Physicians' beliefs and perceived importance of traumatic brain injury-associated agitation in critically ill patients: a survey of Canadian intensivists.

PURPOSE: Agitation is a common behavioural problem following traumatic brain injury (TBI). Intensive care unit (ICU) physicians' perspectives regarding TBI-associated agitation are unknown. Our objective was to describe physicians' beliefs and perceived importance of TBI-associated agitation in critically ill patients. METHODS: Following current standard guidance, we built an electronic, self-administrated, 42-item survey, pretested it for reliability and validity, and distributed it to 219 physicians working in 18 ICU level-1 trauma centres in Canada. We report the results using descriptive statistics. RESULTS: The overall response rate was 93/219 (42%), and 76/93 (82%) respondents completed the full survey. Most respondents were men with ten or more years of experience. Respondents believed that pre-existing dementia (90%) and regular recreational drug use (86%) are risk factors for agitation. Concerning management, 91% believed that the use of physical restraints could worsen agitation, 90% believed that having family at the bedside reduces agitation, and 72% believed that alpha-2 adrenergic agonists are efficacious for managing TBI agitation. Variability was observed in beliefs on epidemiology, sex, gender, age, socioeconomic status, and other pharmacologic options. Respondents considered TBI agitation frequent enough to justify the implementation of management protocols (87%), perceived the current level of clinical evidence on TBI agitation management to be insufficient (84%), and expressed concerns about acute and long-term detrimental outcomes and burden to patients, health care professionals, and relatives (85%). CONCLUSION: Traumatic brain injury-associated agitation in critically ill patients was perceived as an important issue for most ICU physicians. Physicians agreed on multiple approaches to manage TBI-associated agitation although agreement on epidemiology and risk factors was variable.

RéSUMé: OBJECTIF: L'agitation est un problème de comportement courant à la suite d'un traumatisme crânien (TC). Le point de vue des médecins des unités de soins intensifs (USI) sur l'agitation associée aux traumatismes crâniens est inconnu. Notre objectif était de décrire les croyances et l'importance perçue par les médecins de l'agitation associée aux traumatismes crâniens chez les patient·es gravement malades. MéTHODE: Conformément aux lignes directrices standard actuelles, nous avons élaboré un sondage électronique auto-administré de 42 questions, l'avons testé au préalable pour en vérifier la fiabilité et la validité, et l'avons distribué à 219 médecins travaillant dans les USI de 18 centres de traumatologie de niveau 1 au Canada. Les résultats sont présentés à l'aide de statistiques descriptives. RéSULTATS: Le taux de réponse global a été de 93 sur 219 (42 %) et 76 sur 93 (82 %) personnes interrogées ont répondu à l'ensemble du sondage. La plupart des répondant·es étaient des hommes comptant dix ans ou plus d'expérience. Les répondant·es sont d'avis que la démence préexistante (90 %) et la consommation régulière de drogues à des fins récréatives (86 %) sont des facteurs de risque d'agitation. En ce qui concerne la prise en charge, 91 % des répondant·es estiment que l'utilisation de contentions physiques peut aggraver l'agitation, 90 % croient que le fait d'avoir de la famille au chevet du patient ou de la patiente réduit l'agitation et 72 % pensent que les agonistes alpha-2 adrénergiques sont efficaces pour gérer l'agitation causée par les traumatismes crâniens. Une variabilité a été observée dans les croyances concernant l'épidémiologie, le sexe, le genre, l'âge, le statut socio-économique et d'autres options pharmacologiques. Les répondant·es considéraient que l'agitation liée aux traumatismes crâniens était suffisamment fréquente pour justifier la mise en œuvre de protocoles de prise en charge (87 %), estimaient que le niveau actuel de données probantes cliniques sur la prise en charge de l'agitation causée par un traumatisme crânien était insuffisant (84 %), et se sont dit·es préoccupé·es par les conséquences préjudiciables aiguës et à long terme et par le fardeau pour les patient·es, les professionnel·les de la santé et les proches (85 %). CONCLUSION: L'agitation associée à un traumatisme crânien chez les patient·es gravement malades était perçue comme un problème important pour la plupart des médecins des soins intensifs. Les médecins s'entendaient sur plusieurs approches pour gérer l'agitation associée aux traumatismes crâniens, bien que l'accord sur l'épidémiologie et les facteurs de risque était variable.

