TABLE 5.

Death concept dependent research agenda

		Death concept
#	Empirical question	PCC	ICC	PCIC	ICIC	PCBF	ICBF
1	What is the physiologic rationale for defining and determining death in cDCDD, and what are the conceptual implications for circulatory death determination frameworks?	✓	✓	✓	✓	✓	✓
2	What measurements are optimal triggers for defining WIT onset?	✓	✓	✓	✓	✓	✓
3	What are the allowable time limits from WIT onset to circulatory arrest for each transplantable organ among adult and pediatric populations?	✓	✓	✓	✓	✓	✓
4	Can WIT limits be extended when recovery includes in situ and/or ex situ perfusion techniques?	✓	✓	✓	✓	✓	✓
5	How can the accuracy of predictive tools for time to death be improved in adult, neonate, and pediatric populations?	✓	✓	✓	✓	✓	✓
6	How do withdrawal practices impact management of suffering during end-of-life care and time to death after WLSM?	✓	✓	✓	✓	✓	✓
7	What is the temporal relationship between the cessation of circulatory and neurologic function (including brainstem function) in adult, pediatric, and neonatal patients, and patients previously supported with mechanical circulatory assistance?					✓	✓
8	Are there feasible monitoring modalities that can reliably confirm the absence of brain (including brainstem) function following circulatory arrest within the time constraints of cDCDD?					✓	✓
9	What is the lower limit of time following cardiac arrest past which brain activity and function is irreversible?						✓
10	To what extent do practice-level factors (eg, withdrawal practices) influence the temporal relationship between the cessation of circulatory and neurologic function?					✓	✓
11	What is the minimum pulse pressure and pulse frequency that generates (a) cerebral blood flow, (b) perfusion, and (c) function across all patient populations?			✓	✓	✓	✓
12	Are there modalities to accurately evaluate brainstem flow, perfusion, and function within the time constraints of cDCDD?			✓	✓	✓	✓
13	What is the optimal observation period for neonates and pediatric patients?	✓	✓	✓	✓	✓	✓
14	Are there alternative monitoring modalities that directly or indirectly confirm the absence of (a) circulation, (b) brain perfusion, and (c) brain function that do not have the disadvantage of prolonging WIT?	✓	✓	✓	✓	✓	✓
15	Is the accuracy of alternative monitoring modalities generalizable among patient populations (eg, neonates and pediatric patients)?	✓	✓	✓	✓	✓	✓
16	What is the optimal length of time DCDD donors should undergo NRP (according to organ type)?			✓		✓	✓a
17	Are in situ postmortem reperfusion NRP methods (whether coupled with ex situ perfusion or not) superior to ex situ perfusion techniques in terms of cost and improving organ viability, graft outcomes, and the number of organs recovered per donor?			✓		✓	✓a
18	Are surgical safeguards to preclude the resumption of intracranial blood flow effective in A-NRP and TA-NRP?			✓		✓
19	In comparison with tidal ventilation, is static ventilation superior as an organ-preserving measure?	✓	✓	✓	✓	✓	✓
20	What are the optimal methods to preclude resumption of circulation and the possibility of the restoration of intracranial flow in postmortem tidal ventilation?	✓	✓	✓	✓	✓	✓

^aProvided restoration of brain function is impossible with current technologies.

A-NRP, abdominal normothermic regional perfusion; cDCDD, controlled donation after circulatory determination of death; DCDD, donation after circulatory determination of death; ICBF, irreversible cessation of brain function; ICC, irreversible cessation of circulation; ICIC, irreversible cessation of intracranial circulation; PCBF, permanent cessation of brain function; PCC, permanent cessation of circulation; PCIC, permanent cessation of intracranial circulation NRP, normothermic regional perfusion; TA-NRP, thoraco-abdominal normothermic regional perfusion; WIT, warm ischemic time; WLSM, withdrawal of life-sustaining measures.