**2. Case vignette**

A 65-year-old male presents via aeromedical flight after a head-on, two-car collision in which he was the restrained passenger. The crash occurred at 7:45 pm–approximately 45 min prior to his arrival at the regional Trauma Center. The patient's wife, the driver, was pronounced dead at the scene. According to the Emergency Medical Services (EMS) report, the patient had Glasgow Coma Scale (GCS) of 9 shortly after the incident and was complaining of left-sided chest pain. It took 30 min to extract the patient from the car.

The patient arrived at the regional Trauma Center at 8:32 pm. On initial assessment, blood pressure was 90/65 mmHg, pulse was 120 beats/min, respiratory rate was 28 breaths/min and the patient had a GCS of 4. Intravenous fluid administration was started and the patient was immediately tracheally intubated. The FAST ultrasound exam was negative. Chest radiograph showed multiple rib fractures and a pneumothorax on the left, for which a chest tube was placed. The secondary trauma survey showed an obvious deformity of the left parietal skull, a left chest wall injury, and a visibly displaced left-sided hip fracture.

Hypertonic saline infusion was begun for treatment of a presumed severe traumatic brain injury (TBI). Detailed timeline of subsequent events now follows:

> • 9:25 pm: The patient's neurological exam was consistent with brain death, as confirmed by two independent physicians credentialed in this clinical area of expertise. Confirmatory testing in the form of cerebral perfusion study was ordered and the patient was taken to the intensive care unit (ICU) in the interim for ongoing medical management. In accordance with applicable State Laws, The Local Organ Procurement Organization (OPO) was con-

M.D. Image used under Creative Commons Attribution-Share Alike 4.0 International license.

**Figure 1.** An example of a Tc-99 m radionuclide cerebral blood flow study showing typical appearance of "no flow" within the cranial vault (e.g., the white appearance). At the same time, the facial region is richly perfused with blood (e.g., the "hot-nose" sign), providing a stark comparison to the lack of intracranial flow. **Credit**: Jason Robert Young,

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• 10:30 pm: The patient's family arrived at the hospital and discussed prognosis and goals of care with the clinical team. At that time, his family members indicated understanding of the diagnosis, and the gravity and irreversibility of his condition. They informed staff that the patient was an organ donor and that they would like to honor his wishes in the event of brain death. Medical management and stabilization continued in anticipation of

tacted for possible organ donation.

the cerebral perfusion study.


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of organs for transplantation [2, 3]. This includes increased use of organs from donors after cardiac death (DCD) as well as the inclusion of "expanded criteria" donors (ECD) and the introduction of information technology-based tools for better organ allocation [3]. Despite tremendous progress, major challenges remain including the growing number of patients

It has long been known that more organs may be available than are being currently captured within the existing organ procurement organization (OPO) network [5]. In addition, some organs are lost through suboptimal organ donor resuscitation and/or lack of timely OPO notification [6, 7]. In this chapter, the authors will discuss the modern process of OPNLD, beginning with potential donor identification, then proceeding with physiological optimization, and finally ending with the procurement procedure. To illustrate key points more effectively,

A 65-year-old male presents via aeromedical flight after a head-on, two-car collision in which he was the restrained passenger. The crash occurred at 7:45 pm–approximately 45 min prior to his arrival at the regional Trauma Center. The patient's wife, the driver, was pronounced dead at the scene. According to the Emergency Medical Services (EMS) report, the patient had Glasgow Coma Scale (GCS) of 9 shortly after the incident and was complaining of left-sided

The patient arrived at the regional Trauma Center at 8:32 pm. On initial assessment, blood pressure was 90/65 mmHg, pulse was 120 beats/min, respiratory rate was 28 breaths/min and the patient had a GCS of 4. Intravenous fluid administration was started and the patient was immediately tracheally intubated. The FAST ultrasound exam was negative. Chest radiograph showed multiple rib fractures and a pneumothorax on the left, for which a chest tube was placed. The secondary trauma survey showed an obvious deformity of the left parietal

Hypertonic saline infusion was begun for treatment of a presumed severe traumatic brain

• 9:00 pm: Once the patient was hemodynamically stabilized, he was taken for computed tomography (CT) of the head, cervical spine, chest, abdomen and pelvis. Immediate review of imaging confirmed left hip fracture-dislocation, multiple left-sided rib fractures and a pneumothorax on the left. Of special concern was the presence of large left epidural and subdural hematomas with evidence of diffuse axonal injury, as well as extensive subarachnoid hemorrhage. The patient was found to have 1.5 cm midline shift with uncal herniation. • 9:15 pm: Emergent neurosurgery consultation was placed, with immediate arrival of the on-call neurosurgeon. The patient experienced a brief period of hemodynamic instability featuring both bradycardia and tachycardia, followed by the appearance of severe hypertension (systolic blood pressures >200 mmHg), and finally the appearance of bilaterally

dilated, unresponsive pupillary exam. The injury was deemed non-survivable.

entering transplant waiting lists [4].

