The diagnostic criteria of brain death are reliable
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Peer-reviewed literature and consensus guidelines report that brain death determination relies on established clinical and ancillary diagnostic criteria, such as neurologic examinations and EEGs, which function reliably under standardized conditions.
<h4>Purpose</h4>Ancillary tests are frequently used in death determination by neurologic criteria (DNC), particularly when the clinical neurologic examination is unreliable. Nevertheless, their diagnostic accuracy has not been extensively studied. Our objective was to synthesize the sensitivity and specificity of commonly used ancillary tests for DNC.<h4>Source</h4>We performed a systematic review and meta-analysis by searching MEDLINE, EMBASE, Cochrane databases, and CINAHL Ebsco from their inception to 4 February 2022. We selected cohort and case-control studies including patients with 1) clinically diagnosed death by neurologic criteria or 2) clinically suspected death by neurologic criteria who underwent ancillary testing for DNC. We excluded studies without a priori diagnostic criteria and studies conducted solely on pediatric patients. Accepted reference standards were clinical examination, four-vessel conventional angiography, and radionuclide imaging. Data were directly extracted from published reports. We assessed the methodological quality of studies with the QUADAS-2 tool and estimated ancillary test sensitivities and specificities using hierarchical Bayesian models with diffuse priors.<h4>Principal findings</h4>Overall, 137 records met the selection criteria. One study (0.7%) had a low risk of bias in all QUADAS-2 domains. Among clinically diagnosed death by neurologic criteria patients (n = 8,891), ancillary tests had similar pooled sensitivities (range, 0.82-0.93). Sensitivity heterogeneity was greater within (σ = 0.10-0.15) than between (σ = 0.04) ancillary test types. Among clinically suspected death by neurologic criteria patients (n = 2,732), pooled ancillary test sensitivities ranged between 0.81 and 1.00 and specificities between 0.87 and 1.00. Most estimates had high statistical uncertainty.<h4>Conclusion</h4>Studies assessing ancillary test diagnostic accuracy have an unclear or high risk of bias. High-quality studies are required to thoroughly
Sensitivity heterogeneity was greater within (σ = 0.10–0.15) than between (σ = 0.04) ancillary test types. Among clinically suspected death by neurologic criteria patients ( n = 2,732), pooled ancillary test sensitivities ranged between 0.81 and 1.00 and specificities between 0.87 and 1.00. Most estimates had high statistical uncertainty. Conclusion Studies assessing ancillary test diagnostic accuracy have an unclear or high risk of bias. High-quality studies are required to thoroughly validate ancillary tests for DNC. Study registration PROSPERO (CRD42013005907); registered 7 October 2013.
Accurate death determination by neurologic criteria (DNC) is essential to providing closure to relatives and to ceasing somatic mechanical support in the deceased individual. Patients who are diagnosed with death by neurologic criteria often become organ donors; they are in fact the major source of transplantable organs for individuals with terminal heart, lung, liver, and kidney disease. 1 The cornerstone of DNC is a reliable clinical neurologic examination showing permanent cessation of consciousness and loss of brainstem reflexes, including central apnea as shown by an apnea test.
We included cohort and case–control studies, as well as case series, without restriction by language of publication. As this review principally concerns adult patients, we included study samples composed of at least 80% of adults (18 yr or older). We excluded studies from which we could not obtain or calculate the true and false positive and negative rates from the text, appendices or after contacting the main authors. Studies for which the objective was to determine diagnostic criteria of a specific ancillary test with no a priori definition of the diagnostic criteria for death by neurologic criteria were also excluded.
To estimate ancillary test diagnostic accuracy, we performed two meta-analyses. We conducted the first meta-analysis among studies involving only clinically diagnosed death by neurologic criteria patients (where ancillary tests are used in a confirmatory role). For these studies, only sensitivity could be calculated, since all are either true positives or false negatives. We conducted the second meta-analysis among studies involving
1 Flowchart diagram Descriptive analyses We included 137 studies (Table 1 ). Ninety-six studies (70%) had been conducted solely on patients clinically diagnosed with death by neurologic criteria and the remaining 41 (30%) included patients with clinically suspected death by neurologic criteria. Studies reported data on a variety of brain injury etiologies: 111 (81%) with traumatic brain injury, 107 (78%) with intracranial hemorrhage, 83 (61%) with hypoxemic-ischemic brain injury/cerebral anoxia, 77 (56%) with ischemic stroke, and 95 (69%) with other causes.
