Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

Prognostic value of near-infrared spectroscopy regional oxygen saturation and cerebrovascular reactivity index in acute traumatic neural injury: a CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Cohort Study.

BACKGROUND: Near-infrared spectroscopy regional cerebral oxygen saturation (rSO2) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR) due to its noninvasive nature and high spatial resolution. However, the prognostic utility of these parameters has not yet been determined. This study aimed to identify threshold values of rSO2 and rSO2-based CVR at which outcomes worsened following traumatic brain injury (TBI). METHODS: A retrospective multi-institutional cohort study was performed. The cohort included TBI patients treated in four adult intensive care units (ICU). The cerebral oxygen indices, COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and arterial blood pressure) were calculated for each patient. Grand mean thresholds along with exposure-based thresholds were determined utilizing sequential chi-squared analysis and univariate logistic regression, respectively. RESULTS: In the cohort of 129 patients, there was no identifiable threshold for raw rSO2 at which outcomes were found to worsen. For both COx and COx_a, an optimal grand mean threshold value of 0.2 was identified for both survival and favorable outcomes, while percent time above - 0.05 was uniformly found to have the best discriminative value. CONCLUSIONS: In this multi-institutional cohort study, raw rSO2was found to contain no significant prognostic information. However, rSO2-based indices of CVR, COx and COx_a, were found to have a uniform grand mean threshold of 0.2 and exposure-based threshold of - 0.05, above which clinical outcomes markedly worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

Neurologic Complications in Critically Ill Patients with Toxic Alcohol Poisoning: A Multicenter Population-Based Cohort Study.

BACKGROUND: Toxic alcohol poisoning is regularly encountered in emergency departments and intensive care units (ICUs). Most patients present with an altered level of consciousness, but the subsequent course and spectrum of neurologic complications and outcomes is highly variable. METHODS: We performed a population-based, multicenter retrospective cohort study of critically ill patients with toxic alcohol poisoning admitted to ICUs in Alberta, Canada, between 2007 and 2019 to describe neurologic sequelae, including seizures, coma, neuroimaging abnormalities, persistent cognitive or visual impairment, and mortality. Multivariate analysis was performed to identify predictors of poor outcome. RESULTS: We identified 104 patients, including 55 (53%) with methanol ingestion, 36 (35%) with ethylene glycol ingestion, and 13 (13%) with isopropanol ingestion. In patients who underwent neuroimaging, abnormalities were detected in 9 of 24 (38%) with methanol toxicity, 5 of 20 (25%) with ethylene glycol toxicity, and 0 of 10 with isopropanol toxicity (p = 0.07). Basal ganglia were commonly involved with both methanol and ethylene glycol poisoning, but prominent subcortical involvement and restricted diffusion were observed only with methanol poisoning. The composite of death, persistent cognitive impairment, or visual loss occurred in 13 (24%) patients with methanol poisoning, compared with one (3%) with ethylene glycol poisoning and none with isopropanol poisoning (p = 0.006). Among patients with methanol toxicity, greater elevation of the anion gap and lower Glasgow Coma Scale score were independent predictors of poor outcome. No patient with an anion gap ≥ 28 at presentation had a favorable recovery. Progression to death by neurologic criteria occurred in 3 of 55 (5%) patients with methanol poisoning and in none with other toxic alcohols. CONCLUSIONS: Methanol overdose is the most common form of toxic alcohol poisoning to result in ICU admission. Poor neurologic outcomes may occur especially with methanol poisoning, with more than one in five patients dying or having persistent cognitive or visual impairment. A wide anion gap independently predicts poor outcome, emphasizing the importance of expeditious recognition and treatment.

Postarrest Neuroprognostication: Practices and Opinions of Canadian Physicians.

