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This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists’ Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society. Supplementary Information The online version contains supplementary material available at 10.1007/s12630-023-02431-4.

Background and Objectives:There is a paucity of data on the frequency and prognosis of infratentorial brain injury among patients suspected of death by neurologic criteria (DNC), which likely contributes to scientific uncertainty regarding the role of isolated brainstem death in DNC determination. Our aim was to synthesize the prevalence, characteristics and evolution of infratentorial brain injury, including isolated brainstem death, among patients suspected of DNC.Methods:We conducted a systematic review by searching Medline, Embase, EBM Reviews, CINAHL Complete and the grey literature from inception to March 26 2021. We selected cohort and cross-sectional studies, as well as case reports and case series, that included patients suspected of DNC. Two study investigators independently performed study selection, data collection and risk of bias assessment. Our primary outcomes were the respective prevalence of infratentorial brain injury and of isolated brainstem death, which we meta-analyzed using mixed-effects Bayesian hierarchical models with diffuse priors. Our secondary outcomes were the characteristics and evolution of patients with infratentorial brain injury and with isolated brainstem death.Results:Twenty-one studies met the selection criteria, most of which were of moderate to high risk of bias. Among patients suspected of DNC, the prevalence of infratentorial brain injury ranged from 2 to 16% (n=3602, mean prevalence: 6.3%, 95% highest density interval [2.4-14.2%]), whereas the prevalence of isolated brainstem death ranged from 1 to 4% (n=3692, mean prevalence: 1.5%, 95% highest density interval [0.5-3.9%]). A total of 38 isolated brainstem death cases with data on clinical characteristics and/or evolution were included. All had infratentorial strokes. Twenty patients had EEG background activity in the alpha or theta frequencies, 19 had preserved cerebral blood flow, 2 had preserved supratentorial cerebral perfusion, 2 had cortical responses to visual evoked potentials and 1 had cortical responses to somatosensory evoked potentials. At the latest follow-up, 28 had progressed to whole-brain death.Discussion:Studies with moderate to high risk of bias suggest that infratentorial brain injury is relatively uncommon among patients suspected of DNC. Isolated brainstem death is rarer and appears to carry a high risk of progressing to whole-brain death. These findings require further high-quality investigation.

Purpose We performed a systematic review and meta-analysis to determine the diagnostic test accuracy of ancillary investigations for declaration of death by neurologic criteria (DNC) in infants and children. Source We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases from their inception to June 2021 for relevant randomized controlled trials, observational studies, and abstracts published in the last three years. We identified relevant studies using Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology and a two-stage review. We assessed the risk of bias using the QUADAS-2 tool, and applied Grading of Recommendations Assessment, Development, and Evaluation methodology to determine the certainty of evidence. A fixed-effects model was used to meta-analyze pooled sensitivity and specificity data for each ancillary investigation with at least two studies. Principal findings Thirty-nine eligible manuscripts assessing 18 unique ancillary investigations ( n = 866) were identified. The sensitivity and specificity ranged from 0.00 to 1.00 and 0.50 to 1.00, respectively. The quality of evidence was low to very low for all ancillary investigations, with the exception of radionuclide dynamic flow studies for which it was graded as moderate. Radionuclide scintigraphy using the lipophilic radiopharmaceutical 99m Tc-hexamethylpropyleneamine oxime (HMPAO) with or without tomographic imaging were the most accurate ancillary investigations with a combined sensitivity of 0.99 (95% highest density interval [HDI], 0.89 to 1.00) and specificity of 0.97 (95% HDI, 0.65 to 1.00). Conclusion The ancillary investigation for DNC in infants and children with the greatest accuracy appears to be radionuclide scintigraphy using HMPAO with or without tomographic imaging; however, the certainty of the evidence is low. Nonimaging modalities performed at the bedside require further investigation. Study registration: PROSPERO (CRD42021278788); registered 16 October 2021. Supplementary Information The online version contains supplementary material available at 10.1007/s12630-023-02418-1.

There are two anatomic formulations of death by neurologic criteria accepted worldwide: whole-brain death and brainstem death. As part of the Canadian Death Definition and Determination Project, we convened an expert working group and performed a narrative review of the literature. Infratentorial brain injury (IBI) with an unconfounded clinical assessment consistent with death by neurologic criteria represents a nonrecoverable injury. The clinical determination of death cannot distinguish between IBI and whole-brain cessation of function. Current clinical, functional, and neuroimaging assessments cannot reliably confirm the complete and permanent destruction of the brainstem. No patient with isolated brainstem death has been reported to recover consciousness and all patients have died. Studies suggest a significant majority of isolated brainstem death will evolve into whole-brain death, influenced by time/duration of somatic support and impacted by ventricular drainage and/or posterior fossa decompressive craniectomy. Acknowledging variability in intensive care unit (ICU) physician opinion on this matter, a majority of Canadian ICU physicians would perform ancillary testing for death determination by neurologic criteria in the context of IBI. There is currently no reliable ancillary test to confirm complete destruction of the brainstem; ancillary testing currently includes evaluation of both infratentorial and supratentorial flow. Acknowledging international variability in this regard, the existing evidence reviewed does not provide sufficient confidence that the clinical exam in IBI represents a complete and permanent destruction of the reticular activating system and thus the capacity for consciousness. On this basis, IBI consistent with clinical signs of death by neurologic criteria without significant supratentorial involvement does not fulfill criteria for death in Canada and ancillary testing is required.