Showing papers by "Deborah J. Cook published in 2017"

The ICM research agenda on intensive care unit-acquired weakness

Abstract: We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, amplifying the effects of each individual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.

Recovery after critical illness: putting the puzzle together-a consensus of 29.

Abstract: In this review, we seek to highlight how critical illness and critical care affect longer-term outcomes, to underline the contribution of ICU delirium to cognitive dysfunction several months after ICU discharge, to give new insights into ICU acquired weakness, to emphasize the importance of value-based healthcare, and to delineate the elements of family-centered care. This consensus of 29 also provides a perspective and a research agenda about post-ICU recovery.

Severity of Hypoxemia and Effect of High-Frequency Oscillatory Ventilation in Acute Respiratory Distress Syndrome

Abstract: Rationale: High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality.Objectives: The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV.Methods: After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects.Measurements and Main Results: Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline PaO2/FiO2 of 114 ± 39 mm Hg; 40% had severe ARDS (PaO2/FiO2 <100 mm Hg). Mortality ...

Withholding Pantoprazole for Stress Ulcer Prophylaxis in Critically Ill Patients: A Pilot Randomized Clinical Trial and Meta-Analysis.

Abstract: Introduction: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 fe

Gender Parity in Critical Care Medicine.

Abstract: Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. These documents inform and shape patient care around the world. In this Perspective we discuss the importance of diversity on guideline panels, the disproportionately low representation of women on critical care guideline panels, and existing initiatives to increase the representation of women in corporations, universities, and government. We propose five strategies to ensure gender parity within critical care medicine.

Management of Acute Respiratory Distress Syndrome and Refractory Hypoxemia. A Multicenter Observational Study

Abstract: Rationale: Clinicians’ current practice patterns in the management of acute respiratory distress syndrome (ARDS) and refractory hypoxemia are not well described.Objectives: To describe mechanical ventilation strategies and treatment adjuncts for adults with ARDS, including refractory hypoxemia.Methods: This was a prospective cohort study (March 2014–February 2015) of mechanically ventilated adults with moderate-to-severe ARDS requiring an FiO2 of 0.50 or greater in 24 intensive care units.Results: We enrolled 664 patients: 222 (33%) with moderate and 442 (67%) with severe ARDS. On Study Day 1, mean Vt was 7.5 (SD = 2.1) ml/kg predicted body weight (n = 625); 80% (n = 501) received Vt greater than 6 ml/kg. Mean positive end-expiratory pressure (PEEP) was 10.5 (3.7) cm H2O (n = 653); 568 patients (87%) received PEEP less than 15 cm H2O. Treatment adjuncts were common (n = 440, 66%): neuromuscular blockers (n = 276, 42%), pulmonary vasodilators (n = 118, 18%), prone positioning (n = 67, 10%), extracorporeal ...

Experiences and Expressions of Spirituality at the End of Life in the Intensive Care Unit

Abstract: Rationale: The austere setting of the intensive care unit (ICU) can suppress expressions of spirituality.Objectives: To describe how family members and clinicians experience and express spirituality during the dying process in a 21-bed medical–surgical ICU.Methods: Reflecting the care of 70 dying patients, we conducted 208 semistructured qualitative interviews with 76 family members and 150 clinicians participating in the Three Wishes Project. Interviews were recorded and transcribed verbatim. Data were analyzed by three investigators using qualitative interpretive description.Measurements and Main Results: Participants characterize dying as a spiritual event. Spirituality is an integral part of the life narrative of the patient before, during, and after death. Experiences and expressions of spirituality for patients, families, and clinicians during end-of-life care in the ICU are supported by eliciting and implementing wishes in several ways. Eliciting wishes stimulates conversations for people of divers...