BACKGROUND: Objective, evidence-based neuroprognostication of postarrest patients is crucial to avoid inappropriate withdrawal of life-sustaining therapies or prolonged, invasive, and costly therapies that could perpetuate suffering when there is no chance of an acceptable recovery. Postarrest prognostication guidelines exist; however, guideline adherence and practice variability are unknown. OBJECTIVE: To investigate Canadian practices and opinions regarding assessment of neurological prognosis in postarrest patients. METHODS: An anonymous electronic survey was distributed to physicians who care for adult postarrest patients. RESULTS: Of the 134 physicians who responded to the survey, 63% had no institutional protocols for neuroprognostication. While the use of targeted temperature management did not affect the timing of neuroprognostication, an increasing number of clinical findings suggestive of a poor prognosis affected the timing of when physicians were comfortable concluding patients had a poor prognosis. Variability existed in what factors clinicians' thought were confounders. Physicians identified bilaterally absent pupillary light reflexes (85%), bilaterally absent corneal reflexes (80%), and status myoclonus (75%) as useful in determining poor prognosis. Computed tomography, magnetic resonance imaging, and spot electroencephalography were the most useful and accessible tests. Somatosensory evoked potentials were useful, but logistically challenging. Serum biomarkers were unavailable at most centers. Most (79%) physicians agreed ≥2 definitive findings on neurologic exam, electrophysiologic tests, neuroimaging, and/or biomarkers are required to determine a poor prognosis with a high degree of certainty. Distress during the process of neuroprognostication was reported by 70% of physicians and 51% request a second opinion from an external expert. CONCLUSION: Significant variability exists in post-cardiac arrest neuroprognostication practices among Canadian physicians.

Death determination by neurologic criteria-what do families understand?

PURPOSE: Currently, there is little empirical data on family understanding about brain death and death determination. The purpose of this study was to describe family members' (FMs') understanding of brain death and the process of determining death in the context of organ donation in Canadian intensive care units (ICUs). METHODS: We conducted a qualitative study using semistructured, in-depth interviews with FMs who were asked to make an organ donation decision on behalf of adult or pediatric patients with death determination by neurologic criteria (DNC) in Canadian ICUs. RESULTS: From interviews with 179 FMs, six main themes emerged: 1) state of mind, 2) communication, 3) DNC may be counterintuitive, 4) preparation for the DNC clinical assessment, 5) DNC clinical assessment, and 6) time of death. Recommendations on how clinicians can help FMs to understand and accept DNC through communication at key moments were described including preparing FMs for death determination, allowing FMs to be present, and explaining the legal time of death, combined with multimodal strategies. For many FMs, understanding of DNC unfolded over time, facilitated with repeated encounters and explanation, rather than during a single meeting. CONCLUSION: Family members' understanding of brain death and death determination represented a journey that they reported in sequential meeting with health care providers, most notably physicians. Modifiable factors to improve communication and bereavement outcomes during DNC include attention to the state of mind of the family, pacing and repeating discussions according to families' expressed understanding, and preparing and inviting families to be present for the clinical determination including apnea testing. We have provided family-generated recommendations that are pragmatic and can be easily implemented.

RéSUMé: OBJECTIF: À l'heure actuelle, il y a peu de données empiriques sur la compréhension des familles de la mort cérébrale et de la détermination du décès. Le but de cette étude était de décrire la compréhension des membres de la famille de la mort cérébrale et du processus de détermination du décès dans le contexte du don d'organes dans les unités de soins intensifs (USI) canadiennes. MéTHODE: Nous avons mené une étude qualitative à l'aide d'entrevues semi-structurées et approfondies avec des membres de la famille à qui on a demandé de prendre une décision de don d'organes au nom de patients adultes ou pédiatriques dont le décès avait été déterminé selon des critères neurologiques (DCN) dans les unités de soins intensifs canadiennes. RéSULTATS: Sur la base d'entrevues avec 179 membres de la famille, six thèmes principaux ont émergé : 1) l'état d'esprit, 2) la communication, 3) le DCN peut être contre-intuitif, 4) la préparation à l'évaluation clinique pour un DCN, 5) l'évaluation clinique pour un DCN et 6) le moment du décès. Des recommandations sur la façon dont les cliniciens peuvent aider les membres de la famille à comprendre et à accepter un DCN par la communication à des moments clés ont été décrites, y compris la préparation des membres de la famille à la détermination du décès, l'autorisation de la présence des membres de la famille et l'explication de l'heure légale du décès, combinées à des stratégies multimodales. Pour de nombreux membres de la famille, la compréhension du DCN s'est développée au fil du temps et a été facilitée par des rencontres et des explications répétées plutôt qu'au cours d'une seule rencontre. CONCLUSION: La compréhension qu'ont les membres de la famille de la mort cérébrale et de la détermination du décès représente un parcours qu'ils ont décrit lors de rencontres successives avec des acteurs de soins de santé, et particulièrement avec des médecins. Les facteurs modifiables pour améliorer la communication et les issues du deuil pendant un DCN comprennent l'attention portée à l'état d'esprit de la famille, le rythme et la répétition des discussions en fonction de la compréhension exprimée par les familles, ainsi que la préparation et l'invitation des familles à être présentes pour la détermination clinique, y compris pendant le test d'apnée. Nous avons fourni des recommandations familiales qui sont pragmatiques et peuvent être facilement mises en œuvre.