Use of actigraphy for monitoring agitation and rest-activity cycles in patients with acute traumatic brain injury in the ICU.

BACKGROUND: In traumatic brain injury patients (TBI) admitted to the intensive care unit (ICU), agitation can lead to accidental removal of catheters, devices as well as self-extubation and falls. Actigraphy could be a potential tool to continuously monitor agitation. The objectives of this study were to assess the feasibility of monitoring agitation with actigraphs and to compare activity levels in agitated and non-agitated critically ill TBI patients. METHODS: Actigraphs were placed on patients' wrists; 24-hour monitoring was continued until ICU discharge or limitation of therapeutic efforts. Feasibility was assessed by actigraphy recording duration and missing activity count per day. RESULTS: Data from 25 patients were analyzed. The mean number of completed day of actigraphy per patient was 6.5 ± 5.1. The mean missing activity count was 20.3 minutes (±81.7) per day. The mean level of activity measured by raw actigraphy counts per minute over 24 hours was higher in participants with agitation than without agitation. CONCLUSIONS: This study supports the feasibility of actigraphy use in TBI patients in the ICU. In the acute phase of TBI, agitated patients have higher levels of activity, confirming the potential of actigraphy to monitor agitation.

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.

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.

Safety of dexmedetomidine for the control of agitation in critically ill traumatic brain injury patients: a descriptive study.

BACKGROUND: Behavioural disturbances such as agitation are common following traumatic brain injury and can interfere with treatments, cause self-harm and delay rehabilitation. As there is a lack of evidence on the optimal approach to manage agitation in recovering TBI patients, various pharmacological agents are used including antipsychotics, anticonvulsants and sedative agents. Among sedatives, the safety and efficacy of dexmedetomidine to control agitation in traumatic brain injury patients is not well documented. OBJECTIVE: To describe the safety, use and efficacy of dexmedetomidine for the management of agitation following traumatic brain injury in the intensive care unit. METHODS: Medical records of all patients admitted to the intensive care unit of the Hôpital Sacré-Coeur de Montréal for a traumatic brain injury who received dexmedetomidine for agitation between 1 January 2017 and 31 December 2017 were reviewed. Patients who received dexmedetomidine for indications other than agitation were excluded. Data on dexmedetomidine prescription practices and safety were extracted. Frequency of agitation and concomitant psychoactive medication use was explored over a period starting two days prior to the initiation of dexmedetomidine to six days after or discontinuation, whichever came first. RESULTS: We identified 41 patients in whom dexmedetomidine was initiated. Dexmedetomidine was started on median ICU day 3 (25th -75th percentiles: 2-7) and had a median treatment duration of 3 days (25th -75th percentiles: 3-6) and a mean average rate of 0.62 mcg/kg/h (SD 0.25). Although hypotension (76%) and bradycardia (54%) were common, only one patient required intervention. The proportion of patients with at least one episode of agitation decreased from 100% on day 0, to 88%, 69% and 63% on days 1, 2 and 3 of dexmedetomidine, respectively. The decrease was statistically significant difference between days 0 and 2 as well as between days 0 and 3. Concomitant use of propofol and benzodiazepines also decreased over the course of dexmedetomidine treatment. CONCLUSION: Dexmedetomidine use was safe and associated with a reduction in agitation in traumatic brain injury patients in the 96 hours following its initiation.

Attitude and knowledge of medical students about organ donation - training needs identified from a Canadian survey.

BACKGROUND: Appropriate training of health professionals has been recommended to increase organ donation rates. Some studies have shown insufficient knowledge among medical students. This survey aims to describe their knowledge and attitude toward organ donation (OD). METHOD: We designed, pre-tested and conducted an online survey of all undergraduate medical students from Montreal, Laval and Sherbrooke universities in 2016-2017. Multivariate linear regression identified factors associated with a better knowledge score. RESULTS: Twenty-two percent (750/3344) of students completed the survey. Ninety-one percent of students adequately knew that neurological death is irreversible; 76% acknowledged that someone could be neurologically deceased while his heart is still beating; 69% were not aware of circulatory determination of death. For only one knowledge item, senior students had a better answer than junior students. Total knowledge score was associated with exposure to OD during medical studies and comfort in answering patients' questions about OD (p < 0,001). Regarding attitude, 96% of respondents wished to become organ donors after death and 92% supported OD training during their medical training. CONCLUSION: Despite a favourable attitude, medical students have limited knowledge of OD. Findings suggest the need for a formal curriculum about OD, as students expressed.

