Intensive care practices in brain death diagnosis ... - Wiley Online Library

Anaesthesia 2015, 70, 1130–1139

doi:10.1111/anae.13065

Original Article Intensive care practices in brain death diagnosis and organ donation D. Escudero,1 M. O. Valentın,2 J. L. Escalante,3 A. Sanmartın,4 M. Perez-Basterrechea,5 J. de Gea,4 M. Martın,6 J. Velasco,7 T. Pont,8 N. Masnou,8 B. de la Calle,9 B. Marcelo,10 M. Lebr on,11 J. M. Perez,12 M. Burgos,12 R. Gimeno,13 P. Kot,14 S. Yus,14 I. Sancho,15 A. Zabalegui,16 M. Arroyo,16 E. Mi~ nambres,17 J. Elizalde,18 J. C. Montejo,19 B. Domınguez-Gil2 and R. Matesanz20 1 Head of Department, 6 Staff Intensivist, Intensive Care Unit, 5 Clinical Researcher, Unit of Transplants, Cell Therapy and Regenerative Medicine, Central University Hospital of Asturias, Oviedo, Spain 2 Staff Nephrologist, 20 Chief Director, Spanish National Transplant Organization (ONT), Madrid, Spain 3 Staff Intensivist and Head of Hospital’s Transplant Program, 9 Head of Department, Intensive Care Unit, Gregorio Mara~ non University Hospital, Madrid, Spain 4 Staff Intensivist, Intensive Care Unit, Virgen de la Arrixaca Hospital, Murcia, Spain 7 Staff Intensivist, Intensive Care Unit, Son Espases University Hospital, Palma de Mallorca, Spain 8 Staff Intensivist, Intensive Care Unit, Vall D0 Hebron Hospital, Barcelona, Spain 10 Staff Intensivist, Intensive Care Unit, Infanta Cristina University Hospital, Badajoz, Spain 11 Staff Intensivist, Intensive Care Unit, Carlos Haya Hospital, Malaga, Spain 12 Staff Intensivist, Intensive Care Unit, Virgen de las Nieves University Hospital, Granada, Spain 13 Staff Intensivist, Intensive Care Unit, La Fe University Hospital, Valencia, Spain 14 Staff Intensivist, Intensive Care Unit, La Paz University Hospital, Madrid, Spain 15 Staff Intensivist, Intensive Care Unit, Miguel Servet University Hospital, Zaragoza, Spain 16 Staff Intensivist, Intensive Care Unit, General Yag€ ue Hospital, Burgos, Spain 17 Staff Intensivist, Intensive Care Unit, Marques de Valdecilla University Hospital, Santander, Spain 18 Staff Intensivist, Intensive Care Unit, Asistential Complex of Navarra, Pamplona, Spain 19 Head of Department, Intensive Care Unit, 12 de Octubre University Hospital, Madrid, Spain

Summary We conducted a multicentre study of 1844 patients from 42 Spanish intensive care units, and analysed the clinical characteristics of brain death, the use of ancillary testing, and the clinical decisions taken after the diagnosis of brain death. The main cause of brain death was intracerebral haemorrhage (769/1844, 42%), followed by traumatic brain injury (343/1844, 19%) and subarachnoid haemorrhage (257/1844, 14%). The diagnosis of brain death was made rapidly (50% in the first 24 h). Of those patients who went on to die, the Glasgow Coma Scale on admission was ≤ 8/ 15 in 1146/1261 (91%) of patients with intracerebral haemorrhage, traumatic brain injury or anoxic encephalopathy; the Hunt and Hess Scale was 4–5 in 207/251 (83%) of patients following subarachnoid haemorrhage; and the National Institutes of Health Stroke Scale was ≥ 15 in 114/129 (89%) of patients with strokes. Brain death was diagnosed exclusively by clinical examination in 92/1844 (5%) of cases. Electroencephalography was the most frequently used ancillary test (1303/1752, 70.7%), followed by transcranial Doppler (652/1752, 37%). Organ donation took place in 70% of patients (1291/1844), with medical unsuitability (267/553, 48%) and family refusal (244/553, 13%) the main reasons for loss of potential donors. All life-sustaining measures were withdrawn in 413/553 of non-donors (75%). .................................................................................................................................................................

