- Email: [email protected]
Severe Supratentorial Intracerebral Hemorrhage: Factors Related to Brain Death Development
Severe Supratentorial Intracerebral Hemorrhage: Factors Related to Brain Death Development J.J. Egea-Guerreroa,*, A.M. Ferrete-Araujoa, A. Vilches-Arenasb, M.D. Freire-Aragóna, G. Rivera-Rubialesa, M. Quintana-Díazc, D.A. Godoyd, and F. Murillo-Cabezasa a Unidad de Neurocríticos, Hospital Universitario Virgen del Rocío, IBIS/CSIC/Universidad de Sevilla, Sevilla, bDepartmento de Medicina Preventiva y Salud Pública, Universidad de Sevilla, IBIS/CSIC/Universidad de Sevilla, Sevilla, cUnidad de Cuidados Intensivos, Hospital Universitario de La Paz, La Paz, Spain; and dUnidad de Cuidados Neurointensivos, Sanatorio Pasteur, Unidad de Terapia Intensiva, Hospital Interzonal de Agudos “San Juan Bautista,” Catamarca, Argentina
ABSTRACT Objective. This study sought to identify clinical variables that may contribute to the development of brain death (BD) in patients with severe supratentorial intracerebral hemorrhage (ICH). Methods. A prospective observational study was carried out from 2012 to 2014 and included patients with severe supratentorial ICH (Glasgow Coma Score 8). Exclusion criteria included aneurysmal or traumatic hemorrhage origin and hemorrhagic transformation of previous ischemic stroke. The following data were collected: clinical variables (past medical history, clinical severity at admission), head computed tomography scan findings, laboratory data, neurosurgical procedures, and immediate complications. Univariate tests and logistic regression analyses were performed to assess the predictive ability of these variables and identify patients at high risk of progression to BD. Results. A total of 140 patients with severe supratentorial ICH (median age, 60; 68.6% male) were included. Of these 140 cases, 24 progressed to BD. In the multivariate analysis, the following variables were independently associated with BD outcome after supratentorial ICH: a history of arterial hypertension (odds ratio [OR], 11.254; P ¼ .003), anticoagulant therapy (OR, 3.561; P ¼ .050), presence of photomotor impairment at admission (OR, 7.095; P ¼ .001), rebleeding after supratentorial ICH (OR, 5.613; P ¼ .010), and no neurosurgical hematoma evacuation in ICH (OR, 8.314; P ¼ .001). Conclusions. Certain clinical variables are predictive of an increased risk for BD development after supratentorial ICH. This information would be useful for transplant coordinators, permitting early identification of at-risk patients and increasing the availability of potential donors.
E
FFORTS AIMED at the prevention of traumatic illness, mostly from traffic or work-related accidents, are reducing trauma injuries worldwide. This fact, although positive for society as a whole, also alters the profile of donors after brain death (BD). The decline in potential donors after traumatic brain injury has made severe spontaneous intracerebral hemorrhage (ICH) the leading cause of BD in Spain [1]. Early identification of ICH patients at high risk for BD development would enable transplant coordinators to increase the availability of potential organ donors [2].