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.

Variability in deceased donor care in Canada: a report of the Canada-DONATE cohort study.

PURPOSE: Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices. METHODS: This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces. RESULTS: Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34-35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces. CONCLUSION: These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.

RéSUMé: OBJECTIF: Les pratiques canadiennes de prise en charge des donneurs n'ont pas été rapportées. Notre objectif était d'informer les cliniciens et autres parties intéressées quant à l'éventail des pratiques actuelles. MéTHODE: Cette étude de cohorte observationnelle et prospective a recruté des donneurs d'organes consécutifs ayant récemment consenti au don entre le 1er août 2015 et le 31 juillet 2018 dans 27 unités de soins intensifs universitaires et cinq unités de soins intensifs pour adultes en milieu communautaire en Colombie-Britannique, en Alberta, en Ontario et au Québec. Le personnel de recherche a enregistré de manière prospective les données de prise en charge des donneurs. Les organismes de dons d'organes provinciaux ont vérifié les organes donnés. Nous avons formellement comparé les pratiques d'une province à l'autre. RéSULTATS: Sur une période médiane de collecte de huit mois, 622 donneurs potentiels ont été catégorisés au départ comme ayant un diagnostic de décès neurologique (donneurs DDN; n = 403) ou un décès cardiocirculatoire (donneurs DDC; n = 219). Parmi les donneurs DDN, 85,6 % ont subi un test d'apnée (rarement avec insufflation de dioxyde de carbone), 33,2 % ont subi des tests complémentaires, et une hypothermie thérapeutique subséquente (34-35°C) était rare. Les donneurs par diagnostic de décès neurologique étaient plus instables hémodynamiquement, la plupart ayant reçu des perfusions de vasopressine et de norépinéphrine, et une vaste majorité de ces donneurs ont reçu des corticostéroïdes à forte dose ainsi que de la thyroxine intraveineuse. Parmi les donneurs par DDC, 61,6 % avaient reçu des corticostéroïdes, et 8,9 % de la thyroxine. La plupart des donneurs n'avaient pas bénéficié de stratégies de ventilation protectrice des poumons. Les interventions invasives réalisées après le consentement au don comprenaient la bronchoscopie (71,7 %), le cathétérisme cardiaque (donneurs DDN seulement; 21,3 %) et les transfusions sanguines (19,3 %). Les médecins ont prescrit de l'héparine intraveineuse ante mortem chez 94,8 % des donneurs DDC. La cohorte a donné 1629 organes, résultant en 1532 greffes. La sélection de cas, la détermination de décès et les pratiques hormonales, nutritionnelles et hépariniques variaient toutes d'une province à l'autre. CONCLUSION: Ces résultats soulignent des domaines propices à la transmission de connaissances et aux recherches cliniques plus poussées. Les différences interprovinciales poseront probablement des défis uniques pour les études randomisées nationales. Enregistrement de l'étude : www.clinicaltrials.gov (NCT03114436); enregistrée le 10 avril 2017.

Modifiable Risk Factors for Delirium in Critically Ill Trauma Patients: A Multicenter Prospective Study.

