Early In-Bed Cycle Ergometry in Mechanically Ventilated Patients.

BACKGROUND: Critical illness requiring invasive mechanical ventilation can precipitate important functional disability, contributing to multidimensional morbidity following admission to an intensive care unit (ICU). Early in-bed cycle ergometry added to usual physiotherapy may mitigate ICU-acquired physical function impairment. METHODS: We randomly assigned 360 adult ICU patients undergoing invasive mechanical ventilation to receive 30 minutes of early in-bed Cycling + Usual physiotherapy (n=178) or Usual physiotherapy alone (n=182). The primary outcome was the Physical Function ICU Test-scored (PFIT-s) at 3 days after discharge from the ICU (the score ranges from 0 to 10, with higher scores indicating better function). RESULTS: Cycling began within a median (interquartile range) of 2 (1 to 3) days of starting mechanical ventilation; patients received 3 (2 to 5) cycling sessions for a mean (±standard deviation) of 27.2 ± 6.6 minutes. In both groups, patients started Usual physiotherapy within 2 (2 to 4) days of mechanical ventilation and received 4 (2 to 7) Usual physiotherapy sessions. The duration of Usual physiotherapy was 23.7 ± 15.1 minutes in the Cycling + Usual physiotherapy group and 29.1 ± 13.2 minutes in the Usual physiotherapy group. No serious adverse events occurred in either group. Among survivors, the PFIT-s at 3 days after discharge from the ICU was 7.7 ± 1.7 in the Cycling + Usual physiotherapy group and 7.5 ± 1.7 in the Usual physiotherapy group (absolute difference, 0.23 points; 95% confidence interval, -0.19 to 0.65; P=0.29). CONCLUSIONS: Among adults receiving mechanical ventilation in the ICU, adding early in-bed Cycling to usual physiotherapy did not improve physical function at 3 days after discharge from the ICU compared with Usual physiotherapy alone. Cycling did not cause any serious adverse events. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov numbers, NCT03471247 [full randomized clinical trial] and NCT02377830 [CYCLE Vanguard 46-patient internal pilot].).

Critical Care Cycling to Improve Lower Extremity Strength (CYCLE): protocol for an international, multicentre randomised clinical trial of early in-bed cycling for mechanically ventilated patients.

INTRODUCTION: In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults. METHODS AND ANALYSIS: We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups. ETHICS AND DISSEMINATION: Critical Care Cycling to improve Lower Extremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot).

Vasopressin Use in the Support of Organ Donors: Physiological Rationale and Review of the Literature.

The objective of this review was to depict the physiological and clinical rationale for the use of vasopressin in hemodynamic support of organ donors. After summarizing the physiological, pharmacological concepts and preclinical findings, regarding vasopressin's pathophysiological impacts, we will present the available clinical data. DATA SOURCES: Detailed search strategies in PubMed, OVID Medline, and EMBASE were undertaken using Medical Subject Headings and Key Words. STUDY SELECTION: Physiological articles regarding brain death, and preclinical animal and human studies about the use of vasopressin or analogs, as an intervention in organ support for donation, were considered. DATA EXTRACTION: Two authors independently screened titles, abstracts, and full text of articles to determine eligibility. Data encompassing models, population, methodology, outcomes, and relevant concepts were extracted. DATA SYNTHESIS: Following brain death, profound reduction in sympathetic outflow is associated with reduced cardiac output, vascular tone, and hemodynamic instability in donors. In addition to reducing catecholamine needs and reversing diabetes insipidus, vasopressin has been shown to limit pulmonary injury and decrease systemic inflammatory response in animals. Several observational studies show the benefit of vasopressin on hemodynamic parameters and catecholamine sparing in donors. Small trials suggest that vasopressin increase organ procurement and have some survival benefit for recipients. However, the risk of bias is overall concerning, and therefore the quality of the evidence is deemed low. CONCLUSIONS: Despite potential impact on graft outcome and a protective effect through catecholamine support sparing, the benefit of vasopressin use in organ donors is based on low evidence. Well-designed observational and randomized controlled trials are warranted.

Left ventricular ejection fraction using a simplified wall motion score based on mid-parasternal short axis and apical four-chamber views for non-cardiologists.