A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline.

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.

RéSUMé: Ces Lignes directrices de pratique clinique 2023 Lignes directrices de pratique clinique dicale du décès basée sur l'arrêt permanent de la fonction cérébrale qui s'applique à toute personne, ainsi que des recommandations pour la détermination du décès par des critères circulatoires pour des donneurs d'organes potentiels et des recommandations pour la détermination du décès par des critères neurologiques pour tous les patients sous ventilation mécanique, indépendamment de leur potentiel de donneur d'organes. Les présentes Lignes directrices sont approuvées par la Société canadienne de soins intensifs, l'Association médicale canadienne, l'Association canadienne des infirmiers/infirmières en soins intensifs, la Société canadienne des anesthésiologistes, la Fédération des sciences neurologiques du Canada (représentant la Société canadienne de neurologie, la Société canadienne de neurochirurgie, la Société canadienne de neurophysiologie clinique, l'Association canadienne de neurologie pédiatrique, la Société canadienne de neuroradiologie et le Consortium neurovasculaire canadien), la Société canadienne du sang, le Programme de recherche en don et transplantation du Canada, l'Association canadienne des médecins d'urgence, l'Association des infirmières et infirmiers praticiens du Canada, et la Société canadienne de soins intensifs cardiovasculaires (CANCARE) et la Société canadienne de pédiatrie.

The experiences of family members of deceased organ donors and suggestions to improve the donation process: a qualitative study.

BACKGROUND: Decisions about organ donation are stressful for family members of potential organ donors. We sought to comprehensively explore the donation process from interviews conducted with family members of patients admitted to pediatric and adult intensive care units in Canada. METHODS: We conducted a qualitative study using semistructured, in-depth interviews with 271 family members asked to make an organ donation decision. We recruited participants from all provinces with an organ donation organization (n = 10), and analyzed themes using a modified grounded theory approach. On the basis of these interviews, suggestions were made by researchers and family members on how to improve the process of organ donation. RESULTS: We identified 3 main themes and 9 subthemes. Families need more comprehensive support around the time of donation, including having access to someone with shared experiences, support during specific moments as needed and better support during critical transitions (e.g., when the donor body goes to the operating room). The theme of better connection to recipient(s) included receiving information about the donation surgery (e.g., which organs were recovered), establishing connection with recipients (e.g., via social networks or letters) and planned encounters. Support after donation, such as updates on organ transplantation, early mental health checks and continued connection to donor organizations, could be improved. We derived 20 suggestions for improving the organ donation process, derived from interviews with family members of pediatric and adult organ donors. INTERPRETATION: We found gaps in family support during end-of-life and donation care. Feelings of abandonment, lack of support and poor-to-little follow-up provide the empirical findings needed for hospitals and organ donor organizations to provide better support to donor families.

Neurological Determination of Death Following Infratentorial Stroke: A Population-Based Cohort Study.