OBJECTIVE:: Intensive care unit (ICU)-acquired delirium has been associated with increased morbidity and mortality. Prevention strategies including modification of delirium risk factors are emphasized by practice guidelines. No study has specifically evaluated modifiable delirium risk factors in trauma ICU patients. Our goal was to evaluate modifiable risk factors for delirium among trauma patients admitted to the ICU. DESIGN:: Prospective observational study. SETTING:: Two level 1 trauma ICU centers. PATIENTS:: Patients 18 years of age or older admitted for trauma including mild to moderate traumatic brain injury were eligible for the study. INTERVENTIONS AND MEASUREMENTS:: Delirium was assessed daily using the confusion assessment method for the ICU (CAM-ICU). The effect of modifiable risk factors was assessed using multivariate Cox regression analysis adjusting for severity of illness and significant nonmodifiable risk factors. MAIN RESULTS:: A total of 58 of 150 recruited patients (38.7%; 95% confidence interval [CI] 30.9-46.5) screened positive for delirium during ICU stay. When adjusting for significant nonmodifiable risk factors, physical restraints (hazard ratio [HR]: 2.13; 95% CI: 1.07-4.24) and active infection or sepsis (HR: 2.12; 95% CI: 1.18-3.81) significantly increased the risk of delirium, whereas opioids (HR: 0.35; 95% CI: 0.13-0.98), episodes of hypoxia (HR: 0.55; 95% CI: 0.31-0.95), access to a television/radio in the room (HR: 0.26; 95% CI: 0.11-0.62), and number of hours mobilized per day (HR: 0.77; 95% CI: 0.68-0.88) were associated with significantly less risk of delirium. CONCLUSION:: We have identified modifiable risk factors for delirium. Future studies should aim at implementing strategies to modify these risk factors and evaluate their impact on the risk of delirium.

A systematic review of interventions to facilitate extubation in patients difficult-to-wean due to delirium, agitation, or anxiety and a meta-analysis of the effect of dexmedetomidine.

BACKGROUND: Delirium, agitation, and anxiety may hinder weaning from mechanical ventilation and lead to increased morbidity and healthcare costs. The most appropriate clinical approach to weaning in these contexts remains unclear and challenging to clinicians. The objective of this systematic review was to identify effective and safe interventions to wean patients that are difficult-to-wean from mechanical ventilation due to delirium, agitation, or anxiety. METHODS: A systematic review was performed using MEDLINE, EMBASE, and PubMed. Studies evaluating mechanically ventilated patients deemed difficult-to-wean due to delirium, agitation, or anxiety, and comparing the effects of an intervention with a comparator arm were sought. Time-to-extubation was the primary outcome while the secondary outcome was intensive care unit (ICU) length of stay. RESULTS: From 10,860 studies identified, eight met the inclusion criteria: six studies assessed dexmedetomidine while the remaining two assessed loxapine and biofeedback. Pooled analysis of studies assessing dexmedetomidine showed reduced time-to-extubation (six studies, n = 303) by 10.9 hr compared with controls (95% confidence interval [CI], -15.7 to -6.1; I2 = 68%) and ICU length of stay (four studies, n = 191) by 2.6 days (95% CI, 1.9 to 3.3; I2 = 0%). Nevertheless, the evidence was deemed to be of low quality given the small sample sizes and high heterogeneity. Studies assessing other interventions did not identify improvements compared with controls. Safety assessment was globally poorly reported. CONCLUSIONS: This systematic review and meta-analysis provides low quality evidence to suggest the use of dexmedetomidine in patients deemed difficult-to-wean due to agitation, delirium, or anxiety. Insufficient evidence was found regarding other interventions to provide any recommendation. TRIAL REGISTRATION: PROSPERO (CRD42016042528); registered 15 July, 2016.

