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Purpose: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs). Methods: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing. Results: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as “rarely” (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care. Conclusions: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients.

Purpose: We aimed to describe the Canadian public’s understanding and perception of how death is determined in Canada, their level of interest in learning about death and death determination, and their preferred strategies for informing the public. Methods: We conducted a nationwide cross-sectional survey of a representative sample of the Canadian public. The survey presented two scenarios of a man who met current criteria for neurologic death determination (scenario 1) and a man who met current criteria for circulatory death determination (scenario 2). Survey questions evaluated understanding of how death is determined, acceptance of death determination by neurologic and circulatory criteria, and interest and preferred strategies in learning more about the topic. Results: Among 2,000 respondents (50.8% women; n= 1,015), nearly 67.2% believed that the man in scenario 1 was dead (n= 1,344) and 81.2% (n= 1,623) believed that the man in scenario 2 was dead. Respondents who believed that the man was not dead or were unsure endorsed several factors that may increase their agreement with the determination of death, including requiring more information about how death was determined, seeing the results of brain imaging/tests, and a third doctor’s opinion. Predictors of disbelief that the man in scenario 1 is dead were younger age, being uncomfortable with the topic of death, and subscribing to a religion. Predictors of disbelief that the man in scenario 2 is dead were younger age, residing in Quebec (compared with Ontario), having a high school education, and subscribing to a religion. Most respondents (63.3%) indicated interest in learning more about death and death determination. Most respondents preferred to receive information about death and death determination from their health care professional (50.9%) and written information provided by their health care professional (42.7%). Conclusion: Among the Canadian public, the understanding of neurologic and circulatory death determination is variable. More uncertainty exists with death determination by neurologic criteria than with circulatory criteria. Nevertheless, there is a high level of general interest in learning more about how death is determined in Canada. These findings provide important opportunities for further public engagement.

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists’ Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.

Purpose: We sought to explore the lived experiences of a professionally diverse sample of healthcare workers (HCWs) in a single intensive care unit (ICU) serving a large and generalizable Canadian population. We aimed to understand how working during the COVID-19 pandemic affected their professional and personal lives, including their perceptions of institutional support, to inform interventions to ameliorate impacts of the COVID-19 and future pandemics. Methods: In this qualitative descriptive study, 23 ICU HCWs, identified using convenience purposive sampling, took part in individual semistructured interviews between July and November 2020, shortly after the first wave of the pandemic in Ontario. We used inductive thematic analysis to identify major themes. Results: We identified five major themes related to the COVID-19 pandemic: 1) communication and informational needs (e.g., challenges communicating policy changes); 2) adjusting to restricted visitation (e.g., spending less time interacting with patients); 3) staffing and workplace supports (e.g., importance of positive team dynamics); 4) permeability of professional and personal lives (e.g., balancing shift work and childcare); and 5) a dynamic COVID-19 landscape (e.g., coping with constant change). The COVID-19 pandemic contributed to HCWs in the ICU experiencing varied negative repercussions on their work environment, including staffing and institutional support, which carried into their personal lives. Conclusion: Healthcare workers in the ICU perceived that the COVID-19 pandemic had negative repercussions on their work environment, including staffing and institutional support, as well as their professional and personal lives. Understanding both the negative and positive experiences of all ICU HCWs working during the COVID-19 pandemic is critical to future pandemic preparedness. Their perspectives will help to inform the development of mental health and wellbeing interventions to support staff during the COVID-19 pandemic and beyond.

Objective:Concerns that medical assistance in dying (MAiD) may harm vulnerable groups unable to access medical treatments and social supports have arisen since the legalization of MAiD on June 17, 2016; however, there is little research on the topic. The purpose of this study is to investigate the socioeconomic status (SES) of patients who request MAiD at the London Health Sciences Centre (LHSC). Methods:A retrospective analysis of patients from the LHSC MAiD database between June 6, 2016 and December 20, 2019 was conducted. Patients were linked to income data from the 2016 Canadian Census, and their corresponding income quintile was a proxy for SES. Geographic information system (GIS) mapping software was used to visualize the distribution of income and MAiD requests. Results:39.4% of the LHSC catchment area was classified as low SES. Two hundred thirty-seven (58.1%) MAiD requests came from low SES patients and 171 (41.9%) requests came from high SES patients. Two hundred fifty-nine (63.5%) patients who requested a MAiD assessment did not receive MAiD following their request. Of the 237 lower SES patients, 150 (63.3% [95% CI 57.2-69.3]) did not receive MAiD. Of the 171 higher SES patients, 109 (63.7% [95% CI 56.5-70.9]) did not receive MAiD. Conclusion:A disproportionate number of requests for a MAiD assessment at LHSC came from lower SES patients; however, similar proportions of patients who requested MAiD from each SES group received aid in dying. Future research should explore why a disproportionately high number of low SES patients request MAiD at LHSC.

Supplemental Digital Content is available in the text.Donation after circulatory death determination frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: (1) describe heparin administration practices and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting donation after circulatory death determination heparin practices including use, dosage, and timing (objective 1). To explore associations between antemortem heparin and transplant outcomes (objective 2), we (1) summarized within-study comparisons and (2) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8%–100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life-sustaining therapy. For objective 2, 7 studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 y, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, retransplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted.

