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.

Strategies for the Prevention and Treatment of Iatrogenic Withdrawal from Opioids and Benzodiazepines in Critically Ill Neonates, Children and Adults: A Systematic Review of Clinical Studies.

BACKGROUND: Critically ill patients are at high risk of iatrogenic withdrawal syndrome (IWS), due to exposure to high doses or prolonged periods of opioids and benzodiazepines. PURPOSE: To examine pharmacological management strategies designed to prevent and/or treat IWS from opioids and/or benzodiazepines in critically ill neonates, children and adults. METHODS: We included non-randomised studies of interventions (NRSI) and randomised controlled trials (RCTs), reporting on interventions to prevent or manage IWS in critically ill neonatal, paediatric and adult patients. Database searching included: PubMed, CINAHL, Embase, Cochrane databases, TRIP, CMA Infobase and NICE evidence. Additional grey literature was examined. Study selection and data extraction were performed in duplicate. Data collected included: population, definition of opioid, benzodiazepine or mixed IWS, its assessment and management (drug or strategy, route of administration, dosage and titration), previous drug exposures and outcomes measures. Methodological quality assessment was performed by two independent reviewers using the Cochrane risk of bias tool for RCTs and the ROBINS-I tool for NRSI. A qualitative synthesis of the results is provided. For the subset of studies evaluating multifaceted protocolised care, we meta-analysed results for 4 outcomes and examined the quality of evidence using GRADE post hoc. RESULTS: Thirteen studies were eligible, including 10 NRSI and 3 RCTs; 11 of these included neonatal and paediatric patients exclusively. Eight studies evaluated multifaceted protocolised interventions, while 5 evaluated individual components of IWS management (e.g. clonidine or methadone at varying dosages, routes of administration and duration of tapering). IWS was measured using an appropriate tool in 6 studies. Ten studies reported upon occurrence of IWS, showing significant reductions (n = 4) or no differences (n = 6). Interventions failed to impact duration of mechanical ventilation, ICU length of stay, and adverse effects. Impact on opioid and/or benzodiazepine total doses and duration showed no differences in 4 studies, while 3 showed opioid and benzodiazepine cumulative doses were significantly reduced by 20-35% and 32-66%, and treatment durations by 1.5-11 and 19 days, respectively. Variable effects on intervention drug exposures were found. Weaning durations were reduced by 6-12 days (n = 4) for opioids and/or methadone and by 13 days (n = 1) for benzodiazepines. In contrast, two studies using interventions centred on transition to enteral routes or longer tapering durations found significant increases in intervention drug exposures. Interventions had overall non-significant effects on additional drug requirements (except for one study). Included studies were at high risk of bias, relating to selection, detection and reporting bias. CONCLUSION: Interventions for IWS management fail to impact duration of mechanical ventilation or ICU length of stay, while effect on occurrence of IWS and drug exposures is inconsistent. Heterogeneity in the interventions used and methodological issues, including inappropriate and/or subjective identification of IWS and bias due to study design, limited the conclusions.

Validation of the Withdrawal Assessment Tool-1 in Adult Intensive Care Patients.

BACKGROUND: The Withdrawal Assessment Tool-1 (WAT-1) has been validated for assessing iatrogenic withdrawal syndrome in critically ill children receiving mechanical ventilation, but little is known about this syndrome in critically ill adults. OBJECTIVE: To evaluate the validity and reliability of the WAT-1 in critically ill adults. METHODS: A prospective, observational, open-cohort pilot study of critically ill adults receiving mechanical ventilation and regular administration of opioids for at least 72 hours. Patients were assessed for withdrawal twice daily on weekdays and once daily on weekends using the WAT-1 after an opioid weaning episode. The presence of iatrogenic withdrawal syndrome was evaluated once daily using modified Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) criteria. All evaluations were blinded and performed independently. The criterion validity of the WAT-1 and the interrater reliability for WAT-1 and DSM-5 evaluations were determined. RESULTS: During 8 months, 52 adults (median age, 51.5 years) were enrolled. Eight patients (15%) had at least 1 positive assessment during their intensive care unit stay using the DSM-5, compared with 19 patients (37%) using the WAT-1. The overall sensitivity of the WAT-1 was 50%, and its specificity was 65.9%. Agreement between WAT-1 and DSM-5 assessments was poor (κ = 0.102). The interrater reliability for the WAT-1 was 89.1% and for the DSM-5 was 90.1%. CONCLUSION: Despite showing reliability, the WAT-1 is not a valid tool for assessing the presence of iatrogenic withdrawal syndrome in adults.

