines no longer support the use of ‘triple-H’ therapy.4
Another interesting aspect of our survey relates to the use of endovascular methods to treat symptomatic vasospasm, which was also noticeably different among countries. Nearly all respondents used either intra-arterial vasodilators or cerebral angioplasty. However, 25% did not use angioplasty, reflecting the reluctance of some neuroradiologists to perform this procedure. Milrinone for intra-arterial vasodilatation was used mostly in France and very little elsewhere. This may be explained by the publication of a prospective trial with milrinone by a French team in 2008 showing the importance of communication for changing medical practice.27
Our survey can be compared with a previous survey published in 2009 but undertaken in 2006.10 The authors noted heterogeneous clinical practices of ICU physicians treating SAH. This has not changed in the subsequent 6 years, although some practices seem to have evolved. The aneurysm is now secured earlier, within 24 h for the large majority of respondents. Endovascular treatment is not used much more frequently than 6 years ago, and in some countries, surgery is still widely performed. This reflects persistent uncertainty as to the best treatment in a large proportion of patients, despite the results of the ISAT trial showing better short-and long-term outcomes with coiling in selected patients.12,13 Prevention of delayed ischaemic deficits is probably the most important issue in the ICU once the aneurysm has been secured. Arterial hypertension is still the preferred treatment used by the vast majority of physicians, although no clear threshold for MAP was identified. In this survey, 25% of respondents never used endovascular treatment for vasospasm compared with 39% in 2009. This increase in use occurred in spite of a negative study of prophylactic angioplasty with procedure-related deaths published in 2008.28
Our survey has several limitations, particularly with regard to responder bias and generalisability. First, the number of respondents was probably low and we cannot accurately estimate it. This is because many respondents were recruited through a link to a website rather than directly by e-mail. Furthermore, in this study, we chose to evaluate reported practices and beliefs rather than actual practices. Therefore, the reported responses may reflect the ‘politically desirable’ answers rather than the actual practice of the respondents. Although it is possible that the survey respondents are representative of the broader population of physicians who manage SAH, we are not able to confirm this. We therefore believe that further studies are needed to evaluate current European practices regarding SAH management.
In conclusion, this survey revealed large degrees of heterogeneity in anaesthetic and intensive care management of SAH throughout Europe. We did not observe any clear improvement from 2006 to 2012 in the variability of practice, in spite of the publication of the AHA guidelines in 2007 and the Neurocritical Care European guidelines in 2011.7 One hypothesis to explain this is that the guidelines were not universally accepted by clinicians. More probably, this heterogeneity in clinical practice reflects differences in healthcare systems and the paucity of high-quality prospective randomised trials for establishing recommendations. This survey suggests areas for further research in neuroanaesthesia and the neurocritical care of SAH patients with regard to seizure prophylaxis with new antiepileptic agents and the treatment of vasospasm with intra-arterial therapies.
Acknowledgements relating to this article
Assistance with the survey: we would like to thank the following societies and their members who responded to the survey: Association des Neuro-Anesthésistes-Réanimateurs de Langue Française (ANARLF); Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI); Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor (SEDAR); Gruppo di Studio di Neuroanestesia e Neurorianimazione, della Societa Italiana di Anestesia, Analgesia, Rianimazione e Terapia Intensiva (SIAARTI); and the Neuroanaesthesia Society of Great Britain and Ireland (NASGBI).
Financial support and funding: none.
Conflicts of interest: none.
Presentation: this work was presented in part at the Annual Congress of the ESA, Barcelona, June 2013.
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