Airway Management Strategies for Brain-injured Patients Meeting Standard Criteria to Consider Extubation. A Prospective Cohort Study

Abstract: Rationale: Patients with acute brain injury are frequently capable of breathing spontaneously with minimal ventilatory support despite persistent neurological impairment.Objectives: We sought to describe factors associated with extubation timing, success, and primary tracheostomy in these patients.Methods: We conducted a prospective multicenter observational cohort study in three academic hospitals in Toronto, Canada. Consecutive brain-injured adults receiving mechanical ventilation for at least 24 hours in three intensive care units were screened by study personnel daily for extubation consideration criteria. We monitored all patients until hospital discharge and used logistic regression models to examine associations with extubation failure and delayed extubation.Measurements and Main Results: Of 192 patients included, 152 (79%) were extubated and 40 (21%) received a tracheostomy without an extubation attempt. The rate of extubation failure within 72 hours was 32 of 152 (21%), which did not vary signifi...

The Use of Bowel Protocols in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis.

Abstract: Objective:Constipation is common among critically ill patients and has been associated with adverse patient outcomes. Many ICUs have developed bowel protocols to treat constipation; however, their effect on clinical outcomes remains uncertain. We conducted a systematic review to determine the impact

Predictors, Prognosis, and Management of New Clinically Important Atrial Fibrillation After Noncardiac Surgery: A Prospective Cohort Study.

Abstract: BACKGROUND:Despite the frequency of new clinically important atrial fibrillation (AF) after noncardiac surgery and its increased association with the risk of stroke at 30 days, there are limited data informing their prediction, association with outcomes, and management.METHODS:We used the data from

Vasopressor Use for Severe Hypotension-A Multicentre Prospective Observational Study.

Abstract: BACKGROUND The optimal approach to titrate vasopressor therapy is unclear. Recent sepsis guidelines recommend a mean arterial pressure (MAP) target of 65 mmHg and higher for chronic hypertensive patients. As data emerge from clinical trials comparing blood pressure targets for vasopressor therapy, an accurate description of usual care is required to interpret study results. Our aim was to measure MAP values during vasopressor therapy in Canadian intensive care units (ICUs) and to compare these with stated practices and guidelines. METHOD In a multicenter prospective cohort study of critically ill adults with severe hypotension, we recorded MAP and vasopressor doses hourly. We investigated variability across patients and centres using multivariable regression models and Analysis of variance (ANOVA), respectively. RESULTS We included data from 56 patients treated in 6 centers. The mean (standard deviation [SD]) age and Acute Physiology and Chronic Health Evaluation (APACHE) II score were 64 (14) and 25 (8). Half (28 of 56) of the patients were at least 65 years old, and half had chronic hypertension. The patient-averaged MAP while receiving vasopressors was 75 mm Hg (6) and the median (1st quartile, 3rd quartile) duration of vasopressor therapy was 43 hours (23, 84). MAP achieved was not associated with history of underlying hypertension (p = 0.46) but did vary by center (p<0.001). CONCLUSIONS In this multicenter, prospective observational study, the patient-level average MAP while receiving vasopressors for severe hypotension was 75 mmHg, approximately 10 mmHg above current recommendations and stated practices. Moreover, our results do not support the notion that clinicians tailor vasopressor therapy to individual patient characteristics such as underlying chronic hypertension but MAP achieved while receiving vasopressors varied by site.

High-Quality Randomized Controlled Trials in Pediatric Critical Care: A Survey of Barriers and Facilitators.

