Showing papers by "Deborah J. Cook published in 2016"

One-Year Outcomes in Caregivers of Critically Ill Patients

Abstract: Background Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU). Methods We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge. Results The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time. Conclusions In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).

The RECOVER Program: Disability Risk Groups and 1-Year Outcome after 7 or More Days of Mechanical Ventilation.

Abstract: Rationale: Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design.Objectives: To stratify patients for post-ICU disability and recovery to 1 year after critical illness.Methods: We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling.Measurements and Main Results: The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk...

An introduction to multiplicity issues in clinical trials: the what, why, when and how.

Abstract: In clinical trials it is not uncommon to face a multiple testing problem which can have an impact on both type I and type II error rates, leading to inappropriate interpretation of trial results. Multiplicity issues may need to be considered at the design, analysis and interpretation stages of a trial. The proportion of trial reports not adequately correcting for multiple testing remains substantial. The purpose of this article is to provide an introduction to multiple testing issues in clinical trials, and to reduce confusion around the need for multiplicity adjustments. We use a tutorial, question-and-answer approach to address the key issues of why, when and how to consider multiplicity adjustments in trials. We summarize the relevant circumstances under which multiplicity adjustments ought to be considered, as well as options for carrying out multiplicity adjustments in terms of trial design factors including Population, Intervention/Comparison, Outcome, Time frame and Analysis (PICOTA). Results are presented in an easy-to-use table and flow diagrams. Confusion about multiplicity issues can be reduced or avoided by considering the potential impact of multiplicity on type I and II errors and, if necessary pre-specifying statistical approaches to either avoid or adjust for multiplicity in the trial protocol or analysis plan.

Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial.

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

Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials

Abstract: The relative efficacy and safety of proton pump inhibitors (PPIs) compared to histamine-2-receptor antagonists (H2RAs) should guide their use in reducing bleeding risk in the critically ill. We searched the Cochrane library, MEDLINE, EMBASE, ACPJC, clinical trials registries, and conference proceedings through November 2015 without language or publication date restrictions. Only randomized controlled trials (RCTs) of PPIs vs H2RAs for stress ulcer prophylaxis in critically ill adults for clinically important bleeding, overt gastrointestinal (GI) bleeding, nosocomial pneumonia, mortality, ICU length of stay and Clostridium difficile infection were included. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess our confidence in the evidence for each outcome. In 19 trials enrolling 2117 patients, PPIs were more effective than H2RAs in reducing the risk of clinically important GI bleeding (RR 0.39; 95 % CI 0.21, 0.71; P = 0.002; I 2 = 0 %, moderate confidence) and overt GI bleeding (RR 0.48; 95 % CI 0.34, 0.66; P < 0.0001; I 2 = 3 %, moderate confidence). PPI use did not significantly affect risk of pneumonia (RR 1.12; 95 % CI 0.86, 1.46; P = 0.39; I 2 = 2 %, low confidence), mortality (RR 1.05; 95 % CI 0.87, 1.27; P = 0.61; I 2 = 0 %, moderate confidence), or ICU length of stay (mean difference (MD), –0.38 days; 95 % CI –1.49, 0.74; P = 0.51; I 2 = 30 %, low confidence). No RCT reported Clostridium difficile infection. PPIs were superior to H2RAs in preventing clinically important and overt GI bleeding, without significantly increasing the risk of pneumonia or mortality. Their impact on Clostridium difficile infection is yet to be determined.

The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness

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

Modified Early Warning Score (MEWS) Identifies Critical Illness among Ward Patients in a Resource Restricted Setting in Kampala, Uganda: A Prospective Observational Study.

Abstract: Introduction Providing optimal critical care in developing countries is limited by lack of recognition of critical illness and lack of essential resources. The Modified Early Warning Score (MEWS), based on physiological parameters, is validated in adult medical and surgical patients as a predictor of mortality. The objective of this study performed in Uganda was to determine the prevalence of critical illness on the wards as defined by the MEWS, to evaluate the MEWS as a predictor of death, and to describe additional risk factors for mortality. Methods We conducted a prospective observational study at Mulago National Referral Teaching Hospital in Uganda. We included medical and surgical ward patients over 18 years old, excluding patients discharged the day of enrolment, obstetrical patients, and patients who self-discharged prior to study completion. Over a 72-hour study period, we collected demographic and vital signs, and calculated MEWS; at 7-days we measured outcomes. Patients discharged prior to 7 days were assumed to be alive at study completion. Descriptive and inferential statistical analyses were performed. Results Of 452 patients, the median age was 40.5 (IQR 29-54) years, 53.3% were male, 24.3% were HIV positive, and 45.1% had medical diagnoses. MEWS ranged from 0 to 9, with higher scores representing hemodynamic instability. The median MEWS was 2 [IQR 1-3] and the median length of hospital stay was 9 days [IQR 4-24]. In-hospital mortality at 7-days was 5.5%; 41.4% of patients were discharged and 53.1% remained on the ward. Mortality was independently associated with medical admission (OR: 7.17; 95% CI: 2.064-24.930; p = 0.002) and the MEWS ≥ 5 (OR: 5.82; 95% CI: 2.420-13.987; p Conclusion There is a significant burden of critical illness at Mulago Hospital, Uganda. Implementation of the MEWS could provide a useful triage tool to identify patients at greatest risk of death. Future research should include refinement of MEWS for low-resource settings, and development of appropriate interventions for patients identified to be at high risk of death based on early warning scores.