BACKGROUND: There is a need for a convenient, yet reliable method to assess left ventricular ejection fraction (LVEF) with point-of-care ultrasound study (POCUS). We aim to validate a novel and simplified wall motion score LVEF based on the analysis of a simplified combination of echocardiographic views. METHODS: In this retrospective study, transthoracic echocardiograms of randomly selected patients were analysed by the standard 16-segments wall motion score index (WMSI) to derive the reference semi-quantitative LVEF. To develop our semi-quantitative simplified-views method, a limited combination of imaging views and only 4 segments per view were tested: (1) A combination of the three parasternal short-axis views (PSAX BASE, MID-, APEX); (2) A combination of the three apical views (apical 2-chamber, 3-chamber and 4-chamber) and (3) A more limited combination of PSAX-MID and apical 4-chamber is called the MID-4CH. Global LVEF is obtained by averaging segmental EF based on contractility (normal = 60%, hypokinesia = 40%, and akinesia = 10%). Accuracy of the novel semi-quantitative simplified-views WMS method compared to the reference WMSI was evaluated using Bland-Altman analysis and correlation was assessed in both emergency physicians and cardiologists. RESULTS: In the 46 patients using the 16 segments WMSI method, the mean LVEF was 34 ± 10%. Among the three combinations of the two or three imaging views analysed, the MID-4CH had the best correlation with the reference method (r2 = 0.90) with very good agreement (mean LVEF bias = - 0.2%) and precision (± 3.3%). CONCLUSIONS: Cardiac POCUS by emergency physicians and other non-cardiologists is a decisive therapeutic and prognostic tool. A simplified semi-quantitative WMS method to assess LVEF using the easiest technically achievable combination of mid-parasternal and apical four-chamber views provides a good approximative estimate for both non-cardiologist emergency physicians and cardiologists.

Self-perceived role and knowledge of community pharmacists in organ donation.

BACKGROUND: Although a majority of North Americans is in favor of organ donation, registration remains challenging. Community pharmacists are highly accessible frontline health care professionals that could contribute to a new common registration donation consent system. AIM: The objective of the study was to assess self-perceived professional role and organ donation knowledge of community pharmacists in Quebec. METHOD: We designed a telephone interview survey using a three round modified Delphi process. Following questionnaires testing, we randomly sampled 329 community pharmacists in Quebec. Following administration, we validated the questionnaire by conducting an exploratory factorial analysis using principal component followed by a varimax rotation and rearranging domains and items accordingly. RESULTS: A total of 443 pharmacists were contacted, 329 provided answers to the self-perception role and 216 of them completed the knowledge questionnaire. Overall, community pharmacists of Quebec had a positive view on organ donation and demonstrated interest in acquiring knowledge. Respondents have identified lack of time and high pharmacy attendance as non-limiting barriers to implementing the intervention. The average score on the knowledge questionnaire was 61.2%. CONCLUSION: With the implementation of an appropriate education program to address this knowledge gap, we believe that community pharmacists could be key players in registered organ donation consent.

Impact of clinical variables on outcomes in refractory cardiac arrest patients undergoing extracorporeal cardiopulmonary resuscitation.

Background: In the past two decades, extracorporeal resuscitation (ECPR) has been increasingly used in the management of refractory cardiac arrest (CA) patients. Decision algorithms have been used to guide the care such patients, but the effectiveness of such decision-making tools is not well described. The aim of this study was to compare the rate of survival with a good neurologic outcome of patients treated with ECPR meeting all criteria of a clinical decision-making tool for the initiation of ECPR to those for whom ECPR was implemented outside of the algorithm. Methods: All patients who underwent E-CPR between January 2014 and December 2021 at the Montreal Heart Institute were included in this retrospective analysis. We dichotomized the cohort according to adherence or non-adherence with the ECPR decision-making tool, which included the following criteria: age ≤65 years, initial shockable rhythm, no-flow time <5 min, serum lactate <13 mmol/L. Patients were included in the "IN" group when they met all criteria of the decision-making tool and in the "OUT" group when at least one criterion was not met. Main outcomes and measures: The primary outcome was survival with intact neurological status at 30 days, defined by a Cerebral Performance Category (CPC) Scale 1 and 2. Results: A total of 41 patients (IN group, n = 11; OUT group, n = 30) were included. A total of 4 (36%) patients met the primary outcome in the IN group and 7 (23%) in the OUT group [odds ratio (OR): 1.88 (95% CI, 0.42-8.34); P = 0.45]. However, survival with a favorable outcome decreased steadily with 2 or more deviations from the decision-making tool [2 deviations: 1 (11%); 3 deviations: 0 (0%)]. Conclusion and relevance: Most patients supported with ECPR fell outside of the criteria encompassed in a clinical decision-making tool, which highlights the challenge of optimal selection of ECPR candidates. Survival rate with a good neurologic outcome did not differ between the IN and OUT groups. However, survival with favorable outcome decreased steadily after one deviation from the decision-making tool. More studies are needed to help select proper candidates with refractory CA patients for ECPR.