Numerous factors, such as infratentorial hemorrhage origin, are known to be indicative of poor prognosis in patients with ICH [3]. However, there are no specific studies Conflict of interest. None. *Address correspondence to Juan José Egea-Guerrero, MD, PhD, Unidad de Neurocríticos, Hospital Universitario Virgen del Rocío, IBIS/CSIC/Universidad de Sevilla, Avda Manuel Siurot s/n, PC 41013 Seville, Spain. E-mail: [email protected] or [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.09.055
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2564
Transplantation Proceedings, 47, 2564e2566 (2015)
SEVERE SUPRATENTORIAL INTRACEREBRAL HEMORRHAGE
on potential prognostic variables for BD development in patients with supratentorial ICH. The purpose of this study is to identify clinical variables that are associated with a greater likelihood of BD outcome in patients with severe supratentorial ICH. METHODS A prospective multicenter observational study was carried out at the Virgen del Rocío University Hospital from 2012 to 2014. The study was approved by the local Ethics and Research Committee. Inclusion criteria were admission to the intensive care unit during the first 48 hours after hemorrhage owing to low consciousness level (Glasgow Coma Score 8), and supratentorial ICH confirmed by cranial computed tomography scan. Exclusion criteria included aneurysmal or traumatic hemorrhage origin and hemorrhagic transformation of previous ischemic stroke. Patients were divided into 2 groups: progression or no progression to BD. The following variables were collected: age, sex, medical history (hypertension, dyslipidemia, diabetes mellitus, smoking, alcoholism), anticoagulant or antiplatelet therapy, consciousness level and photomotor impairment at admission, supratentorial ICH volume, presence of intraventricular hemorrhage and Graeb score, Acute Physiology And Chronic Health Evaluation (APACHE) II severity score at admission and modified ICH score, laboratory data (hemoglobin and blood glucose at admission and at 24 hours), surgical treatment or external ventricular drainage (EVD) insertion, and rebleeding or hydrocephalus within the first few hours after admission. Patient management was in accordance with international guidelines and local protocols [4]. For the descriptive analysis, analytical variables were represented using absolute and relative frequencies. For the comparative analyses, we used Pearson’s c2 test or Fisher’s exact test for qualitative data and the Student’s t test for quantitative variables. Univariate and multivariate logistic regression analyses were performed to assess each variable’s prognostic ability in predicting BD development. Adjusted odds ratios (OR) with 95% CIs were also calculated. All statistical analyses were conducted using software from SPSS for windows (v20.0; SPSS, Inc, Chicago, IL).
RESULTS
A total of 140 patients with severe supratentorial ICH were included. Among them, 24 progressed to BD. No differences were found in age and gender distribution between the 2 groups. BD patients had a greater proportion of hypertension (87.5%; P ¼ .049) and anticoagulant treatment (33%; P ¼ .0005). This group also showed greater photomotor impairment at admission (54.8%; P ¼ .03), higher APACHE II scores (14 vs 18; P ¼ .020), hyperglycemia at admission (114.5 vs 194; P ¼ .003), larger volume hemorrhages (36.5 vs 64.5; P ¼ .002), and a high rate of intraventricular hemorrhage (91.7%; P ¼ .039). Rebleeding was also more frequent in the BD group (41.7%; P ¼ .038). In patients without BD development, we found a higher rate of surgical hematoma intervention (59.5% vs 20.8%; P ¼ .001). In the univariate analysis, patients with no neurosurgical procedures had a higher risk of BD development (Table 1). Multivariate analysis identified the following variables as independently associated with BD development: a history of arterial hypertension (OR,
2565 Table 1. Results From Univariate Analysis to Determine Each Variable’s Predictive Ability for Brain Death Development After Spontaneous Supratentorial Intracerebral Hemorrhage Brain Death Variable
OR
95% CI
P
Age Arterial hypertension Anticoagulants APACHE II Photomotor alteration Glycaemia at admission (mg/dL) Intraventricular hemorrhage Hematoma volume [mL] Rebleeding No hematoma evacuation Acute and symptomatic hydrocephalus
1.047 3.684 4.773 1.124 4.400 1.007 1.14 1.014 2.738 5.579 2.879
1.002e1.093 1.036e13.104 1.667e13.662 1.033e1.224 1.760e10.999 1.000e1.013 1.016e20.476 1.002e1.025 1.083e6.923 1.947e15.983 1.006e8.238
.041 .044 .004 .007 .002 .041 .48 .020 .033 .001 .049
Abbreviations: APACHE, Acute Physiology And Chronic Health Evaluation; OR, odds ratio.
