Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (843 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A state of prolonged irreversible cessation of all brain activity, including lower brain stem function with the complete absence of voluntary movements, responses to stimuli, brain stem reflexes, and spontaneous respirations. Reversible conditions which mimic this clinical state (e.g., sedative overdose, hypothermia, etc.) are excluded prior to making the determination of brain death. (From Adams et al., Principles of Neurology, 6th ed, pp348-9)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Death, Brain; Coma Depasse; Brain Dead; Brain Deads; Irreversible Coma; Coma, Irreversible.
Where it fits in the MeSH classification
- Broader topics
- Brain Diseases; Coma; Death
Research landscape
PubMed indexes 10,117 records tagged with the MeSH heading “Brain Death” (counts retrieved 2026-10-29). 1,504 of them (14.9%) were published from 2020 onward, and the busiest period so far is through 1999 with 4,399 records.
Reviews account for 1,213 records (12.0%) and meta-analyses for 43. Randomized controlled trials number 70 (0.7%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 4,399 |
| 2000-2009 | 1,800 |
| 2010-2019 | 2,414 |
| 2020 onward | 1,504 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,213 | 12.0% |
| Meta-analyses | 43 | 0.4% |
| Randomized controlled trials | 70 | 0.7% |
Method: PubMed query "Brain Death"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in neuroscience
Neuroscience draws on tools with different strengths: cellular and animal work can manipulate circuits directly, while human imaging and electrophysiology observe the living brain at lower resolution. Small imaging studies are prone to false positives, and findings in animals do not always carry over to people. Clinical neurology and psychiatry rely on trials and cohort studies whose outcomes are often symptom scales. Check the species, the sample size, how the outcome was measured and whether results were replicated.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Hypothermic Oxygenated Machine Perfusion of Liver Grafts from Brain-Dead Donors [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Hypothermic oxygenated machine perfusion (HOPE) was introduced in liver transplantation (LT) to mitigate ischemia-reperfusion injury.
- Closing excerpt
- HOPE determines a significant reduction of ischemia reperfusion injury in DBD LT.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (195 words)
Hypothermic oxygenated machine perfusion (HOPE) was introduced in liver transplantation (LT) to mitigate ischemia-reperfusion injury. Available clinical data mainly concern LT with donors after circulatory-determined death, whereas data on brain-dead donors (DBD) are scarce. To assess the impact of end-ischemic HOPE in DBD LT, data on primary adult LTs performed between March 2016 and June 2018 were analyzed. HOPE was used in selected cases of donor age >80 years, apparent severe graft steatosis, or ischemia time ≥10 hours. Outcomes of HOPE-treated cases were compared with those after static cold storage. Propensity score matching (1:2) and Bayesian model averaging were used to overcome selection bias. During the study period, 25 (8.5%) out of 294 grafts were treated with HOPE. After matching, HOPE was associated with a lower severe post-reperfusion syndrome (PRS) rate (4% versus 20%, p = 0.13) and stage 2-3 acute kidney injury (AKI) (16% versus 42%, p = 0.046). Furthermore, Bayesian model averaging showed lower transaminases peak and a lower early allograft dysfunction (EAD) rate after HOPE. A steeper decline in arterial graft resistance throughout perfusion was associated with lower EAD rate. HOPE determines a significant reduction of ischemia reperfusion injury in DBD LT.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31249370 · DOI · PMC6597580
Normothermic Regional Perfusion and Hypothermic Oxygenated Machine Perfusion for Livers Donated After Controlled Circulatory Death With Prolonged Warm Ischemia Time: A Matched Comparison With Livers From Brain-Dead Donors [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Prolonged warm ischemia time (WIT) has a negative prognostic value in liver transplantation (LT) using grafts procured after circulatory death (DCD).
- Closing excerpt
- In conclusion, the association of A-NRP + D-HOPE in DCD LT with prolonged WIT allows achieving comparable outcomes to DBD LT.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (194 words)
Prolonged warm ischemia time (WIT) has a negative prognostic value in liver transplantation (LT) using grafts procured after circulatory death (DCD). To assess the value of abdominal normothermic regional perfusion (A-NRP) associated with dual hypothermic oxygenated machine perfusion (D-HOPE) in controlled DCD LT, prospectively collected data on LTs performed between January 2016 and July 2021 were analyzed. Outcome of controlled DCD LTs performed using A-NRP + D-HOPE (n = 20) were compared to those performed with grafts procured after brain death (DBD) (n = 40), selected using propensity-score matching. DCD utilization rate was 59.5%. In the DCD group, median functional WIT, A-NRP and D-HOPE time was 43, 246, and 205 min, respectively. Early outcomes of DCD grafts recipients were comparable to those of matched DBD LTs. In DCD and DBD group, incidence of anastomotic biliary complications and ischemic cholangiopathy was 15% versus 22% (p = 0.73) and 5% versus 2% (p = 1), respectively. One-year patient and graft survival was 100% versus 95% (p = 0.18) and 90% versus 95% (p = 0.82). In conclusion, the association of A-NRP + D-HOPE in DCD LT with prolonged WIT allows achieving comparable outcomes to DBD LT.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35529593 · DOI · PMC9072630
Neuroscience and Brain Death Controversies: The Elephant in the Room [3]
Abstract reading summary — source excerpts
- Opening excerpt
- The conception and the determination of brain death continue to raise scientific, legal, philosophical, and religious controversies.