Parameters associated with successful weaning of veno-arterial extracorporeal membrane oxygenation: a systematic review.

PURPOSE: Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) can be used to restore organ perfusion in patients with cardiogenic shock until native heart recovery occurs. It may be challenging, however, to determine when patients can be weaned successfully from ECMO-surviving without requiring further mechanical support or heart transplant. We aimed to systematically review the medical literature to determine the biomarkers, hemodynamic and echocardiographic parameters associated with successful weaning of VA-ECMO in adults with cardiogenic shock and to present an evidence-based weaning algorithm incorporating key findings. METHOD: We systematically searched PubMed, Embase, ProQuest, Google Scholars, Web of Science and the Grey literature for pertinent original research reports. We excluded studies limited to extracorporeal cardiopulmonary resuscitation (ECPR) as the neurological prognosis may significantly alter the decision-making process surrounding the device removal in this patient population. Studies with a mixed population of VA-ECMO for cardiogenic shock or cardiac arrest were included. We excluded studies limited to patients in which ECMO was only used as a bridge to VAD or heart transplant, as such patients are, by definition, never "successfully weaned." We used the Risk of Bias Assessment tool for Non-Randomized Studies. The study was registered on the International prospective register of systematic reviews (PROSPERO CRD42020178641). RESULTS: We screened 14,578 records and included 47 that met our pre-specified criteria. Signs of lower initial severity of shock and myocardial injury, early recovery of systemic perfusion, left and right ventricular recovery, hemodynamic and echocardiographic stability during flow reduction trial and/or pump-controlled retrograde trial off predicted successful weaning. The most widely used parameter was the left ventricular outflow tract velocity time integral, an indicator of stroke volume. Most studies had a moderate or high risk of bias. Heterogeneity in methods, timing, and conditions of measurements precluded any meta-analysis. CONCLUSIONS: In adult patients on VA-ECMO for cardiogenic shock, multiple biomarkers, hemodynamic and echocardiographic parameters may be used to track resolution of systemic hypoperfusion and myocardial recovery in order to identify patients that can be successfully weaned.

Research interrupted: applying the CONSERVE 2021 Statement to a randomized trial of rehabilitation during critical illness affected by the COVID-19 pandemic.

RATIONALE: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) statement as a framework to report the impact of the pandemic on CYCLE and describe our mitigation approaches. METHODS: On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy) and collect the primary outcome (physical function 3-days post-ICU discharge) and 90-day outcomes. We advised sites to prioritize data for the study's primary outcome. We sought feedback on pandemic barriers related to trial procedures. RESULTS: Our main Methods Centre mitigation strategies included identifying patients at risk for protocol deviations, communicating early and frequently with sites, developing standardized internal tools focused on high-risk points in the protocol for monitoring patient progress, data entry, and validation, and providing guidance to conduct some research activities remotely. For study sites, our strategies included determining how institutional pandemic research policies applied to CYCLE, communicating with the Methods Centre about capacity to continue any part of the research, and developing contingency plans to ensure the protocol was delivered as intended. From 15 active sites (12 Canada, 2 US, 1 Australia), 5 patients were still receiving the study intervention in ICUs, 6 required primary outcomes, and 17 required 90-day assessments. With these mitigation strategies, we attempted 100% of ICU interventions, 83% of primary outcomes, and 100% of 90-day assessments per our protocol. CONCLUSIONS: We retained all enrolled patients with minimal missing data using several time-sensitive strategies. Although CONSERVE recommends reporting only major modifications incurred by extenuating circumstances, we suggest that it also provides a helpful framework for reporting mitigation strategies with the goal of improving research transparency and trial management. TRIAL REGISTRATION: NCT03471247. Registered on March 20, 2018.

Right ventricular ejection fraction with cardiac magnetic resonance using a wall motion score.

