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Rationale: Studies suggest that reduced cerebral perfusion may contribute to delirium development in the intensive care unit (ICU). However, evidence is limited because of factors including small s... more...

Objectives The objective of the study is to externally validate three primary subarachnoid hemorrhage (pSAH) identification models. Study Design and Setting We evaluated three models that identify pSAH using recursive partitioning (A), logistic regression (B), and a prevalence-adjusted logistic regression(C), respectively. Blinded chart review and/or linkage to existing registries determined pSAH status. We included all patients aged ≥18 in four participating center registries or whose discharge abstracts contained ≥1 administrative codes of interest between January 1, 2012 and December 31, 2013. Results A total of 3,262 of 193,190 admissions underwent chart review (n = 2,493) or registry linkage (n = 769). A total of 657 had pSAH confirmed (20·1% sample, 0·34% admissions). The sensitivity, specificity, and positive predictive value (PPV) were as follows: i) model A: 98·3% (97·0–99·2), 53·5% (51·5–55·4), and 34·8% (32·6–37·0); ii) model B (score ≥6): 98·0% (96·6–98·9), 47·4% (45·5–49·4), and 32·0% (30·0–34·1); and iii) model C (score ≥2): 95·7% (93·9–97·2), 85·5% (84·0–86·8), and 62·3 (59·3–65·3), respectively. Model C scores of 0, 1, 2, 3, or 4 had probabilities of 0·5% (0·2–1·5), 1·5% (1·0–2·2), 24·8% (21·0–29·0), 90·0% (86·8–92·0), and 97·8% (88·7–99·6), without significant difference between centers (P = 0·86). The PPV of the International Classification of Diseases code (I60) was 63·0% (95% confidence interval: 60·0–66·0). Conclusions All three models were highly sensitive for pSAH. Model C could be used to adjust for misclassification bias. more...

We surveyed Canadian critical care physicians who may care for patients who are potential organ donors to understand their attitudes and knowledge of legislation governing the deceased organ donation system. We used a web-based, self-administered survey that included questions related to opt-out consent and mandatory referral legislation. Potential participants were identified through membership lists of professional societies and manual searches. We designed our survey using standardized methods and administered it in February and March 2018. Fifty percent (263/529) of potential participants completed the questionnaire. A majority (61%; 144/235) supported a change towards an opt-out consent model, and 77% (181/235) stated they believe it would increase donation rates. Asked if opt-out consent would change their practices, 71% (166/235) stated an opt-out model would not change how or if they approach families to discuss donation. Fifty-six percent (139/249) supported mandatory referral laws, while only 42% (93/219) of those working in provinces with mandatory referral correctly stated that such laws exist in their province. Respondents gave variable responses on who should be accountable when patients are not referred, and 16% (40/249) believed no one should be held accountable. While a majority of critical care physicians supported opt-out consent and mandatory referral, many were neutral or against it. Many were unaware of existing laws and had variable opinions on how to ensure accountability. Efforts to increase understanding of how legislative models influence practice are required for any law to achieve its desired effect. more...

Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices. 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. 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. 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. more...

The accuracy of the signs and tests that clinicians use to diagnose ventilator-associated pneumonia (VAP) and initiate antibiotic treatment has not been well characterized. We sought to characterize and compare the accuracy of physical examination, chest radiography, endotracheal aspirate (ETA), bronchoscopic sampling cultures (protected specimen brush [PSB] and bronchoalveolar lavage [BAL]), and CPIS > 6 to diagnose VAP. We searched six databases from inception through September 2019 and selected English-language studies investigating accuracy of any of the above tests for VAP diagnosis. Reference standard was histopathological analysis. Two reviewers independently extracted data and assessed study quality. We included 25 studies (1639 patients). The pooled sensitivity and specificity of physical examination findings for VAP were poor: fever (66.4% [95% confidence interval [CI]: 40.7–85.0], 53.9% [95% CI 34.5–72.2]) and purulent secretions (77.0% [95% CI 64.7–85.9], 39.0% [95% CI 25.8–54.0]). Any infiltrate on chest radiography had a sensitivity of 88.9% (95% CI 73.9–95.8) and specificity of 26.1% (95% CI 15.1–41.4). ETA had a sensitivity of 75.7% (95% CI 51.5–90.1) and specificity of 67.9% (95% CI 40.5–86.8). Among bronchoscopic sampling methods, PSB had a sensitivity of 61.4% [95% CI 43.7–76.5] and specificity of 76.5% [95% CI 64.2–85.6]; while BAL had a sensitivity of 71.1% [95% CI 49.9–85.9] and specificity of 79.6% [95% CI 66.2–85.9]. CPIS > 6 had a sensitivity of 73.8% (95% CI 50.6–88.5) and specificity of 66.4% (95% CI 43.9–83.3). Classic clinical indicators had poor accuracy for diagnosis of VAP. Reliance upon these indicators in isolation may result in misdiagnosis and potentially unnecessary antimicrobial use. Electronic supplementary material The online version of this article (10.1007/s00134-020-06036-z) contains supplementary material, which is available to authorized users. more...

Intensive care physicians play an important role in the identification and referral of potential organ donors in Canada. Nevertheless, little is known about intensivists’ attitudes or behaviours in situations where families override previously expressed consent to donate; nor why physicians elect not to refer patients who are potential donors to provincial organ donation organizations (physician non-referral). We integrated questions regarding family override and physician non-referral into an online, self-administered survey of Canadian intensivists. We report results descriptively. Fifty percent of targeted respondents (n = 550) participated. Fifty-five percent reported having witnessed family override situations and 44% reported having personally not referred patients who were potential donors. Fifty-six percent of respondents stated they would not pursue donation in the face of family override; 2% stated they would continue with the donation process. Fear of loss of trust in the donation system (81%) and obligation to respect the grief and desires of surrogate decision makers (71%) were frequently reported reasons to respect family override requests. Respondents who chose not to refer patients often did so based on organ dysfunction they assumed would preclude donation (59%), or a perception that the family was too distressed to consider donation (42%). No respondents reported that personally held beliefs against organ donation influenced their decision. Physicians caring for patients who are potential organ donors commonly encounter both family override and physician non-referral situations. Knowledge translation of optimal practices in identification and referral could help ensure that physician practices align with legal requirements and practice recommendations. more...

Introduction: Patients with intracranial hemorrhage (including intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic hemorrhage) are commonly admitted to the intensive care unit (ICU). Although indications for oral antiplatelet agents are increasing, the impact of preadmission use on outcomes in patients with intracranial hemorrhage admitted to the ICU is unknown. We sought to evaluate the association between preadmission oral antiplatelet use, in-hospital mortality, resource utilization, and costs among ICU patients with intracranial hemorrhage. Methods: We retrospectively analyzed a prospectively collected registry (2011-2016) and included consecutive adult patients from 2 hospitals admitted to ICU with intracranial hemorrhage. Patients were categorized on the basis of preadmission oral antiplatelet use. We excluded patients with preadmission anticoagulant use. The primary outcome was in-hospital mortality and was analyzed using a multivariable logistic regression model. Contributors to total hospital cost were analyzed using a generalized linear model with log link and gamma distribution. Results: Of 720 included patients with intracranial hemorrhage, 107 (14.9%) had been using an oral antiplatelet agent at the time of ICU admission. Oral antiplatelet use was not associated with in-hospital mortality (adjusted odds ratio: 1.31 [95% confidence interval [CI]: 0.93-2.22]). Evaluation of total costs also revealed no association with oral antiplatelet use (adjusted ratio of means [aROM]: 0.92 [95% CI: 0.82-1.02, P = .10]). Total cost among patients with intracranial hemorrhage was driven by illness severity (aROM: 1.96 [95% CI: 1.94-1.98], P < .001), increasing ICU length of stay (aROM: 1.05 [95% CI: 1.05-1.06], P < .001), and use of invasive mechanical ventilation (aROM: 1.76 [95% CI: 1.68-1.86], P < .001). Conclusions: Among ICU patients admitted with intracranial hemorrhage, preadmission oral antiplatelet use was not associated with increased in-hospital mortality or hospital costs. These findings have important prognostic implications for clinicians who care for patients with intracranial hemorrhage. more...

The use of standardized management protocols (SMPs) may improve patient outcomes for some critical care diseases. Whether SMPs improve outcomes after subarachnoid hemorrhage (SAH) is currently unknown. We aimed to study the effect of SMPs on 6-month mortality and neurologic outcomes following SAH. A systematic review of randomized control trials (RCTs) and observational studies was performed by searching multiple indexing databases from their inception through January 2019. Studies were limited to adult patients (age ≥ 18) with non-traumatic SAH reporting mortality, neurologic outcomes, delayed cerebral ischemia (DCI) and other important complications. Data on patient and SMP characteristics, outcomes and methodologic quality were extracted into a pre-piloted collection form. Methodologic quality of observational studies was assessed using the Newcastle–Ottawa scale, and RCT quality was reported as per the Cochrane risk of bias tool. A total of 11,260 studies were identified, of which 37 (34 full-length articles and 3 abstracts) met the criteria for inclusion. Two studies were RCTs and 35 were observational. SMPs were divided into four broad domains: management of acute SAH, early brain injury, DCI and general neurocritical care. The most common SMP design was control of DCI, with 22 studies assessing this domain of care. Overall, studies were of low quality; most described single-center case series with small patient sizes. Definitions of key terms and outcome reporting practices varied significantly between studies. DCI and neurologic outcomes in particular were defined inconsistently, leading to significant challenges in their interpretation. Given the substantial heterogeneity in reporting practices between studies, a meta-analysis for 6-month mortality and neurologic outcomes could not be performed, and the effect of SMPs on these measures thus remains inconclusive. Our systematic review highlights the need for large, rigorous RCTs to determine whether providing standardized, best-practice management through the use of a protocol impacts outcomes in critically ill patients with SAH. Trial registration Registration number: CRD42017069173. more...