BACKGROUND: There is international variability in whether neurological determination of death (NDD) is conceptually defined based on permanent loss of brainstem function or "whole brain death." Canadian guidelines are not definitive. Patients with infratentorial stroke may meet clinical criteria for NDD despite persistent cerebral blood flow (CBF) and relative absence of supratentorial injury. METHODS: We performed a multicenter cohort study involving patients that died from ischemic or hemorrhagic stroke in Alberta intensive care units from 2013 to 2019, focusing on those with infratentorial involvement. Medical records were reviewed to determine the incidence and proportion of patients that met clinical criteria for NDD; whether ancillary testing was performed; and if so, whether this demonstrated the absence of CBF. RESULTS: There were 95 (27%) deaths from infratentorial and 263 (73%) from supratentorial stroke. Sixteen patients (17%) with infratentorial stroke had neurological examination consistent with NDD (0.55 cases per million per year). Among patients that underwent confirmatory evaluation for NDD with an apnea test, ancillary test (radionuclide scan), or both, ancillary testing was more common with infratentorial compared with supratentorial stroke (10/12 (85%) vs. 25/47 (53%), p = 0.04). Persistent CBF was detected in 6/10 (60%) patients with infratentorial compared with 0/25 with supratentorial stroke (p = 0.0001). CONCLUSIONS: Infratentorial stroke leading to clinical criteria for NDD occurs with an annual incidence of about 0.55 per million. There is variability in clinicians' use of ancillary testing. Persistent CBF was detected in more than half of patients that underwent radionuclide scans. Canadian consensus is needed to guide clinical practice.

Premortem anticoagulation timing and dose in donation after circulatory death: multicentre study of associations with graft function.

BACKGROUND: In controlled donation after circulatory determination of death (DCD), it is common to administer premortem heparin to potential donors. This practice remains controversial because there is limited evidence for it and there is the possibility of inducing hemorrhage. To our knowledge, no previous studies have assessed the effects of heparin timing and dose on graft function. METHODS: We performed a multicentre cohort study of consecutive DCD donors and the recipients of their organs. Anticoagulation administration was considered early if given near the time of withdrawal of life-sustaining measures and late if delayed until the onset of donor hypoxemia (oxygen saturation < 70%) or hypotension (systolic blood pressure < 60 mm Hg or mean blood pressure < 50 mm Hg). The anticoagulation dose was considered high if it was 300 units/kg or greater. RESULTS: Donor anticoagulation data were available for 301 kidney, 75 liver and 46 lung recipients. Heparin was administered in 92% of cases and was most commonly withheld in donors with cerebrovascular causes of death (p = 0.01). Administration was late in 59% and the dose was low in 27%. Among kidney recipients, there were no significant differences in need for dialysis, glomerular filtration rate over the first year after transplantation or graft survival on the basis of whether or not the donor received heparin, the timing of heparin administration or the dose of heparin. Among liver recipients, alkaline phosphatase concentrations over the first year were significantly higher among recipients who received organs from donors to whom lower doses of heparin had been administered. CONCLUSION: Premortem heparin is widely used in DCD cases, but there is variability in timing and dose, which was not associated with kidney outcomes in this study. Donor anticoagulation may have a greater impact in preventing biliary complications following liver transplantation.

Findings Predictive of Poor Outcome in Grade 5 Subarachnoid Hemorrhage: A Cohort Study.

BACKGROUND: Most patients with World Federation of Neurological Surgeons (WFNS) grade 5 subarachnoid hemorrhage (SAH) have poor outcomes. Accurate assessment of prognosis is important for treatment decisions and conversations with families regarding goals of care. Unjustified pessimism may lead to "self-fulfilling prophecy," where withdrawal of life-sustaining measures (WLSM) is invariably followed by death. METHODS: We performed a cohort study involving consecutive patients with WFNS grade 5 SAH to identify variables with >= 90% and >= 95% positive predictive value (PPV) for poor outcome (1-year modified Rankin Score >= 4), as well as findings predictive of WLSM. RESULTS: Of 140 patients, 38 (27%) had favorable outcomes. Predictors with >= 95% PPV for poor outcome included unconfounded 72-hour Glasgow Coma Scale motor score <= 4, absence of >= 1 pupillary light reflex (PLR) at 24 hours, and intraventricular hemorrhage (IVH) score of >= 20 (volume >= 54.6 ml). Intracerebral hemorrhage (ICH) volume >= 53 ml had PPV of 92%. Variables associated with WLSM decisions included a poor motor score (p < 0.0001) and radiographic evidence of infarction (p = 0.02). CONCLUSIONS: We identified several early predictors with high PPV for poor outcome. Of these, lack of improvement in motor score during the initial 72 hours had the greatest potential for confounding from "self-fulfilling prophecy." Absence of PLR at 24 hours, IVH score >= 20, and ICH volume >= 53 ml predicted poor outcome without a statistically significant effect on WLSM decisions. More research is needed to validate prognostic variables in grade 5 SAH, especially among patients who do not undergo WLSM.

