Brain Death Epidemiology in Uruguay and Utilization of the Glasgow Coma Score in Acute Brain Injured Patients as a Predictor of Brain Death

Brain Death Epidemiology in Uruguay and Utilization of the Glasgow Coma Score in Acute Brain Injured Patients as a Predictor of Brain Death R. Mizraji, S. Perez-Protto, A. Etchegaray, A. Castro, M. Lander, E. Buccino, L. Severo, and I. Alvarez ABSTRACT Objective. The knowledge of brain death (BD) epidemiology and the acute brain injury (ABI) progression profile are relevant to improve public health programs, organ procurement strategies, as well as intensive care unit (ICU) protocols aiming to increase the detection of potential donors. The aim of this study was to analyze the BD epidemiology and the ABI progression profile among subjects admitted to ICUs with a Glasgow Coma Score (GCS) ⱕ 8. Materials and Methods. This was a prospective, observational study of BD reported to the National Institute of Donation and Transplantation from 2000 –2006. The patients with ABI and GCS ⱕ 8 who were admitted to 5 ICUs with In-hospital Transplant Coordination were analyzed over the period of 2005–2007. Results. The BD detection increased from 28.7 in 2000 to 58.5 BD pmp in 2006. The real donor global rate increased from 10 to 24.6 pmp from 2000 to 2006. The ABI patients with GCS ⱕ 8 had a global mortality rate of 56%, including 23.4% who evolved to BD. Conclusions. This study showed a 200% increment of detected BD and 150% of real donors, although these results are still below the international figures. GCS follow-up appeared to be a good tool to predict the BD outcome. The follow-up of patients with ABI allowed us to improve our BD detection strategy. RGAN TRANSPLANTATION is one of the best available treatments to save or improve the quality of life of patients. The main obstacle is the increasing gap between the availability of and the demand for organs, which leads to a high mortality rate or a long time on waiting lists. Improvements in the vital support of donors, in organ preservation techniques, and in immunomodulation treatments have rendered cadaveric sources as an excellent donor alternative, showing similar outcomes compared with living donors without the mutilation of a human being. The brain death (BD) diagnosis and detection is the first step toward obtaining a cadaveric organ donor.1,2 Only 1% to 4% of hospital deaths and 10% of intensive care unit (ICU) deaths are due to BD. Only 35% to 50% of BD individuals become organ donors, mainly due to family refusal, medical contraindications, or cardiac arrest.3 With the aim to increase BD detection seeking to augment organ and tissue donors, the Transplant Coordination (or Organ Procurement Organization), a department of the National Institute of Donation and Transplantation, was established

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in Uruguay in 2000. This department is structured with a chairman, 5 extra-hospital transplant coordinators, 5 intrahospital transplant coordinators, and 3 psychologists.4,5 The continuous quality control of the activity is one of the foremost activities of the department; this study is a result of this program. MATERIALS AND METHODS The primary aim of this study was to analyze BD epidemiology in Uruguay. The secondary objectives included: to evaluate the performance of transplant coordinators by conversion rates of potential (PD) to real donors (RD) over the number of brain From the Instituto Nacional de Donación y Trasplantes, INDT (National Institute of Donation and Transplants), Montevideo, Uruguay. Address reprint requests to Dr Raul Mizraji, Instituto Nacional de Donación y Trasplantes, Coordinación de Trasplantes, Rafael Patoriza 1322, CP 11300, Montevideo, Uruguay. E-mail: rmizraji@ gmail.com

© 2009 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710

0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.09.008

Transplantation Proceedings, 41, 3489 –3491 (2009)

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deaths: PD/BD and RD/BD; to calculate the donor capacity index as BD pmp and RD pmp; to evaluate the cause for donor loss, namely, family refusals, medical contraindications, or cardiac arrest; to describe the profile of BD individuals (cause of death, age, sex); and to examine the progression profile of patients with acute brain injury (ABI) who were admitted to the ICU with a GCS ⱕ 8. All BDs detected by the Transplant Coordination since 2000 were prospectively enrolled in the quality control program. A subprogram quality control project of Intra-hospital Transplant Coordinators from January 2005 through April 2007 included all patients admitted to their ICUs with a diagnosis of ABI and GCS ⱕ 8. These 3 hospitals have a total of 1529 beds, including 73 ICU beds with a neurosurgery program and 15 ICU beds without a neurosurgery program. Data were recorded on electronic case report forms with each patient followed until death by cardiac arrest or BD.

