In a serious attempt to homogenize donation programs throughout the world, The third World Health Organization (WHO) Global Consultation on Organ Donation and Transplantation, held in Madrid (Spain)1 called upon governments to advance toward self-sufficiency in transplantation, and thus to cover the needs of patients using all the resources available to increase organ availability. Despite the many initiatives to increase the number of organ donors, further effort is needed in this field, since there is a constant and growing need for organs for transplantation. Although the total deceased solid organ donors reached 1655 in Spain in 2013 (a figure similar to those of previous years),2 the number of patients on the waiting list for organ transplantation has remained stable or has even increased in recent years.

Up until now, most organs for transplantation in Spain have come from patients who die in hospital under conditions of brain death (BD).3 Brain death has been estimated to represent 2.3% of all in-hospital fatalities and 12.4% of all deaths in the Intensive Care Unit (ICU).4 Although these indicators are based on retrospective analyses of deaths occurring in critical care settings, they serve as a reference for calculating donation potential in our centers. The quality assurance program of the Spanish National Transplant Organization (Organización Nacional de Trasplantes, ONT), designed to determine the donation potential of critical care units (based on internal and external audits that evaluate the ultimate circumstances in which patients die in such units), retrospectively identifies the “losses” of potential donors not identified by the transplant coordinators in real time, and helps to define areas for improvement in the audited hospitals. These audits show that the number of donors could be 21.6% greater if all potential donors were identified (i.e., patients with a clinical condition suggesting compliance with BD criteria)5 and all possible losses were avoided.

In order to estimate the BD donation potential, other authors have considered it more appropriate to analyze the number of patients admitted in coma to the ICU,6 and even to hospital,7 since certain decisions referred to diagnosis and treatment in the course of the neurocritical patient care process could influence the final number of possible donors. In this regard, the impact of end of life care decisions upon donation potential has been little studied to date. The Ethicus8 study showed life support therapy limitation (LSTL) to be a common practice in European ICUs (being applied to 10% of the admitted patients and to 73% of the patients that die in such units). Although less information is available regarding the incidence of LSTL in other hospital areas, studies published in the last decade indicate that the proportion of patients receiving LSTL in the emergency services is significant–particularly among elderly subjects with multiple comorbid conditions.9,10

The changing profile of potential donors in Spain, and the new reality of our healthcare system–with more limited resources–make it necessary to optimize the detection of potential donors both within and outside the ICU.11 In this context, the present study was carried out to analyze the profile of neurocritical patients admitted not only to the ICU but also to any other hospital area; the incidence of LSTL in this group of patients; and the BD organ donation potential.

This is the first study to prospectively evaluate the donation potential of BD and the effectiveness of the organ donation process among patients admitted to hospital with coma defined as GCS<8. The main finding of the study is that the death in BD potential is 24.2%. Other relevant findings were the fact that LSTL was applied in 32.1% of the patients and that in 44.3% of these cases LSTL consisted of non-admission to the ICU. Furthermore, LSTL was associated to non-evolution toward BD.

In the 1990s, the efforts to increase the number of organs amenable to transplantation focused on optimization of the donation in BD process. However, such measures were not enough to cover the rising demand for organs, largely because of the decrease in incidence of BD (fewer traffic accidents, prevention of cerebrovascular disease). In the last decade in Spain and from the National Transplant Organization, a project known as Plan 40 was promoted11,17 with the aim of raising the donation rate to 40 per million population (pmp) in the country. In addition to contemplating optimization of the donation in BD process, the mentioned project included increased detection of possible donors outside the critical care areas, expanding the use of all possible dead donors–including donation in asystolia (controlled and uncontrolled), and the implementation of live donation as a complement to dead donor use.

The present study shows the potential and effectiveness of donation in BD in 9 Spanish centers, including neurocritical patients with GCS<8 admitted both to the ICU and to other areas of the hospital. One out of every 5 patients (24.2%) admitted to these centers evolved toward BD, and a little over one-half of them were finally organ donors (56.4%).

In contrast to other studies, calculation of the potential and effectiveness of donation in these centers was made on a prospective basis. Most previous studies designed to evaluate donation potential have involved retrospective analyses (based on case history reviews) corresponding to cases of patients who died in ICUs or in other areas of the hospital.7 Senouci et al.6 conducted a similar prospective predictive study but only included patients admitted to the ICU. The authors found that subjects with clinical criteria of BD represented 15.1% of the patients admitted to the ICU with GCS<8. The fact that the proportion of patients with GCS<8 admitted to hospital and who died in BD in our series was higher than in the study of Senouci et al. suggests that there is a proportion of patients who might not be admitted to intensive care due to different reasons and who presumably could evolve toward BD. In the present study, the proportion of neurocritical patients admitted to the ICU was less than 70%, which leaves a significant proportion of patients who could possibly serve as donors in other areas of the hospital outside the ICU.