BACKGROUND: The volumetric method in cardiac magnetic resonance (CMR), the reference standard for right ventricular ejection fraction (RVEF), requires expertise because of the complex right ventricular geometry and anatomical landmarks. AIM: The aim of our retrospective study was to describe a new method to evaluate RVEF based on wall motion score index (WMSI) in CMR. METHODS: Visual assessment of wall motion was performed using an eight-segment model (normokinesia=1, hypokinesia=2, akinesia=3). Correlation between WMSI (WMS/8) and the reference volumetric RVEF was analysed. A regression equation was derived to convert the WMSI into RVEF. The accuracy of CMR WMSI-derived RVEF compared with CMR volumetric RVEF was evaluated using Bland-Altman analysis. RESULTS: In the 112 patients using the volumetric method, the mean RVEF was 48±14%. Fifty-nine patients had normal RV kinetics (WMSI=1), which corresponded to a volumetric RVEF of 56% (standard deviation 7%; range 43-76%). CMR WMSI showed a strong correlation with CMR volumetric RVEF (Spearman's Rho=-0.69). A regression equation was created: RVEF=80-22×WMSI. Overall, the WMSI-derived RVEF resulted in good agreement with the CMR volumetric RVEF (mean bias-3%, standard deviation±7.5%). In addition, using a WMSI cut-off of≥1.5 was highly accurate (92%) to predict a reference RVEF of˂45%, an important prognostic indicator in CMR. CONCLUSIONS: Our results suggest that using the WMS in CMR (eight-segment) to estimate RVEF is accurate, and correlates well with the volumetric method. A WMSI≥1.5 is optimal to categorize patients in the higher-risk subset of CMR RVEF˂45%.

The Suitability of Potential Organ Donors Using Real Case-Scenarios; Do we Need to Create a "Donor Board" Process for Donors Perceived as Unlikely Suitable?

Introduction: Despite availability of selection criteria, different interpretations can lead to variability in the appreciation of donor eligibility with possible viable organs missed. Our primary objective was to test the perception of feasibility of potential organ donors through the survey of a small sample of external evaluators. Methods: Clinical scenarios summarizing 66 potential donors managed in the first year of our Organ Recovery Center were sent to four critical care physicians to evaluate the feasibility of the potential donors and the probability of organ procurement. Results: Potential donors procuring at least one organ were identified in 55 of the 66 cases (83%). Unanimity was reached in 38 cases, encompassing 35 out of the 55 converted and 3 of the non-converted donors. The overall agreement was moderate (kappa = 0.60, 95% CI: 0.37-0.82). For the organs finally procured for transplantation, organ donation was predicted for the majority of the cases, but high discrepancy was present with the final outcome of organs not procured (particularly liver and kidney). Conclusion: The assessment of a potential donor is a complex dynamic process. In order to increase organ availability, standardized electronically clinical data, as well a "donor board" structure of decision might inform future systems.

Modalities of Left Ventricle Decompression during VA-ECMO Therapy.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used to sustain circulatory and respiratory support in patients with severe cardiogenic shock or refractory cardiac arrest. Although VA-ECMO allows adequate perfusion of end-organs, it may have detrimental effects on myocardial recovery. Hemodynamic consequences on the left ventricle, such as the increase of afterload, end-diastolic pressure and volume, can lead to left ventricular (LV) distention, increase of myocardial oxygen consumption and delayed LV function recovery. LV distention occurs in almost 50% of patients supported with VA-ECMO and is associated with an increase in morbidity and mortality. Thus, recognizing, preventing and treating LV distention is key in the management of these patients. In this review, we aim to discuss the pathophysiology of LV distention and to describe the strategies to unload the LV in patients supported with VA-ECMO.

Early experience with critically ill patients with COVID-19 in Montreal.

PURPOSE: Montreal has been the epicentre of the coronavirus disease (COVID-19) pandemic in Canada. Given the regional disparities in incidence and mortality in the general population, we aimed to describe local characteristics, treatments, and outcomes of critically ill COVID-19 patients in Montreal. METHODS: A single-centre retrospective cohort of consecutive adult patients admitted to the intensive care unit (ICU) of Hôpital du Sacré-Coeur de Montréal with confirmed COVID-19 were included. RESULTS: Between 20 March and 13 May 2020, 75 patients were admitted, with a median [interquartile range (IQR)] age of 62 [53-72] yr and high rates of obesity (47%), hypertension (67%), and diabetes (37%). Healthcare-related infections were responsible for 35% of cases. The median [IQR] day 1 sequential organ failure assessment score was 6 [3-7]. Invasive mechanical ventilation (IMV) was used in 57% of patients for a median [IQR] of 11 [5-22] days. Patients receiving IMV were characterized by a moderately decreased median [IQR] partial pressure of oxygen:fraction of inspired oxygen (day 1 PaO2:FiO2 = 177 [138-276]; day 10 = 173 [147-227]) and compliance (day 1 = 48 [38-58] mL/cmH2O; day 10 = 34 [28-42] mL/cmH2O) and very elevated estimated dead space fraction (day 1 = 0.60 [0.53-0.67]; day 10 = 0.72 [0.69-0.79]). Overall hospital mortality was 25%, and 21% in the IMV patients. Mortality was 82% in patients ≥ 80 yr old. CONCLUSIONS: Characteristics and outcomes of critically ill patients with COVID-19 in Montreal were similar to those reported in the existing literature. We found an increased physiologic dead space, supporting the hypothesis that pulmonary vascular injury may be central to COVID-19-induced lung damage.

