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.).

Variability in criteria for death determination in the intensive care unit.

PURPOSE: Variability in practice exists in death determination by circulatory criteria in the context of organ donation. We sought to describe the practices of intensive care health care professionals for death determination by circulatory criteria with and without organ donation. METHODS: This study is a retrospective analysis of prospectively collected data. We included patients with death determination by circulatory criteria in intensive care units at 16 hospitals in Canada, three in the Czech Republic, and one in the Netherlands. Results were recorded using a checklist for the determination of death questionnaire. RESULTS: A total of 583 patients had their death determination checklist reviewed for statistical analysis. The mean (standard deviation) age in years was 64 (15). Three hundred and fourteen (54.0%) patients were from Canada, 230 (39.5%) were from the Czech Republic, and 38 (6.5%) were from the Netherlands. Fifty-two (8.9%) patients proceeded with donation after death determination by circulatory criteria (DCD). The most common diagnostic tests reported for the whole group were absent heart sounds by auscultation (81.8%), flat continuous arterial blood pressure (ABP) tracing (77.0%), and flat electrocardiogram tracing (73.2%). In patients who successfully underwent DCD (N = 52), death was determined most frequently using a flat continuous ABP tracing (94%), absent pulse oximetry (85%), and absent palpable pulse (77%). CONCLUSION: In this study, we have described practices for death determination by circulatory criteria both within and between countries. Though some variability exists, we are reassured that appropriate criteria are almost always used in the context of organ donation. In particular, the use of continuous ABP monitoring in DCD was consistent. It highlights the need for standardization of practice and up to date guidelines, especially within the context of DCD where there is both an ethical and a legal requirement to adhere to the dead donor rule, while minimizing time between death determination and organ procurement.

RéSUMé: OBJECTIF: Il existe de la variabilité dans la pratique en matière de détermination du décès selon des critères circulatoires dans le contexte d'un don d'organes. Nous avons cherché à décrire les pratiques des professionnels de la santé en soins intensifs en ce qui touche à la détermination du décès selon des critères circulatoires avec et sans don d'organes. MéTHODE: Cette étude est une analyse rétrospective de données recueillies prospectivement. Nous avons inclus des patients dont le décès avait été déterminé par des critères circulatoires dans les unités de soins intensifs de 16 hôpitaux au Canada, trois en République tchèque et un aux Pays-Bas. Les résultats ont été consignés à l'aide de la liste de contrôle d'un questionnaire sur la détermination du décès. RéSULTATS: Au total, les listes de contrôle pour la détermination du décès de 583 patients ont été examinées à des fins d'analyse statistique. L'âge moyen (écart type) en années était de 64 ans (15). Trois cent quatorze (54,0 %) patients provenaient du Canada, 230 (39,5 %) de la République tchèque et 38 (6,5 %) des Pays-Bas. Cinquante-deux (8,9 %) patients ont procédé au don après la détermination du décès selon des critères circulatoires (DCC). Les tests diagnostiques les plus fréquemment rapportés pour l'ensemble du groupe étaient l'absence de bruits cardiaques à l'auscultation (81,8 %), le tracé plat continu de la tension artérielle (TA) (77,0 %) et le tracé plat à l'électrocardiogramme (73,2 %). Chez les patients ayant été soumis avec succès à un DCD (N = 52), le décès a été déterminé le plus souvent à l'aide d'un tracé continu plat de la TA (94 %), d'une oxymétrie de pouls absente (85 %) et d'un pouls palpable absent (77 %). CONCLUSION: Dans cette étude, nous avons décrit les pratiques de détermination du décès selon des critères circulatoires à la fois à l'intérieur et entre les pays. Bien qu'il existe une certaine variabilité, nous sommes rassurés par le fait que des critères appropriés sont presque toujours utilisés dans le contexte du don d'organes. En particulier, l'utilisation du monitorage continu de la TA était constant en cas de DCC. Cela souligne la nécessité de normaliser la pratique et de disposer de lignes directrices mises à jour, en particulier dans le contexte de DCC où il existe une exigence à la fois éthique et légale de respecter la règle du donneur décédé, tout en minimisant le temps entre la détermination du décès et la collecte d'organes.

Is the process of withdrawal of life-sustaining measures in the intensive care unit different for deceased organ donors compared with other dying patients? A secondary analysis of prospectively collected data.

