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Background: Most deaths in critically ill patients with severe traumatic brain injury are associated with a decision to withdraw life-sustaining treatments. We aimed to identify the behavioural determinants that influence recommendations by critical care physicians to consider the withdrawal of life-sustaining treatments in this population.Methods: We conducted a descriptive qualitative study based on the Theoretical Domains Framework of critical care physicians caring for patients with severe traumatic brain injury across Canada. We stratified critical care physicians by regions and used a purposive sampling strategy. We conducted semistructured phone interviews using a piloted and pretested interview guide. We transcribed the interviews verbatim and verified the content for accuracy. We performed the analysis using a 3-step approach: coding, generation of specific beliefs and generation of specific themes.Results: We recruited 20 critical care physicians across 4 geographic regions. After reaching saturation, we identified 7 core themes across 4 Theoretical Domains Framework domains for factors relevant to the decision to withdraw life-sustaining treatments. Four factors (i.e., clinical triggers, social triggers, interaction with families and intentions with medical decisions) were identified before the decision is made and 3 were identified during the decision-making process (i.e., considerations, priorities and knowledge needs). We identified multiple themes reflecting internal (n = 18, 8 Theoretical Domains Framework domains) and external (n = 15, 6 Theoretical Domains Framework domains) influences on the decision to withdraw life-sustaining treatments.Interpretation: We identified several core themes and domains considered by critical care physicians in Canada in the decision to withdraw life-sustaining treatments in critically ill patients with severe traumatic brain injury. Future research should aim at identifying the factors influencing surrogate decision-makers in the decision to withdraw life-sustaining treatments in these patients. [ABSTRACT FROM AUTHOR]

Importance: Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock-a condition due to excessive vasodilation, most frequently from severe infection. Blood pressure support with a noncatecholamine vasopressor may reduce stimulation of adrenergic receptors and decrease myocardial oxygen demand. Atrial fibrillation is common with catecholamines and is associated with adverse events, including mortality and increased length of stay (LOS).Objectives: To determine whether treatment with vasopressin + catecholamine vasopressors compared with catecholamine vasopressors alone was associated with reductions in the risk of adverse events.Data Sources: MEDLINE, EMBASE, and CENTRAL were searched from inception to February 2018. Experts were asked and meta-registries searched to identify ongoing trials.Study Selection: Pairs of reviewers identified randomized clinical trials comparing vasopressin in combination with catecholamine vasopressors to catecholamines alone for patients with distributive shock.Data Extraction and Synthesis: Two reviewers abstracted data independently. A random-effects model was used to combine data.Main Outcomes and Measures: The primary outcome was atrial fibrillation. Other outcomes included mortality, requirement for renal replacement therapy (RRT), myocardial injury, ventricular arrhythmia, stroke, and LOS in the intensive care unit and hospital. Measures of association are reported as risk ratios (RRs) for clinical outcomes and mean differences for LOS.Results: Twenty-three randomized clinical trials were identified (3088 patients; mean age, 61.1 years [14.2]; women, 45.3%). High-quality evidence supported a lower risk of atrial fibrillation associated with vasopressin treatment (RR, 0.77 [95% CI, 0.67 to 0.88]; risk difference [RD], -0.06 [95% CI, -0.13 to 0.01]). For mortality, the overall RR estimate was 0.89 (95% CI, 0.82 to 0.97; RD, -0.04 [95% CI, -0.07 to 0.00]); however, when limited to trials at low risk of bias, the RR estimate was 0.96 (95% CI, 0.84 to 1.11). The overall RR estimate for RRT was 0.74 (95% CI, 0.51 to 1.08; RD, -0.07 [95% CI, -0.12 to -0.01]). However, in an analysis limited to trials at low risk of bias, RR was 0.70 (95% CI, 0.53 to 0.92, P for interaction = .77). There were no significant differences in the pooled risks for other outcomes.Conclusions and Relevance: In this systematic review and meta-analysis, the addition of vasopressin to catecholamine vasopressors compared with catecholamines alone was associated with a lower risk of atrial fibrillation. Findings for secondary outcomes varied. [ABSTRACT FROM AUTHOR]

Purpose: Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.Methods: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration's instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.Results: Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87-1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33-6.74).Conclusions: Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients. [ABSTRACT FROM AUTHOR]