Abstract: OBJECTIVES High-quality, adequately powered, randomized controlled trials are needed to inform the care of critically ill children. Unfortunately, such evidence is not always available. Our objective was to identify barriers and facilitators of conducting high-quality randomized controlled trials in pediatric critical care, from the perspective of trialists in this field. DESIGN Self-administered online survey. Respondents rated the importance of barriers and effectiveness of facilitators on seven-point scales. SETTING Authors of 294 pediatric critical care randomized controlled trials (published 1986 to June 2015). SUBJECTS One hundred sixteen researchers from 25 countries participated. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Respondents reported a median (Q1, Q3) of 21 years (15, 26 yr) of experience and 41 (36%) had authored more than one randomized controlled trial. More survey respondents, compared with nonrespondents, had published more than one trial (35% vs 26%; p = 0.002) and their trials were more often cited (median citations/yr, 2.4 vs 1.5; p < 0.001). Of the barriers listed, the five most important were primarily related to lack of funding. The five facilitators perceived as most effective were protected time for research, ability to recruit participants 24 hours per day/7 days per week, conducting randomized controlled trials in collaboration with a research network, funding from government agencies specifically for randomized controlled trials in critically ill children, and academic department support for conducting randomized controlled trials. Respondent experience and country income level were associated with differences in importance ratings for eight of 41 barriers. There were fewer such differences for facilitators. CONCLUSIONS Lack of funding and time are major barriers to conducting pediatric critical care randomized controlled trials worldwide. Although barriers varied among country income levels, the facilitators of such trials were more consistent. In addition to increased funding, respondents identified other strategies such as research networks that are within the purview of the pediatric critical care research community, to facilitate the conduct of rigorous randomized controlled trials.

Outcomes of elderly critically ill medical and surgical patients: a multicentre cohort study.

Abstract: Very elderly (over 80 yr of age) critically ill patients admitted to medical-surgical intensive care units (ICUs) have a high incidence of mortality, prolonged hospital length of stay, and dependent living conditions should they survive. The primary purpose of this study is to describe the outcomes and differences in outcomes between very elderly medical patients and their surgical counterparts admitted to Canadian ICUs, thereby informing decision-making for clinicians and substitute decision-makers. This was a prospective multicentre cohort study of very elderly medical and surgical patients admitted to 22 Canadian academic and non-academic ICUs. Outcome measures included ICU length of stay and mortality, hospital length of stay and mortality, and disposition following hospital discharge. There were 1,671 patients evaluated in this study. Patient demographics included a mean age of 84.5 yr, baseline Acute Physiology and Chronic Health Evaluation (APACHE) II score of 22.4, baseline Sequential Organ Failure Assessment (SOFA) score of 5.3, overall ICU mortality of 21.8%, and overall hospital mortality of 35.0%. Medical patient median ICU length of stay was 4.1 days, hospital length of stay was 16.2 days, ICU mortality was 26.5%, and hospital mortality was 41.5%. Surgical patient median ICU length of stay was 3.8 days, hospital length of stay was 20.1 days, ICU mortality was 18.7%, and hospital mortality was 31.6%. Only 45.0% of medical patients and 41.6% of surgical emergency patients were able to return home to live. In this large sample of critically ill medical and surgical patients, the admission SOFA score and hospital lengths of stay were not different between the two groups, but medical patients had longer ICU lengths of stay and higher ICU and hospital mortality than surgical patients.

Fluids in Sepsis and Septic Shock (FISSH): protocol for a pilot randomised controlled trial.

Abstract: Introduction Observational evidence suggests physiological benefits and lower mortality with lower chloride solutions; however, 0.9% saline remains the most widely used fluid worldwide. Given uncertainty regarding the association of lower chloride on mortality, it is unlikely that practice will change without direct randomised clinical trial (RCT) evidence. This pilot RCT will investigate the feasibility of a large-scale trial directly comparing low chloride with high chloride fluids in patients with septic shock. Methods and analysis This is a randomised, concealed, blinded parallel-group multicentre pilot trial. We will include adult critically ill patients with septic shock, defined as ongoing hypotension despite 1 L of fluid, or a serum lactate >4 mmol/L, who are within 6 hours of hospital presentation or rapid response team activation. We will exclude patients if they have an aetiology of shock other than sepsis, if they have acute burn injury, elevated intracranial pressure, intent to withdraw life support or previous enrolment in this or a competing trial. Following informed consent, patients will be randomised to a low chloride fluid strategy or a high chloride fluid strategy for the duration of their ICU stay or until 30 days postrandomisation. Clinicians, patients, families and research staff will be blinded. The primary outcome for this trial will be feasibility, assessed by consent rate, recruitment success and protocol adherence. Patient-important clinical outcomes include mortality, receipt of renal replacement therapy, intensive care unit and hospital lengths of stay and surrogate outcomes of incidence of acidosis, hyperkalaemia and acute kidney injury. Ethics and dissemination This pilot trial will test the feasibility of conducting the main trial, which will examine the effect of high versus low chloride fluids in patients with septic shock on patient-important outcomes. Trial registration number NCT02748382, registered 8 April 2016. Protocol date 1 July 2016.