RESULTS

During the study period, 963 BDs were detected. In 2000 the rate of detection was 28.7 BD, while in 2006 it was 58.5 BD pmp, showing an approximately 200% increment. The RD rate changed from 10 to 24.6 pmp, which implied a 150% growth over 6 years, which allowed doubling of the transplant rate (Table 1). Among 963 BD, 363 became RD (38%) with conversion rates fluctuating between 35% and 40% over the whole period. The causes of donor loss were mostly due to medical contraindications in 267 cases (28%); the other reasons were family refusal (n ⫽ 169; 18%), failure to consent during life registration (n ⫽ 114; 12%), and cardiac arrest during donor maintenance (n ⫽ 42; 4%). Family refusal during the consent interview was 65% in 2000, with a steady annual decrement to 20% in 2006. The medical unsuitability distribution was due to the following causes: chronic severe illness with multiorgan repercussion (n ⫽ 60), chronic severe hypertension (n ⫽ 52), tumors (n ⫽ 42), severe sepsis (n ⫽ 28), advanced age restriction (n ⫽ 28), severe hemodynamic instability (n ⫽ 20), intravenous drug addiction (n ⫽ 12), chronic severe hypertension and advanced age (n ⫽ 7), and diabetes mellitus (n ⫽ 6). Regarding the donor profile, 58% (560) of the BD were males and 42% (403) were females. The average age of the BD was 37.2 years, while the average age of the RD was 36.3 years. Table 2 shows the number of BD detected per age group. The distribution of causes of death included: stroke (45%; n ⫽ 430) with subarachnoid hemorrhage in 46%; cranial trauma (34%; n ⫽ 331) with 37% (121) being Table 1. Brain Death Detection and Real Donor Evolution From 2000 Through 2006

BD BD pmp RD RD pmp Family refusal (%)

2000

2001

2002

2003

2004

2005

2006

89 28.7 31 10 65

105 33.8 36 11.6 55

117 37.7 45 14.8 47

140 45.2 49 16.1 40

145 46.7 56 18.1 38

159 48.7 64 21.3 30

193 58.5 79 24.6 20

Table 2. Brain Death Distribution in All Age Categories BD Age (y)

General Population

No.

%

0–4 5–9 10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79

7.5 8.2 8.1 8.0 7.5 7.8 6.8 6.2 6.4 5.9 5.4 4.6 4.3 3.7 3.6 2.7

37 29 33 80 93 88 67 76 106 102 115 99 71 43 34 9

3.3 2.6 4.7 7.1 8.3 7.9 6.0 6.8 9.5 9.1 10.3 8.9 6.3 3.8 3.0 0.8

gunshot injuries; postanoxic encephalopathy following cardiac arrest (6%; n ⫽ 55); and central nervous system tumors (3%; n ⫽ 24; Table 3). The most frequent cause of death among the BD subjects younger than 30 years was cranial trauma, while stroke was the primary etiology among the group older than 45 years. Subprogram Quality Control Results

In the study period, 92,872 patients were admitted to the 3 hospitals with In-hospital Transplant Coordination with 12,075 admitted to ICUs. Hospital mortality was 5% (4871) and the ICU mortality was 22% (2629), including 146 cases of BD, which represented 3% of hospital deaths and 6% of ICU deaths. The Transplant Coordination followed 1120 patients with ABI admitted to the ICU with GCS ⱕ 8. Their outcomes were: 56% died and 44% were discharged from the hospital. There were 146 BD among 623 patients who died, which represented 23.4%. Table 4 shows the principal causes of coma and the outcomes for each one. DISCUSSION

Detection of BD is the first step in the donation-transplantation process. After the Transplant Coordination was established in our country, BD detection as well as the actual donor rates increased exponentially.6,7 According to international figures, 1% to 4% of the deaths are due to Table 3. Cause of Brain Death Distribution