Stress Ulcer Prophylaxis

Abstract: Objectives:Stress ulcer prophylaxis is commonly administered to critically ill patients for the prevention of clinically important stress-related mucosal bleeding from the upper gastrointestinal tract. Despite widespread incorporation of stress ulcer prophylaxis into practice around the world, quest

TryCYCLE: A Prospective Study of the Safety and Feasibility of Early In-Bed Cycling in Mechanically Ventilated Patients.

Abstract: Introduction The objective of this study was to assess the safety and feasibility of in-bed cycling started within the first 4 days of mechanical ventilation (MV) to inform a future randomized clinical trial. Methods We conducted a 33-patient prospective cohort study in a 21-bed adult academic medical-surgical intensive care unit (ICU) in Hamilton, ON, Canada. We included adult patients (≥ 18 years) receiving MV who walked independently pre-ICU. Our intervention was 30 minutes of in-bed supine cycling 6 days/week in the ICU. Our primary outcome was Safety (termination), measured as events prompting cycling termination; secondary Safety (disconnection or dislodgement) outcomes included catheter/tube dislodgements. Feasibility was measured as consent rate and fidelity to intervention. For our primary outcome, we calculated the binary proportion and 95% confidence interval (CI). Results From 10/2013-8/2014, we obtained consent from 34 of 37 patients approached (91.9%), 33 of whom received in-bed cycling. Of those who cycled, 16(48.4%) were female, the mean (SD) age was 65.8(12.2) years, and APACHE II score was 24.3(6.7); 29(87.9%) had medical admitting diagnoses. Cycling termination was infrequent (2.0%, 95% CI: 0.8%-4.9%) and no device dislodgements occurred. Cycling began a median [IQR] of 3 [2, 4] days after ICU admission; patients received 5 [3, 8] cycling sessions with a median duration of 30.7 [21.6, 30.8] minutes per session. During 205 total cycling sessions, patients were receiving invasive MV (150 [73.1%]), vasopressors (6 [2.9%]), sedative or analgesic infusions (77 [37.6%]) and dialysis (4 [2.0%]). Conclusions Early cycling within the first 4 days of MV among hemodynamically stable patients is safe and feasible. Research to evaluate the effect of early cycling on patient function is warranted. Trial Registration Clinicaltrials.gov: NCT01885442

Risk factors for mortality in patients admitted to intensive care units with pneumonia

Abstract: Despite the high mortality in patients with pneumonia admitted to an ICU, data on risk factors for death remain limited. In this secondary analysis of PROTECT (Prophylaxis for Thromboembolism in Critical Care Trial), we focused on the patients admitted to ICU with a primary diagnosis of pneumonia. The primary outcome for this study was 90-day hospital mortality and the secondary outcome was 90-day ICU mortality. Cox regression model was conducted to examine the relationship between baseline and time-dependent variables and hospital and ICU mortality. Six hundred sixty seven patients admitted with pneumonia (43.8 % females) were included in our analysis, with a mean age of 60.7 years and mean APACHE II score of 21.3. During follow-up, 111 patients (16.6 %) died in ICU and in total, 149 (22.3 %) died in hospital. Multivariable analysis demonstrated significant independent risk factors for hospital mortality including male sex (hazard ratio (HR) = 1.5, 95 % confidence interval (CI): 1.1 - 2.2, p-value = 0.021), higher APACHE II score (HR = 1.2, 95 % CI: 1.1 - 1.4, p-value < 0.001 for per-5 point increase), chronic heart failure (HR = 2.9, 95 % CI: 1.6 - 5.4, p-value = 0.001), and dialysis (time-dependent effect: HR = 2.7, 95 % CI: 1.3 - 5.7, p-value = 0.008). Higher APACHE II score (HR = 1.2, 95 % CI: 1.1 - 1.4, p-value = 0.002 for per-5 point increase) and chronic heart failure (HR = 2.6, 95 % CI: 1.3 – 5.0, p-value = 0.004) were significantly related to risk of death in the ICU. In this study using data from a multicenter thromboprophylaxis trial, we found that male sex, higher APACHE II score on admission, chronic heart failure, and dialysis were independently associated with risk of hospital mortality in patients admitted to ICU with pneumonia. While high illness severity score, presence of a serious comorbidity (heart failure) and need for an advanced life support (dialysis) are not unexpected risk factors of mortality, male sex might necessitate further exploration. More studies are warranted to clarify the effect of these risk factors on survival in critically ill patients admitted to ICU with pneumonia. ClinicalTrials.gov Identifier: NCT00182143 .