Canada-DONATE study protocol: a prospective national observational study of the medical management of deceased organ donors

Abstract: Introduction Research on the management of deceased organ donors aims to improve the number and quality of transplants and recipient outcomes. In Canada, this research is challenged by regionalisation of donation services within provinces and the geographical, clinical and administrative separation of donation from transplantation services. This study aims to build a national platform for future clinical trials in donor management. Objectives are to engage collaborators at donation hospitals and organ donation organisations (ODOs) across Canada, describe current practices, evaluate the effectiveness of donation-specific interventions and assess the feasibility of future clinical trials. Methods and analysis This ongoing prospective observational study of the medical management of deceased organ donors will enrol more than 650 consented potential donors from adult intensive care units at 33 hospital sites across Canada, each participating for 12 months. ODOs ensure enrolment of consecutive eligible participants. Research staff record detailed data about participants, therapies, organ assessments, death declaration procedures and adverse clinical exposures from the time of donation consent to organ recovery. ODOs provide reasons that organs are declined, dates and places of transplantation, and recipient age and sex. Descriptive analyses will summarise current practices. Effectiveness analyses will examine donation-specific interventions with respect to the number of transplants, using multilevel regression models to account for clustering by donor, hospitals and ODOs. Feasibility analyses will focus on acceptance of the research consent model; participation of academic and community hospitals as well as ODOs; and accessibility of recipient data. Ethics and dissemination This study uses a waiver of research consent. Hospitals will receive reports on local practices benchmarked to (1) national practices and (2) national donor management guidelines. We will report findings to donation and transplant collaborators (ie, clinicians, researchers, ODOs) and publish in peer-reviewed journals. Trial registration number NCT03114436.

Need for a Randomized Controlled Trial of Stress Ulcer Prophylaxis in Critically Ill Children: A Canadian Survey.