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Escudero et al. | Brain death diagnosis and organ donation

Anaesthesia 2015, 70, 1130–1139

Correspondence to: D. Escudero Email: [email protected] Accepted: 13 February 2015

Introduction The diagnosis of brain death has important medical, ethical and legal implications, because it may entail the withdrawal of all life-sustaining measures, or the recovery of organs for transplantation. Brain death diagnosis is based on clinical examination, in accordance with international standards [1–3]; nevertheless, under certain clinical conditions, ancillary testing might also be necessary. These tests vary according to legislation in different countries; in Spain, the law clearly defines the circumstances under which ancillary testing is mandatory [4]. Electrophysiological studies, including electroencephalography (EEG) and evoked potentials, may be performed; assessment of cerebral blood flow is recommended, however, if the patient has received sedative drugs, has severe facial trauma, or will not tolerate the apnoea test. These tests include four-vessel cerebral angiography, multi-section computed tomography (CT) cerebral angiography [5, 6], cerebral scintigraphy [7] and transcranial Doppler [8]. There is significant variation in how brain death is diagnosed in different countries with differing legal provisions, and even between different geographical areas and hospitals within the same country. Significant variability has also been observed regarding the clinical decisions made once brain death is confirmed [9–14]. These differences have previously been addressed, with the aim of working towards uniformity and standardisation of the diagnosis of brain death [15–17]. In Spain, a clinical condition consistent with brain death is present in 8% of deaths occurring in intensive care units (ICUs) of hospitals without neurosurgery and in 13% of deaths in hospitals with neurosurgery [18], rising to as high as 33% in hospitals with neurocritical care units [19]. However, the potential for organ donation following brain death is diminishing; potential donors after brain death in Spain decreased from 65.2 cases per million population in 2001, to 49 cases per million population in 2010 [18]. Neverthe© 2015 The Association of Anaesthetists of Great Britain and Ireland

less, the actual proportion of organ donors has been maintained at over 30 donors per million population [20]. In 2012, 4211 solid organs were transplanted, of which 90% were obtained from donors following brain death. Nevertheless, the shortage of organs for transplantation remains a problem, resulting in the death of about 10% of patients on the transplant waiting list, and efforts must continue to be made to optimise the process of donation after brain death. This study aimed to: (i) increase knowledge of the epidemiological and clinical features of patients diagnosed with brain death; (ii) investigate the process of determination of death based on neurological criteria; (iii) analyse the clinical decisions made after the diagnosis of brain death; and (iv) study differences in practice among hospitals with and without neurosurgery.

Methods We performed a multicentre, observational study in Spain, in collaboration with the Working Group on Transplantation of the Spanish Society of Intensive and Critical Care and Coronary Units (SEMICYUC), and the Spanish National Transplant Organization (ONT). Approval from an Ethics Committee was not considered necessary because of the observational design of the study, which expanded on data routinely collected by the Spanish Quality Assurance Program during the deceased donation process [18]. Forty-two Spanish ICUs, 30 from hospitals with neurosurgery and 12 from hospitals without it, with a total of 1827 beds, participated in the study (Appendix 1). All the hospitals were provided with an identification code to assure confidentiality of the data obtained. We included patients diagnosed with brain death during the period between 1 January 2010 and 30 June 2012. Brain death was diagnosed in the presence of a severe structural brain lesion, a Glasgow Coma Scale (GCS) of 3/15, and absence of brainstem reflexes in normothermic patients who had no significant metabolic abnormalities, or residual effects of 1131