RéSUMé: OBJECTIF: Montréal a été l'épicentre de la pandémie du coronavirus (COVID-19) au Canada. Étant donné les disparités régionales dans l'incidence et la mortalité dans la population générale, nous avons tenté de décrire les caractéristiques locales, les traitements et le devenir des patients atteints de la COVID-19 en état critique à Montréal. MéTHODE: Notre étude de cohorte rétrospective monocentrique a inclus tous les patients adultes admis consécutivement à l'unité de soins intensifs de l'Hôpital du Sacré-Cœur de Montréal avec un diagnostic confirmé de COVID-19. RéSULTATS: Soixante-quinze patients ont été admis entre le 20 mars et le 13 mai 2020. Ceux-ci avaient un âge médian [écart interquartile (ÉIQ)] de 62 [53­72] ans et présentaient une incidence élevée d'obésité (47 %), d'hypertension (67 %) et de diabète (37 %). Les transmissions associées aux soins de santé étaient responsables de 35 % des cas. Au jour 1, le score SOFA (Sequential Organ Failure Assessment ­ évaluation séquentielle de défaillance des organes) médian [ÉIQ] était de 6 [3­7]. La ventilation mécanique invasive (VMI) a été utilisée chez 57 % des patients, pour une durée médiane [ÉIQ] de 11 [5­22] jours. Les patients ayant reçu une VMI étaient caractérisés par une médiane [ÉIQ] modérément réduite de la pression partielle de la fraction d'oxygène inspiré (jour 1 PaO2:FiO2 = 177 [138­276]; jour 10 = 173 [147­227]), de la compliance (jour 1 = 48 [38­58] mL/cmH2O; jour 10 = 34 [28­42] mL/cmH2O), ainsi que par une fraction d'espace mort estimé très élevée (jour 1 = 0,60 [0,53-0,67]; jour 10 = 0,72 [0,69-0,79]). La mortalité hospitalière était de 25 % globalement, et de 21 % chez les patients avec VMI. La mortalité a atteint 82 % chez les patients agés de ≥ 80 ans. CONCLUSION: Les caractéristiques et le devenir des patients en état critique atteints de la COVID-19 à Montréal étaient semblables à ceux rapportés dans la littérature existante. Nous avons observé un espace mort physiologique augmenté, ce qui appuie l'hypothèse que des lésions vasculaires pulmonaires seraient primordiales dans les lésions pulmonaires induites par la COVID-19.

Veno-Venous Extracorporeal Membrane Oxygenation to Treat Acute Respiratory Distress Syndrome in an Adult with Fontan Palliation.

In patients with Fontan palliation, the systemic and pulmonary circulation is in series and supported by a single ventricle, resulting in fragile hemodynamics. Cardiac output is driven by low pressure nonpulsatile pulmonary flow and is highly dependent on pulmonary vascular resistance. An acute respiratory distress syndrome (ARDS) can rapidly alter this physiology and lead to severe cardiogenic shock. Herein, we describe the case of a 40 year old man with a classic modified Fontan procedure and bidirectional Glenn shunt who developed ARDS with cardiogenic shock following a resuscitated cardiac arrest with presumed aspiration pneumonia. In light of poorly tolerated positive end-expiratory pressure ventilation and underlying anatomical complexities, a multidisciplinary team was convened to optimize care. In part owing to the lack of femoral venous access, a veno-venous extracorporeal membrane oxygenation circuit was devised using bilateral internal jugular venous access. Under fluoroscopic guidance in a hybrid operating room, one cannula was placed in the inferior vena cava by means of the right internal jugular venous access, with the second cannula positioned in the right pulmonary artery through the left internal jugular vein. Oxygenation and hemodynamic status promptly improved, allowing the patient to recover from ARDS.