11.254; 95% CI, 2.264e55.934; P ¼ .003); anticoagulant therapy (OR, 3.561; 95% CI, 0.999e12.694; P ¼ .050); photomotor impairment at admission (OR, 7.095; 95% CI, 12.174e23.149; P ¼ .001), rebleeding after supratentorial ICH (OR, 5.613; 95% CI, 1.480e18.012; P ¼ .010), and no surgical hematoma evacuation in ICH (OR, 5.579; 95% CI, 1.947e15.983; P ¼ .001). DISCUSSION
The decrease in the number of patients that progress to BD and, as a consequence, in the number of organ donors, has generated new strategies to compensate this loss, including types II and III asystole organ donation [1,2,5]. Therefore, we must continue to strengthen early identification efforts of patients at risk for BD, and thus avoid the loss of even more potential donors. For this reason, our group has established follow-up protocols for neurocritical patients admitted to our center, based on cerebral biomarkers after traumatic brain injury, or on our analysis of emergency head computed tomography scan studies carried out in our hospital [4,6]. Despite these efforts, we found that very few studies explore clinical predictors for BD development in this ICH neocritical patient group [7]. Those studies that do are retrospective, involving generic databases without specific study designs, and patients with infratentorial ICH, which, along with age, are well-known indicators of poor prognosis in this illness [3,7]. In conclusion, certain variables in our cohort are predictors of an increased risk for BD development after supratentorial ICH. This information could be useful in the ever-growing search to find potential organ donors. REFERENCES [1] Escudero D, Valentín MO, Escalante JL, et al. Intensive care practices in brain death diagnosis and organ donation. Anaesthesia 2015;70:1130e9.
2566 [2] Kompanje EJ, Bakker J, Slieker FJ, et al. Organ donations and unused potential donations in traumatic brain injury, subarachnoid haemorrhage and intracerebral haemorrhage. Intensive Care Med 2006;32:217e22. [3] Bruce SS, Appelboom G, Piazza M, et al. A comparative evaluation of existing grading scales in intracerebral hemorrhage. Neurocrit Care 2011;15:498e505. [4] Revuelto-Rey J, Aldabó-Pallás T, Egea-Guerrero JJ, et al. Computed tomography as a tool to detect potential brain-dead donors. Med Clin (Barc) 2015;144:531e5.
EGEA-GUERRERO, FERRETE-ARAUJO, VILCHES-ARENAS ET AL [5] Pérez-Villares JM, Lara-Rosales R, Pino-Sánchez F, et al. Alpha code. The start of a new non-heart beating donor program. Med Intensiva 2013;37:224e31. [6] Egea-Guerrero JJ, Murillo-Cabezas F, Gordillo-Escobar E, et al. S100B protein may detect brain death development after severe traumatic brain injury. J Neurotrauma 2013;30:1762e9. [7] Galbois A, Boëlle PY, Hainque E, et al. Prediction of evolution toward brain death upon admission to ICU in comatose patients with spontaneous intracerebral hemorrhage using simple signs. Transpl Int 2013;26:517e26.
ABSTRACT Objective. This study sought to identify clinical variables that may contribute to the development of brain death (BD) in patients with severe supratentorial intracerebral hemorrhage (ICH). Methods. A prospective observational study was carried out from 2012 to 2014 and included patients with severe supratentorial ICH (Glasgow Coma Score 8). Exclusion criteria included aneurysmal or traumatic hemorrhage origin and hemorrhagic transformation of previous ischemic stroke. The following data were collected: clinical variables (past medical history, clinical severity at admission), head computed tomography scan findings, laboratory data, neurosurgical procedures, and immediate complications. Univariate tests and logistic regression analyses were performed to assess the predictive ability of these variables and identify patients at high risk of progression to BD. Results. A total of 140 patients with severe supratentorial ICH (median age, 60; 68.6% male) were included. Of these 140 cases, 24 progressed to BD. In the multivariate analysis, the following variables were independently associated with BD outcome after supratentorial ICH: a history of arterial hypertension (odds ratio [OR], 11.254; P ¼ .003), anticoagulant therapy (OR, 3.561; P ¼ .050), presence of photomotor impairment at admission (OR, 7.095; P ¼ .001), rebleeding after supratentorial ICH (OR, 5.613; P ¼ .010), and no neurosurgical hematoma evacuation in ICH (OR, 8.314; P ¼ .001). Conclusions. Certain clinical variables are predictive of an increased risk for BD development after supratentorial ICH. This information would be useful for transplant coordinators, permitting early identification of at-risk patients and increasing the availability of potential donors.