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.

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.

Opioid-associated iatrogenic withdrawal in critically ill adult patients: a multicenter prospective observational study.

BACKGROUND: Opioids and benzodiazepines are frequently used in the intensive care unit (ICU). Regular use and prolonged exposure to opioids in ICU patients followed by abrupt tapering or cessation may lead to iatrogenic withdrawal syndrome (IWS). IWS is well described in pediatrics, but no prospective study has evaluated this syndrome in adult ICU patients. The objective of this study was to determine the incidence of IWS caused by opioids in a critically ill adult population. This multicenter prospective cohort study was conducted at two level-1 trauma ICUs between February 2015 and September 2015 and included 54 critically ill patients. Participants were eligible if they were 18 years and older, mechanically ventilated and had received more than 72 h of regular intermittent or continuous intravenous infusion of opioids. For each enrolled patient and per each opioid weaning episode, presence of IWS was assessed by a qualified ICU physician or senior resident according to the 5th edition of Diagnostic and Statistical Manual of Mental Disorders criteria for opioid withdrawal. RESULTS: The population consisted mostly of males (74.1%) with a median age of 50 years (25th-75th percentile 38.2-64.5). The median ICU admission APACHE II score was 22 (25th-75th percentile 12.0-28.2). The overall incidence of IWS was 16.7% (95% CI 6-27). The median cumulative opioid dose prior to weaning was higher in patients with IWS (245.7 vs. 169.4 mcg/kg, fentanyl equivalent). Patients with IWS were also exposed to opioids for a longer period of time as compared to patients without IWS (median 151 vs. 125 h). However, these results were not statistically significant. CONCLUSIONS: IWS was occasionally observed in this very specific population of mechanically ventilated, critically ill ICU patients. Further studies are needed to confirm these preliminary results and identify risk factors.

Fulminant legionellosis in two patients treated with infliximab for Crohn's disease: case series and literature review.

Two cases of fulminant pulmonary legionellosis, complicated by prolonged intensive care unit stays and acute respiratory distress syndrome, and who were recently treated with infliximab for Crohn's disease, are described. A review of the literature revealed three additional cases in patients with inflammatory bowel disease, and a total of 22 cases of Legionella pneumophila pneumonia in the context of treatment with antitumour necrosis (TNF)-alpha medications. The median age of the patients was 49 years, and men and women were affected equally. The case fatality rate was 14% (three of 22). Early recognition and treatment of this anti-TNF-alpha-related complication would likely result in reduced mortality and morbidity. Physicians prescribing anti-TNF-alpha drugs should be aware of this association.

Interferon beta-induced panniculitis mimicking acute appendicitis.

BACKGROUND: As immunomodulatory therapies such as recombinant human interferon beta gain clinical applicability, patients are likely to experience some of their numerous cutaneous adverse effects at injection sites. We describe a case of interferon beta-induced septal panniculitis. OBSERVATIONS: A 43-year-old woman with multiple sclerosis treated with subcutaneous interferon beta presented with right lower abdominal quadrant pain, fever, and an indurated McBurney point. An abdominal computed tomographic scan showed an inflammatory subcutaneous fat infiltration reaching the surface of the right lateral rectus muscle. The patient was brought to the operating room, where a laparoscopic appendectomy was performed. She returned a week later unimproved. The infiltration near a site of subcutaneous injection progressed with areas of liquefaction. Histologic examination of a deep cutaneous biopsy specimen revealed a septal panniculitis without vasculitis. CONCLUSIONS: Panniculitides encompass various clinical syndromes characterized by inflammation of the fibrous septae, fatty lobules, or both components of the subcutaneous tissue. Interferon beta-1b should be considered among the list of putative agents.