Exploratory Evaluation of the Relationship Between iNKT Cells and Systemic Cytokine Profiles of Critically Ill Patients with Neurological Injury.

BACKGROUND: Neurological injury can alter the systemic immune system, modifying the functional capacity of immune cells and causing a dysfunctional balance of cytokines, although mechanisms remain incompletely understood. The objective of this study was to assess the temporal relationship between changes in the activation status of circulating invariant natural killer T (iNKT) cells and the balance of plasma cytokines among critically ill patients with neurological injury. METHODS: We conducted an exploratory prospective observational study of adult (18 years or older) intensive care unit (ICU) patients with acute neurological injury (n = 20) compared with ICU patients without neurological injury (n = 22) and healthy controls (n = 10). Blood samples were collected on days 1, 2, 4, 7, 14, and 28 following ICU admission to analyze the activation status of circulating iNKT cells by flow cytometry and the plasma concentration of inflammation-relevant immune mediators, including T helper 1 (TH1) and T helper 2 (TH2) cytokines, by multiplex bead-based assay. RESULTS: Invariant natural killer T cells were activated in both ICU patient groups compared with healthy controls. Neurological patients had decreased levels of multiple immune mediators, including TH1 cytokines (interferon-γ, tumor necrosis factor-α, and interleukin-12p70), indicative of immunosuppression. This led to a greater than twofold increase in the ratio of TH2/TH1 cytokines early after injury (days 1 - 2) compared with healthy controls, a shift that was also observed for ICU controls. Systemic TH2/TH1 cytokine ratios were positively associated with iNKT cell activation in the neurological patients and negatively associated in ICU controls. These relationships were strongest for the CD4+ iNKT cell subset compared with the CD4- iNKT cell subset. The relationships to individual cytokines similarly differed between patient groups. Forty percent of the neurological patients developed an infection; however, differences for the infection subgroup were not identified. CONCLUSIONS: Critically ill patients with neurological injury demonstrated altered systemic immune profiles early after injury, with an association between activated peripheral iNKT cells and elevated systemic TH2/TH1 cytokine ratios. This work provides further support for a brain-immune axis and the ability of neurological injury to have far-reaching effects on the body's immune system.

Donation after circulatory determination of death in western Canada: a multicentre study of donor characteristics and critical care practices.

PURPOSE: Donation after circulatory determination of death (DCD) has been performed in Canada since 2006. Numerous aspects of donor management remain controversial. METHODS: We performed a multicentre cohort study involving potential DCD donors in western Canada (2008-2017), as well as recipients of their organs, to describe donor characteristics and critical care practices, and their relation to one-year recipient and graft survival. RESULTS: There were 257 patients in four provinces that underwent withdrawal of life-sustaining therapies (WLST) in anticipation of possible DCD. The proportion of patients that died within two hours of WLST ranged from 67% to 88% across provinces (P = 0.06), and was predicted by deeper coma (P = 0.01), loss of pupillary light or corneal reflexes (P = 0.02), and vasopressor use (P = 0.01). There were significant differences between provinces in time intervals from onset of hypotension to death (9-11 min; P = 0.02) and death to vascular cannulation (7-10 min; P < 0.001). There was inconsistency in pre-mortem heparin administration (82-96%; P = 0.03), including timing (before vs after WLST; P < 0.001) and dose (≥ 300 vs < 300 units·kg-1; P < 0.001). Donation after circulatory death provided organs for 321 kidney, 81 liver, and 50 lung transplants. One-year recipient and graft survival did not differ among provinces (range 85-90%, P = 0.45). Predictors of death or graft failure included older recipient age (odds ratio [OR] per year, 1.04; 95% confidence interval [CI],1.01 to 1.07) and male donor sex (OR, 3.35; 95% CI, 1.39 to 8.09), but not time intervals between WLST and cannulation or practices related to heparin use. CONCLUSION: There is significant variability in critical care DCD practices in western Canada, but this has not resulted in significant differences in recipient or graft survival. Further research is required to guide optimal management of potential DCD donors.