Potential risks in using midodrine for persistent hypotension after cardiac surgery: a comparative cohort study.

BACKGROUND: Persistent hypotension is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). Midodrine, an orally administered alpha agonist, could potentially reduce intravenous vasopressor use and accelerate ICU discharge of otherwise stable patients. The main objective of this study was to explore the clinical impacts of administering midodrine in patients with persistent hypotension after CPB. Our hypothesis was that midodrine would safely accelerate ICU discharge and be associated with more days free from ICU at 30 days. RESULTS: We performed a retrospective cohort study that included all consecutive patients having received midodrine while being on vasopressor support in the ICU within the first week after cardiac surgery with CPB, between January 2014 and January 2018 at the Montreal Heart Institute. A contemporary propensity score matched control group that included patients who presented similarly prolonged hypotension after cardiac surgery was formed. After matching, 74 pairs of patients (1:1) fulfilled inclusion criteria for the study and control groups. Midodrine use was associated with fewer days free from ICU (25.8 [23.7-27.1] vs 27.2 [25.9-28] days, p = 0.002), higher mortality (10 (13.5%) vs 1 (1.4%), p = 0.036) and longer ICU length of stay (99 [68-146] vs 68 [48-99] hours, p = 0.001). There was no difference in length of intravenous vasopressors (63 [40-87] vs 44 [26-66] hours, p = 0.052), rate of ICU readmission (6 (8.1%) vs 2 (2.7%), p = 0.092) and occurrence of severe kidney injury (11 (14.9%) vs 10 (13.5%) patients, p = 0.462) between groups. CONCLUSION: The administration of midodrine for sustained hypotension after cardiac surgery with CPB was associated with fewer days free from ICU and higher mortality. Routine prescription of midodrine to hasten ICU discharge after cardiac surgery should be used with caution until further prospective studies are conducted.

Worldwide management of donors after neurological death: a systematic review and narrative synthesis of guidelines.

OBJECTIVE: The objectives of this study were to systematically identify and describe guidelines for the care of neurologically deceased donors and to evaluate their methodological quality, with the aim of informing and supporting the new Canadian guidelines for the management of organ donors. METHODOLOGY: Following a systematic search, we included any document endorsed by an organ donation organization, a professional society, or a government, that aims to direct the medical management of adult, neurologically deceased, multi-organ donors. We extracted recommendations pertaining to six domains: the autonomic storm, hemodynamic instability, hormone supplementation, ventilation, blood product transfusions, and general intensive care unit (ICU) care. Methodological quality of the guidelines was assessed by the validated AGREE-II tool. MAIN FINDINGS: This review includes 27 clinical practice guidelines representing 26 countries published between 1993 and 2019. Using the AGREE-II validated tool for the evaluation of guidelines' quality, documents generally scored well on their scope and clarity of presentation. Nevertheless, quality was limited in terms of the scientific rigor of guideline development. Recommendations varied substantially across the domains of managing the autonomic storm, subsequent management of hemodynamic instability, hormone therapy, mechanical ventilation, blood product transfusion, and general ICU care. We found consistent recommendations for low tidal volume ventilation subsequent to the publication of a landmark clinical trial. CONCLUSION: Highly inconsistent recommendations for deceased donor care summarized in this review likely reflect the relatively slow emergence of high-quality clinical research in this field, as well as a late uptake of recent validated guideline methodology. Even in this context of few randomized-controlled trials, our group supported the need for new Canadian guidelines for the management of organ donors that follow rigorous recognized methodology and grading of the evidence. TRIAL REGISTRATION: PROSPERO (CRD42018084012); registered 25 February 2016.

