Brain death worldwide

Methods.

The National Library of Medicine’s search service (PUBMED) was used to identify published articles addressing brain death criteria from 1968 to 2000. The criteria from official documents were tabulated and summarized. In addition, the directory of the American Academy of Neurology was used to ask international members through a personal letter to submit published guidelines. The Congress of Neurologic Surgeons Directory was used to contact international members to complete several missing countries throughout the world. Personal letters were sent to physicians in 107 countries. In addition, foreign physicians at the Mayo Clinic were contacted by e-mail to provide contacts with neurologists from their homeland. Simple questions were asked. Is there a legal provision of organ transplantation and brain death in your country? What are the specific guidelines, mandatory qualifications of the physicians, number of physicians needed to declare brain death, time of observation, and need for confirmatory laboratory tests? Some documents were reviewed with the Legal Department at the Mayo Medical Center.

Results.

The United Nations lists 189 member states. Data on adult brain death criteria in 80 countries (42%) were obtained and are shown in the table. European, South American, and Asiatic countries are well represented. The United Kingdom criteria for brainstem death permeate in the previously colonized countries, and Central and South American countries generally follow the United States position on whole brain death.

Countries with brain death guidelines typically specify exclusion of confounders, irreversible coma, absent motor response to pain stimulus, and the absence of all brainstem reflexes. Official legal standards on organ donation were present in 55 of 80 countries (69%). Brain death guidelines or codes of practice were present in 70 of 80 surveyed countries (88%). To make a definitive diagnosis, one physician was required in 31 guidelines (44%), two physicians in 24 guidelines (34%), and more than two physicians (as many as four) in 11 guidelines (16%). The number of physicians was not specified in four guidelines (6%; see the table). All the recommended guidelines required strict definition ofbrainstem reflexes, but the presence of apnea using a PCO₂ target value was recommended in only 41 guidelines (59%). Preoxygenation with 100% oxygen followed by 10 minutes of disconnection, with clinical examination for apnea required in 20 of 71 guidelines (29%; see the table). Confirmatory laboratory tests were often mandatory in Europe and Asia. In addition, confirmatory laboratory tests were commonly used to shorten the recommended observation time. Confirmatory tests were not required in many developing countries. (This is probably because these technologic devices were not available on a timely basis.) The observation period for a brain-dead body before final diagnosis was established varied markedly (see the table). The most striking differences in guidelines for the determination of brain death are summarized here per continent.

Comments and suggestions.

The landmark Harvard criteria published in 1968 have held ground tenaciously over the years.52 However, a major diversity in clinical criteria has evolved worldwide.

In this comprehensive survey, the first of its kind, brain death criteria in some countries are left to the discretion of the physician; in others the criteria have been substantially expanded. Unlike the US statutes, legal standards on organ donation and brain death may specify the methods of clinical determination. There are major differences in number of required physicians, in level of experience and academic rank of physicians, in specialty preferences, and in recommendations for confirmatory tests. Observation time after declaration of brain death varies greatly or is not specified. The “anoxia” provision of 24-hour observation is prevalent. It can be traced to the President Commission recommendations,3 and this amendment may have been prompted by additional presence in some patients of cardiogenic shock and thus uncertainty about irreversibility. In addition, brain edema develops later and confirmatory tests may more often show residual brain function when performed soon after clinical assessment. Many nations in the world and several US states require confirmation by a second physician, but there are no data that would give credence to go beyond two. Finally, the apnea test is not consistently performed using PCO₂ monitoring. If the premise of documenting apnea using acute hypercarbia to maximally stimulate the respiratory centers is accepted, it can be concluded that in half of the countries, the apnea test is not performed adequately. Disconnection alone may not be sufficient to document apnea due to posthyperventilation apnea.

The differences between US state laws are noteworthy. The New Jersey religious exemption remains contentious and arguments against it have been published.53 Other differences involve the specific mention of exclusion of physicians involved in recovery of vital organs; a few states require two physicians and board-eligible or board-certified physicians. It is surprising that two states allow registered nurses, after physician certification, to make the diagnosis of brain death, but it can be assumed this practice is uncommon.

How these striking differences—likely a result of collective decisions by task forces—have evolved is not known. At a philosophical level, it can be argued that these differences could have resulted from dissatisfaction with the original concept of brain death and could reflect cultural attitudes. This argument could certainly apply to countries with extended observation times. However, comparison of the protocols reveals differences in procedural matters, expertise and experience of physicians, method of apnea testing, and preferences for certain confirmatory tests. In many countries, the guidelines seem unnecessarily complicated.

Despite an aggressive effort to obtain data, this survey of brain death throughout the world is not complete. However, to disarm criticism, it includes a large number of densely populated countries. In some countries, transplantation programs never existed or faltered due to economic decline, thus eliminating the need to establish brain death criteria for donation. It is also conceivable that even further modifications of the official guidelines have been introduced in hospital policy manuals, but this could not be investigated with the current data set. Another potential caveat is that despite national guidelines, doubts and misconceptions about the concept of brain death may still prevail with the public. The principle of brain death may conflict with staunch personal beliefs of practicing physicians and may even potentially undermine the initiation of the transplant procedure.

So where do we stand? What can we learn from this survey? The results of this study could suggest further standardization of the determination of brain death. An international task force could specifically address the most important inconsistencies in guidelines and develop criteria for the apnea test. (For example, the apnea test only requires serial measurement of arterial PCO₂, which currently can be measured at the bedside.) This survey shows the need to critically assess the requirements of confirmatory tests and the long periods of observation, and perhaps the anoxia clause may be revisited. Maybe we could do away with confirmatory testing altogether. However, such a task force may be forced to venture into complicated cultural and religious territory and it may be difficult to persuade countries to accept a uniform agreement. Alternatively, representatives from each country may take a second look at their code of practice and recommend a revision. It remains to be seen whether it is possible to scale back the requirements. In some countries, apprehension about errors and physician qualifications could have impacted the development of diagnostic criteria, and these concerns cannot be airily dismissed. In other countries, cultural rejection of the concept of brain death and absence of transplantation programs may have deferred development of clinical guidelines. However, this survey shows that major differences are not so much in the acceptance of the concept of brain death, but in the procedures physicians use to make the final diagnosis.