Stroke Cranial trauma Gunshot injury Encephalopathy following cardiac arrest

2000

2001

2002

2003

2004

2005

2006

33 33 27 4

44 30 15 4

46 29 14 3

56 16 15 4

58 18 12 5

74 42 18 14

119 42 20 21

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Table 4. Causes of Coma and Outcomes of the Patients Admitted to the ICU With ABI and GCS < 8 Cause of Coma

GCS ⱕ 8

Deaths

Cranial trauma Gunshot injury Ischemic stroke Hemorrhagic stroke Subarachnoid hemorrhage Encephalopathy following cardiac arrest Tumor Other Total

280 (25) 45 (4) 101 (9) 313 (28) 112 (10) 135 (12)

54 (19) 36 (80) 72 (71) 208 (66) 90 (80) 103 (76)

25 (46) 17 (47) 20 (27) 32 (15) 37 (41) 5 (5)

22 (2) 112 (10) 1120 (100)

15 (68) 56 (50) 623 (56)

3 (20) 7 (12) 146 (23)

BD/Deaths

Data are presented as numbers (%).

BD. In our country, 30,000 people die per year, so our goal is to reach recognition of 300 BD per year, which would amount to 90 BD pmp. Our conversion rate was 38%, which is still below international standards, even after enormously decreasing family refusals. One of the reasons is because we do not have our own liver transplant program, which led us to reject some suitable liver donors who were unsuitable for kidney transplantation, especially because of age or cardiovascular comorbidities. Regarding the BD profile, we observed that the average age has been increasing, due to increased detection of BD among stroke patients. This study led us to identify 2 donor profiles: young donors, predominantly male, with cranial trauma as the cause of death, and older donors with stroke as the cause of death. The age distribution among actual donors should be analyzed in detail, because we have a large group of potentially suboptimal donors because of age and comorbidities; also, the low proportion of BD in pediatric groups may lead to infrequent detection. The subprogram of quality control showed the high-risk set of patients for follow-up to enhance BD recognition. Bustos et al8 performed a follow-up of ABI patients with GCS ⬍ 8, showing a high rate of cardiac arrest which was a preventable cause of donor loss. Based on our study, we have made guidelines to improve BD detection across our country.

In conclusion, knowing the BD epidemiology of the country is a key to improve donation and transplantation processes. This study showed that our current BD detection is 50 to 60 BD pmp, which we seek to augment, in addition to the conversion rate which is still 38%. The GCS follow-up in ABI patients allowed us to recognize the high mortality among the GCS ⬍ 8 group; this is a predictor of BD. This practice should be applied as an indicator of the donor potential of an ICU. The donor profile in our country has been changing. Nowadays, there is an increase among elderly donors with stroke as the cause of death, which has led us to review the assignment criteria at our institution. With this study, we also noted scarce detection among the pediatric group by comparing the proportions of donors in each age group versus those the general in population. Critical Care Medicine is responsible for taking care of patients at high risk of dying due to BD, but Transplant Coordination has become a subspecialty within Critical Care Medicine charged with increasing BD detection and with conversion of these individuals to real organ donors. REFERENCES 1. Cuende N, Cañón JF, Miranda B, et al: The organ donation process: a program for its evaluation and improvement. Organs Tissues 5:109, 2002 2. Rico J, Miranda B, Cañón JF, et al: Presentación de la Organización Nacional de Trasplantes. Nefrologı´a 23(suppl 5):1, 2003 3. Cuende Melero N, Cañón Campos JF, Alonso Gil M, et al: Evaluación del proceso de donación: programa de garantı´a de calidad de la Organización Nacional de Trasplantes. Rev Esp Traspl 10:185, 2001 4. Mizraji R, Pérez S, Alvarez I: Epidemiologı´a de la muerte encefálica. Capacidad generadora de donantes. Control de calidad. Rev Esp Traspl 12:6, 2003 5. Mizraji R, Pérez S, Álvarez I: Epidemiology of the encephalic death. Generating capacity of donors. Control of quality. Transplant Proc 36:1641, 2004 6. Available at: http://www.grupopuntacana.org/index.htm 7. International figures on organ donation and transplantation— 2006. News Letter Transplant 2007 8. Bustos JL, Surt K, Soratti C: Glasgow Coma Scale 7 or less surveillance program for brain death identification in Argentina: epidemiology and outcome. Transplant Proc 38:3697, 2006