Abstract: Background: Stress ulcer prophylaxis is commonly used in pediatric critical care, to prevent upper gastrointestinal bleeding. The most frequently used agents are histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). The risk–benefit ratio for stress ulcer prophylaxis is uncertain, because data from randomized clinical trials (RCTs) on the effectiveness and harms of prophylaxis in children are limited. Objective: To describe the views of Canadian pediatric intensivists about a future RCT of stress ulcer prophylaxis. Methods: We conducted an online survey of Canadian pediatric critical care physicians. We e-mailed information about the study and a link to a 10-item survey to 111 potential respondents, with 2 reminders for nonrespondents. We assessed the relationship between respondents’ characteristics and their views about the need for and potential participation in a trial using logistic regression and assessed regional differences using the 2 test. Results: The 68 physicians who replied (61% of potential respondents) had a median of 12 (interquartile range 5–20) years of experience. Fortyfour (65%) of the respondents stated that a large, rigorous RCT of stress ulcer prophylaxis in children is needed, and 94% (62 of 66) indicated that it should include a placebo group. The 3 most common designs suggested were a 3-arm trial comparing PPI, H2RA, and placebo (56% [37 of 66 respondents to this question]) and 2-arm trials comparing PPI with placebo (15% [n = 10]) and H2RA with placebo (8% [n = 5]). The 5 patient groups that respondents most commonly stated should be excluded (because they should not receive placebo) were children receiving acid suppression at home (66% [42 of 64 respondents to this question]) or corticosteroids (59% [n = 38]), those with severe coagulopathy or receiving extracorporeal membrane oxygenation (both 36% [n = 23]), and those with burns (31% [n = 20]). Most respondents indicated a willingness to participate in an RCT (64% [42 of 66 respondents to this question]), whereas some (29% [n = 19]) indicated that participation would depend on trial design or funding; only 8% (n = 5) were disinclined to participate. Conclusions: There is considerable interest in a placebo-controlled RCT of stress ulcer prophylaxis among pediatric critical care physicians in Canada, but consensus on key elements of the trial design is needed. RESUME Contexte : La prophylaxie de l’ulcere de stress est frequemment employee en soins intensifs pediatriques afin de prevenir les saignements du tractus gastro-intestinal superieur. Les agents les plus souvent employes sont les antagonistes des recepteurs H2 de l’histamine (anti-H2) et les inhibiteurs de la pompe a protons (IPP). Le rapport benefice-risque pour la prophylaxie de l’ulcere de stress est incertain, car les donnees provenant d’essais cliniques a repartition aleatoire (ECRA) sur l’efficacite et les dangers de la prophylaxie chez l’enfant sont peu nombreuses. Objectif : Decrire les points de vue des pediatres intensivistes canadiens a propos d’un futur ECRA sur la prophylaxie de l’ulcere de stress. Methodes : Nous avons realise un sondage en ligne aupres de medecins canadiens en soins intensifs pediatriques. Nous avons envoye par courriel de l’information sur l’etude, dont un lien menant au sondage en dix points, a 111 repondants potentiels et deux rappels a ceux n’ayant pas repondu d’emblee. Nous avons evalue, au moyen d’un modele de regression logistique, les points de vue des repondants a propos de la necessite d’un essai et de leur participation potentielle a celui-ci en fonction de leurs caracteristiques individuelles et, a l’aide d’un test de 2, les differences regionales. Resultats : Les 68 medecins (61 % des repondants potentiels) qui ont repondu avaient une mediane de 12 (ecart interquartile de 5 a 20) annees d’experience. Quarante-quatre (65 %) des repondants indiquaient qu’il serait necessaire de proceder a un important et rigoureux ECRA sur la prophylaxie de l’ulcere de stress chez l’enfant et 94 % (62 des 66 repondants) indiquaient que l’etude devrait comprendre un groupe placebo. Les trois plans experimentaux les plus souvent suggeres etaient : un essai a trois groupes comparant les IPP, les anti-H2 et le placebo (56 % [37 des 66 repondants a cette question]), un essai a deux groupes comparant les IPP au placebo (15 % [n = 10]) et un essai a deux groupes comparant les anti-H2 au placebo (8 % [n = 5]). Les cinq groupes de patients que les repondants indiquaient le plus souvent comme ceux devant etre exclus (parce qu’ils ne devraient pas recevoir de placebo) etaient : les enfants recevant un traitement de suppression de la secretion d’acide a la maison (66% [42 des 64 repondants a cette question]), ceux traites a l’aide de corticoides (59 % [n = 38]), ceux atteints d’une coagulopathie grave ou ceux traites par oxygenation extracorporelle sur oxygenateur a membrane (36 % chacun [n = 23]) et ceux souffrant de brulures (31% [n = 20]). La plupart des repondants ont indique etre prets a participer a un ECRA (64% [42 des 66 repondants a cette question]), alors que certains (29 % [n = 19]) ont indique que leur participation dependrait du plan de l’etude ou de son financement; seulement 8% (n = 5) n’etaient pas enclins a participer. Conclusions : On constate parmi les medecins canadiens en soins intensifs pediatriques un interet marque pour la tenue d’un ECRA comparatif contre placebo sur la prophylaxie de l’ulcere de stress, mais il est d’abord necessaire d’obtenir un consensus sur les elements cles du plan experimental.

The association between platelet transfusions and bleeding in critically ill patients with thrombocytopenia.