Resuscitation after out-of-hospital cardiac arrest can be one of the most challenging scenarios in acute-care medicine. The devastating effects of postcardiac arrest syndrome carry a substantial morbidity and mortality that persist long after return of spontaneous circulation. Management of these patients requires the clinician to simultaneously address multiple emergent priorities including the resuscitation of the patient and the efficient diagnosis and management of the underlying etiology. This review provides a concise evidence-based overview of the core concepts involved in the early postcardiac arrest resuscitation. It will highlight the components of an effective management strategy including addressing hemodynamic, oxygenation, and ventilation goals as well as carefully considering cardiac catheterization and targeted temperature management. An organized approach is paramount to providing effective care to patients in this vulnerable time period. more...

Background Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are life-threatening complications of diabetes mellitus which require prompt treatment with large volume crystalloid fluid administration. A variety of crystalloid fluids is currently available for use and differs in their composition and ion concentrations. While there are potential pros and cons for different crystalloid fluids, it remains unknown if any particular fluid confers a clinical outcome benefit over others in the treatment of hyperglycemic emergencies. Methods A systematic search of MEDLINE, Embase, and the Cochrane Library of Systematic Reviews will be conducted to identify eligible studies, which will include observational and interventional studies involving adult and pediatric patients admitted to the hospital with either DKA or HHS. The interventions will include intravenous treatment with 0.9% saline versus other buffered (Ringer’s lactate, Hartmann’s, etc.), and non-buffered (0.45% saline) crystalloid fluids. The primary outcome is mortality at the latest follow-up time point. Secondary outcomes will include mortality at specific time points, length of hospital stay, development of acute kidney injury, requirement for renal replacement therapy, altered level of consciousness, and the time to normalization of several serum biochemical parameters. Where appropriate, meta-analyses will be performed for the outcomes and conducted separately for adult and pediatric patient populations. Discussion DKA and HHS are dangerous complications of diabetes mellitus and account for significant morbidity and mortality. Given the importance of crystalloid fluid administration in the management of these conditions, a systematic synthesis of the existing evidence base will identify potential evidence gaps and may help guide future clinical practice. more...

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. more...

Restrictive transfusion strategies have been advocated in critically ill patients. Nevertheless, considerable uncertainty exists regarding optimal transfusion thresholds in traumatic brain injury (TBI) patients because the injured brain is susceptible to hypoxemic damage. We aimed to identify the determinants of red blood cell (RBC) transfusion and the perceived optimal transfusion thresholds in adult patients with moderate-to-severe TBI. We conducted an electronic, self-administered survey targeting critical care specialists and neurosurgeons from Canada, Australia, and the United Kingdom caring for TBI patients. The questionnaire was initially developed by a panel of experts using a structured process (domains/items generation and reduction). The questionnaire was validated for clinical sensibility, reliability, and content. The response rate was 28.7% (218/760). When presented with the hypothetical scenario of a young adult TBI patient, a wide range of transfusion practices was observed, with 47 (95% confidence interval [CI], 41 to 54)% favouring RBC transfusion at a hemoglobin level of ≤ 70 g·L–1 in the acute phase of care, while 73 (95% CI, 67 to 79)% would use this trigger in the plateau phase of care. Multiple trauma, neuro-monitoring data, hemorrhagic shock, and planned surgery were the main factors that influenced the need for transfusion. The lack of clinical evidence and guidelines was responsible for uncertainty regarding RBC transfusion strategies in this patient population. In our survey about critically ill TBI patients, transfusion practice was found to be mainly influenced by the acuity of care, patient characteristics, and neuro-monitoring. Clinical equipoise regarding optimal transfusion strategy is believed to be mainly attributed to the lack of clear clinical evidence and guidelines. Appropriate randomized-controlled trials are required to determine the optimal transfusion strategies in TBI patients. more...

Background:Mean cerebral blood flow velocity (mean-CBFV) obtained from Transcranial Doppler (TCD) poorly predicts cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Variability descriptors of mean-CBFV obtained during extended TCD recordings may improve this prediction. We assessed the feasibility of generating reliable linear and non-linear descriptors of mean-CBFV variability using extended recordings in aSAH patients and in healthy controls. We also explored which of those metrics might have the ability to discriminate between aSAH patients and healthy controls, and among patients who would go on to develop vasospasm and those who would not.Methods:Bilateral mean-CBFV, blood pressure, and heart rate were continuously recorded for 40 minutes in aSAH patients (n = 8) within the first 5 days after ictus, in age-matched healthy controls (n = 8) and in additional young controls (n = 8). We obtained linear [standard deviation, coefficient of variations, and the very-low (0.003–0.040 Hz), low (0.040–0.150 Hz), and high-frequency (0.15–0.4 Hz) power spectra] and non-linear (Fractality, deterministic Chaos analyses) variability metrics.Results:We successfully obtained TCD recordings from patients and healthy controls and calculated the desired metrics of mean-CBFV variability. Differences were appreciable between aSAH patients and healthy controls, as well as between aSAH patients who later developed vasospasm and those who did not.Conclusions:A 40-minute TCD recording provides reliable variability metrics in aSAH patients and healthy controls. Future studies are required to determine if mean-CBFV variability metrics remain stable over time, and whether they may serve to identify patients who are at greatest risk of developing cerebral vasospasm after aSAH. more...

Background and Purpose: Pulmonary function testing is a standard part of care for patients admitted to hospital with a myasthenia gravis exacerbation. It may inform clinicians’ decisions to intubate patients. It is known that pulmonary function declines with age in healthy adults. We studied the effect of age on pulmonary function and serious respiratory events, including intubation, in patients admitted to hospital for a myasthenia gravis exacerbation. Methods: Single center, retrospective cohort of consecutive patients treated for a myasthenia gravis exacerbation. Demographics, pulmonary function tests (PFTs), and respiratory events requiring intubation or emergency respiratory therapy were recorded for each encounter. Relationship of PFTs to age was analyzed using age as a continuous and as a dichotomous (cut-value 70 years) variable. Results: Forty-nine encounters from 39 patients were included. Slow vital capacity (SVC) was negatively correlated with age ( R 0.46, P value .002). Maximum inspiratory pressure (MIP) and SVC were significantly reduced in elderly versus nonelderly patients (MIP-20.0 vs −30.0 cm H2O, P value .004; SVC 16.5 vs 23.4 mL/kg, P value .013). The incidence of respiratory events did not significantly differ between elderly and nonelderly patients (χ2 P value .08). Conclusions: In patients treated for a myasthenia gravis exacerbation, pulmonary function values are significantly reduced in elderly patients compared to nonelderly patients. Despite very low SVC and MIP values most elderly patients do not require intubation however they do require intensive monitoring for serious respiratory complications. more...

This systematic review and meta-analysis addresses the efficacy and safety of corticosteroids in critically ill patients with sepsis.We updated a comprehensive search of MEDLINE, EMBASE, CENTRAL, and LILACS, and unpublished sources for randomized controlled trials that compared any corticosteroid to placebo or no corticosteroid in critically ill children and adults with sepsis.Reviewers conducted duplicate screening of citations, data abstraction, and, using a modified Cochrane risk of bias tool, individual study risk of bias assessment.A parallel guideline committee provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. We assessed overall certainty in evidence using Grading of Recommendations Assessment, Development and Evaluation methodology and performed all analyses using random-effect models. For subgroup analyses, we performed metaregression and considered p value less than 0.05 as significant.Forty-two randomized controlled trials including 10,194 patients proved eligible. Based on low certainty, corticosteroids may achieve a small reduction or no reduction in the relative risk of dying in the short-term (28-31 d) (relative risk, 0.93; 95% CI, 0.84-1.03; 1.8% absolute risk reduction; 95% CI, 4.1% reduction to 0.8% increase), and possibly achieve a small effect on long-term mortality (60 d to 1 yr) based on moderate certainty (relative risk, 0.94; 95% CI, 0.89-1.00; 2.2% absolute risk reduction; 95% CI, 4.1% reduction to no effect). Corticosteroids probably result in small reductions in length of stay in ICU (mean difference, -0.73 d; 95% CI, -1.78 to 0.31) and hospital (mean difference, -0.73 d; 95% CI, -2.06 to 0.60) (moderate certainty). Corticosteroids result in higher rates of shock reversal at day 7 (relative risk, 1.26; 95% CI, 1.12-1.42) and lower Sequential Organ Failure Assessment scores at day 7 (mean difference, -1.39; 95% CI, -1.88 to -0.89) (high certainty). Corticosteroids likely increase the risk of hypernatremia (relative risk, 1.64; 95% CI, 1.32-2.03) and hyperglycemia (relative risk, 1.16; 95% CI, 1.08-1.24) (moderate certainty), may increase the risk of neuromuscular weakness (relative risk, 1.21; 95% CI, 1.01-1.52) (low certainty), and appear to have no other adverse effects (low or very low certainty). Subgroup analysis did not demonstrate a credible subgroup effect on any of the outcomes of interest (p0.05 for all).In critically ill patients with sepsis, corticosteroids possibly result in a small reduction in mortality while also possibly increasing the risk of neuromuscular weakness. more...

