For many patients with terminal heart, lung, liver or kidney disease, organ transplantation is the treatment of choice and most often their only hope for survival. In 2011, 4,660 patients were on the waiting lists for transplantation in Canada and 285 died waiting for an organ . Organs harvested after the neurological determination of death (NDD) are the principal source of organs transplanted in Canada. In 2011, 466 patients with NDD provided a total of 1,518 organs for transplantation. In comparison, 152 organs were transplanted using 92 donations after cardiac death . The only sources for heart, pancreas and intestine transplantation are NDD donors.
Before retrieving a vital organ from a donor with the aim of transplantation, clinicians have to be 100% sure that the donor is deceased. Social laws and norms around the world follow what is termed the ‘dead donor rule’: that is, organ retrieval itself cannot cause death . As such, death must be diagnosed before the retrieval of an organ.
Organs can be obtained from donors after either cardiac death or brain death. NDD is a socially accepted determination of death which describes the concept of irreversible loss of capacity for consciousness combined with the irreversible loss of all brainstem functions including the capacity to breathe . When a patient meets the required criteria for NDD, they are legally declared dead. Life–sustaining therapy can then be withdrawn and, if the patient is eligible for organ donation, their organs can be retrieved for transplantation.
This diagnosis of brain death is predominantly clinical . The essential clinical diagnostic components of brain death vary between jurisdictions but usually include evidence for an established etiology capable of causing brain death, one or two independent clinical confirmations of the absence of all brainstem reflexes and an apnea test, and exclude confounders that can mimic brain death [5, 6]. Numerous confounders, such as the use of barbiturates or other medications, severe craniofacial trauma that prevents an appropriate clinical neurological examination, and high cervical spine injuries that prevent the performance of the apnea test, can render the NDD virtually impossible.
In situations where a complete and accurate clinical evaluation is impossible, clinicians must use additional tests, called ancillary tests, to confirm the neurological death of the patient [5, 6]. Ancillary tests should be able to demonstrate the absence of brain blood flow in the cerebral hemispheres and in structures from the posterior fossa . An ideal test should never give any false-positive results (brain death when in fact the patient is not dead) and should be fast to perform, safe, readily available, accessible, non-invasive, inexpensive, not susceptible to confounding factors and standardized [4–6, 8].
Limitations of evidence
Brain blood flow imaging, such as four-vessel angiography, and functional tests, such as radionuclide imaging, have traditionally been used as the gold standard ancillary tests for NDD . Recently, several additional ancillary tests, such as computed tomography (CT) angiography, CT perfusion, magnetic resonance angiography and xenon CT, have been proposed as replacements for these traditional tests to confirm NDD  and their clinical use despite the absence of proper validation is growing [7, 9]. From a recent American survey, physicians used several different ancillary tests for the same patient and often used tests that were either not recommended or not validated . Significant institutional and clinical practice variability thus remains in the use of ancillary tests, their indication and their diagnostic criteria [4, 9, 10]. Furthermore, when ancillary tests were applied on clinically brain-dead patients, a small proportion of the patients presented detectable brain perfusion, suggesting at best inaccuracy in the diagnostic criteria used for these ancillary tests and at worst a population that would have received a diagnosis of brain death based on current clinical criteria but in whom there is residual blood flow [11, 12]. Recently, the traditionally accepted accuracy of four-vessel angiography for NDD has even been challenged . Although a recent Canadian expert consensus reported that the validation of ‘current or evolving techniques of brain blood flow imaging should not evolve into practice in a manner similar to cerebral angiography and radionuclide scanning, based on clinical application’, it is acknowledged that currently used ancillary tests and even traditionally accepted gold standards for NDD have not been subjected to rigorous evaluation . The same group issued recommendations for more research to confirm the validity and accuracy of current ancillary reference tests and to develop new techniques for NDD .