Some tests have, however, been subject to less investigation, such as CTP and MRI. The recent World Brain Death Project offers guidance on ancillary testing for DNC, some of which is supported by our findings. 2 First, the project recommendations suggest that four-vessel angiography, TCD, and radionuclide imaging combining diffusible radiopharmaceuticals and SPECT are the three ancillary tests deemed most appropriate for DNC. Our analysis indeed shows that these tests have the most robust diagnostic accuracy based on currently available data, which we reiterate is subject to significant bias.
26 , 27 Nevertheless, until significant diagnostic advances in ancillary testing are made, clinical examination should remain the cornerstone of DNC and ancillary testing should retain its role in providing further assurance to the presence of death by neurologic criteria in situations where the clinical examination may be unreliable or impossible to complete. In conclusion, clinicians employing ancillary tests in DNC should be aware that the studies assessing their diagnostic accuracy have modest methodological quality and are subject to significant risk of bias.
The purpose of this article was to sum up the problems raised by diagnosis of brain death in the child through a review of the literature. The clinical and paraclinical criteria of the diagnosis are considered in terms of the respective value and complementarity of different examinations. The fact that organ removal has become increasingly frequent in the child requires a rapid and reliable determination of the irreversibility of brain damage. The guidelines set up after conferences in which American authors participated to reach a consensus opinion relate to the child's age, the etiology, of the coma and the results of various paraclinical examinations. The diagnostic value of these examinations is assessed and the limitations of the various approaches are considered, particularly as regards certain etiologies in the newborn. It is suggested that it would be useful to inquire into the different diagnostic means used in France with respect to this difficult problem. Finally, the ethical and moral problems raised by some recent practices such as organ removal in anencephalic patients are discussed.
<h4>Introduction</h4>In brain death determination (BDD), electroencephalography (EEG) is a commonly used diagnostic method in Germany for proving irreversibility of previously clinically proven loss of brain function. Despite the comprehensive availability of EEG in intensive care units, the reliability of EEG readings is often limited by biological or technical artefacts. This study aimed to determine the detection rate of electrocerebral inactivity (ECI) with a special focus on reliability and challenges of using EEG in BDD.<h4>Methods</h4>A retrospective monocentric analysis of all BDD EEG data acquired from January 2015 to December 2025 at our tertiary care hospital was conducted. All identified BDD EEG reports were systematically analysed for their evaluability and for technical and biological artefacts. In addition, sociodemographic and patient-specific parameters that could influence the accuracy of EEG readings (e.g., craniotomies or intracranial drainages) were recorded.<h4>Results</h4>A total of 47 BDD EEG reports from 42 patients (women: 38.1%, mean age: 48.4 ± 14.4 years, median age: 52 years, age range: 21-78 years) were identified. In 81.0% of the patients, BDD could be confirmed using EEG. While biological artefacts did not significantly limit the evaluability of the EEG readings (<i>p</i> > 0.05), technical artefacts were significantly associated with a higher risk for limited EEG readability (<i>p</i> = 0.0309, relative risk: 4.2, 95% confidence interval: 1.3-13.8). This finding was primarily attributable to electrode artefacts (<i>p</i> = 0.0030), while other artefacts such as electrocardiogram or ventilation artefacts did not significantly impair readability (<i>p</i> > 0.05). Neither the aetiology of brain damage nor other patient-specific or sociodemographic parameters had any influence on the usability of EEG in BDD.<h4>Discussion</h4>We conclude that EEG is a reliable diagnostic tool in BDD in most cases if technically accurately recorded. Fur
Introduction In brain death determination (BDD), electroencephalography (EEG) is a commonly used diagnostic method in Germany for proving irreversibility of previously clinically proven loss of brain function. Despite the comprehensive availability of EEG
Discussion We conclude that EEG is a reliable diagnostic tool in BDD in most cases if technically accurately recorded. Further studies are required to optimise existing technical errors in selected patients to increase the already high level of methodological reliability. anoxic brain injury electroencephalography hypoxic brain injury intensive care neurocritical care organ donation resuscitation The author(s) declared that financial support was received for this work and/or its publication. Open Access funding enabled and organized by Projekt DEAL.