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sedative drugs. Clinical examination, atropine testing, an apnoea test based on the absence of spontaneous ventilation with partial pressure of carbon dioxide > 7.98 kPa, and ancillary tests were performed, following international scientific recommendations [1–3, 5–8] and Spanish legislation [4]. In Spain, the law mandates that three medical doctors confirm the diagnosis of brain death; one of them must be a neurologist or neurosurgeon. We defined an actual donor as being a person from whom at least one organ was recovered for transplantation, and circulatory arrest as asystole occurring after the diagnosis of brain death, and before organ recovery for transplantation. We collected information including age and sex, the aetiology of the condition, hospital and ICU length of stay, and severity scores on admission, according to the different diagnoses. The GCS [21] was used for traumatic brain injury, intracerebral haemorrhage and anoxic encephalopathy, the Hunt & Hess Scale [22] for subarachnoid haemorrhage, and the National Institutes of Health Stroke Scale for stroke [23]. Ancillary tests used for the diagnosis of brain death were analysed, and the following were also studied: whether organ donation occurred; causes of potential donor losses; and clinical decisions made after the diagnosis of brain death, when organ donation did not occur. Chi-squared or Fisher’s exact testing was performed where appropriate. We used one-factor ANOVA for comparison when the variables were normally distributed, and the Mann–Whitney U-test when they

were not normally distributed. Statistical significance was considered as a p value < 0.05. SPSS 15.0 (SPSS Inc., Chicago, IL, USA) was used for the analysis.

Results During the study period, a total of 1844 patients were diagnosed with brain death, 1620 (88%) in ICUs of hospitals with neurosurgery, and 224 (12%) in ICUs of hospitals without it (Table 1). The most frequent cause of brain death was intracerebral haemorrhage, followed by traumatic brain injury, subarachnoid haemorrhage, stroke, anoxic encephalopathy and brain tumours (Table 1). When comparing hospitals with or without neurosurgery, there were statistically significant differences in patterns of brain injury, with intracerebral haemorrhage more frequent in those hospitals without it, while traumatic brain injury was more frequent in hospitals that offered neurosurgery. A majority (1090, 59%) of patients were males, and the remainder (754, 41%) were females. Mean age was significantly higher in those hospitals without neurosurgery and the age of patients differed depending on the cause of death (Table 1). Barbiturates were used in 276 patients (15%), with a significantly higher frequency in those hospitals with neurosurgery (17% vs 3%; p < 0.0001). The admission GCS was ≤ 8/15 in 91% of patients who went on to die due to intracerebral haemorrhage, traumatic brain injury or anoxic encephalopathy, while the Hunt and Hess Scale was 4–5 in 83% of those who died following a subarachnoid haemorrhage, and

Table 1 Aetiology of brain death and comparison between hospitals with or without neurosurgery. Values are number (proportion) or mean (SD). Hospitals with neurosurgery

Total n Intracerebral haemorrhage Traumatic brain injury Road traffic collision-related Other trauma Subarachnoid haemorrhage Anoxic encephalopathy Stroke Brain tumours Other causes Total

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769 343 131 212 257 174 173 31 97 1844

(42%) (19%) (7%) (12%) (14%) (9%) (9%) (2%) (5%) (100%)

Age

n

64 52 44 57 58 47 62 48 48 58

643 324 125 198 227 156 156 29 85 1620

(14) (22) (23) (19) (13) (21) (14) (21) (21) (18)

(40%) (20%) (8%) (12%) (14%) (10%) (10%) (2%) (5%) (88%)

Hospitals without neurosurgery Age

n

63 52 43 57 57 47 61 48 45 58

126 19 6 14 30 18 17 2 12 224

(15) (22) (23) (19) (13) (21) (15) (21) (20) (18)

(57%) (10%) (3.2%) (7.4%) (14%) (8%) (8%) (1%) (5%) (12%)

Age

p value

69 59 46 65 66 49 66 55 70 66

< 0.001 NS NS NS < 0.001 NS NS NS < 0.001 < 0.001

(13) (19) (20) (14) (15) (16) (15) (11) (15)



