There is insufficient evidence to support an evidence-based recommendation on the timing of organ donation.

In the absence of direct scientific evidence, EXPERT CONSENSUS concluded that:

• After declaration of death by neurologic criteria following pTBI, organ donation should proceed as soon as organ function has been optimized to maximize organ function in recipients. (93.3% consensus)

No evidence or expert opinion supported distinct recommendations based on patient gender, wounding mechanism, or military vs. civilian context.

A nihilistic approach to pTBI is highly discouraged. However given the severity of brain injury that is often inherent to pTBI many pTBI victims will progress to death by neurological criteria. Thus end of life care is an important topic in pTBI care.

The Uniform Determination of Death Act was approved by the American Medical Association in 1980 and the American Bar Association in 1981.7 It defines death as either the irreversible cessation of all brain functions including the brain stem, or the irreversible cessation of circulatory and respiratory functions. Though the law has been adopted in all states, medical standards used to determine neurologic brain death vary slightly amongst jurisdictions and institutions.

Every effort should be made to aggressively treat patients per best practice guidelines until a judgement is made by an experienced provider that such treatment is, in fact, futile or the patient has lost all neurological function. When death by neurological criteria occurs, it must be remembered that this tragedy affords the opportunity to fulfil prior stated wishes for organ donation amongst many critically ill patients, to save other lives. Organ donations from heart-beating and non-heart beating donors serve a multitude of transplant recipients with acute or chronic organ failures. For optimal success, transitions of care from aggressive care to end of life care must be smooth, streamlined and carefully organized, coupled with providing support to the patients' near and dear ones.

The previous guidelines do not provide any recommendations for timing of organ donation following pTBI and there was no attempt to address this topic.

We found no studies that specifically addressed this question in patients with penetrating TBI. However, there were a few studies that attempt to address the issue of timing of organ donation following declaration of brain death in the broader population that include pTBI patients. Two non-randomized studies mentioned the timing of organ donation, interventions to stabilize patients for better outcomes of organ donation or greater number of organs donated prior to death by neurologic criteria caused by a head injury.2,3

Kogan, et al. published a non-randomized study of 173 brain dead donors which included TBI patients prospectively followed heart transplant recipients for 10 years after receiving the organ donation in Israel over a 20-year period (1997 to 2017).2 The study reported 10-year survival of recipients was similar between short and long time interval groups based on the median time from injury to brain death, from brain death to aortic cross-clamp in donors, and time from donor aortic cross-clamp to unclamping in the recipient. The study reported no differences in the rate of 10-year survival and no major adverse events when the time from injury to declaration of brain death was less than 97 hours or 97 hours and longer. For these groups, the study also reported no differences in in-hospital mortality or the mean total rejection score of recipients. In addition, the study reported there were no differences in the rate of survival without rejection in any of the groups but did not report the specific data. This study does suggest that delaying donation until the patient is hemodynamically stable may not worsen recipient outcomes.

Resnick, et al investigated nearly 300 brain dead donors retrospectively reviewed the Gift of Life database, which serves parts of Pennsylvania, New Jersey, and all of Delaware, for organ donors between 2011 and 2015 who progressed to brain death after a head trauma.3 Twenty-eight per cent had a penetrating injury. The aim of the study was to determine if organ procurement should be delayed allowing for more donor management goals to be met. Based on the stated national goal for organ donation to be 3.75 organs transplanted per donor, the study compared characteristics of donors who donated more than four organs with those who donated four or less organs. For the donor management goals, four of the seven goals showed no differences between groups in the percent who met that goal. The study reported significantly shorter mean time, for those who donated more than four organs, from admission to declaration of brain death and between admission and organ procurement with those who donated four or less organs, however there was no difference in the time between declaration of brain death and organ procurement. This study suggests that a shorter time from admission to brain death and from admission to organ procurement is associated with a greater number of organs donated, but numbers of organs donated was not associated with time from brain death to organ procurement.

As there is no data to guide the timing of organ donation following declaration of death by neurological criteria specific to patients with penetrating TBI, extrapolation from other donor populations implies that proactive organ donor management should be attempted and that longer times from declaration of death to donation do not necessarily result in adverse outcomes for recipients. The recommendations within this document are limited to expert opinion but are consistent with other published guidelines.4-6 The main impetus to wait to proceed with organ donation following declaration of death by neurological criteria is to allow for the physiological derangement that occurs following brain death to be mitigated by organ donor management. Organ donation following donation after cardiac death from termination of futile care is somewhat different as there are set ischemic times following onset of terminal hypotension and / or hypoxia.

There are a number of physiological derangements that occur following progression to death by neurologic criteria as a result of loss of central regulatory mechanisms. This results in significant alterations in hemodynamics, endocrine function, and temperature.7,8 Frequent complications of brain death include, but are not limited to, hypotension, hypothermia, diabetes insipidus, coagulopathy, hyperglycemia, arrythmias, and respiratory failure.4,8 In order to optimize recipient outcomes, the process of organ donor management is recommended whereby specific goals for organ function are attempted.9,10 There are also several variations in donor management goals, which may be based on organ procurement organization or medical institution policy.10,11

Examples of donor management goals are:11

• Mean arterial pressure, mm Hg: 60-110
• Central venous pressure, mm Hg: 4-12
• Ejection fraction, %: ≥50
• Low-dose vasopressors (dopamine at 10 µg/kg/min or less, neosynephrine at 60 µg/min or less, and norepinephrine at 10 µg/min or less) No. of agents: ≤1
• Arterial blood gas, pH: 7.3-7.5
• PaO2:FIO2 ratio: ≥300
• Serum sodium, mEq/L: ≤155
• Urine output, mL/kg/h over 4 hours: ≥0.5
• Glucose, mg/dL: ≤150

Optimization of the organ donor following declaration of death by neurologic criteria in a patient with TBI can take time however and the optimal timing of organ donation and procurement is unknown.

The expert panelists were reluctant to opine on issues pertaining to brain death and organ donation fearing that it could promote a nihilistic approach to pTBI patients. Indeed, these patients are often subject to overt nihilism and the incorrect view that pTBI is synonymous with medical futility. The experts note that many pTBI patients can achieve acceptable outcomes if given the chance. Aggressive care is perhaps the single most important factor in pTBI patient outcomes. In military neurosurgeons' experience, better outcomes are achieved compared to civilian patients despite treating injuries from higher velocity firearms. pTBI patients should not simply be viewed as a potential source of organs for donation. The prime duty of medical personnel is to give the pTBI patient the best chance for an optimal outcome.

The key message of this chapter is that donor organs have the best chance of positively impacting their recipients if organs are implanted early after donor physiology is optimized.

Optimization of donor recipient outcomes should be the goal once declaration of death or termination of care occurs in the pTBI patient, and subsequently (or concurrently) the decision is made to proceed with organ donation. There is a large body of literature that addresses newer and novel techniques to improve organ function and maximize recipient outcomes, such as continual renal replacement therapy and direct personal resuscitation. Further research aiming to optimize organ recovery and transplant recipient outcomes should be pursued. Although it is unlikely that donor patients with pTBI would be optimally treated with a unique and distinct protocol, investigators should be open to such a possibility.