In contrast to many other countries, the concept of organ donation after circulatory death has not yet been established in Germany. Donation after brain death or BDD to determine individual death is based on a two-step process consisting of at least one structured clinical examination to determine brain dysfunction and either a further clinical examination at a defined time interval or additional diagnostic testing to prove that the dysfunction is irreversible. The sequence of examinations and the eligibility for all or only certain additional diagnostic procedures are dependent on age and the pattern of damage present ( 1–3 ).
As an additional diagnostic tool in BDD, EEG is established and frequently used due to its broad and bedside availability. Based on the German recommendations for BDD, brain death can be confirmed through an EEG reading showing electrocerebral inactivity (ECI) defined as proof of isoelectric EEG (<2 μV) in a special BDD montage with double electrode distances (≥10 cm) and stringent technical and operational requirements (e.g., electrode impedances of <10 kΩ, lower cut-off frequency of 0.53 Hz, upper cut-off frequency of 70 Hz and at least 30 min of artefact-free recording).
Patients were admitted to our ICU following initial work-up, where treating physicians suspected irreversible brain death on the basis of three criteria: (a) acute severe primary or secondary brain damage, (b) pathological clinical signs (coma, brainstem areflexia, or apnoea), and (c) absence of clinical improvement over an appropriate observation period or indication for confirmatory testing. Brain death was confirmed when all three criteria were met. EEG for BDD may be performed in Germany for primary supratentorial, primary infratentorial, or secondary brain damage in patients aged three years or older.
When EEG is selected as the confirmatory method, no other ancillary tests are conducted (e.g., brainstem auditory evoked potentials, somatosensory evoked potentials, transcranial Doppler ultrasonography, CT angiography, scintigraphy, or digital subtraction angiography) ( 1 , 4 , 5 ). Accordingly, our study included patients undergoing brain death determination by EEG exclusively, in accordance with German guidelines ( 1–3 ). All EEG recordings met the required technical acceptance criteria as specified by current standards. Each recording was independently reviewed by two experienced specialists as part of the routine diagnostic work-up, ensuring consistent interpretation.
After successful BDD through EEG, organ donation based on the documented or presumed wishes of the patients was possible in 74% of the cases. However, clear communication of BDD and the use of additional diagnostic tools to technically confirm the irreversible cessation of brain function may help to increase the acceptance of individual death among relatives and thus indirectly improve their willingness. Since the dataset presented was derived from real-world neurocritical care practice over a period of more than 10 years, we consider its robustness to be a major advantage. However, the retrospective single-centre study design limits generalisability ( 39 ).
Background: The guidelines for the determination of cerebral circulatory arrest (brain death) include clinical criteria and, depending on countries, some confirmatory testing like TCD, EEG, Evoced potential, CT angiography, brain scintigraphy. Brain death is the process and its confirmation must be done with responsibility and proven reliability, particularly in the situations of planned organ transplantation. In donor management protocol in our practice, after brain stem death determined by clinical examination, we perform EEG and TCD monitoring followed by brain scintigraphy and in exceptional conditions, cerebral angiography as additional diagnostic test for brain death confirmation. Methods: We present a case of patient which fulfilled clinical criteria of brain death due to a massive intracerebral hemorrhage (coma, absence of brainstem reflexes, apnea) in whom we monitored EEG and TCD. Initially, on the first day of clinical proven brain death, brain scintigraphy detected only minimal signs of cerebral flow in sagital venous sinus and cerebral angiography showed minimum sustained flow in the M2 segment of the right MCA. Results: During the nine days of monitoring, persisting EEG activity was obtained on right temporoparietal regions and TCD showed blood flow in right MCA on insonnation thought temporal bone window.On the tenth day TCD shows a “pattern of cerebral circulatory arrest” with absence of previously demonstrated flow with short enduring systolic spikes (125ms)
There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries. To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel. Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery. Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed. Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH <7.30 and Paco2 ≥60 mm Hg. If the clinical examination cannot be completed, ancillary testing may be considered with blood flow studies or electrophysiologic testing. Special consideration is needed for children, for persons receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia, as well as for factors such as religious, societal, and cultural perspectives; legal requirements; and resource availability. This report provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.
Brain death, defined as the irreversible cessation of all brain and brainstem functions, is legally and medically recognized as death, yet families often struggle to accept it. We report the case of a 65-year-old man admitted to the intensive care unit with a massive intracerebral hemorrhage. Despite maximal interventions, he progressed to brain death confirmed by neurological examination and apnea testing. While the patient's wife and daughter gradually accepted the diagnosis, his son reacted with disbelief, anger, and persistent denial, rejecting the medical declaration of death and complicating end-of-life communication. This case illustrates how such reactions can be interpreted through cognitive dissonance theory. Recognizing these mechanisms provides a novel clinical insight into the need for structured, empathetic, and repeated communication strategies that explicitly address cognitive dissonance, particularly for family members in emotionally dominant roles, to reduce conflict, improve acceptance of brain death, and support ethically complex end-of-life discussions, including those related to organ donation.