RéSUMé: CONTEXTE: Le délirium, l'agitation et l'anxiété peuvent compliquer le sevrage de la ventilation mécanique et aboutir à une augmentation de la morbidité et du coût des soins de santé. L'approche clinique la plus adaptée au sevrage dans ces circonstances n'est pas claire et reste un défi pour les cliniciens. L'objectif de cette étude systématique était d'identifier des interventions efficaces et sécuritaires pour sevrer les patients « difficiles à sevrer ¼ de la ventilation mécanique en raison d'un délirium, d'une agitation ou d'anxiété. MéTHODES: Une revue systématique a été menée en utilisant les bases de données MEDLINE, EMBASE et PubMed. Les études évaluant des patients sous ventilation mécanique jugés difficiles à sevrer en raison d'un délirium, d'une agitation ou d'anxiété, comparant les effets d'une intervention à celle d'un bras comparateur ont été recherchées. Le critère d'évaluation principal a été le délai jusqu'à l'extubation et le critère d'évaluation secondaire a été la durée de séjour en unité de soins intensifs (USI). RéSULTATS: À partir de 10 860 études identifiées, huit satisfaisaient les critères d'inclusion : six études ont évalué la dexmédétomidine tandis que les deux dernières ont évalué la loxapine et le biofeedback. L'analyse groupée des études évaluant la dexmédétomidine a montré une réduction du délai d'extubation (six études, n = 303) de 10,9 heures comparativement aux contrôles (intervalle de confiance [IC] à 95 % : -15,7 à -6,1; I2 = 68 %) et de la durée du séjour en USI (quatre études, n = 191) de 2,6 jours (IC à 95 % : 1,9 à 3,3; I2 = 0 %). Néanmoins, les résultats sont de faible qualité compte tenu de la petite taille des échantillons et d'une grande hétérogénéité. Les études évaluant d'autres interventions n'ont pas identifié d'améliorations par rapport aux contrôles. D'une manière générale, les évaluations de l'innocuité ont été médiocrement décrites. CONCLUSIONS: Cette étude systématique et la méta-analyse procurent une preuve de qualité basse pour suggérer l'utilisation de la dexmédétomidine chez des patients considérés difficiles à sevrer en raison d'un délirium, d'une agitation ou d'anxiété. Les données probantes concernant les autres interventions ont été jugées insuffisantes pour permettre des recommandations quelconques. ENREGISTREMENT DE L'ESSAI CLINIQUE: PROSPERO (CRD42016042528); enregistré le 15 juillet 2016.

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.

Frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in critically Ill neonates, children and adults: A systematic review of clinical studies.

WHAT IS KNOWN AND OBJECTIVE: Many critically ill patients are exposed to opioids and benzodiazepines at high doses for prolonged periods, and upon discontinuation of these drugs, they may be at risk for iatrogenic withdrawal. Although this syndrome was associated with worse outcomes in the critically ill, limited guidance exists regarding its evaluation, prevention and treatment. This systematic review examined the frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and/or benzodiazepines in critically ill neonates, children and adults. METHODS: The literature search was conducted in PubMed, Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane register of systematic reviews, DARE, CINAHL, Trip database, CMA infobase and NICE evidence from inception to February 2018. Grey literature was examined. We included studies reporting frequency, risk factors or symptomatology of iatrogenic withdrawal of opioids, benzodiazepines (or both) in critically ill patients. We considered all study designs except case reports and case series. We excluded studies on neonatal abstinence syndrome, alcohol withdrawal, studies on chronic opioid and/or benzodiazepine users and studies on prevention or treatment of withdrawal in critical care patients. Two independent reviewers applied the inclusion and exclusion criteria. Pairs of reviewers independently abstracted data and evaluated methodological quality using the Cochrane Collaboration Tool, Newcastle-Ottawa or QUADAS-2. Details regarding study design, outcomes, definition, evaluation and type of withdrawal (opioid, benzodiazepine or mixed) were collected. Cumulative doses and duration of opioids and benzodiazepines were collected. RESULTS AND DISCUSSION: We identified 21 866 unique citations and 153 full texts were assessed for eligibility. Thirty-four studies were included; the majority were observational and few included adults. In prospective studies, mixed withdrawal was observed in 7.5%-100% of patients in paediatric studies and ranged from 16.7% to 55% in adults. Symptomatology of withdrawal was not well described. Risk factors included higher cumulative dose and prolonged administration of opioids and benzodiazepines. WHAT IS NEW AND CONCLUSION: Iatrogenic withdrawal appears to be a frequent syndrome in critical care patients who received regular doses of opioids and/or benzodiazepines for ≥72 hours. Larger studies are required, especially in critically ill adults, to better define the syndrome and its symptomatology.

Hamilton-DONATE: a city-wide pilot observational study of the ICU management of deceased organ donors.