RéSUMé: OBJECTIF: Le don d'organes après décès cardiocirculatoire (DDC) est pratiqué au Canada depuis 2006. De nombreux aspects touchant à la prise en charge des donneurs demeurent controversés. MéTHODE: Nous avons réalisé une étude de cohorte multicentrique auprès de donneurs potentiels de DDC dans l'Ouest canadien (2008­2017), ainsi qu'auprès des récipiendaires de leurs organes, afin de décrire les caractéristiques des donneurs et les pratiques de soins intensifs, ainsi que la relation entre ces éléments et la survie à un an des récipiendaires et des organes greffés. RéSULTATS: Au total, 257 patients provenant de quatre provinces ont subi une interruption des traitements de survie en vue d'un possible DDC. La proportion de patients décédés dans les deux heures suivant l'interruption des traitements de survie allait de 67 % à 88 % dans toutes les provinces à l'étude (P = 0,06) et pouvait être prédite par une profondeur du coma plus importante (P = 0,01), la perte de la réaction pupillaire à la lumière ou des réflexes cornéens (P = 0,02), et l'utilisation de vasopresseurs (P = 0,01). Des différences significatives ont été observées entre les différentes provinces dans les intervalles de temps entre le début de l'hypotension et le décès (9­11 min; P = 0,02) et entre le décès et la canulation vasculaire (7­10 min; P < 0,001). Il y avait divergence dans l'administration d'héparine avant le décès (82-96 %; P = 0,03), notamment en ce qui concerne le moment d'administration (avant vs après l'interruption des traitements de survie; P < 0,001) et la posologie (≥ 300 vs < 300 unités·kg−1; P < 0,001). Le don après décès cardiocirculatoire a permis de procurer des organes pour 321 greffes rénales, 81 greffes hépatiques et 50 greffes pulmonaires. La survie à un an du récipiendaire et du greffon ne différait pas d'une province à l'autre (allant de 85 à 90 %, P = 0,45). Les prédicteurs de décès ou de la défaillance du greffon incluaient l'âge plus avancé du récipiendaire (rapport de cotes [RC] par année, 1,04; intervalle de confiance [IC] 95 %, 1,01 à 1,07) et un donneur de sexe masculin (RC, 3,35; IC 95 %, 1,39 à 8,09), mais pas les intervalles de temps entre l'interruption des traitements de survie et la canulation, ni les pratiques liées à l'utilisation d'héparine. CONCLUSION: Il existe une importante variabilité dans les pratiques de soins intensifs pour le DDC dans l'Ouest canadien, mais cette variabilité n'a pas résulté en différences significatives en matière de survie des récipiendaires ou des greffons. Des recherches supplémentaires sont nécessaires afin d'aiguiller la prise en charge optimale des donneurs potentiels de DDC.

Deceased organ donation potential in Canada: a review of consecutive deaths in Alberta.