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the National Institutes of Health Stroke Scale was ≥ 15 in 89% of those who died due to stroke (Table 2). The length of ICU stay was ≤ 24 h in 50% of cases (Fig. 1). Nevertheless, we observed significant differences when comparing hospitals with or without neurosurgery; the proportion of patients who died within the first 24 h was higher in those without it (59% vs 48%, p = 0.005). The median (IQR) length of stay also differed according to severity at admission, with statistically significant increases in length of stay in less severely brain-injured patients: one (1–2) day for patients with GCS 3–5; two (1–5) days for

patients with GCS 6–8; and three (2–8) days for those with GCS > 8 (p < 0.0001 for 3–5 days vs 6–8 days and > 8 days; and p = 0.002 for 6–8 vs > 8). Finally, median (IQR) length of ICU stay was longer in patients who had received barbiturates compared with those who had not: two (1–5) vs one (1–4) day, p = 0.002). The diagnosis of brain death was based exclusively on clinical examination in only 92 patients (5%), while at least one ancillary test was used in 1752 patients (95%). The ancillary tests most frequently used were EEG (74%), transcranial Doppler

Table 2 Severity scores on admission at ICUs. Values are number (proportion). Hospitals with neurosurgery n

Hospitals without neurosurgery n

Scale

Total n

Intracerebral haemorrhage, traumatic brain injury and anoxic encephalopathy

GCS 3–5 GCS 6–8 GCS > 8 Total

966 180 115 1,261

(77%) (14%) (9%) (100%)

830 162 109 1,101

(75%) (15%) (10%) (100%)

136 18 6 160

(85%) (11%) (4%) (100%)

Subarachnoid haemorrhage

HHS 1 HHS 2 HHS 3 HHS 4 HHS 5 Total

6 12 26 70 137 251

(2%) (5%) (10%) (28%) (55%) (100%)

6 10 23 65 121 225

(3%) (4%) (10%) (29%) (54%) (100%)

0 2 3 5 16 26

(8%) (12%) (19%) (62%) (100%)

15 33 59 22 129

(12%) (26%) (46%) (17%) (100%)

13 32 53 20 118

(11%) (27%) (45%) (17%) (100%)

2 1 6 2 11

(18%) (9%) (55%) (18%) (100%)

Stroke

NIHSS NIHSS NIHSS NIHSS Total

< 15 15–19 20–25 > 25

GCS, Glasgow Coma Scale; HHS, Hunt & Hess Scale; NIHSS, National Institutes of Health Stroke Scale.

Figure 1 Length of ICU stay in hospitals with (black) and without (grey) neurosurgery. © 2015 The Association of Anaesthetists of Great Britain and Ireland

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(37%), cerebral scintigraphy (8%), CT with cerebral angiography (2.5%), evoked potentials (2%) and fourvessel cerebral angiography (0.5%) (Fig. 2). The ancillary tests were used with the same frequency in hospitals with and without neurosurgery, except for CT with cerebral angiography, which was performed more commonly in hospitals without it (12% vs 3%, p < 0.000). Moreover, 413 patients (22%) had brain death diagnosed by clinical examination, EEG and one additional ancillary test. Transcranial Doppler was the investigation most commonly used in those cases (356 patients).

A total of 1291 of the 1844 patients (70%) became actual organ donors (Fig. 2). There were no significant differences between hospitals with or without neurosurgery. The most frequent causes of loss of potential donors of the 553 patients who did not go on to donate were medical unsuitability in 267 patients (48%), and relatives’ refusal in 244 (44%). Circulatory arrest during potential donor management occurred in only nine of the non-proceeding donors (2%). Clinical decisions made regarding patients who did not donate organs were as follows: withdrawal of all life-sustaining measures (including mechanical ventilation); partial

Figure 2 Patients studied and outcomes following the diagnosis of brain death. CT, computed tomography; LST, life-sustaining treatment; MV, mechanical ventilation. 1134



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withdrawal, with suspension of the use of vasoactive drugs; progressive withdrawal; and no withdrawal at all, with full organ support. Withdrawal of all types of life-sustaining treatments was performed in 413 (75%) of the 553 patients diagnosed with brain death who did not become actual donors (Fig. 2).