PURPOSE: Improving the medical care of deceased organ donors to increase transplant rates and improve allograft function requires an understanding of the current epidemiology and clinical practices of deceased donation within intensive care units (ICUs). Herein, we report the results of our investigation into the feasibility of a multicentre prospective cohort study addressing the afformentioned issues. METHODS: We conducted a 12-month prospective observational cohort study in six ICUs and one coronary care unit in Hamilton, Canada. We included consecutive children and adults following consent for deceased organ donation (including neurologic determination of death [NDD] or donation after circulatory death [DCD]). Intensive care unit research staff recorded donor management data from hospital records, extending from one day prior to the consent for organ donation up to the time of organ retrieval. The provincial Organ Donation Organization (ODO) supplemented these data and, additionally, provided data on corresponding organ recipients. We identified, evaluated, and measured three potential obstacles to the feasibility of a national cohort study: obtaining authorization to implement the study with a waiver of research consent, accessibility of transplant recipient data, and the time required to complete very detailed case report forms (CRFs), with valuable lessons learned for implementation in future projects. RESULTS: The local Research Ethics Board and the ODO Privacy Office both authorized the recording of donor and recipient study data with a waiver of research consent. Sixty-seven consecutive consented donors were included (31 NDD and 36 DCD donors); 50 of them provided 144 organs for transplantation to 141 recipients. We identified the age and sex of the recipients as well as the location and date of transplant for all organ recipients in Ontario; however, we obtained no recipient data for six organs transported outside of Ontario. Intensive care unit research staff estimated that future CRF completion will require five to seven hours per patient. CONCLUSION: The Hamilton-DONATE pilot study supports the feasibility of a larger cohort study to describe the epidemiology and clinical practices related to deceased donor care in Canada. TRIAL REGISTRATION: wwwclinicaltrials.gov (NCT02902783). Registered 16 September 2016.

A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension.

PURPOSE: Clinicians must balance the risks from hypotension with the potential adverse effects of vasopressors. Experts have recommended a mean arterial pressure (MAP) target of at least 65 mmHg, and higher in older patients and in patients with chronic hypertension or atherosclerosis. We conducted a systematic review of randomized-controlled trials comparing higher vs lower blood pressure targets for vasopressor therapy administered to hypotensive critically ill patients. METHODS: We searched MEDLINE®, EMBASE™, and the Cochrane Central Register of Controlled Trials for studies of higher vs lower blood pressure targets for vasopressor therapy in critically ill hypotensive adult patients. Two reviewers independently assessed trial eligibility based on titles and abstracts, and they then selected full-text reports. Outcomes, subgroups, and analyses were prespecified. We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the overall confidence in the estimates of intervention effects. RESULTS: Of 8001 citations, we retrieved 57 full-text articles and ultimately included two randomized-controlled trials (894 patients). Higher blood pressure targets were not associated with lower mortality (relative risk [RR], 1.05; 95% confidence interval [CI], 0.90 to 1.23; P = 0.54), and neither age (P = 0.17) nor chronic hypertension (P = 0.32) modified the overall effect. Nevertheless, higher blood pressure targets were associated with a greater risk of new-onset supraventricular cardiac arrhythmia (RR, 2.08; 95% CI, 1.28 to 3.38; P < 0.01). CONCLUSION: Current evidence does not support a MAP target > 70 mmHg in hypotensive critically ill adult patients requiring vasopressor therapy.

Febuxostat as a novel option to optimize thiopurines' metabolism in patients with inadequate metabolite levels.

OBJECTIVE: To report the use of febuxostat in order to potentiate thiopurines' metabolism in a patient on azathioprine (AZA) therapy with low metabolite 6-thioguanine nucleotides (6-TGN) levels and elevated metabolite 6-methylmercaptopurine (6-MMP) levels. CASE SUMMARY: A 44-year-old woman with a history of anti-signal recognition particle necrotizing myopathy was treated with AZA-allopurinol combination therapy. When she developed an atypical drug-induced hypersensitivity syndrome, allopurinol was replaced by the new xanthine oxidase (XO) inhibitor febuxostat, at a daily dose of 40 mg. Febuxostat-AZA combination was successful with 6-TGN reaching therapeutic levels while 6-MMP levels remained low. After 5 months, she developed similar manifestations that she had presented on AZA-allopurinol combination. Febuxostat and AZA were then stopped. DISCUSSION: AZA and 6-MP are both inactive pro-drugs that undergo a complex metabolic transformation leading to active 6-TGN and potentially hepatotoxic 6-MMP. Some patients with unfavorable thiopurine metabolism might benefit from addition of XO inhibitor allopurinol in order to potentiate 6-TGN and reduce 6-MMP levels. It is likely that febuxostat, via its XO inhibition, would exhibit the same effect on thiopurines' metabolism. CONCLUSION: It has been shown that low dose of febuxostat was able to prevent hypermethylation and to potentiate 6-TGN levels in an AZA-treated patient. Thus, febuxostat could be useful in optimizing thiopurines' metabolism, but more data are needed before this practice can be recommended. The mechanisms by which febuxostat optimizes thiopurines' metabolism remain to be confirmed. Also, the optimal dose of febuxostat for this use remains to be determined.