Purpose We aimed to evaluate the association between transfusion practices and clinical outcomes in patients with traumatic brain injury. Material and methods We conducted a retrospective cohort study of adult patients with moderate or severe traumatic brain injury admitted to the intensive care unit (ICU) of a level I trauma center between 2009 and 2013. The associations between hemoglobin (Hb) level, red blood cell (RBC) transfusion and clinical outcomes were estimated using robust Poisson models and proportional hazard models with time-dependent variables, adjusted for confounders. Results We included 215 patients. Sixty-six patients (30.7%) were transfused during ICU stay. The median pre-transfusion Hb among transfused patients was 81 g/L (IQR 67–100), while median nadir Hb among non-transfused patients was 110 g/L (IQR 93–123). Poor outcomes were significantly more frequent in patients who were transfused (mortality risk ratio [RR]: 2.15 [95% CI 1.37–3.38] and hazard ratio: 3.06 [95% CI 1.57–5.97]; neurological complications RR: 3.40 [95% CI 1.35–8.56]; trauma complications RR: 1.65 [95% CI 1.31–2.08]; ICU length of stay geometric mean ratio: 1.42 [95% CI 1.06–1.92]). Conclusions During ICU stay, transfused patients tended to have lower Hb levels and worse outcomes than patients who did not receive RBCs, after adjustment for confounders. more...

Objectives The aim of the study was to determine the impact of using the win ratio approach and investigate whether this approach alters the interpretations or conclusions of a randomized trial in kidney transplantation. Study Design and Setting We present an application of the win ratio approach in a kidney transplant trial that assessed the clinical effectiveness of ramipril treatment vs. placebo. The primary composite outcome included the time to death, kidney transplant failure, or doubling of serum creatinine. We compare the win ratio to a conventional hazard ratio (HR) from the original trial. A win ratio with a lower 95% confidence limit greater than 1 indicates a positive treatment effect with statistical significance. Results For the primary composite end point, ramipril treatment resulted in a win ratio of 1.21 (95% confidence interval [CI], 0.55-2.59) vs. a HR of 0.76 (95% CI, 0.38-1.51). With extended follow-up (mean 48 months), ramipril was associated with a win ratio of 1.02 (95% CI, 0.54-1.83) vs. a HR of 0.96 (95% CI, 0.55-1.65). Conclusion The win ratio approach produced results similar to the original time-to-event analysis. Using this approach would not alter the conclusion of the original trial and lessens concerns associated with composite components of unequal clinical importance. more...

OBJECTIVES Spontaneous intracranial hemorrhage, including subarachnoid hemorrhage and intracerebral hemorrhage, is associated with significant morbidity and mortality. Although many of these patients will require ICU admission, little is known regarding their outcomes and the costs incurred. We evaluated this population in order to identify outcomes and cost patterns. DESIGN Retrospective cohort analysis of a health administrative database. SETTING Two ICUs within a single hospital system. PATIENTS Eight-thousand four-hundred forty-seven patients admitted to ICU from 2011 to 2014, of whom 332 had a diagnosis of spontaneous intracranial hemorrhage. Control patients were defined as randomly selected age, sex, and comorbidity index-matched nonintracranial hemorrhage ICU patients (1:4 matching ratio). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Mean age of ICU intracranial hemorrhage patients was 60.1 years, and 120 (36.1%) died prior to discharge. Intracranial hemorrhage was associated with a mean total cost of $75,869, compared with $52,471 in control patients (p < 0.01). Mean cost per survivor of intracranial hemorrhage patients was $118,813. Subarachnoid hemorrhage was associated with significantly higher mean total costs than intracerebral hemorrhage ($92,794 vs $53,491; p < 0.01) and higher mean cost per day ($4,377 vs $3,604; p < 0.01). Patients with intracranial hemorrhage who survived to hospital discharge were significantly costlier than decedents ($100,979 vs $30,872; p < 0.01). Intracranial hemorrhage associated with oral anticoagulant use had a mean total cost of $152,373, compared with $66,548 in nonoral anticoagulant intracranial hemorrhage (p < 0.01). CONCLUSIONS Patients admitted to ICU with intracranial hemorrhage have high costs and high mortality, leading to elevated cost per survivor. Subarachnoid hemorrhage patients incur greater costs than intracerebral hemorrhage patients, and oral anticoagulant-associated intracerebral hemorrhage is particularly costly. Our findings provide novel information regarding financial impact of this common ICU population. more...

Create practice guidelines for the appropriate use of red blood cell transfusions in hepatectomy.Hepatectomy is associated with a high prevalence of transfusions. A transfusion can be life-saving, but can be associated with important adverse effects. Given the prevalence, the potential for benefit and harm, and the difficulty in conducting clinical trials, transfusion in hepatectomy is well-suited for a study of appropriateness.Using the RAND/UCLA appropriateness method, an international, multidisciplinary expert panel in hepatobiliary surgery, anesthesia, transfusion medicine, and critical care rated a series of 468 perioperative scenarios for transfusion appropriateness. Scenarios were rated individually, and again during an inperson group moderated session. Median scores and level of agreement were calculated to classify each scenario as appropriate, inappropriate, or uncertain.Approximately, 47.4% of scenarios were rated as appropriate for transfusion, 28.2% were inappropriate, and 24.4% were uncertain. The key recommendations for intraoperative transfusion were (i) it is never inappropriate to transfuse for significant bleeding or ST segment changes; (ii) it is never inappropriate to transfuse for an intraoperative hemoglobin ≤75 g/L; and (iii) in the absence of significant bleeding or ST changes, transfusion for hemoglobin of ≥95 g/L is inappropriate, and transfusion for hemoglobin of ≥85 g/L requires strong justification. The key recommendations for postoperative transfusions were: (i) in a stable, asymptomatic patient, an appropriate transfusion trigger is 70 g/L (without coronary artery disease) or 80 g/L (with coronary artery disease) and (ii) it is appropriate to transfuse any patient for a hemoglobin of ≤75 g/L either immediately post-operative, or with a significant decrease from the previous day (15 g/L).Based on best available evidence and expert opinion, criteria for appropriate perioperative red blood cell transfusions in hepatectomy were determined. more...

Background Development of intraoperative techniques and blood management strategies in liver resection, and the multidisciplinary nature of perioperative transfusion decision making, creates an opportunity for practice variation. The aim of this study was to describe the current practices in perioperative blood management and explore differences between surgeons and anesthesiologists. Study design and methods A Web-based survey was developed, piloted, and circulated to Canadian liver surgeons and anesthesiologists. The survey focused on management of preoperative anemia, blood conservation strategies, estimation of blood loss, and transfusion decision making in a multidisciplinary setting. Results A total of 198 physicians received the survey, with 117 responding (59%). Most responding surgeons (67%) perform more than 20 liver resections per year, while most responding anesthesiologists (90%) take part in fewer than 20. Anesthesiologists most commonly stated that preoperative anemia is managed by someone else (38%), while surgeons most commonly reported "no specific treatment" (45%). The most common intraoperative blood conservation technique used is administration of antifibrinolytics (63% used them at least occasionally). The most important factor for anesthesiologists when deciding on an intraoperative transfusion was hemoglobin value (47%); for surgeons, it was patient hemodynamics (33%). Compared to when they started their career, 60% of respondents felt that they were less likely to transfuse a patient now. Conclusion The results of our survey provide insights into current transfusion practice and decision making in liver resection, including a comparison between anesthesiologist and surgeon transfusion behavior. Management of preoperative anemia, increased use of intraoperative blood conservation techniques, and improved communication between providers were identified as targets for quality improvement. more...

A decreased frequency of upper gastrointestinal bleeding and a possible association of proton pump inhibitor use with Clostridium difficile and ventilator-associated pneumonia have raised concerns recently. The Reevaluating the Inhibition of Stress Erosions Pilot Trial determined the feasibility of undertaking a larger trial investigating the efficacy and safety of withholding proton pump inhibitors in critically ill patients.In 10 ICUs, we randomized adult ICU patients anticipated to be mechanically ventilated for greater than or equal to 48 hours to receive 40 mg of IV pantoprazole daily or placebo. We excluded patients who had acute or recent gastrointestinal bleed, used dual antiplatelet agents, had a medical condition requiring proton pump inhibitor treatment, or had already received more than one dose of acid suppression daily. Patients, families, clinicians, and research staff were blinded. We conducted a systematic review and meta-analysis of similar trials.Ninety-one patients (49 pantoprazole and 42 placebo) from 10 centers in Canada, Saudi Arabia, and Australia were enrolled. All feasibility goals were met: 1) recruitment rate was 2.6 patients per month; 2) consent rate was 77.8%; and 3) protocol adherence was 97.7%. Upper gastrointestinal bleeding developed in 6.1% of patients in the pantoprazole group and 4.8% in the placebo group (p = 1.0). Ventilator-associated pneumonia developed in 20.4% of patients in the pantoprazole group and 14.3% in the placebo group (p = 0.58). C. difficile was identified in 4.1% pantoprazole patients and in 2.4% placebo patients (p = 1.0). We meta-analyzed five trials (604 patients) of proton pump inhibitors versus placebo; there was no statistically significant difference in the risk of upper gastrointestinal bleeding, infections, or mortality.Our results support the feasibility of a larger trial to evaluate the safety of withholding stress ulcer prophylaxis. Although the results are imprecise, there was no alarming increase in the risk of upper gastrointestinal bleeding; the effect of proton pump inhibitors on ventilator-associated pneumonia and C. difficile remain unclear. more...