27]. Furthermore, the majority (89%) of patients who died due to stroke had a National Institutes of Health Stroke Scale score of ≥ 15, which predicts severe neurological deficit and high mortality [28]. Length of ICU stay depended on severity at admission: as severity increased, the length of stay decreased. In general, patients deteriorated rapidly to brain death (50% in the first 24 h). Such a short stay may justify the use of an ICU bed for those patients in whom ongoing treatment has been ruled out based on futility of further therapy, to facilitate organ donation following brain death. It has been estimated that a multi-organ donation of six organs provides 55.8 years of life to the various recipients [29], which supports this practice from the perspective of the bioethical principle of justice. As already stated, these cases do not consume significant resources, since most patients rapidly evolve to brain death. For these reasons, it is routine practice within Spanish ICUs to admit patients with catastrophic brain injury, in whom rapid deterioration to brain death is anticipated. This fact may contribute to the high rates of organ donation in Spain. Healthcare professionals should enquire as to the patient’s wishes regarding organ donation after death, and/or obtain consent from the patient’s relatives before admission to the ICU. Furthermore, the likelihood of evolving to brain death should be assessed [30]. Although indicators of poor prognosis are not infallible in predicting either mortality or the time to death, they may help to identify a group of patients who are a priori expected to deteriorate, and be diagnosed with brain death. The GCS on admission and a haematoma volume ≥ 60 ml are the most important factors predicting mortality in intracerebral haemorrhage [31], with a worse prognosis if there is an associated intraventricular haemorrhage [32]. Hemphill’s Intracerebral Haemorrhage Score may also be useful [33]. Some authors have proposed the concept of imminent brain death to recognise potential donors. This is defined as a state of deep coma (GCS 3/15), with irreversible catastrophic brain injury of known aetiology, and the absence of three or more brainstem reflexes, in a patient requiring mechanical ventilation who is admitted to an ICU [34]. Jansen et al. reviewed 4814 deaths in ICUs of university hospitals in the

Discussion This is, to our knowledge, the largest published series providing specific clinical data on brain death in intensive care. The 1844 patients included in the study account for 30% of cases of brain death reported to the National Quality Assurance Program in the Deceased Donation Process in Spain during the same period [18]. Our results have confirmed the trend towards increased mean age, as well as a change in the aetiology of brain death over the years in Spain. The decline in traumatic brain injury as a cause of brain death can be explained by the decrease in traffic accidents common to many European countries [24]. The reduced incidence of subarachnoid haemorrhage in our series possibly resulted from a better clinical approach to this pathology, including the development of an Interventional Neuroradiology Services Network for early endovascular treatment. In contrast to other European studies [25], the most frequent cause of brain death in Spain was intracerebral haemorrhage. We hypothesise that the cause for this is the widespread practice in our country of admitting all patients with devastating intracerebral haemorrhage, including those of advanced age, to critical care, to allow for the possibility of donation once ongoing active care has been deemed futile. All categories of brain injury were of high severity on admission to the ICU. The GCS was ≤ 8/15 in 91% of the patients admitted, with 77% of those having a GCS ≤ 5/15. Patients admitted to hospitals without neurosurgery were older, and had even higher injury scores. The higher age and severity of those patients with catastrophic neurological injuries may explain the clinical decisions made to not transfer those patients to neurosurgical referral centres. More than 80% of patients who died due to subarachnoid haemorrhage scored 4–5 on the Hunt & Hess Scale, while a further 10% scored 3. This also confirms the high severity on admission, and hence a high expected mortality [26, © 2015 The Association of Anaesthetists of Great Britain and Ireland