Albumin administration is associated with acute kidney injury in cardiac surgery: a propensity score analysis.

INTRODUCTION: The risk of acute kidney injury (AKI) with the use of albumin-containing fluids compared to starches in the surgical intensive care setting remains uncertain. We evaluated the adjusted risk of AKI associated with colloids following cardiac surgery. METHODS: We performed a retrospective cohort study of patients undergoing on-pump cardiac surgery in a tertiary care center from 2008 to 2010. We assessed crystalloid and colloid administration until 36 hours after surgery. AKI was defined by the RIFLE (risk, injury, failure, loss and end-stage kidney disease) risk and Acute Kidney Injury Network (AKIN) stage 1 serum creatinine criterion within 96 hours after surgery. RESULTS: Our cohort included 984 patients with a baseline glomerular filtration rate of 72 ± 19 ml/min/1.73 m(2). Twenty-three percent had a reduced left ventricular ejection fraction (LVEF), thirty-one percent were diabetics and twenty-three percent underwent heart valve surgery. The incidence of AKI was 5.3% based on RIFLE risk and 12.0% based on the AKIN criterion. AKI was associated with a reduced LVEF, diuretic use, anemia, heart valve surgery, duration of extracorporeal circulation, hemodynamic instability and the use of albumin, pentastarch 10% and transfusions. There was an important dose-dependent AKI risk associated with the administration of albumin, which also paralleled a higher prevalence of concomitant risk factors for AKI. To address any indication bias, we derived a propensity score predicting the likelihood to receive albumin and matched 141 cases to 141 controls with a similar risk profile. In this analysis, albumin was associated with an increased AKI risk (RIFLE risk: 12% versus 5%, P = 0.03; AKIN stage 1: 28% versus 13%, P = 0.002). We repeated this methodology in patients without postoperative hemodynamic instability and still identified an association between the use of albumin and AKI. CONCLUSIONS: Albumin administration was associated with a dose-dependent risk of AKI and remained significant using a propensity score methodology. Future studies should address the safety of albumin-containing fluids on kidney function in patients undergoing cardiac surgery.

Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial.

INTRODUCTION: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk. METHODS AND ANALYSIS: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation. ETHICS AND DISSEMINATION: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309). TRIAL REGISTRATION NUMBER: NCT05148715.

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.

Pharmacotherapeutic Interventions in People Living With HIV Undergoing Solid Organ Transplantation: A Scoping Review.

The pharmacotherapeutic management of people living with HIV (PLWHIV) undergoing solid organ transplantation (SOT) is clinically challenging, mainly due to the frequent occurrence of complex drug-drug interactions. Although various strategies have been proposed to improve treatment outcomes in these patients, several uncertainties remain, and consensus practice guidelines are just beginning to emerge. The main objective of this scoping review was to map the extent of the literature on the pharmacotherapeutic interventions performed by healthcare professionals for PLWHIV undergoing SOT. Methods: We searched Medline, Embase, and the Cochrane databases as well as gray literature for articles published between January 2010 and February 2020. Study selection was performed by at least 2 independent reviewers. Articles describing pharmacotherapeutic interventions in PLWHIV considered for or undergoing SOT were included in the study. Results: Of the 12 599 references identified through our search strategy, 209 articles met the inclusion criteria. Results showed that the vast majority of reported pharmacotherapeutic interventions concerned the management of immunosuppressive and antimicrobial therapy, including antiretrovirals. Analysis of the data demonstrated that for several aspects of the pharmacotherapeutic management of PLWHIV undergoing SOT, there were differing practices, such as the choice of immunosuppressive induction and maintenance therapy. Other important aspects of patient management, such as patient counseling, were rarely reported. Conclusions: Our results constitute an extensive overview of current practices in the pharmacotherapeutic management of SOT in PLWHIV and identify knowledge gaps that should be addressed to help improve patient care in this specific population.