The use of sedative medications is commonplace in intensive care units (ICUs) and an invaluable clinical tool for the intensive care physician. Sedation for critically ill, mechanically ventilated patients provides an opportunity to reduce anxiety, discomfort as well as ventilator intolerance and dyssynchrony. Alpha-2 agonists in particular have become increasingly popular for use in the neurocritical care population due to their proposed effectiveness in facilitating examinations and procedures as well as reducing the need for adjunctive agents. However, there is a paucity of literature to assess the safety of their use in the neurocritically ill patients, a population that presents unique sensitivities and considerations for management of global and cerebral hemodynamics, agitation and facilitation of neurological assessments. This review assesses the safety and efficacy of alpha-2 agonists for non-procedural sedation in critically ill brain-injured patients on mechanical ventilation. In June 2016, we searched the EMBASE, MEDLINE and CENTRAL Cochrane Databases for randomized controlled trials, prospective and retrospective cohort studies examining neurocritically ill adult patients aged 18 years and older who are on mechanical ventilation and receiving alpha-2 agonists for non-procedural sedation. Primary outcomes of interest include mean arterial pressure (MAP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). Secondary outcomes include adverse events, duration of mechanical ventilation, 30-day mortality, ICU length of stay, incidence of delirium, and quality of sedation. We identified 17 studies for inclusion, all reporting on dexmedetomidine use, only 7 of which reported on our primary outcomes of interest. We found mixed results with regard to statistically significant changes in ICP, CPP, and MAP but did not find evidence of severe hemodynamic disturbances. However, the studies are notably limited by lack of reporting on sedative and hemodynamic adjuncts. Based on the limited available data, dexmedetomidine does not appear to result in severe, uncompensated hemodynamic disturbances (cerebral or systemic). The validation of an effective and safe agent with reporting of dosing strategy, sedation protocol use, co-interventions administered, and a priori defined adverse events is recommended. more...

Background Some patients admitted to acute care hospital require supportive services after discharge. The objective of our review was to identify models and variables that predict the need for supportive services after discharge from acute care hospital. Methods We performed a systematic review searching the MEDLINE, CINAHL, EMBASE, and COCHRANE databases from inception to May 1st 2017. We selected studies that derived and validated a prediction model for the need for supportive services after hospital discharge for patients admitted non-electively to a medical ward. We extracted cohort characteristics, model characteristics and variables screened and included in final predictive models. Risk of bias was assessed using the Quality in Prognostic Studies tool. Results Our search identified 3362 unique references. Full text review identified 6 models. Models had good discrimination in derivation (c-statistics > 0.75) and validation (c-statistics > 0.70) cohorts. There was high quality evidence that age, impaired physical function, disabilities in performing activities of daily living, absence of an informal care giver and frailty predict the need for supportive services after discharge. Stroke was the only unique diagnosis with at least moderate evidence of an independent effect on the outcome. No models were externally validated, and all were at moderate or higher risk of bias. Conclusions Deficits in physical function and activities of daily living, age, absence of an informal care giver and frailty have the strongest evidence as determinants of the need for support services after hospital discharge. Trial registration This review was registered with PROSPERO #CRD42016037144. more...

Background: Characterization of the mesenchymal stromal cell (MSC) safety profile is important as this novel therapy continues to be evaluated in clinical trials for various inflammatory conditions. Due to an increase in published randomized controlled trials (RCTs) from 2012–2019, we performed an updated systematic review to further characterize the MSC safety profile. Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science (to May 2018) were searched. RCTs that compared intravascular delivery of MSCs to controls in adult populations were included. Pre-specified adverse events were grouped according to: (1) immediate, (2) infection, (3) thrombotic/embolic, and (4) longer-term events (mortality, malignancy). Adverse events were pooled and meta-analyzed by fitting inverse-variance binary random effects models. Primary and secondary clinical efficacy endpoints were summarized descriptively. Findings: 7473 citations were reviewed and 55 studies met inclusion criteria (n = 2696 patients). MSCs as compared to controls were associated with an increased risk of fever (Relative Risk (RR) = 2·48, 95% Confidence Interval (CI) = 1·27–4·86; I2 = 0%), but not non-fever acute infusional toxicity, infection, thrombotic/embolic events, death, or malignancy (RR = 1·16, 0·99, 1·14, 0·78, 0·93; 95% CI = 0·70–1·91, 0·81–1·21, 0·67–1·95, 0·65–0·94, 0·60–1·45; I2 = 0%, 0%, 0%, 0%, 0%). No included trials were ended prematurely due to safety concerns. Interpretations: MSC therapy continues to exhibit a favourable safety profile. Future trials should continue to strengthen study rigor, reporting of MSC characterization, and adverse events. Funding: Stem Cell Network, Ontario Institute for Regenerative Medicine and Ontario Research Fund Keywords: Mesenchymal stem cells, Safety, Adverse events, Systematic review more...

Background In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. Methods We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes. Results Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30–676.00 pg/mL] vs 42 pg/mL [IQR 30.46–87.34 pg/mL] in controls; P P P = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels (P P P = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors (P P = 0.003). In the placebo group, a baseline ANG I/II ratio P = 0.01) on unadjusted analyses. Conclusions Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction. Trial registration ClinicalTrials.gov identifier NCT02338843. Registered 14 January 2015. more...

IntroductionIn Canada, deceased organ donation provides over 80% of transplanted organs. At the time of death, families, friends or others assume responsibility as substitute decision-makers (SDMs) to consent to organ donation. Despite their central role in this process, little is known about what barriers, enablers and beliefs influence decision-making among SDMs. This study aims to explore the experiences and perspectives of SDMs involved in making decisions around the withdrawal of life-sustaining therapies, end-of-life care and deceased organ donation.Methods and analysisSDMs of 60 patients admitted to intensive care units will be enrolled for this study. Ten hospitals across five provinces in Canada in a prospective multicentre qualitative cohort study. We will conduct semistructured telephone interviews in English or French with SDMs between 6 and 8 weeks after the patient’s death. Our sampling frame will stratify SDMs into three groups: SDMs who were not approached for organ donation; SDMs who were approached and consented to donate and SDMs who were approached but did not consent to donate. We will use two complementary theoretical frameworks—the Common-Sense Self-Regulation Model and the Theoretical Domains Framework— to inform our interview guide. Interview data will be analysed using deductive directed content analysis and inductive thematic analysis.Ethics and disseminationThis study has been approved by the Centre Hospitalier de l’Université de Montréal Research Ethics Board. The findings from this study will help identify key factors affecting substitute decision-making in deceased organ donation, reasons for non-consent and barriers to achieve congruency between SDM and patient wishes. Ultimately, these data will contribute to the development and evaluation of tools and training for healthcare providers to support SDMs in making decisions about organ donation.Trial registration numberNCT03850847. more...

Collection and analysis of health data are crucial to achieving high-quality clinical care, research, and quality improvement. This review explores existing hospital, regional, provincial and national data platforms in Canada to identify gaps and barriers, and recommend improvements for data science. The Canadian Critical Care Trials Group and the Canadian Critical Care Translational Biology Group undertook an environmental survey using list-identified names and keywords in PubMed and the grey literature, from the Canadian context. Findings were grouped into sections, corresponding to geography, purpose, and patient sub-group initiatives, using a narrative qualitative approach. Emerging themes, impressions, and recommendations towards improving data initiatives were generated. In Canada, the Canadian Institute for Health Information Discharge Abstract Database contains high-level clinical data on every adult and child discharged from acute care facilities; however, it does not contain data from Quebec, critical care-specific severity of illness risk-adjustment scores, physiologic data, or data pertaining to medication use. Provincially mandated critical care platforms in four provinces contain more granular data, and can be used to risk adjust and link to within-province data sets; however, no inter-provincial collaborative mechanism exists. There is very limited infrastructure to collect and link biological samples from critically ill patients nationally. Comprehensive international clinical data sets may inform future Canadian initiatives. Clinical and biological data collection among critically ill patients in Canada is not sufficiently coordinated, and lags behind other jurisdictions. An integrated and inclusive critical care data platform is a key clinical and scientific priority in Canada. more...

Objective: To create an accurate prediction model using variables collected in widely available health administrative data records to identify hospitalizations for primary subarachnoid hemorrhage (SAH). Methods: A previously established complete cohort of consecutive primary SAH patients was combined with a random sample of control hospitalizations. Chi-square recursive partitioning was used to derive and internally validate a model to predict the probability that a patient had primary SAH (due to aneurysm or arteriovenous malformation) using health administrative data. Results: A total of 10,322 hospitalizations with 631 having primary SAH (6.1%) were included in the study (5,122 derivation, 5,200 validation). In the validation patients, our recursive partitioning algorithm had a sensitivity of 96.5% (95% confidence interval [CI] 93.9–98.0), a specificity of 99.8% (95% CI 99.6–99.9), and a positive likelihood ratio of 483 (95% CI 254–879). In this population, patients meeting criteria for the algorithm had a probability of 45% of truly having primary SAH. Conclusions: Routinely collected health administrative data can be used to accurately identify hospitalized patients with a high probability of having a primary SAH. This algorithm may allow, upon validation, an easy and accurate method to create validated cohorts of primary SAH from either ruptured aneurysm or arteriovenous malformation. more...