Abstract: Background Platelet transfusions are commonly used to treat critically ill patients with thrombocytopenia Whether platelet transfusions are associated with a reduction in the risk of major bleeding is unknown Patients/Methods Observational cohort study nested in a previous multicenter, randomized thromboprophylaxis trial in the intensive care unit (ICU) The objective was to evaluate the association between platelet transfusions and adjudicated major bleeding events Platelet transfusion episodes were reviewed for timing of administration, product type, and dose Major bleeding with and without platelet transfusions was adjusted for severity of thrombocytopenia, use of anti-platelet agents, surgery and other covariates Secondary outcomes were thrombosis, death in ICU and platelet count increment Results Among 2,256 patients, 71 (31%) received 190 platelet transfusions Of those, 121 (637%) were administered to 54 non-bleeding, thrombocytopenic patients Adjusted rates of major bleeding were not statistically different with or without the administration of platelet transfusions (hazard ratio for transfused patients 085; 95% confidence interval, 042-172) We did not find a significant association between platelet transfusion use and thrombosis or death in ICU in adjusted analyses Thrombocytopenia, anemia, major or minor bleeding and use of anticoagulants were associated with platelet transfusion administration The median post-transfusion platelet count increment was 20×109/L at 35 hours post-transfusion Conclusions Rates of major bleeding were not different for patients who did and did not receive platelet transfusions Inferences were limited by the small number of transfused patients Clinical trials are needed to better investigate the potential hemostatic benefit and potential harms of platelet transfusions for this high-risk population

Pediatric intensive care stress ulcer prevention (PIC-UP): a protocol for a pilot randomized trial.

Abstract: Despite sparse pediatric data on effectiveness, the majority of critically ill children receive medications to prevent gastrointestinal (GI) bleeding. Stress ulcer prophylaxis may have unintended consequences—increasing the risk of nosocomial infections—which may be more serious and common than the bleeding which these drugs are prescribed to prevent. Randomized controlled trials (RCTs) in pediatric critical care are exceptionally challenging to complete, thus a rigorous pilot RCT is crucial. The objective of this pilot RCT is to assess the feasibility of a large multicentre RCT of stress ulcer prophylaxis with pantoprazole to prevent upper GI bleeding vs. placebo. A multi-centre blinded pilot RCT of 120 children in six Canadian PICUs. Children expected to require mechanical ventilation for more than 48 h will be randomized to receive intravenous pantoprazole 1 mg/kg or identical placebo once daily until they no longer need mechanical ventilation. We have four feasibility outcomes and will consider the trial successful if we achieve: There are many uncertainties about the risks and benefits of stress ulcer prophylaxis. In an era of widespread use—where clinicians prescribe prophylaxis to the more severely ill—a large, rigorous RCT is required. A trial to determine if a strategy of withholding stress ulcer prophylaxis is not inferior to a strategy of routine stress ulcer prophylaxis will be challenging. A carefully designed and implemented pilot trial is essential. ClinicalTrials.gov: NCT02929563 (Registered October 3, 2016).

Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study.

Abstract: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75–80 mmHg) versus lower (60–65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured.

2009-2010 Influenza A(H1N1)-related critical illness among Aboriginal and non-Aboriginal Canadians.