E
FFORTS AIMED at the prevention of traumatic illness, mostly from traffic or work-related accidents, are reducing trauma injuries worldwide. This fact, although positive for society as a whole, also alters the profile of donors after brain death (BD). The decline in potential donors after traumatic brain injury has made severe spontaneous intracerebral hemorrhage (ICH) the leading cause of BD in Spain [1]. Early identification of ICH patients at high risk for BD development would enable transplant coordinators to increase the availability of potential organ donors [2].
Numerous factors, such as infratentorial hemorrhage origin, are known to be indicative of poor prognosis in patients with ICH [3]. However, there are no specific studies Conflict of interest. None. *Address correspondence to Juan José Egea-Guerrero, MD, PhD, Unidad de Neurocríticos, Hospital Universitario Virgen del Rocío, IBIS/CSIC/Universidad de Sevilla, Avda Manuel Siurot s/n, PC 41013 Seville, Spain. E-mail: [email protected] or [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.09.055
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2564
Transplantation Proceedings, 47, 2564e2566 (2015)
SEVERE SUPRATENTORIAL INTRACEREBRAL HEMORRHAGE
on potential prognostic variables for BD development in patients with supratentorial ICH. The purpose of this study is to identify clinical variables that are associated with a greater likelihood of BD outcome in patients with severe supratentorial ICH. METHODS A prospective multicenter observational study was carried out at the Virgen del Rocío University Hospital from 2012 to 2014. The study was approved by the local Ethics and Research Committee. Inclusion criteria were admission to the intensive care unit during the first 48 hours after hemorrhage owing to low consciousness level (Glasgow Coma Score 8), and supratentorial ICH confirmed by cranial computed tomography scan. Exclusion criteria included aneurysmal or traumatic hemorrhage origin and hemorrhagic transformation of previous ischemic stroke. Patients were divided into 2 groups: progression or no progression to BD. The following variables were collected: age, sex, medical history (hypertension, dyslipidemia, diabetes mellitus, smoking, alcoholism), anticoagulant or antiplatelet therapy, consciousness level and photomotor impairment at admission, supratentorial ICH volume, presence of intraventricular hemorrhage and Graeb score, Acute Physiology And Chronic Health Evaluation (APACHE) II severity score at admission and modified ICH score, laboratory data (hemoglobin and blood glucose at admission and at 24 hours), surgical treatment or external ventricular drainage (EVD) insertion, and rebleeding or hydrocephalus within the first few hours after admission. Patient management was in accordance with international guidelines and local protocols [4]. For the descriptive analysis, analytical variables were represented using absolute and relative frequencies. For the comparative analyses, we used Pearson’s c2 test or Fisher’s exact test for qualitative data and the Student’s t test for quantitative variables. Univariate and multivariate logistic regression analyses were performed to assess each variable’s prognostic ability in predicting BD development. Adjusted odds ratios (OR) with 95% CIs were also calculated. All statistical analyses were conducted using software from SPSS for windows (v20.0; SPSS, Inc, Chicago, IL).