Le Conte et al.9 found that 78.8% of the patients who died in the emergency service had been subjected to some type of LSTL, particularly individuals over 80 years of age, with a history of metastatic cancer, or with previous functional limitations. A posterior analysis conducted by the same group18 found that 7% of the elderly patients who die in the emergency service with neurological disease could have been selected and evaluated as potential organ donors–though the authors did not include information referred to the full diagnosis of BD.

It is well known that among patients admitted due to acute disease, acute neurological cases are those most frequently targeted for some type of LSTL in the ICU.8 Although we have tools for predicting a fatal outcome in diseases that most often produce neurological damage (brain hemorrhage based on the ICH score,19 clinical and electrophysiological data in anoxic encephalopathy,20,21 for example), the early decision to apply LSTL in different disease conditions has been widely debated,22,23 since LSTL has been associated to increased mortality. It is clear that end of life decisions cannot be based only on the degree of severity of the neurocritical patient but must also consider patient evolution during the first few days, neuromonitoring data,24 treatment response25 and, particularly, the wish of the patient (as expressed either personally or through the family) regarding the care received.26

The present study shows that LSTL was applied to one out of every three patients admitted to hospital due to critical neurological disease (GCS<8), and almost one-half of these subjects were not admitted to the ICU. The median time from admission to the application of LSTL was three days. Of the 176 patients in which LSTL was decided, 71 (40.3%) had no contraindications for donation. In the present study, LSTL was associated to a lesser evolution toward BD and, specifically, in 9 patients under 80 years of age without contraindications for organ donation and with GCS≤4, LSTL was applied within the first four days of admission to hospital–this representing a potential loss rate of 12%. The question here is whether these individuals could have been evaluated as possible donors if LSTL had not been applied.

Considering the published articles on the impact upon which early LSTL may have fatal outcome in neurocritical patients and potential donation, we see that more extensive studies are needed to assess the effect of a change in the initial approach toward patients of this kind.

Another important issue is the participation of the transplant coordinator in the decision making process in the end of life care setting in neurocritical patients. In our study group, evaluation by the transplant coordinator in the course of hospital admission was associated to a lesser incidence of LSTL only in the univariate analysis. However, it is important to point out that in 53 cases in which LSTL was decided, the coordinator had not evaluated the patient at any time. Therefore, the patient wish regarding organ or tissue donation had not been examined by talking to the family.

An ethical dilemma remains27–29 regarding the instauration of life supporting treatments not in the benefit of the patient as such but in wait of BD among neurocritical patients with inevitable imminent death, and in which measures for treating the background disease would not be indicated. Although such measures are not adopted with the purpose of healing or improving the patient condition, there is an agreement in our setting that they are justified provided they are made in accordance with the patient's wish referred to organ donation. Talking with the family is needed in this regard, offering clear and transparent information, and including all the possible options referred to end of life care on the basis of patient evolution in the first few days. In this way we can make a decision based on consensus between the medical team and the family of the patient.

The present study did not aim to analyze donation potential in controlled asystolia (Maastricht type III). No analysis was made of the type of LSTL or the timing of death after LSTL. Although donors of this kind have been shown to be less profitable in terms of organ harvesting compared with BD donors, they are a valid option in concrete cases. Specifically, we refer to patients admitted to the ICU with GCS<8, exhibiting a poor prognosis, in which a fatal outcome is expected following trial treatment, management proves futile, and LSTL is decided when it is seen that evolution toward BD does not occur. Evidently, in accordance with current legislation30 and the good donation in asystolia practice recommendations,31 the donation process is independent of the decision to apply LSTL. Donation always must abide with the wish of the deceased patient (as previously expressed by the patient in person or by the family on occasion of the donation interview), with the absence of contraindications.

Our study has a few limitations. The group of hospitals and the causes of coma were heterogeneous, and so the findings cannot be generalized to all neurological disorders and to all settings. However, the large number of cases included allows us to extract important information regarding the donation potential and the incidence of LSTL. Although the cases were included on a prospective basis, no specification was made of the ultimate factors conditioning the decision and the timing of LSTL, or of the specific limited life support measure involved (no start or suspension) in each case. Nevertheless, it has been seen that while LSTL is common in this group of patients, it is less frequent in the first few days of admission.

In conclusion, this study evidences the real potential for organ donation in BD and the high incidence of LSTL in neurocritical patients in our hospitals. It shows that although the application of LSTL is more frequent in patients with contraindications for organ donation, it is associated to evolution toward non-BD, with cases that are limited to the first few days even in the absence of contraindications for organ donation. It is therefore important for health professionals involved in the care of patients with serious brain damage in both the ICU and in other areas of the hospital (particularly the emergency service) to receive adequate training, with the capacity to identify patients in which BD is imminent and the possibility of postulating them as organ donors. The key principal is to provide quality end of life care in line with the current recommendations. The participation of the transplant coordinator is important for including the option of organ donation according to the wish of the patient, and always offering the family sensible, clear and transparent information.

The authors declare that they have no conflicts of interest.