OBJECTIVE: To investigate whether observable differences exist between patterns of withdrawal of life-sustaining measures (WLSM) for patients eligible for donation after circulatory death (DCD) in whom donation was attempted compared with those patients in whom no donation attempts were made. SETTING: Adult intensive care units from 20 centres in Canada, the Czech Republic and the Netherlands. DESIGN: Secondary analysis of quantitative data collected as part of a large, prospective, cohort study (the Death Prediction and Physiology after Removal of Therapy study). PARTICIPANTS: Patients ≥18 years of age who died after a controlled WLSM in an intensive care unit. Patients were classified as not DCD eligible, DCD eligible with DCD attempted or DCD eligible but DCD was not attempted. PRIMARY AND SECONDARY OUTCOME MEASURES: The process of WLSM (timing and type and, if applicable, dosages of measures withdrawn, dosages of analgesics/sedatives) was compared between groups. RESULTS: Of the 635 patients analysed, 85% had either cardiovascular support stopped or were extubated immediately on WLSM. Of the DCD eligible patients, more were immediately extubated at the initiation of WLSM when DCD was attempted compared with when DCD was not attempted (95% vs 61%, p<0.0001). Initiation of WLSM with the immediate cessation of cardiovascular measures or early extubation was associated with earlier time to death, even after adjusting for confounders (OR 2.94, 95% CI 1.39 to 6.23, at 30 min). Other than in a few patients who received propofol, analgesic and sedative dosing after WLSM between DCD attempted and DCD eligible but not attempted patients was not significantly different. All patients died. CONCLUSIONS: Patients in whom DCD is attempted may receive a different process of WLSM. This highlights the need for a standardised and transparent process for end-of-life care across the spectrum of critically ill patients and potential organ donors.

Neurologic Physiology after Removal of Therapy (NeuPaRT) study: study protocol of a multicentre, prospective, observational, pilot feasibility study of neurophysiology after withdrawal of life-sustaining measures.

INTRODUCTION: In donation after circulatory determination of death, death is declared 5 min after circulatory arrest. This practice assumes, but does not explicitly confirm, permanent loss of brain activity. While this assumption is rooted a strong physiological rationale, paucity of direct human data regarding temporal relationship between cessation of brain activity and circulatory arrest during the dying process threatens public and healthcare provider trust in deceased organ donation. METHODS AND ANALYSIS: In this cohort study, we will prospectively record cerebral and brainstem electrical activity, cerebral blood flow velocity and arterial blood pressure using electroencephalography (EEG), brainstem evoked potentials, transcranial doppler and bedside haemodynamic monitors in adult patients undergoing planned withdrawal of life sustaining measures in the intensive care units at five hospital sites for 18 months. We will use MATLAB to synchronise waveform data and compute the time of cessation of each signal relative to circulatory arrest. Our primary outcome is the feasibility of patient accrual, while secondary outcomes are (a) proportion of patients with complete waveform recordings and data transfer to coordinating site and (b) time difference between cessation of neurophysiological signals and circulatory arrest. We expect to accrue 1 patient/site/month for a total of 90 patients. ETHICS AND DISSEMINATION: We have ethics approval from Clinical Trials Ontario (protocol #3862, version 1.0, date 19 January 2022.) and the relevant Research Ethics Board for each site. We will obtain written informed consent from legal substitute decision makers. We will present study results at research conferences including donor family partner forum and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05306327.

Paediatric death after withdrawal of life-sustaining therapies: a scoping review protocol.

INTRODUCTION: The physiology of dying after withdrawal of life-sustaining measures (WLSM) is not well described in children. This lack of knowledge makes predicting the duration of the dying process difficult. For families, not knowing this process's duration interferes with planning of rituals related to dying, travel for distant relatives and emotional strain during the wait for death. Time-to-death also impacts end-of-life care and determines whether a child will be eligible for donation after circulatory determination of death. This scoping review will summarise the current literature about what is known about the dying process in children after WLSM in paediatric intensive care units (PICUs). METHODS AND ANALYSIS: This review will use Joanna Briggs Institute methodology for scoping reviews. Databases searched will include Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials via EBM Reviews Ovid, Ovid PsycINFO, CINAHL and Web of Science. Literature reporting on the physiology of dying process after WLSM, or tools that predict time of death in children after WLSM among children aged 0-18 years in PICUs worldwide will be considered. Literature describing the impact of prediction or timing of death after WLSM on families, healthcare workers and the organ donation process will also be included. Quantitative and qualitative studies will be evaluated. Two independent reviewers will screen references by title and abstract, and then by full text, and complete data extraction and analysis. ETHICS AND DISSEMINATION: The review uses published data and does not require ethics review. Review results will be published in a peer-reviewed scientific journal.

Predicting Time to Death After Withdrawal of Life-Sustaining Measures Using Vital Sign Variability: Derivation and Validation.