Recognizing these mechanisms provides a novel clinical insight into the need for structured, empathetic, and repeated communication strategies that explicitly address cognitive dissonance, particularly for family members in emotionally dominant roles, to reduce conflict, improve acceptance of brain death, and support ethically complex end-of-life discussions, including those related to organ donation.
brain death cognitive dissonance denial family response organ donation pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY Introduction Brain death, also referred to as death by neurologic criteria (BD/DNC), has been recognized for more than four decades as a medically and legally accepted definition of death [ 1 ].
It is defined as the irreversible cessation of all functions of the entire brain, including the brainstem, resulting in the complete and permanent loss of consciousness, spontaneous respiration, and brainstem reflexes [ 1 , 2 , 3 ]. The concept of "irreversibility" implies that neurologic function will not return spontaneously and that no medical intervention can restore brain activity [ 3 ]. From a legal standpoint, BD/DNC is considered equivalent to death determined by cardiopulmonary criteria [ 4 ]. The clinical determination of BD/DNC relies on a rigorous and systematic neurologic examination.
The essential criteria include: (a) the presence of coma of known etiology, (b) the complete absence of all brainstem reflexes, and (c) failure of the apnea test [ 2 , 5 ]. It is equally important to exclude confounding factors such as hypothermia, metabolic disturbances, or drug intoxication that can mimic brain death [ 2 , 5 ]. Ancillary tests, such as electroencephalography (EEG), cerebral angiography, or radionuclide cerebral blood flow studies, may be used in selected circumstances but do not substitute for the clinical examination, which remains the cornerstone of diagnosis [ 2 ].
Despite maximal therapeutic interventions, his neurological status deteriorated rapidly, and clinical findings became strongly indicative of brain death. Neurological examination confirmed coma of known etiology with complete absence of brainstem reflexes, including pupillary light, corneal, oculocephalic,
Apnea testing, performed under standard prerequisites (temperature ≥36 °C, systolic blood pressure ≥100 mmHg, absence of hypoxemia and metabolic disturbances), demonstrated no spontaneous respiratory effort with arterial PaCO₂ exceeding 60 mmHg. These findings, together with the exclusion of confounding factors, confirmed the diagnosis of death by neurologic criteria in accordance with international guidelines (Table 1 ) [ 1 ]. Table 1 Clinical examination of the case study for the determination of brain death inspired by Greer et al.
(2020) (Brain Death/ Death by Neurologic Criteria (BD/DNC)) Summary of the clinical examination components required for the neurologic determination of brain death, consistent with established guidelines [ 1 ]. BD/DNC = Brain Death/Death by Neurologic Criteria. Examination step Clinical findings of the case based on expected findings in BD/DNC Important considerations 1. Pupillary assessment The patient's pupils were mid-sized, remained fixed, and showed no reaction to light. There were no confounding factors affecting the patient's pupil reactions, e.g., no ocular trauma or prior eye surgery, nor the presence of pharmacologic agents. 2.
The patient remained hemodynamically stable throughout the procedure, allowing for a complete and reliable apnea test without the need for ancillary testing. Overall conclusion: Clinical examination and apnea test findings were consistent with BD/DNC, confirming the diagnosis. In line with institutional procedure, the confirmatory examinations were performed twice to validate the diagnosis of brain death. After completing these diagnostic steps, the patient's family, his wife and two children, a daughter and a son, were informed by the treating physician, together with the nurse coordinator for organ donation, in a private setting that ensured quiet and confidentiality.
Involving families in the diagnostic process and providing ongoing emotional support can reduce distress, facilitate acceptance, and improve decision-making at the end of life. Ultimately, recognizing the psychological dimension of brain death determination is essential for fostering trust, guiding families through grief, and supporting ethically sensitive practices such as organ donation.
as Diagnostic of Brain Death The physiological practicalities of functional brain death do … *This is referred to as whole-brain death. The term brain death has become a standard shorthand … a diagnosis of brain death. He dis¬ cusses the anatomical pathology of brain injury, which
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