BACKGROUND: Transplantation is the most effective treatment for many patients with end-stage organ failure. There is a gap between the number of patients who would benefit from transplantation and availability of organs. We assessed maximum potential for deceased donation in Alberta and barriers to increasing the donation rate. METHODS: All deaths that occurred in Alberta in 2015 in areas where mechanical ventilation could be provided were retrospectively identified using administrative data. Medical records were reviewed by donation coordinators and critical care physicians with expertise in donation, using a standardized tool to determine whether deceased patients could potentially have been organ donors. RESULTS: There were 2,706 deaths occurring in either an intensive care unit or emergency department, of which 1,252 were attributable to a non-neurologic cause: 946 involved cardiac arrests with unsuccessful resuscitation, and 57 were not mechanically ventilated. Of the remaining 451 deaths, 117 (28 donors per million population [dpmp]) either were, or could potentially have been, organ donors after neurologic determination of death (NDD). Of these, 19 (4.5 dpmp) were not appropriately identified or referred, and 45 approached families (10.8 dpmp) did not provide consent. Non-identified NDD cases accounted for a larger proportion of deaths due to neurologic causes in emergency departments (18%) than in intensive care units (2%) (P < 0.0001) and in rural (9%) compared with urban centres (3%) (P = 0.05). If routinely available, donation after circulatory death (DCD) could potentially have been possible in as many as 113 (27 dpmp) cases. CONCLUSIONS: Maximum deceased organ donation potential in Alberta is approximately 55 dpmp. The current donation rate has potential to increase with more widespread availability of DCD and a higher consent rate.

Continuous Assessment of "Optimal" Cerebral Perfusion Pressure in Traumatic Brain Injury: A Cohort Study of Feasibility, Reliability, and Relation to Outcome.

BACKGROUND: Guidelines recommend maintaining cerebral perfusion pressure (CPP) between 60 and 70 mmHg in patients with severe traumatic brain injury (TBI), but acknowledge that optimal CPP may vary depending on cerebral blood flow autoregulation. Previous retrospective studies suggest that targeting CPP where the pressure reactivity index (PRx) is optimized (CPPopt) may be associated with improved recovery. METHODS: We performed a retrospective cohort study involving TBI patients who underwent PRx monitoring to assess issues of feasibility relevant to future interventional studies: (1) the proportion of time that CPPopt could be detected; (2) inter-observer variability in CPPopt determination; and (3) agreement between manual and automated CPPopt estimates. CPPopt was determined for consecutive 6-h epochs during the first week following TBI. Sixty PRx-CPP tracings were randomly selected and independently reviewed by six critical care professionals. We also assessed whether greater deviation between actual CPP and CPPopt (ΔCPP) was associated with poor outcomes using multivariable models. RESULTS: In 71 patients, CPPopt could be manually determined in 985 of 1173 (84%) epochs. Inter-observer agreement for detectability was moderate (kappa 0.46, 0.23-0.68). In cases where there was consensus that it could be determined, agreement for the specific CPPopt value was excellent (weighted kappa 0.96, 0.91-1.00). Automated CPPopt was within 5 mmHg of manually determined CPPopt in 93% of epochs. Lower PRx was predictive of better recovery, but there was no association between ΔCPP and outcome. Percentage time spent below CPPopt increased over time among patients with poor outcomes (p = 0.03). This effect was magnified in patients with impaired autoregulation (defined as PRx > 0.2; p = 0.003). CONCLUSION: Prospective interventional clinical trials with regular determination of CPPopt and corresponding adjustment of CPP goals are feasible, but measures to maximize consistency in CPPopt determination are necessary. Although we could not confirm a clear association between ΔCPP and outcome, time spent below CPPopt may be particularly harmful, especially when autoregulation is impaired.

Prevention of Hypoxemia During Apnea Testing: A Comparison of Oxygen Insufflation And Continuous Positive Airway Pressure.

BACKGROUND: Apnea testing is an essential step in the clinical diagnosis of brain death. Current international guidelines recommend placement of an oxygen (O2) insufflation catheter into the endotracheal tube to prevent hypoxemia, but use of a continuous positive airway pressure (CPAP) valve may be more effective at limiting arterial partial pressure of O2 (PO2) reduction. METHODS: We performed a multicenter study assessing consecutive apnea tests in 14 intensive care units (ICUs) in two cities utilizing differing protocols. In one city, O2 catheters are placed and arterial blood gases (ABGs) performed at intervals determined by the attending physician. In the other city, a resuscitation bag with CPAP valve is attached to the endotracheal tube, and ABGs performed every 3-5 min. We assessed arterial PO2, partial pressure of carbon dioxide (PCO2), pH, and blood pressure at the beginning and termination of each apnea test. RESULTS: Thirty-six apnea tests were performed using an O2 catheter and 50 with a CPAP valve. One test per group was aborted because of physiological instability. There were no significant differences in the degree of PO2 reduction (-59 vs. -32 mmHg, p = 0.72), rate of PCO2 rise (3.2 vs. 3.9 mmHg per min, p = 0.22), or pH decline (-0.02 vs. -0.03 per min, p = 0.06). Performance of ABGs at regular intervals was associated with shorter test duration (10 vs. 7 min, p < 0.0001), smaller PCO2 rise (30 vs. 26 mmHg, p = 0.0007), and less pH reduction (-0.20 vs. -0.17, p = 0.0012). Lower pH at completion of the apnea test was associated with greater blood pressure decline (p = 0.006). CONCLUSION: Both methods of O2 supplementation are associated with similar changes in arterial PO2 and PCO2. Performance of ABGs at regular intervals shortens apnea test duration and may avoid excessive pH reduction and consequent hemodynamic effects.