To compare the in-hospital mortality and institutional morbidity from medical therapy (MT), external ventricular drainage (EVD) and suboccipital decompressive craniectomy (SDC) following an acute hemorrhagic posterior cranial fossa stroke (PCFH) in patients admitted to the neurosciences critical care unit (NCCU). Retrospective observational single-center cohort study in a tertiary care center. All consecutive patients (n = 104) admitted with PCFH from January 1st 2005–December 31st 2011 were included in the study. All patients with a PCFH were identified and confirmed by reviewing computed tomography of the brain reported by a specialist neuroradiologist. Management decisions (MT, EVD, and SDC) were identified from operative notes and electronic patient records. Following a PCFH, 47.8 % (n = 11) patients died after EVD placement without decompression, 45.7 % (n = 16) died following MT alone, and 17.4 % (n = 8) died following SDC. SDC was associated with lower mortality compared to MT with or without EVD (χ 2 test p = 0.006, p = 0.008). Age, ICNARC score, brain stem involvement, and hematoma volume did not differ significantly between the groups. There was a statistically significant increase in hydrocephalus and intraventricular bleeds in patients treated with EVD placement and SDC (χ 2 test p = 0.02). Median admission Glasgow Coma Scale scores for the MT only, MT with EVD, and SDC groups were 8, 6, and 7, respectively (ranges 3–15, 3–11 and 3–13) and did not differ significantly (Friedman test: p = 0.89). SDC resulted in a longer NCCU stay (mean of 17.4 days, standard deviation = 15.4, p more...

Introduction With over 1 million units of blood transfused each year in Canada, their use has a significant clinical and economic impact on our health system. Adequate screening of blood donors is important to ensure the safety and clinical benefit of blood products. Some adverse transfusion reactions have been shown to be related to donor factors (eg, lung injury), whereas other adverse outcomes have been theoretically related to donor factors (mortality and infection). Our clinical trial will test whether male donor blood leads to a greater benefit for transfusion recipients compared with female donor blood. Methods and analysis We have designed a pragmatic, double-blind, randomised trial that will allocate transfusion recipients to receive either male-only or female-only donor transfusions. We will enrol 8850 adult patients requiring at least one transfusion at four sites over an approximate 2-year period. Randomisation and allocation will occur in the blood bank prior to release of the units of blood for transfusion. Our primary outcome is mortality. An intent-to-treat analysis will be applied using all randomised and transfused patients. The principal analysis will be a survival analysis comparing the time from randomisation to death between patients allocated to male donor red blood cells (RBCs) and female donor RBCs. Ethics and dissemination Approval has been obtained from research ethics boards of all involved institutions, as well as from privacy offices of Canadian Blood Services, Institute for Clinical Evaluative Science and The Ottawa Hospital Data Warehouse. Our findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. Trial registration number NCT03344887; Pre-results. more...

Kidney transplantation is the optimal treatment for patients with end-stage renal disease; however, long-term outcomes remain suboptimal.The objectives of our study were to examine the variation in survival rates and determine whether center volume and case mix are associated with transplant outcomes and explain the variation across kidney transplant centers in Ontario, Canada.This was a population-based cohort study using health care administrative databases.A total of 5 transplant centers across Ontario, Canada.We included adults (≥18 years) undergoing primary, solitary kidney transplantation between January 1, 2000 to December 31, 2013.The co-primary outcomes were death-censored graft loss and total mortality.Multivariable Cox proportional hazards regression was used to assess potential associations and describe variation, using hazard ratios (HRs) with 95% confidence intervals (CIs) for each center relative to the average across all centers.The study cohort included 5037 patients followed for a median of 5.3 years, interquartile range (2.7-8.6). In multivariable models, recipient age, body mass index, Charlson Index, time on dialysis, donor type, and age were found to be significantly associated with death-censored graft loss, and recipient age and sex, Charlson Index, time on dialysis, donor age, and time era of transplant were associated with total mortality. There was statistically significant variation across centers observed for death-censored graft loss (This study was limited by the small number of centers included.Outcomes differ across the 5 transplant centers in Ontario. We did not find any strong support for our hypotheses that case mix or center volume is responsible for these differences.La transplantation rénale est le meilleur traitement pour l’insuffisance rénale terminale, mais les résultats à long terme demeurent sous-optimaux.Notre étude visait à examiner la variation des taux de survie et à déterminer si la casuistique et le volume du center étaient associés au résultat de la greffe et s’ils permettent d’expliquer les variations observées entre les différents centers de transplantation rénale en Ontario (Canada).Une étude de cohorte réalisée à partir des bases de données administratives du système de santé.Cinq centers de transplantation de l’Ontario (Canada).Les adultes ayant subi une première transplantation d’un rein uniquement entre le 1er janvier 2000 et le 31 décembre 2013.Les issues primaires étaient la perte du greffon après censure des décès et la mortalité totale.Un modèle multivarié de régression à risques proportionnels de Cox a été utilisé pour évaluer les associations potentielles et décrire les variations, en utilisant des rapports de risque (RR) avec intervalles de confiance de 95% pour chaque center par rapport à la moyenne de l’ensemble des centers.La cohorte à l’étude comptait 5 037 patients suivis pour une médiane de 5,3 ans (intervalle interquartile: 2,7 à 8,6 ans). Dans les modèles multivariés, l’âge du receveur, son IMC, l’indice de Charlson, le temps passé en dialyze, le type de donneur et l’âge de ce dernier ont été associés de façon significative à une perte du greffon censurée par le décès, tandis que l’âge et le sexe du receveur, l’indice de Charlson, le temps passé en dialyze, l’âge du donneur et le moment de la greffe ont été associés à la mortalité totale. Une différence significative sur le plan statistique a été observée entre les centers pour la perte du greffon après censure des décès (RR variant entre 0,72 et 1,22 ;Cette étude était limitée par le faible nombre de centers inclus.Les résultats différaient dans les cinq centers de transplantation ontariens inclus à l’étude. L’hypothèse avancée, soit que ces différences s’expliqueraient par le volume du center ou la casuistique, n’a pu être prouvée dans cette étude. more...

Supplemental digital content is available in the text., Background Nephrology trials assessing the impact of interventions on “standard” outcomes, such as doubling of creatinine, end-stage renal disease (ESRD), and/or death, are difficult to conduct given the time required for endpoints to accrue. The objective of this study was to determine if using lesser declines in kidney function would alter the interpretation of a previous randomized controlled trial. Methods This study was a secondary analysis of a kidney transplant trial comparing the use of a 40% or greater, 30% or greater, or 20% or greater decline in estimated glomerular filtration rate (eGFR) as a substitute for doubling of serum creatinine. Declines in eGFR were determined relative to baseline. This trial enrolled 212 kidney transplant patients with proteinuria and assessed the clinical impact of ramipril versus placebo on a primary outcome of doubling of serum creatinine, ESRD, or death. In this analysis, the declines in eGFR replaced doubling of creatinine in the composite endpoint. Results Mean trial follow-up was 41 months. A time-to-event composite of death, ESRD, or a 40% or greater, 30% or greater, or 20% or greater eGFR decline occurred in 45 (26 placebo vs 19 ramipril), 68 (35 vs 33), and 99 (50 vs 49) patients, respectively. Substituting these eGFR declines for doubling of serum creatinine resulted in an increase of 12, 35, and 66 endpoints compared with the original trial. In all 3 eGFR declines, ramipril treatment was not associated with any statistically significant differences despite the increase in events. Conclusions Substituting doubling of serum creatinine for lesser eGFR percentage decline thresholds did not alter trial interpretation but did increase the number of events. more...

Background: Conducting prospective epidemiological studies of hospitalized patients with rare diseases like primary subarachnoid hemorrhage (pSAH) are difficult due to time and budgetary constraints. Routinely collected administrative data could remove these barriers. We derived and validated 3 algorithms to identify hospitalized patients with a high probability of pSAH using administrative data. We aim to externally validate their performance in four hospitals across Canada. Methods: Eligible patients include those ≥18 years of age admitted to these centres from January 1, 2012 to December 31, 2013. We will include patients whose discharge abstracts contain predictive variables identified in the models (ICD-10-CA diagnostic codes I60** (subarachnoid hemorrhage), I61** (intracranial hemorrhage), 162** (other nontrauma intracranial hemorrhage), I67** (other cerebrovascular disease), S06** (intracranial injury), G97 (other postprocedural nervous system disorder) and CCI procedural codes 1JW51 (occlusion of intracranial vessels), 1JE51 (carotid artery inclusion), 3JW10 (intracranial vessel imaging), 3FY20 (CT scan (soft tissue of neck)), and 3OT20 (CT scan (abdominal cavity)). The algorithms will be applied to each patient and the diagnosis confirmed via chart review. We will assess each model’s sensitivity, specificity, negative and positive predictive value across the sites. Discussion: Validating the Ottawa SAH Prediction Algorithms will provide a way to accurately identify large SAH cohorts, thereby furthering research and altering care. more...

