**8. Brain death determination**

Another critically important consideration is the emotional state of a family coming to grips with the untimely and unexpected loss of a loved one. The grief combined with the immense responsibility of determining what a loved one "may have wanted" can place a significant burden on his or her relatives. This can be especially difficult for families of patients with no advance directive, living will, power of attorney, or prior conversation concerning their organ donation wishes. When dealing with issues related to organ donation, health care providers must be extremely sensitive to family needs and ensure that their local OPO is involved early on in the process in order to prevent any potential conflict of interest [7]. The separation of responsibilities during these proceedings is critical in alleviating any concerns regarding the simultaneous provision of care for the patient along with facilitation of the organ donation

**Figure 2.** Simplified schematic of the organ donation process. Following the identification of potential organ donor, a cascade of events takes place that ultimately ends with successful organ transplantation. Further details regarding this

From the time a potential donor arrives to the hospital and is determined to have non-survivable injury, it is important that they are managed under the assumption that they may donate organs, and that care is both optimal and timely [6, 55, 56]. This includes early notification of the local OPO regarding the presence of a potential donor [7]. A great deal of attention must be paid to prevent hypoxia and systemic hypo-perfusion, both of which could compromise the

process by the same individual and/or team [53, 54].

complex process can be obtained from Wojda et al. [7].

76 Organ Donation and Transplantation - Current Status and Future Challenges

When a patient presents to the hospital with concern for altered consciousness, it is imperative to rule out all reversible causes of coma, first excluding the presence of any substances of abuse, medication side effects, electrolyte, metabolic or acid-base derangements [62]. Once these are ruled out, imaging can often shed some light on potential causes of neurological compromise. In the current case vignette, the CT was utilized in order to give the treating physician an indication of the magnitude of injury and likelihood of recovery. With that being said, official declaration of BD is actually a clinical one [63]. From definitional standpoint, BD is considered to be present when there is irreversible damage to the brain and brainstem [36]. In order to assess brain function, several key components are required, with the most important one being a thorough neurological examination including assessment of brainstem reflexes [62]. Various ancillary tests can also be performed to assess cerebral blood flow and brain electrical activity in cases with equivocal exam findings. The final declaration of BD (including the official time of death) rests with the treating physician.

Determination of brain death (BD) can be a complex issue in the evaluation of catastrophic neurological injury. Clinical diagnosis of BD is relatively uncommon in the acute care setting. Usually acute injury does not progress to the degree of absent brainstem reflexes and apnea. "The small percentage of…cases may be related to many factors including early aggressive care like decompressive craniectomies, change in referral patterns, and early withdrawal of care or decision to proceed with a donation after cardiac death protocol" [64]. There are predefined criteria for the clinical determination of BD which may vary slightly from country to country. The neurological assessment of suspected BD typically requires at least 25 tests and verifications. "The overriding principle is simple: establish cause, exclude confounders, determine futility of interventions, examine brainstem reflexes and test for apnea" [64].

of BD also requires excellent coordination between the OPO and the medical management team [7, 64]. The key concerns for the medical team are to ensure hemodynamic stability and avoid the development of hyper/hypo-glycemia, acid-base or electrolyte derangements and pulmonary edema [7]. Many diagnostic tests and interventions occur during this phase specifically to ensure viability of key body systems and organs. Accumulated clinical evidence suggests "that a delay in declaration of brain death not only prolongs the time to organ recovery but also may increase the risks to transplantable organs, resulting in more complicated post-operative phases for the recipient" [64]. Finally, there is also evidence suggesting that second BD examination may negatively affect organ donor physiology due to inherent time

The Process of Organ Donation from Non-Living Donors: A Case-Based Journey from Potential…

http://dx.doi.org/10.5772/intechopen.76078

79

From historical perspective, transplantation of organs was premised on the so-called "dead donor rule", where donors must be declared dead according to established medical and legal criteria prior to donation [75]. According to Chaten [76], "the dead donor rule (DDR) maintains that it is illicit to procure vital organs from donors until after they have been declared dead". This rule also required adherence to strict BD criteria, directly referencing that the "dead donor rule mandates simultaneous life and death within the same body for organ donation, a biological status that is inherently contradictory" [76]. The best way to decrease variability in BD determination is for all hospitals to implement the established set of AAN brain death guidelines [71, 77]. This would lead to less confusion and fewer inconsistencies among institutions. Due to the many complexities of end-of-life discussions, it is imperative that BD determination protocols become increasingly uniform in both content and application. Wahlster et al. [78] looked at practices and perceptions regarding BD declaration in 91 countries, noting that "countries with an organized transplant network were more likely to have a brain death provision compared with countries without" [78]. Barriers to consensus on universal BD standardization include social, religious and economic factors specific to each country and/or culture. Wahlster et al. [78] further note that "future efforts for uniform policies will need to include physicians with neurologic and critical care expertise, representatives of national and international major medical organizations such as the World Health Organization or World Federation of Neurology, and scientific and medical advisors of government agencies" [76].