Decompressive Craniectomy in Patients with Traumatic Brain Injury: Are the Usual Indications Congruent with Those Evaluated in Clinical Trials?

BACKGROUND: In patients with traumatic brain injury (TBI), multicenter randomized controlled trials have assessed decompressive craniectomy (DC) exclusively as treatment for refractory elevation of intracranial pressure (ICP). DC reliably lowers ICP but does not necessarily improve outcomes. However, some patients undergo DC as treatment for impending or established transtentorial herniation, irrespective of ICP. METHODS: We performed a population-based cohort study assessing consecutive patients with moderate-severe TBI. Indications for DC were compared with enrollment criteria for the DECRA and RESCUE-ICP trials. RESULTS: Of 644 consecutive patients, 51 (8 %) were treated with DC. All patients undergoing DC had compressed basal cisterns, 82 % had at least temporary preoperative loss of ≥1 pupillary light reflex (PLR), and 80 % had >5 mm of midline shift. Most DC procedures (67 %) were "primary," having been performed concomitantly with evacuation of a space-occupying lesion. ICP measurements influenced the decision to perform DC in 18 % of patients. Only 10 and 16 % of patients, respectively, would have been eligible for the DECRA and RESCUE-ICP trials. DC improved basal cistern compression in 76 %, and midline shift in 94 % of patients. Among patients with ≥1 absent PLR at admission, DC was associated with lower mortality (46 vs. 68 %, p = 0.03), especially when the admission Marshall CT score was 3-4 (p = 0.0005). No patients treated with DC progressed to brain death. Variables predictive of poor outcome following DC included loss of PLR(s), poor motor score, midline shift ≥11 mm, and development of perioperative cerebral infarcts. CONCLUSIONS: DC is most often performed for clinical and radiographic evidence of herniation, rather than for refractory ICP elevation. Results of previously completed randomized trials do not directly apply to a large proportion of patients undergoing DC in practice.

Ancillary testing in brain death.

Despite worldwide acceptance of the concept of brain death, there is marked variability in the use of ancillary testing. In most countries, ancillary tests are used primarily when confounding factors interfere with reliable completion of a clinical assessment, or physiologic instability precludes performance of an apnea test. Alternatively, in some countries, confirmatory ancillary tests are routinely required before brain death can be diagnosed. Ancillary tests assess brain function (e.g., electroencephalography) or blood flow (e.g., cerebral angiography). Evaluation of blood flow is affected less by confounding clinical factors and is now preferred in most jurisdictions. With angiographic techniques, a significant proportion of patients meeting clinical criteria for brain death have some opacification of proximal intracranial arteries. Consequently, the sensitivity of angiography is strongly influenced by the particular criteria that are used to define intracranial circulatory arrest. Lack of enhancement of the great cerebral and internal cerebral veins has the highest sensitivity. Worldwide experience with newer tests, such as computed tomography and magnetic resonance angiography, is growing. Radionuclide imaging has the advantage of not requiring use of potentially nephrotoxic contrast material. Transcranial Doppler ultrasonography can be brought to the bedside to demonstrate lack of brain blood flow. The specificity of imaging techniques in the detection of intracranial circulatory arrest has not been as well studied as their sensitivity.