Introduction0.9% saline and Ringer’s lactate are the two most common resuscitation crystalloid fluids. 0.9% saline may lead to hyperchloraemic metabolic acidosis and may be associated with impaired kidney function and death. Few large multicentre randomised trials have been conducted to evaluate the effect of these two fluids on clinically important outcomes.MethodsFLUID is a pragmatic pilot cluster randomised crossover trial in which four hospitals will be randomised to normal saline or Ringer’s lactate for 14 weeks, then crossover to the alternative fluid for the subsequent 14 weeks after 1 to 3 week transition. With waiver of informed consent, all adult and paediatric patients admitted to participating sites will be included in the FLUID trial except for neonates. Primary feasibility outcome is study fluid protocol adherence (target:≥80%). Secondary feasibility outcomes include time to research ethics board (REB) approval and readiness to trial initiation (≤3 months from REB submission and approval). Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes for the future large FLUID trial will be described. Protocol adherence will be collected by site at specified time points. All clinical data will be obtained at patient level through provincial health administrative data held at the Institute for Clinical Evaluative Sciences (ICES). Event rates for the primary and secondary outcomes will be described using frequencies and proportions with 95% CIs. Intracluster and interperiod correlation coefficients will be calculated from population-level data available at ICES.Ethics and disseminationThe study protocol has been approved by the Ottawa Health Science Research Ethics Board. The FLUID pilot will determine feasibility, and ICES data across all potential sites in Ontario will allow calculation of sample size parameter estimates to inform the design and implementation of the large trial.Trial registration numberNCT02721485; Pre-results. more...

Background Current guidelines identify the choice of fluid resuscitation as important in minimizing the incidence of secondary brain injury from cerebral edema. It is widely accepted that isotonic crystalloid resuscitation fluids, specifically normal saline (NS), are optimal for resuscitation and that other relatively hypotonic fluids, such as Ringer’s lactate (RL), should be avoided in this patient population. The aim of this review is to systematically compare the use of relatively hypotonic versus isotonic crystalloid resuscitation fluids in clinical and pre-clinical models of acute brain injury and their effect on outcomes. In recognition of the potential need for a network meta-analysis (NMA), we have also included all other relevant crystalloid resuscitation fluids as interventions of relevance to potentially inform indirect comparisons. Methods Systematic searches of MEDLINE, Embase, and Web of Science BIOSIS Previews® will be used to identify eligible clinical and pre-clinical studies, which included studies examining acute brain injury (human and in vivo animal brain injury models) within the first 7 days of therapy. The intervention of interest is the intravenous use of relatively hypotonic crystalloid resuscitation fluids (e.g., Ringer’s lactate, Hartmann’s or Plasma Lyte® fluids). The main comparator of interest is an isotonic crystalloid resuscitation fluid, specifically normal saline (0.9%). Other crystalloid resuscitation fluids (e.g., hypertonic saline (3–23.4%)) will also be included as an additional intervention of interest. The primary outcome measures of interest are intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Secondary outcomes include the effect of resuscitation on cerebral edema, brain and serum osmolarity, and electrolyte concentrations and clinical outcomes including modified Rankin Scale (mRS), (extended) Glasgow Outcome Scale (GOS/eGOS), and mortality. Separate meta-analyses will be conducted to quantify the effects of the different fluid resuscitation on acute brain injury outcomes in clinical and pre-clinical populations. Network meta-analyses to compare interventions will also be performed to compare the effects of different interventions. Discussion This systematic review will comprehensively summarize the difference in treatment efficacy of various crystalloid resuscitation fluids in acute brain injury. This review is essential to underscore the evidence, or lack thereof, present in the literature to date to support current preference-driven practice and to direct future study. Systematic review registration PROSPERO #CRD42016042960 Electronic supplementary material The online version of this article (10.1186/s13643-018-0790-x) contains supplementary material, which is available to authorized users. more...

Background: Whether a restrictive strategy for red blood cell (RBC) transfusion is applied to patients with aneurysmal subarachnoid hemorrhage (aSAH) is unclear. To inform the design and conduct of a future clinical trial, we sought to describe transfusion practices, hemoglobin (Hb) triggers, and predictors of RBC transfusion in patients with aSAH. Methods: This is a retrospective cohort study of all consecutively admitted adult patients with aSAH at four tertiary care centers from January 1, 2012, to December 31, 2013. Patients were identified from hospital administrative discharge records and existing local aSAH databases. Data collection by trained abstractors included demographic data, aSAH characteristics, Hb and transfusion data, other major aSAH cointerventions, and outcomes using a pretested case report form with standardized procedures. Descriptive statistics were used to summarize data, and regression models were used to identify associations between anemia, transfusion, and other relevant predictors and outcome. Results: A total of 527 patients met inclusion eligibility. Mean (±SD) age was 57 ± 13 years, and 357 patients (67.7%) were female. The median modified Fisher grade was 4 (IQR 3–4). Mean nadir Hb was 98 ± 20 g/L and occurred on median admission day 4 (IQR 2–11). RBC transfusion occurred in 100 patients (19.0%). Transfusion rates varied across centers (12.1–27.4%, p = 0.02). Patients received a median of 1 RBC unit (IQR 1–2) per transfusion episode and a median total of 2 units (IQR 1–4). Median pretransfusion Hb for first transfusion was 79 g/L (IQR 74–93) and did not vary substantially across centers (78–82 g/L, p = 0.37). Of patients with nadir Hb more...

Significant variation in both patient case mix and the structure of care in kidney transplantation has been previously described in the United States.The objective of our study was to characterize patient case mix, patterns of care, and inpatient outcomes across 5 kidney transplant centers in the province of Ontario, Canada.This was a retrospective population-based cohort study using health care administrative databases.The setting is Ontario, Canada.We included adult (≥18 years) transplant recipients who received a primary, solitary kidney between January 1, 2000, and December 31, 2013 (N = 5037).Using linked administrative health care databases, we characterized kidney transplant recipient and donor factors, center characteristics, provider characteristics, and inpatient outcomes across transplant centers in Ontario. To compare case mix-adjusted differences in length of stay across centers, multivariable Cox proportional hazards regression was used to obtain hazard ratios (HRs) for each center relative to the average across all centers. Center volume and provider characteristics were added to the models to examine whether these factors explain differences in length of stay across centers.We noted significant differences across transplant centers in patient race, cause of end-stage renal disease, body mass index, comorbidities, time on dialysis, and donor type. Mean annual transplant center volumes during the study period ranged between 51.5 (9.3) and 101.7 (23.9) transplants/year across centers (Data were missing (0.8%-18.4%) for certain covariates of interest.This study found significant heterogeneity across kidney transplant centers in case mix, practice patterns, and inpatient outcomes. Future studies are needed to examine the influence of length of stay and practice patterns on long-term outcomes such as patient/graft survival and quality of life.Des différences marquées dans la classification diagnostique des patients et la structure des soins offerts en transplantation rénale ont déjà été observées et décrites aux États-Unis.L’étude visait à dresser un portrait de la patientèle et des modèles de soins offerts aux patients de cinq centres de greffe rénale de la province de l’Ontario, au Canada. On s’est également intéressé à l’évolution de l’état de santé des patients hospitalisés dans ces centres au cours de la période couverte par l’étude.Il s’agissait d’une étude de cohorte rétrospective, basée sur la population, et pour laquelle on a eu recours aux bases de données administratives du système de santé. L’étude s’est tenue dans la province de l’Ontario, au Canada.Ont été inclus dans l’étude 5 037 adultes ayant reçu une première greffe d’un seul rein entre le 1er janvier 2000 et le 31 décembre 2013.Nous avons utilisé plusieurs bases de données administratives couplées pour définir les paramètres des donneurs et des receveurs, pour dégager les caractéristiques de chacun des centres de greffe et des fournisseurs de soins, de même que pour suivre les résultats et l’état de santé des patients hospitalisés. Afin de comparer les différences observées dans la durée de séjour à travers les établissements, ajustées en fonction de la répartition des cas, nous avons calculé les risques proportionnels avec le modèle de régression de Cox multivarié, soit les rapports de risque pour chacun des centres de greffe rénale par rapport à la moyenne établie pour l’ensemble des établissements. Le volume de patients traités dans chacun des établissements et les caractéristiques propres à chaque fournisseur de soins ont été intégrés aux modèles d’analyse afin d’établir si ces facteurs avaient une incidence sur les différences observées entre les durées de séjour expérimentées dans les cinq centres.Nous avons observé des différences considérables entre les cinq centres de greffe rénale analysés en regard de l’origine ethnique, des causes qui ont mené à l’insuffisance rénale terminale, de l’indice de masse corporelle et des comorbidités des patients, ainsi que du temps passé en dialyse et du type de donneur. Au cours de l’étude, le volume moyen annuel de patients traités a varié entre 51,5 (9,3) et 101,7 (23,9) transplantations par année (p0,000 1) dans les établissements étudiés. La composition de l’équipe de médecins spécialistes variait de beaucoup d’un établissement à un autre, mais la combinaison la plus fréquente consistait en un néphrologue et un urologue. Moins de 31 patients sont décédés à l’hôpital durant leur admission pour une première transplantation, et le risque de mortalité était homogène pour les cinq centres. Dans l’ensemble, 25,1 % des receveurs ont dû subir un traitement de dialyse à l’hôpital à la suite de la transplantation (entre 18,3 et 33,5 % selon le centre; p0,000 1) et 24,7 % ont dû séjourner à l’unité des soins intensifs (entre 5,7 et 58,0 % selon le centre; p0,000 1). La proportion des patients ayant dû recourir à la dialyse n’a pas varié au fil du temps (p=0,12) alors que la proportion de patients admis aux soins intensifs a augmenté constamment (p0,000 1). La durée médiane du séjour à l’hôpital post-transplantation a varié entre 7 et 9 jours dans les centres de greffe étudiés (p0,000 1) et a largement diminué au fil du temps. Après correction pour tenir compte du mélange de cas des patients et des caractéristiques de l’établissement et des fournisseurs de soins, les rapports de risque pour la durée du séjour, censurés au moment du décès, variaient entre 0,75 (IC à 95 % : 0,69 et 0,82) et 1,29 (IC à 95 % : 1,20 et 1,38) selon les centres. Ni le volume de patients traités ni l’expérience des fournisseurs de soins n’ont été associés de manière indépendante à la durée de l’hospitalisation.Les données étaient manquantes (entre 0,8 et 18.4 %) pour certaines covariables d’intérêt.Cette étude nous a permis d’observer une hétérogénéité importante au sein des cinq centres de greffe rénale analysés en ce qui concerne la composition de la patientèle, les schémas de pratique et les résultats pour les patients hospitalisés. Des études supplémentaires sont requises pour mesurer l’impact de la durée du séjour à l’hôpital et des schémas de pratique sur les résultats à long terme pour le patient, notamment sur la survie du greffon et du patient, de même que sur la qualité de vie du receveur. more...