- Closing excerpt
- This conclusion has profound philosophical, religious, and legal implications that should compel respective authorities to (1) reassess the philosophical rationale for the definition of death, (2) initiate a critical reappraisal of the presumed alignment of brain death with the theological definition of death in Abrahamic faith traditions, and (3) enact new legislation ratifying religious exemption to death determination by neurologic criteria.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (231 words)
The conception and the determination of brain death continue to raise scientific, legal, philosophical, and religious controversies. While both the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research in 1981 and the President's Council on Bioethics in 2008 committed to a biological definition of death as the basis for the whole-brain death criteria, contemporary neuroscientific findings augment the concerns about the validity of this biological definition. Neuroscientific evidentiary findings, however, have not yet permeated discussions about brain death. These findings have critical relevance (scientifically, medically, legally, morally, and religiously) because they indicate that some core assumptions about brain death are demonstrably incorrect, while others lack sufficient evidential support. If behavioral unresponsiveness does not equate to unconsciousness, then the philosophical underpinning of the definition based on loss of capacity for consciousness as well as the criteria, and tests in brain death determination are incongruent with empirical evidence. Thus, the primary claim that brain death equates to biological death has then been de facto falsified. This conclusion has profound philosophical, religious, and legal implications that should compel respective authorities to (1) reassess the philosophical rationale for the definition of death, (2) initiate a critical reappraisal of the presumed alignment of brain death with the theological definition of death in Abrahamic faith traditions, and (3) enact new legislation ratifying religious exemption to death determination by neurologic criteria.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29931477 · DOI · PMC6132575
Etiology- and age-specific timing of death by neurologic criteria evaluation and declaration in clinical practice [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundThe timing of declaration of death by neurologic criteria (DNC) after acute brain injury varies in clinical practice.
- Closing excerpt
- These findings may help to better understand temporal patterns of DNC determination among patients with DNC in clinical practice.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (223 words)
BackgroundThe timing of declaration of death by neurologic criteria (DNC) after acute brain injury varies in clinical practice. However, large-scale data describing etiology- and age-specific timing of DNC evaluation and declaration are limited. This study aimed to characterize these timing patterns in a cohort of patients with DNC.MethodsRetrospective cohort study using registry data from German hospitals reporting cases of guideline-confirmed DNC to the national organ procurement organization. Included were adults (≥ 18 years) who were declared DNC between April 1, 2020, and August 31, 2025. Brain injury was categorized by ICD-10 as traumatic brain injury (TBI), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), acute ischemic stroke (AIS), hypoxic-ischemic encephalopathy (HIE). The primary outcome was time from initiation of mechanical ventilation to DNC declaration; time to first clinical examination fulfilling criteria for DNC was analyzed as a secondary outcome. Time-to-event distributions were summarized using cumulative incidence estimates, and associations of timing with etiology, age, and selected clinical variables were explored using random survival forests.ResultsAmong 6,701 patients with DNC from 716 hospitals, 6,397 had complete timing data (median age, 59 years [IQR, 46-69]; 54% male). Median time to DNC differed across etiologies (p ConclusionsThe timing of DNC evaluation and declaration varies substantially across etiologies and age groups. These findings may help to better understand temporal patterns of DNC determination among patients with DNC in clinical practice.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42106780 · DOI · PMC13159350
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Brain function in coma, vegetative state, and related disorders [5]
- Research article Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project [6]
- Research article Chronic "brain death": meta-analysis and conceptual consequences [7]
- Research article Clinical practice. Neurologic prognosis after cardiac arrest [8]
- Research article The rate of brain death and organ donation in patients resuscitated from cardiac arrest: a systematic review and meta-analysis [9]
- Research article Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline [10]
References
- Patrono D, Surra A, Catalano G, Rizza G, Berchialla P, Martini S, et al.. Hypothermic Oxygenated Machine Perfusion of Liver Grafts from Brain-Dead Donors. . 2019. PMID 31249370 · DOI · PMC6597580
- Patrono D, Zanierato M, Vergano M, Magaton C, Diale E, Rizza G, et al.. Normothermic Regional Perfusion and Hypothermic Oxygenated Machine Perfusion for Livers Donated After Controlled Circulatory Death With Prolonged Warm Ischemia Time: A Matched Comparison With Livers From Brain-Dead Donors. . 2022. PMID 35529593 · DOI · PMC9072630
- Verheijde JL, Rady MY, Potts M. Neuroscience and Brain Death Controversies: The Elephant in the Room. . 2018. PMID 29931477 · DOI · PMC6132575
- Barlinn K, Schoene D, Pleul K, Roessler M, Worm A, Diel NJ, et al.. Etiology- and age-specific timing of death by neurologic criteria evaluation and declaration in clinical practice. . 2026. PMID 42106780 · DOI · PMC13159350
- Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol. 2004. PMID 15324722 · DOI
- Greer DM, Shemie SD, Lewis A, Torrance S, Varelas P, Goldenberg FD, et al.. Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project. JAMA. 2020. PMID 32761206 · DOI
- Shewmon DA. Chronic "brain death": meta-analysis and conceptual consequences. Neurology. 1998. PMID 9855499 · DOI
- Young GB. Clinical practice. Neurologic prognosis after cardiac arrest. N Engl J Med. 2009. PMID 19657124 · DOI
- Sandroni C, D'Arrigo S, Callaway CW, Cariou A, Dragancea I, Taccone FS, et al.. The rate of brain death and organ donation in patients resuscitated from cardiac arrest: a systematic review and meta-analysis. Intensive Care Med. 2016. PMID 27699457 · DOI · PMC5069310
- Greer DM, Kirschen MP, Lewis A, Gronseth GS, Rae-Grant A, Ashwal S, et al.. Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline. Neurology. 2023. PMID 37821233 · DOI · PMC10791061
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.