**2. Case vignette**

a realistic hypothetical case-based scenario will be presented.

70 Organ Donation and Transplantation - Current Status and Future Challenges

chest pain. It took 30 min to extract the patient from the car.

skull, a left chest wall injury, and a visibly displaced left-sided hip fracture.

injury (TBI). Detailed timeline of subsequent events now follows:

**Figure 1.** An example of a Tc-99 m radionuclide cerebral blood flow study showing typical appearance of "no flow" within the cranial vault (e.g., the white appearance). At the same time, the facial region is richly perfused with blood (e.g., the "hot-nose" sign), providing a stark comparison to the lack of intracranial flow. **Credit**: Jason Robert Young, M.D. Image used under Creative Commons Attribution-Share Alike 4.0 International license.


• 8:30 am: After stabilizing the patient sufficiently for transfer to the radiology department for confirmatory brain flow study, determination was made to proceed with such testing (**Figure 1**). Following the confirmatory study to determine brain death, the patient continued to receive maximum medical management to ensure adequate organ perfusion and maintain tissue oxygenation. Representatives of the local OPO were introduced to the family and the formal process of organ donation was initiated.

report of a kidney transplant from a recently deceased donor in the mid-1930s [8, 13, 14]. Although unsuccessful, this procedure foreshadowed the various technical and ethical chal-

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The subsequent years and decades were characterized by a mixture of "trial and error" until the first successful living donor kidney transplant was performed in the mid-1950s by Nobel prize winner, Dr Joseph Murray [8, 11, 13]. The procedure was performed between identical twin brothers, both of whom survived for some time after [15]. Although the understanding of the organ rejection process was still very poor, Murray's successful transplantation strongly implied the need of genetic congruity between donor and recipient. Shortly thereafter, Main and Prehn discovered that chimerism could be induced by using radiation to weaken the immune system of mice, leading to improved acceptance of donor tissue [16, 17]. Several years later, Dr Murray attempted this method in his next successful kidney transplantation, but this was unfortunately preceded by significant mortality among patients who underwent total body irradiation prior to receiving new organs [11, 18]. Of note, this successful non-twintwin transplant recipient was the first well-documented case to recover from rejection [11, 19]. Subsequent failures associated with total body irradiation, including significant morbidity and mortality, led to increased interest in other potential methods of immunosuppression [13]. As a result of intensive research efforts, immunosuppressive medications were soon introduced to help address the problem of graft rejection [20, 21]. Initially the use of monotherapy was attempted with limited effectiveness. It was Dr Thomas Starzl (whose success rates exceeded most in the field at the time) who proposed a cocktail of immunosuppressive agents capable of reversing rejection [11]. This was yet another critical discovery that over time facilitated the expansion of efforts into transplantation of other solid organs, including the first liver transplant in 1963 by Dr Starzl, the pancreas in 1966 by Dr Lillehei and the heart in 1967 by Dr Barnard [8, 22–24]. Although long-term survival of early transplants and their recipients varied, the 1960s ushered in a new era with transplant centers appearing across the world [8, 11, 24]. Organ preservation science developed out of the necessity to ensure organ viability during

Beginning in the early 1900s, Charles Guthrie proposed that cooling of organs may offer a way to preserve them during transport [11]. It was not until the mid-1960s that the use of cooling agents became standard practice with the introduction of the now widely accepted University of Wisconsin solution [11, 26, 27]. With progress being made in multiple aspects of transplantation, new hope arose for patients suffering from various forms of end-stage organ failure. As organ preservation and technical aspects of transplantation advanced, attention shifted to ensuring adequate organ availability [7]. Along with this challenge came the ethical and legal considerations surrounding death and organ donation, which will be addressed in

It is the responsibility of physicians to "above all, do no harm" [28]. This concept should permeate each clinical decision made. In theory, this ethical principle is paramount to an equitable

lenges modern transplantation would face well into the future.

transport from donor to recipient [25].

greater detail later on in this chapter.

**4. Ethical considerations**