ObjectiveTo systematically describe literature that identified patient/family/caregiver priorities for subarachnoid hemorrhage (SAH)–specific patient-reported outcome measures (PROMs), developed novel SAH PROMs by incorporating patient/family/caregiver perspectives, or involved patient/family/caregiver perspectives in evaluating existing SAH PROMs.MethodsWe conducted a scoping review using Embase and Ovid MEDLINE from inception to February 6, 2018. Study eligibility and data extraction was performed independently and in duplicate. For each eligible citation, we abstracted information about study population, design, type of patient involvement, and outcome measures. We planned a descriptive summary of all included studies.ResultsOur search yielded 4,961 citations, of which 15 met our eligibility criteria. Four of these included duplicate data, so our final sample consisted of 12 articles. There were 879 patients with SAH and 241 carers from the 11/12 articles that reported these data. One additional study involved 70 individuals but did not specify the number of carers or patients. We did not find any studies where SAH survivors or their families were directly involved in the full continuum of PROM outcome conceptualization from development to evaluation. We found 41 measures identified by patients with SAH. We identified only 2 PROMs developed with patients and only one that was a post hoc evaluation by patients. These 3 PROMs are subarachnoid hemorrhage outcome tool, Wessex Patient Carer Questionnaire, and Functional Status Examination, respectively.ConclusionWe identified 3 PROMs that have involved patients in some way, but the extent to which they reflect patient priorities remains unclear. More work is needed to ensure SAH research is not overlooking outcomes that are important to patients. more...

Stress ulcer prophylaxis (SUP) using histamine-2-receptor antagonists has been a standard of care in intensive care units (ICUs) for four decades. Proton pump inhibitors (PPIs) are increasingly used despite apparently lower background rates of gastrointestinal bleeding and growing concerns about PPI-associated complications. Our objective was to understand the views and prescribing habits amongst Canadian physicians regarding SUP in the ICU and to gauge interest in a future randomized-controlled trial (RCT). We created a short self-administered survey about SUP for critically ill adults, evaluated its clinical sensibility, and pilot tested the instrument. We surveyed all physician members of the Canadian Critical Care Trials Group (CCCTG) by e-mail and sent reminders three and five weeks later. We received 94 of 111 (85%) surveys from the validated respondent pool between May and June, 2015. Respondents reported use of SUP most commonly in patients 1) receiving invasive mechanical ventilation (62, 66%), 2) expected to be ventilated for ≥ two days (25, 27%), or 3) receiving mechanical ventilation but nil per os (NPO) (20, 21%). Stress ulcer prophylaxis is discontinued when patients no longer receive mechanical ventilation (75%), no longer are NPO (22%), or are discharged from the ICU (19%). Stress ulcer prophylaxis involves PPIs in 68% of centres. Most respondents endorsed the need for a large rigorous RCT of PPI vs placebo to understand the risks and benefits of this practice. Stress ulcer prophylaxis is reportedly used primarily for the duration of mechanical ventilation. The CCCTG physicians believe that a placebo-controlled RCT is needed to evaluate the effectiveness and safety of contemporary SUP with PPIs. more...

Objective We derived and validated a method to screen all hospital admissions for 1° subarachnoid hemorrhage (SAH) by retrospectively implementing recognized diagnostic criteria. Study Design and Setting A screen for 1° SAH was developed using two previously created registries. Screen-positive cases underwent diagnosis confirmation with primary record review. A review of all patient hospital encounters with the diagnostic code for 1° SAH, and cross-referencing with an existing SAH registry was undertaken to identify missed cases. Results Three subscreens were combined to form the 1° SAH screen (sensitivity: 98.4% [95% CI: 91.7–99.7%], specificity: 93.4% [95% CI: 90.4–95.4%], n = 455 patients in validation sample). From 1,699 screen-positive admissions between July 1, 2002 and June 30, 2011, we identified 831 true cases of SAH of which 632 patients had 1° SAH from ruptured aneurysm/arteriovenous malformation (sensitivity: 96.5% [95% CI: 94.8–97.8%], specificity: 40.3% [95% CI: 38.1–42.6%]). A review of all encounters with a diagnostic code for 1° SAH yielded additional 22 true cases. Conclusion When positive, our 1° SAH screen significantly increases the probability of this diagnosis in a particular hospitalization. The addition of patient hospitalizations encoded with the diagnostic code for 1° SAH improved sensitivity. Together, these methods represent the best way to retrospectively identify all cases of 1° SAH within an extensive sampling frame. more...

The purpose of this review is to highlight the role of hemoglobin in cerebral physiology and pathophysiology. We review the existing as well as recent evidence detailing the effects of red blood cell transfusion on cerebral oxygenation and clinical outcome.Hemoglobin is a key component in oxygen delivery, and thus cerebral oxygenation. Higher hemoglobin levels and red blood cell transfusion are associated with higher cerebral oxygen delivery and decreased cerebral ischemic burden. Recent studies suggest that this may be associated with improved clinical outcomes. However, these results are limited to only a few, small studies and the results have not been consistent. Further studies are required.Hemoglobin is important for cerebral oxygenation and strategies to minimize anemia should be undertaken. Although higher hemoglobin levels are associated with less cerebral ischemia and better clinical outcome, whether this remains true whenever red blood cell transfusion is used to achieve this result remains unclear. more...

OBJECTIVEThe aim of this study was to derive a clinically applicable decision rule using clinical, radiological, and laboratory data to predict the development of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients.METHODSPatients presenting over a consecutive 9-year period with subarachnoid hemorrhage (SAH) and at least 1 angiographically evident aneurysm were included. Variables significantly associated with DCI in univariate analysis underwent multivariable logistic regression. Using the beta coefficients, points were assigned to each predictor to establish a scoring system with estimated risks. DCI was defined as neurological deterioration attributable to arterial narrowing detected by transcranial Doppler ultrasonography, CT angiography, MR angiography, or catheter angiography, after exclusion of competing diagnoses.RESULTSOf 463 patients, 58% experienced angiographic vasospasm with an overall DCI incidence of 21%. Age, modified Fisher grade, and ruptured aneurysm location were significantly associated with DCI. This combination of predictors had a greater area under the receiver operating characteristic curve than the modified Fisher grade alone (0.73 [95% CI 0.67–0.78] vs 0.66 [95% CI 0.60–0.71]). Patients 70 years or older with modified Fisher grade 0 or 1 SAH and a posterior circulation aneurysm had the lowest risk of DCI at 1.2% (0 points). The highest estimated risk was 38% (17 points) in patients 40–59 years old with modified Fisher grade 4 SAH following rupture of an anterior circulation aneurysm.CONCLUSIONSAmong patients presenting with aSAH, this score-based clinical prediction tool exhibits increased accuracy over the modified Fisher grade alone and may serve as a useful tool to individualize DCI risk. more...

Background Caring for patients with subarachnoid hemorrhage (SAH) presents unique challenges, due in part to the severity of the underlying insult, competing systemic injuries, and unpredictable clinical course. Even when management occurs in dedicated critical care settings, treatment uncertainty often persists, and morbidity and mortality from the condition remain high. Complex decisions in SAH care may be simplified with the use of standardized management protocols (SMPs). SMPs incorporate evidence-based guidelines into a practical framework for decision-making, thereby providing clinicians with an algorithm for organizing treatments. But despite these potential advantages, it is currently unknown whether SMPs may improve outcomes in the critical care of patients with SAH. Methods We will conduct a systematic review of cohort studies and randomized control trials of adult patients with non-traumatic SAH who received care according to a standardized management protocol. Comprehensive search strategies will be developed for MEDLINE, EMBASE, WoS, CINAHL, and CENTRAL, to identify studies for review. The gray literature will be scanned for further eligible studies. Two reviewers will independently screen the material generated by the search to identify studies for inclusion. A standardized data extraction form will be used to collect information on study design, baseline characteristics, details of the management protocol employed, and primary and secondary outcomes. Where possible, meta-analyses with random-effects models will be used to calculate pooled estimates of effect sizes. Statistical heterogeneity will be evaluated with the I2 statistics, and risk of bias and reporting quality will be assessed independently and in duplicate with standardized scales. Discussion We anticipate a significant degree of clinical heterogeneity in our review, as protocols will likely vary in their content, implementation, and ICU setting. We will aim to summarize the current literature in this domain to understand if SMPs, as a low-cost process-targeted intervention, improve outcomes for critically ill patients with SAH. Our review will additionally inform future research endeavors to improve the processes of care for this patient population. Systematic review registration CRD42017069173 Electronic supplementary material The online version of this article (10.1186/s13643-018-0716-7) contains supplementary material, which is available to authorized users. more...