Abstract: Background Preliminary studies suggested that Aboriginal Canadians had disproportionately higher rates of infection, hospitalization, and critical illness due to pandemic Influenza A(H1N1)pdm09. Methods We used a prospective cohort study of critically ill patients with laboratory confirmed or probable H1N1 infection in Canada between April 16 2009 and April 12 2010. Baseline characteristics, medical interventions, clinical course and outcomes were compared between Aboriginal and non-Aboriginal patients. The primary outcome was hospital mortality. Results Of 647 critically ill adult patients with known ethnicity, 81 (12.5%) were Aboriginal, 566 (87.5%) were non-Aboriginal. Aboriginal patients were younger (mean [SD] age 40.7[13.7] v. 49.0[14.9] years, p < 0.001) and more frequently female (64.2% v. 51.1%, p = 0.027). Rates of any co-morbid illnesses (Aboriginal v. non-Aboriginal, 92.6% v. 91.0%, p = 0.63), time from symptom onset to hospital admission (median [interquartile range] 4 [2–7] v. 4 [2–7] days, p = 0.84), time to ICU admission (5 [3–8] v.5 [3–8] days, p = 0.91), and severity of illness (mean APACHE II score (19.9 [9.6] v. 21.1 [9.9], p = 0.33) were similar. A similar proportion of Aboriginal patients received antiviral medication before ICU admission than non-Aboriginal patients (91.4% v. 93.8%, p = 0.40). Among Aboriginal versus non-Aboriginal patients, the need for mechanical ventilation (93.8% v. 88.6%, p = 0.15), ventilator-free days (14 [3–23] v. 17 [0–24], p = 0.62), durations of stay in ICU (13[7-19.5] v. 11 [5–8] days, p = 0.05), hospital (19 [12.5-33.5] v. 18 [11-35] days, p = 0.63), and hospital mortality were similar (19.8% v. 22.6%, p = 0.56). In multiple logistic regression analyses, higher APACHE II score (1.06; 1.04-1.09, p<0.001) was independently associated with an increased risk of death; antiviral treatment with a lower risk of death (0.34; 0.15 – 0.78, p = 0.01). Ethnicity was not associated with mortality. Interpretation During the 2009-2010 Influenza A (H1N1) pandemic, Aboriginal and non-Aboriginal Canadians with H1N1-related critical illness had a similar risk of death, after adjusting for potential confounding factors.

Correction to: Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials.

Abstract: Owing to an oversight by the authors, all the figures in the last column of Table 2 (upper section: Number needed to treat; lower section: Number needed to harm) in this article were given without the final digit 0 and are thus 10 times too small.

Erratum to: Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine.

Abstract: Unfortunately this article [1] published without its additional files (Additional files 1, 2, 3, 4, 5, 6 and 7). Please see these listed below and attached as additional files to this erratum.

Erratum to: Pediatric intensive care stress ulcer prevention (PIC-UP): a protocol for a pilot randomized trial.

Abstract: [This corrects the article DOI: 10.1186/s40814-017-0142-y.].

DONATE: A 8 centre pilot study

Abstract: Introduction Transplantation is a definitive treatment option for many people suffering from end-stage organ failure. Organ supply, however, far exceeds the supply. While recent studies suggest that improved management of deceased organ donors may increase transplant rates and allograft function, research to support best practices in donor management is sparse. The DONATE Pilot Observational Study aims to identify and to address logistical and regulatory complexities prior to embarking upon a national observational study that will improve the care of organ donors and lay the foundation for future clinical trials. Methods This 12 month prospective cohort study was conducted between September 2015 - April 2017 in the intensive care units (ICUs) of 8 Ontario and Quebec hospitals enrolled consecutively consented adult deceased donors [donation after neurological determination of death (DND) and donation after circulatory determination of death (DCD). The primary outcomes of this pilot study included the successful application of a waived research consent model, the time to complete the case report forms (CRF) and the completeness of transplant recipient data. Detailed data from various hospital sources and provincial organ donation organizations included death determination procedures, cardiopulmonary monitoring technologies, basic and advanced life sustaining therapy, general prophylactic interventions, organ donation specific therapies and clinical complications, defined a priori, from one day prior to donation consent up to the time of organ recovery. We also recorded specific limited data about the transplant recipients. Results In collaboration with ethicists, lawyers and privacy officers, all hospitals obtained authorization to implement this study with a waiver of research consent. The study, includes 180 consecutive deceased donors (58% DND; 42% DCD). The most common critical illness leading to organ donation was global anoxic brain injury (n = 37, 20.,6%). The mean time from donation consent to organ recovery was 2.39 days (SD = 0.72). Research coordinators estimated that prospective data completion required 5-7 hours per participant, but retrospective approaches required more time. With formal data sharing agreements, we obtained recipient data. Conclusion This pilot study identified and addressed some unique logistical and regulatory organ donation research challenges. The process provides a framework for addressing the same issues, and refining data collection, in the context of an upcoming national prospective cohort study. Clinical findings from the national cohort will inform the design of future trials in organ donor management. Canadian Critical Care Trials Group. Canadian National Transplant Research Program.