RéSUMé: OBJECTIF: Les objectifs de cette étude étaient d'identifier et de décrire de façon systématique les lignes directrices concernant les soins à prodiguer aux donneurs suivant un décès neurologique et d'évaluer leur qualité méthodologique, avec pour but d'informer et d'appuyer les nouvelles lignes directrices canadiennes de prise en charge des donneurs d'organes. MéTHODOLOGIE: À la suite d'une recherche systématique, nous avons inclus tout document endossé par un organisme de dons d'organes, une société professionnelle ou un gouvernement et ayant pour but d'orienter la prise en charge médicale des donneurs adultes d'organes multiples à la suite d'un décès neurologique. Nous avons extrait les recommandations touchant six domaines : la tempête catécholaminergique, l'instabilité hémodynamique, la supplémentation hormonale, la ventilation, les transfusions de produits sanguins et les soins généraux à l'unité de soins intensifs (USI). La qualité méthodologique des lignes directrices a été évaluée avec l'outil validé AGREE-II. CONSTATIONS PRINCIPALES: Cette revue porte sur 27 guides d'exercice cliniques représentant 26 pays et publiés entre 1993 et 2019. En se fondant sur l'outil validé AGREE-II pour l'évaluation de la qualité des lignes directrices, les documents ont en règle générale obtenu un bon score en ce qui touchait à leurs objectifs et à la clarté de leur présentation. Toutefois, la qualité était limitée en matière de rigueur scientifique employée pour la mise au point des lignes directrices. Les recommandations variaient considérablement concernant les questions pertinentes à la prise en charge de la tempête catécholaminergique, à la prise en charge subséquente de l'instabilité hémodynamique, à l'hormonothérapie, à la ventilation mécanique, à la transfusion de produits sanguins, et aux soins généraux à l'USI. À la suite de la publication d'une étude clinique importante, les recommandations concernant la ventilation à volume courant bas étaient constantes. CONCLUSION: Le manque de cohérence des lignes directrices touchant les soins aux donneurs décédés résumées dans cette revue est probablement le reflet de l'émergence relativement lente de recherches cliniques de qualité élevée dans ce domaine, ainsi que de l'adoption tardive des méthodologies récentes et validées pour l'élaboration de lignes directrices. Même dans le contexte actuel de rareté d'études randomisées contrôlées, notre groupe appuie la nécessité de nouvelles lignes directrices canadiennes concernant la prise en charge des donneurs d'organes qui respectent une méthodologie reconnue et rigoureuse ainsi qu'une classification des données probantes. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42018084012); enregistrée le 25 février 2016.

Right ventricular dysfunction in neurologically deceased organ donors: An observational study in a tertiary-care organ donor referral centre.

PURPOSE: Right ventricular RV dysfunction among transplant recipients correlates with transplant outcome, but its frequency in donors is unknown. The purpose of this study was to describe the epidemiology of RV dysfunction in potential heart donors." METHODS: In a seven-year retrospective study of potential heart donors, we explored the incidence of RV dysfunction as observed on echocardiography and explored the association of four distinct factors with RV dysfunction: brain injury diagnosis, thoracic trauma, vasopressin infusion and left ventricular (LV) dysfunction. RESULTS: All 123 potential heart donors underwent echocardiography: 55 had RV dysfunction (44.7%). Fourty-one (33.3%) had LV dysfunction. Isolated RV dysfunction was present in 27 subjects (22%). LV dysfunction was the only factor significantly associated with RV dysfunction (OR = 4.6 (95% CI 1.9-11.4)). We observed no difference in heart acceptance between subjects with or without RV dysfunction. CONCLUSION: We observed a high frequency of RV dysfunction in a sample of potential heart donors. However, the temporal evolution of RV dysfunction, the hemodynamic predictors of RV dysfunction, as well the link between donor RV dysfunction and recipient outcomes need to be assessed with further prospective studies.

A Canadian survey of critical care physicians' hemodynamic management of deceased organ donors.

PURPOSE: We sought to characterize Canadian physicians' perspectives and stated practices regarding their hemodynamic care of deceased organ donors. METHODS: We designed a 24-item electronic survey that was independently pretested for relevance, clarity, and intra-rater reliability by ten critical care clinicians. With the help of provincial organ donation organizations (ODO), we identified intensive care units (ICUs) with a high volume of adult deceased donors (defined by the management of five or more donors per year for two consecutive years). Medical directors of these high-volume ICUs helped identify ICU physicians to whom our survey was emailed. RESULTS: Of the 448 ICU physicians from 37 centres in nine provinces that were emailed, 184/448 (41.1%) responded to one or more survey questions. Respondents identified specialist nurses from ODOs as their primary source of guidance in donor care (107/165; 60%). They typically diagnosed an autonomic storm according to a rise in blood pressure (159/165; 96.4%) and/or heart rate (135/165; 81.8%); nevertheless, their stated management varied substantially. After termination of the autonomic storm, preferred first-line vasopressors were norepinephrine (93/164; 56.7%) and vasopressin (68/164; 41.5%). Twenty-one respondents (21/162; 13.0%) reported that they never administer inotropes to donors. Corticosteroid and thyroid hormone prescriptions for all donors was reported by 62/161 (37.6%) and 50/161 (31.1%) respondents, respectively. Respondents perceived an influence from ODO nurses or transplant physicians when prescribing corticosteroids (77/161; 47.8%) and/or thyroid hormones (33/161; 20.5%) CONCLUSION: We observed important variability in self-perceived practices of ICU physicians in the hemodynamic management of deceased donors, particularly in the treatment of the autonomic storm, in the prescription of hormone therapy, and in the administration of inotropes.