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Netherlands [35]. Of the imminent brain death cases, 45.6% ultimately fulfilled formal brain death criteria, compared with 33.6% in the larger group categorised as having severe brain injury. These results show that the concept of imminent brain death enables the recognition of those patients who are likely to deteriorate to brain death. This information may aid the decisionmaking process. In Spain, ancillary tests are only mandatory in cases of persisting effects of sedative drugs, severe facial trauma, inability to perform the apnoea test, or infratentorial lesions. Although it is legally possible to make a diagnosis based exclusively on clinical examination, this was done in only 5% of the cases. This percentage was lower than the 11% found in a Spanish multicentre study performed during 1995–1996 [36]. Besides clinical examination and EEG, an additional instrumental test was carried out in 22% of cases. Compared with the previous study, the use of EEG has decreased from 86% to 74%, while the use of transcranial Doppler has increased from 15% to 37% [37]. These changes can be ascribed to the wide availability of transcranial Doppler in the ICU, which can be performed by intensivists at the bedside. The diagnosis of brain death is thus not dependent on other professionals or additional resources. Ancillary tests that require transferring the patient outside the ICU, such as cerebral scintigraphy or CT with cerebral angiography, were less frequently used. The use of conventional four-vessel cerebral angiography, long considered to be the gold standard, seems to be progressively decreasing, because it is primarily used for endovascular radiological therapy in specialist units. This confirmatory test has largely been replaced by multi-section CT with cerebral angiography, which was used more often in hospitals without neurosurgery. Diagnosing brain death entails great responsibility, because it implies withdrawal of all life-sustaining measures, with the potential recovery of organs for transplantation. This may explain the significant use of ancillary tests, although they may be scientifically unnecessary. Our findings contrast with those of other European studies, which show that brain death testing is not performed in up to 30% of cases with a clinical condition consistent with brain death,

resulting in what could be an avoidable loss of potential donors [35]. Nevertheless, as our study was performed in Spain, comparison with other countries is limited, due to different policies and guidelines for the diagnosis of brain death. The rate of organ donation in our study was high, with 70% of brain death cases becoming actual donors. This conversion rate exceeds that described in other American and European studies [36–40]. A possible explanation for the large number of actual donors may be a consequence of the participation of intensive care specialists in the deceased donation process, which is a key feature of the well-known Spanish model. Our study demonstrated excellent results in terms of donor optimisation; only 0.4% of patients diagnosed with brain death suffered circulatory arrest, compared with 5% observed in previous studies [36]. Medical unsuitability as a reason for potential donor loss has decreased from 26% to 14% of potential donors. This may be due not only to greater transplantation experience, with more organs accepted from extended criteria donors, but also to the high participation of hospitals with neurosurgery. The percentage of relatives who declined consent has decreased significantly from 27% to 13% [36], possibly due to a policy based on media support and widespread acceptance among the Spanish population. Other factors that may be significant include courses provided in Spain that specifically train both intensive care specialists and transplant co-ordinators in the family approach [41]. The decision to withdraw all organ support should be consistently applied following the diagnosis of brain death, and in Spain is regulated by law; an individual is dead from the moment brain death is confirmed [4]. To our knowledge, there are no ethical justifications for artificially maintaining a deceased person on life support, except where organ donation is possible, or in exceptional situations, such as where brain-dead women are pregnant with viable fetuses. Ongoing organ support in all other cases is strongly discouraged, because it results in unnecessary and futile use of resources. Surprisingly, withdrawal of all treatment after the diagnosis of brain death took place in only 75% of the patients who did not go on to become organ donors. This suggests that brain death is still

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not considered equivalent to the death of the person by circulatory criteria by some healthcare professionals, even 45 years after the publication of the first criteria for the diagnosis of brain death [42]. However, considering that withdrawal of all organ support in patients diagnosed as brain dead, but who were not organ donors, took place in only 39% of cases between the years 1995–1996 [36], we may infer that there has been a significant alteration in this clinical decision process. Maintenance of organ support after the diagnosis of brain death has been observed in several studies from different cultural and geographical regions with a limited history in transplantation [10, 43–46]. Despite the aforementioned publications, we are not aware of studies from other countries that evaluate the withdrawal of support in detail, so we cannot compare our results. This analysis of our large case series may provide a basis to establish international comparisons, and gain knowledge to improve end-of-life care practice in our ICUs. Our data also showed that professional practices change slowly, that specific training is required regarding the concept and diagnosis of brain death, and that we should continue to promote good clinical practice to ensure the availability of organs for transplantation.