The shortage of organ donors has prompted resurgence in the utilization of donation after circulatory or cardiac death (DCD) [23, 51, 79]. While the concept of BD has been extensively discussed and there is a reasonable consensus as far as applicable criteria and assessments are concerned, definitive guidelines with respect to DCD continue to pose a challenge. In 1993, the Pittsburg non-beating heart organ donation protocol was proposed in order to provide criterion for organ procurement in the case of circulatory death. This protocol has come under criticism due to its questionable ethical application [80]. Although a definitive consensus is yet to be made from a legal and ethical standpoint, various OPOs are performing organ procurements with their own sets of standards and protocols [80]. Of interest, DCD historically constituted the largest proportion of organ donations prior to the advent of donation after BD. Subsequently, its utilization decreased substantially due to superior graft survival outcomes

delays [74], thus lending indirect support for ancillary/confirmatory BD testing.

**9. Circulatory death determination**

following donation after BD [81, 82].

Due to frequent inconsistencies related to the determination of BD, the Quality Standards Subcommittee of the American Academy of Neurology (AAN) met in the 1990s to establish clear definitions of clinical terms and associated testing. The group also determined the validity of ancillary testing versus the clinical exam and its applicability to the organ donation process. Clinical criteria for BD require a formal assessment and are only undertaken once all other potentially reversible cause are excluded. The initial evaluation needs to ensure there are "no lingering effects of prior sedation, or prior use of illegal drugs or alcohol. A reasonable guideline is to calculate 5–7 times the drug's elimination half-life in hours and allow that time to pass before clinical exam is performed" [64]. A core temperature of 36°C is also recommended which can be aided by use of warming blankets if necessary. As in the current chapter's vignette, neuroimaging such as a CT scan of the head should be performed to help determine cause of mental status deterioration. Clinical examination must include a thorough neurological examination including assessment of patient's level consciousness, as well as evaluation for verbal and motor deficits. The above exam must also include the interrogation of brainstem reflexes including pupillary, corneal, pharyngeal, and tracheal responses, as well as oculocephalic reflexes with doll's eye and cold caloric assessments. Apnea testing requires documentation of absence of a respiratory drive after a CO2 challenge. This methodology also has strict criteria that must be followed to ensure accurate determination of absent respiratory drive [65, 66].

Although ancillary testing, such as electroencephalography (EEG), cerebral angiography, nuclear flow scan, transcranial Doppler, CT angiography and magnetic resonance (MR) angiography, can be utilized in the process of determining BD—due to variability in the interpretation of these studies—it is not a substitute for the clinical examination [67–70]. In aggregate, the above tests can provide additional data on electrical brain function and cerebral blood flow and "…can be used when uncertainty exist about the reliability of parts of the neurological examination or when the apnea test cannot be performed" [71, 72]. Expertise in determining brain death can be inadequate due to multitude of factors, including lack of clinical experience. This is likely one of the reasons why 6 US states require confirmation by a second examiner and some specifically require at least one of these examiners to be either a neurologist, neurosurgeon or intensivist [73].

As one can see, the determination of brain death can be quite complex in and of itself and can be even further complicated when the question of organ donation is raised. This is why we stress the importance of early involvement of a local OPO [73]. After the declaration of BD, assuming the presence of consent for organ and tissue donation, the care of the donor shifts to optimizing organ perfusion and viability [7]. The preservation of organs after determination of BD also requires excellent coordination between the OPO and the medical management team [7, 64]. The key concerns for the medical team are to ensure hemodynamic stability and avoid the development of hyper/hypo-glycemia, acid-base or electrolyte derangements and pulmonary edema [7]. Many diagnostic tests and interventions occur during this phase specifically to ensure viability of key body systems and organs. Accumulated clinical evidence suggests "that a delay in declaration of brain death not only prolongs the time to organ recovery but also may increase the risks to transplantable organs, resulting in more complicated post-operative phases for the recipient" [64]. Finally, there is also evidence suggesting that second BD examination may negatively affect organ donor physiology due to inherent time delays [74], thus lending indirect support for ancillary/confirmatory BD testing.

From historical perspective, transplantation of organs was premised on the so-called "dead donor rule", where donors must be declared dead according to established medical and legal criteria prior to donation [75]. According to Chaten [76], "the dead donor rule (DDR) maintains that it is illicit to procure vital organs from donors until after they have been declared dead". This rule also required adherence to strict BD criteria, directly referencing that the "dead donor rule mandates simultaneous life and death within the same body for organ donation, a biological status that is inherently contradictory" [76]. The best way to decrease variability in BD determination is for all hospitals to implement the established set of AAN brain death guidelines [71, 77]. This would lead to less confusion and fewer inconsistencies among institutions. Due to the many complexities of end-of-life discussions, it is imperative that BD determination protocols become increasingly uniform in both content and application. Wahlster et al. [78] looked at practices and perceptions regarding BD declaration in 91 countries, noting that "countries with an organized transplant network were more likely to have a brain death provision compared with countries without" [78]. Barriers to consensus on universal BD standardization include social, religious and economic factors specific to each country and/or culture. Wahlster et al. [78] further note that "future efforts for uniform policies will need to include physicians with neurologic and critical care expertise, representatives of national and international major medical organizations such as the World Health Organization or World Federation of Neurology, and scientific and medical advisors of government agencies" [76].