RéSUMé: OBJECTIF: Nous avons tenté de caractériser les perspectives et les pratiques déclarées des médecins canadiens concernant les soins hémodynamiques prodigués aux donneurs d'organes décédés. MéTHODE: Nous avons mis au point un sondage électronique comportant 24 éléments et l'avons préalablement testé pour déterminer sa pertinence, sa clarté et sa fidélité interobservateur par dix médecins de soins intensifs. Avec l'aide des organismes de dons d'organes (ODO) provinciaux, nous avons identifié les unités de soins intensifs (USI) prenant en charge un volume élevé de donneurs adultes décédés (prise en charge de cinq donneurs ou plus par an pendant deux années consécutives). Les directeurs médicaux de ces USI à haut volume nous ont aidé à identifier les médecins de l'USI à qui envoyer le sondage par courriel. RéSULTATS: Parmi les 448 médecins de l'USI issus de 37 centres dans neuf provinces ayant reçu le sondage, 184/448 (41,1 %) ont répondu à une question ou plus de notre questionnaire. Les répondants ont identifié les infirmières spécialisées des ODO en tant que source principale de conseils quant aux soins à prodiguer aux donneurs (107/165; 60 %). Un diagnostic de tempête adrénergique était fréquemment posé suite à une augmentation de la tension artérielle (159/165; 96,4 %) et/ou de la fréquence cardiaque (135/165; 81,8 %); toutefois, la prise en charge déclarée variait considérablement. Après la fin de la tempête adrénergique, les vasopresseurs de première intention les plus utilisés étaient la norépinéphrine (93/164; 56,7 %) et la vasopressine (68/164; 41,5 %). Vingt-et-un répondants (21/162; 13,0 %) ont rapporté ne jamais administrer d'inotropes aux donneurs. Les prescriptions systématiques de corticostéroïdes et d'hormones thyroïdiennes à tous les donneurs ont été rapportées par 62/161 (37,6 %) et 50/161 (31,1 %) répondants, respectivement. Les répondants se sentaient influencés par les infirmières des ODO et les médecins spécialisés en greffe lors de la prescription des corticostéroïdes (77/161; 47,8 %) et/ou des hormones thyroïdiennes (33/161; 20,5 %). CONCLUSION: Nous avons observé une variabilité considérable dans les pratiques perçues des médecins de l'USI quant à la prise en charge hémodynamique des donneurs décédés, particulièrement en ce qui a trait au traitement de la tempête adrénergique, à la prescription de thérapie hormonale et à l'administration d'inotropes.

A Pilot Randomized Controlled Trial Comparing Levothyroxine to Placebo in Neurologically Deceased Donors.

BACKGROUND: Although commonly prescribed, the efficacy of levothyroxine to improve heart function in neurologically deceased donors is unclear. We evaluated the feasibility of a randomized controlled trial to compare levothyroxine to placebo on the variation of left ventricular ejection fraction, in hemodynamically unstable donors. METHODS: We conducted a pilot, double-blinded, randomized controlled trial. Deceased donors with reduced left ventricular ejection fraction or needing vasopressors were included. We randomized participants to a 20 µg bolus followed by a 20 µg/h infusion of levothyroxine or an identically appearing placebo. We report the proportion of recruited participants, the time to the administration of the study drug, and protocol violations. RESULTS: Twenty-four participants (N = 24/104; 23.1%) were eligible. Five of them (N = 5/24; 20.8%) were excluded by the attending physician. Four others were not included, due to family refusal for research (n = 2/24;8.3%) and unavailability of research staff (n = 2/24; 8.3%). Fifteen participants were randomized (N = 15/104; 14.4%). Mean time between the echocardiography and the initiation of the drug was 1.73 hours, and14 (93.3%) of 15 of the participants received the drug within 2 hours after the echocardiography. We report no study violation. The study was stopped prematurely because of low recruitment. CONCLUSION: This pilot trial suggests that the success of a definitive randomized control trial to assess the efficacy of levothyroxine in deceased donors could benefit from a multicenter recruitment and education on the evidence surrounding the pharmacological management of organ donors. The need for consent to research interventions in deceased donors should also be clarified.