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Acknowledgements We acknowledge ONT, with special thanks to Mr. L. Gallardo, for providing all the informatics support needed for the development of the study, as well as SEMICYUC for its dedicated support. We also thank Dr. J. Escudero (Department of English Philology, University of Oviedo) for her review of the manuscript, as well as all those investigators who have participated in case collection (Appendix 1).

Competing interests No external funding and no competing interests declared.

References 1. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Practice parameters for determining brain death in adults. Neurology 1995; 45: 1012–4. 2. Wijdicks EFM, Varelas PN, Gronseth G, Greer D. Evidence-based guideline update: determining brain death in adults. Neurology 2010; 74: 1911–8. © 2015 The Association of Anaesthetists of Great Britain and Ireland

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22. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. Journal of Neurosurgery 1968; 28: 14–20. 23. Goldstein LB, Bertels C, Davis JN. Inter-rater reliability of the NIH stroke scale. Archives of Neurology 1989; 46: 660–2. 24. People killed in road accidents. European Commission. Eurostat data. www.epp.eurostat.ec.europa.eu/portal/page/portal/ product_details/dataset?p_product_code=TSDTR420 (accessed 07/22/2013). 25. Kompanje EJ, de Groot YJ, Bakker J. Is organ donation from brain dead donors reaching an inescapable and desirable nadir? Transplantation 2011; 91: 1177–80. 26. Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid haemorrhage. New England Journal of Medicine 2006; 354: 387–96. 27. Wijdicks EFM, Kalmess DF, Manno EM, Fulgham JR, Piepgras DG. Subarachnoid haemorrhage: neurointensive care and aneurysm repair. Mayo Clinic Proceedings 2005; 80: 550–9. 28. Adams HP Jr, Davis PH, Leira EC, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 1999; 53: 126–31. 29. Schnitzler MA, Whiting J, Brennan D, et al. The live years saved by a deceased organ donor. American Journal of Transplantation 2005; 5: 2289–96. 30. Martin-Lefevre L, Jacob JP, Pessionne F. Management of organ donation for patients with severe coma due to cerebrovascular stroke. Revue Neurologique 2011; 167: 463–7. 31. Broderick J, Brott T, Duldner J, Tomsick T, Huster G. Volume of intracerebral haemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 1993; 24: 987–93. 32. Jaffe J, Alkhawam L, Du H, et al. Outcome predictors and spectrum of treatment eligibility with prospective protocolized management of intracerebral haemorrhage. Neurosurgery 2009; 64: 436–45. 33. Hemphill JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral haemorrhage. Stroke 2001; 32: 891–7. 34. De Groot YJ, Jansen NE, Bakker J, et al. Imminent brain death: point of departure for potential heart-beating organ donor recognition. Intensive Care Medicine 2010; 36: 1488–94. 35. Jansen NE, de Groot YJ, van Leiden HA, et al. Imprecise definitions of starting points in retrospectively reviewing potential organ donors causes confusion: call for a reproducible method like ‘imminent brain death’. Transplantation International 2012; 25: 830–7. 36. Escalante JL, Escudero MD, Nolla M, Navarro A y Grupo de Trastico de Muerte bajo de Trasplantes de la SEMICYUC. Diagno ntrico. Revista Portuguesa de MediEncef alica. Estudio multice cina Intensiva 1998; 7: 107. 37. Barber K, Falvey S, Hamilton C, Collett D, Rudge C. Potential for organ donation in the United Kingdom: audit of intensive care records. British Medical Journal 2006; 332: 1124–7. €ller C, Welin A, Henriksson BA, et al. National survey of 38. Mo potential heart beating solid organ donors in Sweden. Transplantation Proceedings 2009; 41: 729–31. 39. Sheehy E, Conrad SL, Brigham LE, et al. Estimating the number of potential organ donors in the United States. New England Journal of Medicine 2003; 349: 667–74. 40. Jansen NE, Van Leiden JA, Haase-Kromwijk B, Hoitsma AJ. Organ donation performance in the Netherlands 2005–08; medical record review in 64 hospitals. Nephrology, Dialysis, Transplantation 2010; 25: 1992–7.