RESULTS
A total of 140 patients with severe supratentorial ICH were included. Among them, 24 progressed to BD. No differences were found in age and gender distribution between the 2 groups. BD patients had a greater proportion of hypertension (87.5%; P ¼ .049) and anticoagulant treatment (33%; P ¼ .0005). This group also showed greater photomotor impairment at admission (54.8%; P ¼ .03), higher APACHE II scores (14 vs 18; P ¼ .020), hyperglycemia at admission (114.5 vs 194; P ¼ .003), larger volume hemorrhages (36.5 vs 64.5; P ¼ .002), and a high rate of intraventricular hemorrhage (91.7%; P ¼ .039). Rebleeding was also more frequent in the BD group (41.7%; P ¼ .038). In patients without BD development, we found a higher rate of surgical hematoma intervention (59.5% vs 20.8%; P ¼ .001). In the univariate analysis, patients with no neurosurgical procedures had a higher risk of BD development (Table 1). Multivariate analysis identified the following variables as independently associated with BD development: a history of arterial hypertension (OR,
2565 Table 1. Results From Univariate Analysis to Determine Each Variable’s Predictive Ability for Brain Death Development After Spontaneous Supratentorial Intracerebral Hemorrhage Brain Death Variable
OR
95% CI
P
Age Arterial hypertension Anticoagulants APACHE II Photomotor alteration Glycaemia at admission (mg/dL) Intraventricular hemorrhage Hematoma volume [mL] Rebleeding No hematoma evacuation Acute and symptomatic hydrocephalus
1.047 3.684 4.773 1.124 4.400 1.007 1.14 1.014 2.738 5.579 2.879
1.002e1.093 1.036e13.104 1.667e13.662 1.033e1.224 1.760e10.999 1.000e1.013 1.016e20.476 1.002e1.025 1.083e6.923 1.947e15.983 1.006e8.238
.041 .044 .004 .007 .002 .041 .48 .020 .033 .001 .049
Abbreviations: APACHE, Acute Physiology And Chronic Health Evaluation; OR, odds ratio.
11.254; 95% CI, 2.264e55.934; P ¼ .003); anticoagulant therapy (OR, 3.561; 95% CI, 0.999e12.694; P ¼ .050); photomotor impairment at admission (OR, 7.095; 95% CI, 12.174e23.149; P ¼ .001), rebleeding after supratentorial ICH (OR, 5.613; 95% CI, 1.480e18.012; P ¼ .010), and no surgical hematoma evacuation in ICH (OR, 5.579; 95% CI, 1.947e15.983; P ¼ .001). DISCUSSION
The decrease in the number of patients that progress to BD and, as a consequence, in the number of organ donors, has generated new strategies to compensate this loss, including types II and III asystole organ donation [1,2,5]. Therefore, we must continue to strengthen early identification efforts of patients at risk for BD, and thus avoid the loss of even more potential donors. For this reason, our group has established follow-up protocols for neurocritical patients admitted to our center, based on cerebral biomarkers after traumatic brain injury, or on our analysis of emergency head computed tomography scan studies carried out in our hospital [4,6]. Despite these efforts, we found that very few studies explore clinical predictors for BD development in this ICH neocritical patient group [7]. Those studies that do are retrospective, involving generic databases without specific study designs, and patients with infratentorial ICH, which, along with age, are well-known indicators of poor prognosis in this illness [3,7]. In conclusion, certain variables in our cohort are predictors of an increased risk for BD development after supratentorial ICH. This information could be useful in the ever-growing search to find potential organ donors. REFERENCES [1] Escudero D, Valentín MO, Escalante JL, et al. Intensive care practices in brain death diagnosis and organ donation. Anaesthesia 2015;70:1130e9.
2566 [2] Kompanje EJ, Bakker J, Slieker FJ, et al. Organ donations and unused potential donations in traumatic brain injury, subarachnoid haemorrhage and intracerebral haemorrhage. Intensive Care Med 2006;32:217e22. [3] Bruce SS, Appelboom G, Piazza M, et al. A comparative evaluation of existing grading scales in intracerebral hemorrhage. Neurocrit Care 2011;15:498e505. [4] Revuelto-Rey J, Aldabó-Pallás T, Egea-Guerrero JJ, et al. Computed tomography as a tool to detect potential brain-dead donors. Med Clin (Barc) 2015;144:531e5.
EGEA-GUERRERO, FERRETE-ARAUJO, VILCHES-ARENAS ET AL [5] Pérez-Villares JM, Lara-Rosales R, Pino-Sánchez F, et al. Alpha code. The start of a new non-heart beating donor program. Med Intensiva 2013;37:224e31. [6] Egea-Guerrero JJ, Murillo-Cabezas F, Gordillo-Escobar E, et al. S100B protein may detect brain death development after severe traumatic brain injury. J Neurotrauma 2013;30:1762e9. [7] Galbois A, Boëlle PY, Hainque E, et al. Prediction of evolution toward brain death upon admission to ICU in comatose patients with spontaneous intracerebral hemorrhage using simple signs. Transpl Int 2013;26:517e26.