Purpose: To evaluate the impact of the COVID-19 pandemic on Canadian intensive care unit (ICU) workers. Methods: Between June and August 2020, we distributed a cross-sectional online survey of ICU workers evaluating the impact of the pandemic, coping strategies, symptoms of post-traumatic stress disorder (PTSD; Impact of Events Scale-Revised), and psychological distress, anxiety, and depression (Kessler Psychological Distress Scale). We performed regression analyses to determine the predictors of psychological symptoms. Results: We analyzed responses from 455 ICU workers (80% women; 67% from Ontario; 279 nurses, 69 physicians, and 107 other healthcare professionals). Respondents felt that their job put them at great risk of exposure (60%), were concerned about transmitting COVID-19 to family members (76%), felt more stressed at work (67%), and considered leaving their job (37%). Overall, 25% had probable PTSD and 18% had minimal or greater psychological distress. Nurses were more likely to report PTSD symptoms (33%) and psychological distress (23%) than physicians (5% for both) and other health disciplines professionals (19% and 14%). Variables associated with PTSD and psychological distress included female sex (beta-coefficient [B], 1.59; 95% confidence interval [CI], 1.20 to 2.10 and B, 3.79; 95% CI, 1.79 to 5.78, respectively; P< 0.001 for differences in scores across groups) and perceived increased risk due to PPE shortage or inadequate PPE training (B, 1.87; 95% CI, 1.51 to 2.31 and B, 4.88; 95% CI, 3.34 to 6.43, respectively). Coping strategies included talking to friends/family/colleagues (80%), learning about COVID-19 (78%), and physical exercise (68%). Over half endorsed the following workplace strategies as valuable: hospital-provided scrubs, clear communication and protocols by hospitals, knowing their voice is heard, subsidized parking, and gestures of appreciation from leadership. Conclusions: This survey study shows that ICU workers have been impacted by the COVID-19 pandemic with high levels of stress and psychological burden. Respondents endorsed communication, protocols, and appreciation from leadership as helpful mitigating strategies.

Purpose: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products. Source: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2:we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology. Principal findings: No eligible studies included COVID-19 patients. Review 1:12 RCTs (n= 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density. Conclusions: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.

Purpose: The number of patients on cardiac transplant waitlists exceeds the number of available donor organs. Cardiac donation is currently limited to those declared dead by neurologic criteria in all but three countries. Cardiac donation after circulatory determination of death (cardiac DCDD) can be conducted using direct procurement and perfusion (DPP) or normothermic regional perfusion (NRP). Implementation of cardiac DCDD in many countries has been slowed by ethical debates within the donation and transplantation community. We conducted a national survey to determine the perceptions of healthcare providers regarding cardiac DCDD. Methods: We conducted an electronic survey of 398 healthcare providers who are involved in the management of heart donors and/or heart transplant recipients in Canada (226 nurses, 82 critical care physicians, 31 donation specialists, and 59 transplant specialists). Our primary outcomes were their attitudes towards and concerns regarding cardiac DCDD protocols and their implementation in Canada. We distributed the survey electronically through several Canadian donation and transplantation organizations. Results: We identified that 361 of 391 respondents (92.3%; 95% confidence interval [CI], 89.6 to 95.1) believed that DPP is acceptable, and 329 of 377 respondents (87.3%; 95% CI, 83.9 to 90.7) supported its implementation in Canada. We found that 301 of 384 respondents (78.4%; 95% CI, 74.2 to 82.6) believed that NRP is acceptable and 266 of 377 respondents (70.6%; 95% CI, 66.0 to 75.2) supported its implementation in Canada. Conclusion: This is the first survey describing the attitudes of healthcare providers towards cardiac DCDD. We identified widespread support for cardiac DCDD and its implementation in Canada among Canadian healthcare providers within the organ donation and transplantation community in Canada.

Purpose: Hemodynamic management of adults with distributive shock often includes the use of catecholamine-based vasoconstricting medications. It is unclear whether adding vasopressin or vasopressin analogues to catecholamine therapy is beneficial in the management of patients with distributive shock. The purpose of this guideline was to develop an evidence-based recommendation regarding the addition of vasopressin to catecholamine vasopressors in the management of adults with distributive shock. Methods: We summarized the evidence informing this recommendation by updating a recently published meta-analysis. Then, a multidisciplinary panel from the Canadian Critical Care Society developed the recommendation using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: The updated systematic review identified 25 randomized controlled trials including a total of 3,737 patients with distributive shock. Compared with catecholamine therapy alone, the addition of vasopressin or its analogues was associated with a reduced risk of mortality (relative risk [RR], 0.91; 95% confidence interval [CI], 0.85 to 0.99; low certainty), reduced risk of atrial fibrillation (RR, 0.77; 95% CI, 0.67 to 0.88; high certainty), and increased risk of digital ischemia (RR, 2.56; 95% CI, 1.24 to 5.25; moderate certainty). Conclusions: After considering certainty in the evidence, values and preferences, cost, and other factors, the expert guideline panel suggests using vasopressin or vasopressin analogues in addition to catecholamines over catecholamine vasopressors alone for the management of distributive shock (conditional recommendation, low certainty evidence).