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Appendix 1: Investigators, participating hospitals and number of patients included. J. de Gea and A. Sanmartın, Virgen De La Arrixaca University Hospital, Murcia (154); D. Escudero and M. Martın, Central University Hospital of Asturias, Oviedo (135); J. Velasco, Son Espasses University Hospital, Palma de Mallorca (119); T. Pont and N. Masnou, Vall D0 Hebron Hospital, Barcelona (108); B. de la Calle and J. L. Escalante, Gregorio Mara~ n on University Hospital, Madrid (93); B. Marcelo, Infanta Cristina University Hospital, Badajoz (82); M. Lebron, Carlos Haya Hospital, Malaga (79); J. M. Perez, Virgen de las Nieves University Hospital, Granada (74); M. Burgos, San Cecilio University Hospital, Granada (72); R. Gimeno and P. Kot, La Fe University Hospital, Valencia (69); S. Yus, La Paz University Hospital, Madrid (67); I. Sancho, Miguel Servet University Hospital, Zaragoza (67); M. Arroyo and A. Zabalegui, General Yag€ ue Hospital, Burgos (66); E. Mi~ nambres, Marques de Valdecilla University Hospital, Santander (63); J. Elizalde, Asistential Complex of Navarra, Navarra (62);



Anaesthesia 2015, 70, 1130–1139

J. C. Montejo, 12 de Octubre University Hospital, Madrid (57); A. Sandiumenge and M. Bodı, Juan XXIII University Hospital, Tarragona (52); F. J. Gil, Santa Marıa del Rosell University Hospital, Cartagena (45); J. L. Iribarren, University Hospital of Canarias, Tenerife (45); M. Martınez, General Hospital of Ciudad Real, Ciudad Real (40); A. Calvo, San Pedro Hospital, Logro~ no (38); J. J. Rubio and G. Vazquez, Puerta de Hierro University Hospital, Madrid (36); R. Montoiro and L. Martın, Lozano Blesa Clinic University Hospital, Zaragoza (32); B. Vidal and E. Bisbal, General Hospital of Castell on, Castell on (31); P. Ucio, Clinic University Hospital of Valladolid, Valladolid (28); L. Ramos, General Hospital General of la Palma, La Palma (22), A. Martınez, Ram on y Cajal University Hospital, Madrid (16); J. Alcoverro, Althaia– Manresa Hospital, Barcelona (13);

A. Domınguez and J. Sanchez, Asistential Complex Hospital of Leon, Leon (13); C. Torrecilla, La Princesa University Hospital, Madrid (13); S. Macıas, Asistential Complex Hospital of Segovia, Segovia (12); I. Sijas, Cruces Hospital, Bilbao (7); T. Honrubia, University Hospital of Mostoles, Madrid (7); A. Fernandez, University Hospital Complex of La Coru~ na, La Coru~ na (5); C. Fraga and C. Ruiz, Nuestra Se~ nora de Candelaria University Hospital, Tenerife (5); D. Daga, Virgen de la Victoria University Hospital, Malaga (5); M. Sison, Dr. Jose Molina Hospital, Lanzarote (3); A. Del Castillo, Son Llatzer Hospital, Mallorca (3); R. Calvo, Sagunto Hospital, Valencia (2); I. Moreno, Infanta Cristina Hospital, Badajoz (2); F. Lopez, University General Hospital of Alicante, Alicante (1); P. Enrıquez, Del Rıo Hortega University Hospital, Valladolid (1).


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