Introduction Sepsis is associated with a dysregulated host response to infection and impaired endogenous corticosteroid metabolism. As such, therapeutic use of exogenous corticosteroids is a promising adjunctive intervention. Despite a large number of trials examining this research question, uncertainty persists regarding the effect of corticosteroids on survival in sepsis. Several large randomised controlled trials have been published recently prompting a re-evaluation of the available literature. Methods and analysis A rigorous and reproducible search and screening process from a Cochrane review on the same topic was comprehensive to October 2014. We will search MEDLINE, EMBASE, LILACS, the Cochrane trial registry and clinicaltrials.gov for eligible randomised controlled trials investigating the use of corticosteroids in patients with sepsis from September 2014. Outcomes have been chosen by a semi-independent guideline panel, created in the context of a parallel BMJ Rapid Recommendation on the topic. This panel includes clinicians, content experts, methodologists and patient representatives, who will help identify patient-important outcomes that are critical for deciding whether to use or not use corticosteroids in sepsis. Two reviewers will independently screen and identify eligible studies; a third reviewer will resolve any disagreements. We will use RevMan to pool effect estimates from included studies for each outcome using a random-effect model. We will present the results as relative risk with 95% CI for dichotomous outcomes and as mean difference or standardised mean difference for continuous outcomes with 95% CI. We will assess the certainty of evidence at the outcome level using the Grading of Recommendations, Assessment, Development and Evaluation approach. We will conduct a priori subgroup analyses, which have been chosen by the parallel BMJ Rapid Recommendation panel. Ethics and dissemination The aim of this systematic review is to summarise the updated evidence on the efficacy and safety of corticosteroids in patients with sepsis. Trial registration number CRD42017058537. more...

BACKGROUND Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 mu g of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P more...

IntroductionSurvivors of critical illness frequently exhibit acute and chronic neurological complications. The underlying aetiology of this dysfunction remains unknown but may be associated with cerebral ischaemia. This study will use near-infrared spectroscopy to non-invasively quantify regional cerebral oxygenation (rSO2) to assess the association between poor rSO2during the first 72 hours of critical illness with delirium severity, as well as long-term sensorimotor and cognitive impairment among intensive care unit (ICU) survivors. Further, the physiological determinants of rSO2will be examined.Methods and analysisThis multicentre prospective observational study will consider adult patients (≥18 years old) eligible for enrolment if within 24 hours of ICU admission, they require mechanical ventilation and/or vasopressor support. For 72 hours, rSO2will be continuously recorded, while vital signs (eg, heart rate) and peripheral oxygenation saturation will be concurrently captured with data monitoring software. Arterial and central venous gases will be sampled every 12 hours for the 72 hours recording period and will include: pH, PaO2, PaCO2, and haemoglobin concentration. Participants will be screened daily for delirium with the confusion assessment method (CAM)-ICU, whereas the brief-CAM will be used on the ward. At 3 and 12 months post-ICU discharge, neurological function will be assessed with the Repeatable Battery for the Assessment of Neuropsychological Status and KINARM sensorimotor and cognitive robot-based behavioural tasks.Ethics and disseminationThe study protocol has been approved in Ontario by a central research ethics board (Clinical Trials Ontario); non-Ontario sites will obtain local ethics approval. The study will be conducted under the guidance of the Canadian Critical Care Trials Group (CCCTG) and the results of this study will be presented at national meetings of the CCCTG for internal peer review. Results will also be presented at national/international scientific conferences. On completion, the study findings will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03141619 more...

Introduction: Elevated intracranial pressure (ICP) is a devastating complication of brain injury, such as traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, and other conditions. Delay to diagnosis and treatment are associated with increased morbidity and mortality. For Emergency Department (ED) physicians, invasive ICP measurement is typically not available. We sought to summarize and compare the accuracy of physical examination, imaging, and ultrasonography of the optic nerve sheath diameter (ONSD) for diagnosis of elevated ICP. Methods: We searched Medline, EMBASE and 4 other databases from inception through August 2018. We included only English studies (randomized controlled trials, cohort and case-control studies). Gold standard was ICP≥20 mmHg on invasive ICP monitoring. Two reviewers independently screened studies and extracted data. We assessed risk of bias using Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Hierarchical Summary Receiver Operating Characteristic model generated summary diagnostic accuracy estimates. Results: We included 37 studies (n = 4,768, kappa = 0.96). Of exam signs, pooled sensitivity and specificity for increased ICP were: mydriasis (28.2% [95% CI: 16.0-44.8], 85.9.0% [95% CI: 74.9-92.5]), motor posturing (54.3% [95% CI: 36.6-71.0], 63.6% [95% CI: 46.5-77.8]) and Glasgow Coma Scale (GCS) ≤8 (75.8% [95% CI: 62.4-85.5], 39.9% [95% CI: 26.9-54.5]). Computed tomography findings: compression of basal cisterns had 85.9% [95% CI: 58.0-96.4] sensitivity and 61.0% [95% CI: 29.1-85.6] specificity; any midline shift had 80.9% [95% CI: 64.3-90.9] sensitivity and 42.7% [95% CI: 24.0-63.7] specificity; midline shift≥1cm had 20.7% [95% CI: 13.0-31.3] sensitivity and 89.2% {95% CI: 77.5-95.2] specificity. Finally, pooled area under the ROC curve describing accuracy for ONSD sonography for ICP was 0.94 (95% CI: 0.91-0.96). Conclusion: The absence of any one physical exam feature (e.g. mydriasis, posturing, or decreased GCS) is not sufficient to rule-out elevated ICP. Significant midline shift is highly suggestive of elevated ICP, but absence of shift does not rule it out. ONSD sonography may be useful in diagnosing elevated ICP. High suspicion of elevated ICP may necessitate treatment and transfer to a centre capable of invasive ICP monitoring. more...

Background Optimisation of healthcare practices in patients sustaining a traumatic brain injury is of major concern given the high incidence of death and long-term disabilities. Considering the brain9s susceptibility to ischaemia, strategies to optimise oxygenation to brain are needed. While red blood cell (RBC) transfusion is one such strategy, specific RBC strategies are debated. We aimed to evaluate RBC transfusion frequency, determinants of transfusions and associated clinical outcomes. Methods We conducted a retrospective multicentre cohort study using data from the National Trauma Registry of Canada. Patients admitted with moderate or severe traumatic brain injury to participating hospitals between April 2005 and March 2013 were eligible. Patient information on blood products, comorbidities, interventions and complications from the Discharge Abstract Database were linked to the National Trauma Registry data. Relative weights analyses evaluated the contribution of each determinant. We conducted multivariate robust Poisson regression to evaluate the association between potential determinants, mortality, complications, hospital-to-home discharge and RBC transfusion. We also used proportional hazard models to evaluate length of stay for time to discharge from ICU and hospital. Results Among the 7062 patients with traumatic brain injury, 1991 patients received at least one RBC transfusion during their hospital stay. Female sex, anaemia, coagulopathy, sepsis, bleeding, hypovolemic shock, other comorbid illnesses, serious extracerebral trauma injuries were all significantly associated with RBC transfusion. Serious extracerebral injuries altogether explained 61% of the observed variation in RBC transfusion. Mortality (risk ratio (RR) 1.23 (95% CI 1.13 to 1.33)), trauma complications (RR 1.38 (95% CI 1.32 to 1.44)) and discharge elsewhere than home (RR 1.88 (95% CI 1.75 to 2.04)) were increased in patients who received RBC transfusion. Discharge from ICU and hospital were also delayed in transfused patients. Conclusions RBC transfusion is common in patients with traumatic brain injury and associated with unfavourable outcomes. Trauma severity is an important determinant of RBC transfusion. Prospective studies are needed to further evaluate optimal transfusion strategies in traumatic brain injury. more...

Background Sedation is an important consideration in the care of the neurocritically ill patient. It provides anxiety and relief, facilitates procedures and nursing tasks, and minimizes intolerance of mechanical ventilation. Alpha-2 agonists such as dexmedetomidine and clonidine have been shown to be an effective alternative in the general critical care population by reducing duration of mechanical ventilation and length of stay in the intensive care unit (ICU), as compared to traditional sedative agents such as propofol or benzodiazepines. However, there is a paucity of literature detailing their utility and safety in neurocritical care, a population that presents unique considerations for management of global and cerebral hemodynamics, agitation, and facilitation of neurological assessments. The objective of this review is to assess the efficacy and safety of alpha-2 agonists for non-procedural sedation in mechanically ventilated brain-injured patients. Methods We will search the Embase and MEDLINE databases for all randomized controlled trials, prospective and retrospective cohort studies examining neurocritically ill adult patients aged 18 years and older who are on mechanical ventilation and receiving alpha-2 agonists for non-procedural sedation. Primary outcomes of interest include effect on mean arterial pressure (MAP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). Secondary outcomes include adverse events, duration of mechanical ventilation, 30-day mortality, ICU length of stay, incidence of delirium, and quality of sedation. Continuous outcomes will be presented as means and mean differences and discrete counting events will be presented as event rates. Pre-defined criteria for heterogeneity are provided for determination of pooling eligibility. Where appropriate, we will pool estimates for individual outcomes. Planned subgroup analyses include specific alpha-2 agonist agent, study design, clinical diagnosis, dosing regimen, and use of adjunctive agents. Quality of evidence for the recommendation will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach where appropriate. Discussion This systematic review will summarize the evidence on the efficacy and safety for the use of alpha-2 agonists as sedative agents in the neurocritical care population. Systematic review registration PROSPERO CRD42016037045 Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0331-4) contains supplementary material, which is available to authorized users. more...