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Objectives: Vasopressors are not recommended by current trauma guidelines, but recent reports indicate that they are commonly used. We aimed to describe the early hemodynamic management of trauma patients outside densely populated urban centers. Methods: We conducted a single-center retrospective cohort study in a Canadian regional trauma center. All adult patients treated for traumatic injury in 2013 who died within 24 hours of admission or were transferred to the intensive care unit were included. A systolic blood pressure <90 mmHg, a mean arterial pressure <60 mmHg, the use of vasopressors or ≥2 L of intravenous fluids defined hemodynamic instability. Main outcome measures were use of intravenous fluids and vasopressors prior to surgical or endovascular management. Results: Of 111 eligible patients, 63 met our criteria for hemodynamic instability. Of these, 60 (95%) had sustained blunt injury and 22 (35%) had concomitant severe traumatic brain injury. The subgroup of patients referred from a primary or secondary hospital (20 of 63, 32%) had significantly longer transport times (243 vs. 61 min, p<0.01). Vasopressors, used in 26 patients (41%), were independently associated with severe traumatic brain injury (odds ratio 10.2, 95% CI 2.7–38.5). Conclusions: In this cohort, most trauma patients had suffered multiple blunt injuries. Patients were likely to receive vasopressors during the early phase of trauma care, particularly if they exhibited signs of neurologic injury. While these results may be context-specific, determining the risk-benefit trade-offs of fluid resuscitation, vasopressors and permissive hypotension in specific patients subgroups constitutes a priority for trauma research going forwards. [ABSTRACT FROM AUTHOR]

Purpose: In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock.Methods: We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60-65 mmHg) versus a higher (75-80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups.Results: A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95% CI 7-11). In the lower and higher MAP groups, we observed deviations on 12 versus 8% of all days on vasopressors (p = 0.059). Risks of cardiac arrhythmias (20 versus 36%, p = 0.07) and hospital mortality (30 versus 33%, p = 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60%, p = 0.03) but not in younger patients.Conclusions: This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy. [ABSTRACT FROM AUTHOR]

Background: Patients with 2009 pandemic influenza A(H1N1pdm09)-related critical illness were frequently treated with systemic corticosteroids. While observational studies have reported significant corticosteroid-associated mortality after adjusting for baseline differences in patients treated with corticosteroids or not, corticosteroids have remained a common treatment in subsequent influenza outbreaks, including avian influenza A(H7N9). Our objective was to describe the use of corticosteroids in these patients and investigate predictors of steroid prescription and clinical outcomes, adjusting for both baseline and time-dependent factors.Methods: In an observational cohort study of adults with H1N1pdm09-related critical illness from 51 Canadian ICUs, we investigated predictors of steroid administration and outcomes of patients who received and those who did not receive corticosteroids. We adjusted for potential baseline confounding using multivariate logistic regression and propensity score analysis and adjusted for potential time-dependent confounding using marginal structural models.Results: Among 607 patients, corticosteroids were administered to 280 patients (46.1%) at a median daily dose of 227 (interquartile range, 154-443) mg of hydrocortisone equivalents for a median of 7.0 (4.0-13.0) days. Compared with patients who did not receive corticosteroids, patients who received corticosteroids had higher hospital crude mortality (25.5% vs 16.4%, p = 0.007) and fewer ventilator-free days at 28 days (12.5 ± 10.7 vs 15.7 ± 10.1, p < 0.001). The odds ratio association between corticosteroid use and hospital mortality decreased from 1.85 (95% confidence interval 1.12-3.04, p = 0.02) with multivariate logistic regression, to 1.71 (1.05-2.78, p = 0.03) after adjustment for propensity score to receive corticosteroids, to 1.52 (0.90-2.58, p = 0.12) after case-matching on propensity score, and to 0.96 (0.28-3.28, p = 0.95) using marginal structural modeling to adjust for time-dependent between-group differences.Conclusions: Corticosteroids were commonly prescribed for H1N1pdm09-related critical illness. Adjusting for only baseline between-group differences suggested a significant increased risk of death associated with corticosteroids. However, after adjusting for time-dependent differences, we found no significant association between corticosteroids and mortality. These findings highlight the challenges and importance in adjusting for baseline and time-dependent confounders when estimating clinical effects of treatments using observational studies. [ABSTRACT FROM AUTHOR]

The article presents a study which systematically analyzed literature reviews of the treatments for sepsis that include animal studies. Data were obtained from EMBASE and MEDLINE. It was found that even though a large percentage of the reviews extrapolated the results to human patients, most of them failed to systematically analyze the clinical significance of preclinical studies and the risk of bias. A framework to improve such features is presented.

The dilemma of whether and when to start renal replacement therapy among critically ill patients with acute kidney injury in the absence of conventional indications has long been a vexing challenge for clinicians. The lack of high-quality evidence has undoubtedly contributed decisional uncertainty and unnecessary practice variation. Recently, two randomized trials (ELAIN and AKIKI) reported specifically on the issue of the timing of initiation of renal replacement therapy in critically ill patients with acute kidney injury. In this commentary, their fundamental differences in trial design, sample size, and widely discrepant findings are considered in context. While both trials are important contributions towards informing practice on this issue, additional evidence from large multicenter randomized trials is needed. [ABSTRACT FROM AUTHOR]