To develop a predictive model using vital sign (heart rate and arterial blood pressure) variability to predict time to death after withdrawal of life-supporting measures. DESIGN: Retrospective analysis of observational data prospectively collected as part of the Death Prediction and Physiology after Removal of Therapy study between May 1, 2014, and May 1, 2018. SETTING: Adult ICU. PATIENTS: Adult patients in the ICU with a planned withdrawal of life-supporting measures and an expectation of imminent death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Vital sign waveforms and clinical data were prospectively collected from 429 patients enrolled from 20 ICUs across Canada, the Czech Republic, and the Netherlands. Vital sign variability metrics were calculated during the hour prior to withdrawal. Patients were randomly assigned to the derivation cohort (288 patients) or the validation cohort (141 patients), of which 103 and 54, respectively, were eligible for organ donation after circulatory death. Random survival forest models were developed to predict the probability of death within 30, 60, and 120 minutes following withdrawal using variability metrics, features from existing clinical models, and/or the physician's prediction of rapid death. A model employing variability metrics alone performed similarly to a model employing clinical features, whereas the combination of variability, clinical features, and physician's prediction achieved the highest area under the receiver operating characteristics curve of all models at 0.78 (0.7-0.86), 0.79 (0.71-0.87), and 0.8 (0.72-0.88) for 30-, 60- and 120-minute predictions, respectively. CONCLUSIONS: Machine learning models of vital sign variability data before withdrawal of life-sustaining measures, combined with clinical features and the physician's prediction, are useful to predict time to death. The impact of providing this information for decision support for organ donation merits further investigation.

Feasibility of implementing Extubation Advisor, a clinical decision support tool to improve extubation decision-making in the ICU: a mixed-methods observational study.

OBJECTIVES: Although spontaneous breathing trials (SBTs) are standard of care to extubation readiness, no tool exists that optimises prediction and standardises assessment. In this study, we evaluated the feasibility and clinical impressions of Extubation Advisor (EA), a comprehensive clinical extubation decision support (CDS) tool. DESIGN: Phase I mixed-methods observational study. SETTING: Two Canadian intensive care units (ICUs). PARTICIPANTS: We included patients on mechanical ventilation for ≥24 hours and clinicians (respiratory therapists and intensivists) responsible for extubation decisions. INTERVENTIONS: Components included a predictive model assessment, feasibility evaluation, questionnaires and interviews with clinicians. RESULTS: We enrolled 117 patients, totalling 151 SBTs and 80 extubations. The incidence of extubation failure was 11% in low-risk patients and 21% in high-risk patients stratified by the predictive model; 38% failed extubation when both the model and clinical impression were at high risk. The tool was well rated: 94% and 75% rated the data entry and EA report as average or better, respectively. Interviews (n=15) revealed favourable impressions regarding its user interface and functionality, but unexpectedly, also concerns regarding EA's potential impact on respiratory therapists' job security. CONCLUSIONS: EA implementation was feasible, and users perceived it to have potential to support extubation decision-making. This study helps to understand bedside implementation of CDS tools in a multidisciplinary ICU. TRIAL REGISTRATION NUMBER: NCT02988167.

Large pH oscillations promote host defense against human airways infection.

The airway mucosal microenvironment is crucial for host defense against inhaled pathogens but remains poorly understood. We report here that the airway surface normally undergoes surprisingly large excursions in pH during breathing that can reach pH 9.0 during inhalation, making it the most alkaline fluid in the body. Transient alkalinization requires luminal bicarbonate and membrane-bound carbonic anhydrase 12 (CA12) and is antimicrobial. Luminal bicarbonate concentration and CA12 expression are both reduced in cystic fibrosis (CF), and mucus accumulation both buffers the pH and obstructs airflow, further suppressing the oscillations and bacterial-killing efficacy. Defective pH oscillations may compromise airway host defense in other respiratory diseases and explain CF-like airway infections in people with CA12 mutations.

Heart Rate Variability, Clinical and Laboratory Measures to Predict Future Deterioration in Patients Presenting With Sepsis.

BACKGROUND: Risk stratification of patients presenting to the emergency department (ED) with sepsis can be challenging. We derived and evaluated performance of a predictive model containing clinical, laboratory, and heart rate variability (HRV) measures to quantify risk of deterioration in this population. METHODS: ED patients aged 21 and older satisfying the 1992 consensus conference criteria for sepsis and able to consent (directly or through a surrogate) were enrolled (n = 1,247). Patients had clinical, laboratory, and HRV data recorded within 1 h of ED presentation, and were followed to identify deterioration within 72 h. RESULTS: Eight hundred thirty-two patients had complete data, of whom 68 (8%) reached at least one endpoint. Optimal predictive performance was derived from a combination of laboratory values and HRV metrics with an area under the receiver-operating curve (AUROC) of 0.80 (95% CI, 0.65-0.92). This combination of variables was superior to clinical (AUROC = 0.69, 95% CI, 0.54-0.83), laboratory (AUROC = 0.77, 95% CI, 0.63-0.90), and HRV measures (AUROC = 0.76, 95% CI, 0.61-0.90) alone. The HRV+LAB model identified a high-risk cohort of patients (14% of all patients) with a 4.3-fold (95% CI, 3.2-5.4) increased risk of deterioration (incidence of deterioration: 35%), as well as a low-risk group (61% of all patients) with 0.2-fold (95% CI 0.1-0.4) risk of deterioration (incidence of deterioration: 2%). CONCLUSIONS: A model that combines HRV and laboratory values may help ED physicians evaluate risk of deterioration in patients with sepsis and merits validation and further evaluation.