Purpose: Cardiac transplantation is a definitive therapy for end-stage heart failure, but demand exceeds supply. Cardiac donation after circulatory determination of death (cardiac DCDD) can be performed using direct procurement and perfusion (DPP), where cardiac activity is restored after heart recovery, or (NRP), where brain blood supply is surgically interrupted, circulation to the thoraco-abdominal organs is restored within the donor’s body, followed by heart recovery. While cardiac DCDD would increase the number of heart donors, uptake of programs has been slowed in part because of ethical concerns within the medical community. These debates have been largely devoid of discussion regarding public perceptions. We conducted a national survey of public perceptions regarding cardiac DCDD. Methods: We surveyed 1,001 Canadians about their attitudes towards cardiac DCDD using a rigorously designed and pre-tested survey. Results: We found that 843 of 1,001 respondents (84.2%; 95% confidence interval [CI], 81.8 to 86.3) accepted the DPP approach, 642 (64.1%; 95% CI, 61.1 to 67.0) would agree to donate their heart using DPP, and 696 (69.5%; 95% CI, 66.6 to 72.3) would consent to the same for a family member. We found that 779 respondents of 1,001 respondents (77.8%; 95% CI, 75.1 to 80.3) accepted the NRP approach, 587 (58.6%; 95% CI, 55.5 to 61.6) would agree to donate their heart using NRP, and 636 (63.5%; 95% CI, 60.5 to 66.4) would consent to the same for a family member. Most respondents supported the implementation of DPP (738 respondents or 73.7%; 95% CI, 70.9 to 76.3) and NRP (655 respondents or 65.4%; 95% CI, 62.4 to 68.3) in Canada. Conclusion: The results of this national survey of public attitudes towards cardiac DCDD will inform the implementation of cardiac DCDD programs in a manner that is consistent with public values.

Purpose: Elevated cardiac troponin concentrations in people with critical illness are associated with an increased risk of death. We aimed to assess the feasibility of a larger study to ascertain the utility of cardiac troponin as a prognostic tool for mortality in critically ill patients. Methods: Patients admitted to participating intensive care units during the one-month enrolment period were eligible. We excluded cardiac surgical patients and patients who were admitted and either died or were discharged within 12 hr. In enrolled patients, we measured high-sensitivity cardiac troponin I (hs-cTnI) and obtained electrocardiograms to ascertain the incidence of myocardial infarction (MI) and isolated troponin elevation. Our feasibility objectives were to measure recruitment rate, the proportion of patients who consented under a deferred consent model, and time required for data collection and study procedures. Results: Over a four-week enrolment period, 280 patients were enrolled using a deferred consent model. We obtained subsequent consent from 81% of patients. Study procedures and data collection required 1.7 hr per participant. Overall, 86 (38%) suffered a MI, 23 (10%) had an isolated hs-cTnI elevation, and 117 (52%) had no hs-cTnI elevation. The crude hospital mortality rate was 10% without an hs-cTnI elevation, 29% with an isolated hs-cTnl elevation (relative risk [RR]) 2.2; 95% confidence interval [CI], 1.0 to 6.0) and 29% with an MI (RR, 2.6; 95% CI, 1.4 to 5.1). Conclusion: Myocardial injury with elevated hs-cTnI concentrations and MIs occur frequently during critical illness. This pilot study has established the feasibility of conducting a large-scale investigation addressing this issue.

Cognitive impairment is common after critical illness and persists beyond the period of acute illness. Clinicians caring for this patient population are encouraged to screen for cognitive impairment and provide supportive measures to mitigate its distressing effects. Further research is needed to evaluate the laboratory and neuroimaging correlates of post-ICU cognitive impairment, which may in turn lead to personalized interventions to address this debilitating complication of critical illness. Further research is needed to evaluate the laboratory and neuroimaging correlates of post-ICU cognitive impairment, which may in turn lead to personalized interventions to address this debilitating complication of critical illness.

While neuropsychological deficits have been reported in healthy individuals who use street cannabis, data in patients with multiple sclerosis (MS) are lacking. Given that MS is associated with cognitive deterioration, the aim of this study was to determine the neuropsychological effects of cannabis use in this population.

Supplemental Digital Content is available in the text.

ObjectiveTo determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19.DesignLiving systematic review and network meta-analysis.Data sourcesWorld Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021.Study selectionRandomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.MethodsRandom effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach.ResultsThe first iteration of this living network meta-analysis includes nine randomised trials—six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain.ConclusionsHydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection.Systematic review registrationThis review was not registered. The protocol established a priori is included as a supplement.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

ObjectiveTo compare the effects of treatments for coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesUS Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020.Study selectionRandomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.Results23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference −4.5 days, low certainty), remdesivir (−2.6 days, moderate certainty), and lopinavir-ritonavir (−1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation.ConclusionGlucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.Systematic review registrationThis review was not registered. The protocol is included as a supplement.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.