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial—PROSPECT: a pilot trial

Abstract: Probiotics are live microorganisms that may confer health benefits when ingested. Randomized trials suggest that probiotics significantly decrease the incidence of ventilator-associated pneumonia (VAP) and the overall incidence of infection in critically ill patients. However, these studies are small, largely single-center, and at risk of bias. The aim of the PROSPECT pilot trial was to determine the feasibility of conducting a larger trial of probiotics to prevent VAP in mechanically ventilated patients in the intensive care unit (ICU). In a randomized blinded trial, patients expected to be mechanically ventilated for ≥72 hours were allocated to receive either 1 × 1010 colony-forming units of Lactobacillus rhamnosus GG or placebo, twice daily. Patients were excluded if they were at increased risk of L. rhamnosus GG infection or had contraindications to enteral medication. Feasibility objectives were: (1) timely recruitment; (2) maximal protocol adherence; (3) minimal contamination; and (4) estimated VAP rate ≥10 %. We also measured other infections, diarrhea, ICU and hospital length of stay, and mortality. Overall, in 14 centers in Canada and the USA, all feasibility goals were met: (1) 150 patients were randomized in 1 year; (2) protocol adherence was 97 %; (3) no patients received open-label probiotics; and (4) the VAP rate was 19 %. Other infections included: bloodstream infection (19.3 %), urinary tract infections (12.7 %), and skin and soft tissue infections (4.0 %). Diarrhea, defined as Bristol type 6 or 7 stools, occurred in 133 (88.7 %) of patients, the median length of stay in ICU was 12 days (quartile 1 to quartile 3, 7–18 days), and in hospital was 26 days (quartile 1 to quartile 3, 14–44 days); 23 patients (15.3 %) died in the ICU. The PROSPECT pilot trial supports the feasibility of a larger trial to investigate the effect of L. rhamnosus GG on VAP and other nosocomial infections in critically ill patients. Clinicaltrials.gov NCT01782755 . Registered on 29 January 2013.

The Effect of Inadequate Initial Empiric Antimicrobial Treatment on Mortality in Critically Ill Patients with Bloodstream Infections: A Multi-Centre Retrospective Cohort Study.

Abstract: Hospital mortality rates are elevated in critically ill patients with bloodstream infections. Given that mortality may be even higher if appropriate treatment is delayed, we sought to determine the effect of inadequate initial empiric treatment on mortality in these patients. A retrospective cohort study was conducted across 13 intensive care units in Canada. We defined inadequate initial empiric treatment as not receiving at least one dose of an antimicrobial to which the causative pathogen(s) was susceptible within one day of initial blood culture. We evaluated the association between inadequate initial treatment and hospital mortality using a random effects multivariable logistic regression model. Among 1,190 patients (1,097 had bacteremia and 93 had candidemia), 476 (40%) died and 266 (22%) received inadequate initial treatment. Candidemic patients more often had inadequate initial empiric therapy (64.5% versus 18.8%), as well as longer delays to final culture results (4 vs 3 days) and appropriate therapy (2 vs 0 days). After adjustment, there was no detectable association between inadequate initial treatment and mortality among bacteremic patients (Odds Ratio (OR): 1.02, 95% Confidence Interval (CI) 0.70-1.48); however, candidemic patients receiving inadequate treatment had nearly three times the odds of death (OR: 2.89, 95% CI: 1.05-7.99). Inadequate initial empiric antimicrobial treatment was not associated with increased mortality in bacteremic patients, but was an important risk factor in the subgroup of candidemic patients. Further research is warranted to improve early diagnostic and risk prediction methods in candidemic patients.

Predicting Performance Status 1 Year After Critical Illness in Patients 80 Years or Older: Development of a Multivariable Clinical Prediction Model.

Abstract: Objective:We sought to develop and internally validate a clinical prediction model to estimate the outcome of very elderly patients 12 months after being admitted to the ICU.Design:Prospective, longitudinal cohort study.Setting:Twenty-two Canadian ICUs.Patients:We recruited 527 patients 80 years or

Duration of Antimicrobial Treatment for Bacteremia in Canadian Critically Ill Patients.

Abstract: Objectives:The optimum duration of antimicrobial treatment for patients with bacteremia is unknown. Our objectives were to determine duration of antimicrobial treatment provided to patients who have bacteremia in ICUs, to assess pathogen/patient factors related to treatment duration, and to assess t

Premature Discontinuation of Randomized Trials in Critical and Emergency Care: A Retrospective Cohort Study.

Abstract: OBJECTIVES Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. DESIGN Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. SETTING Randomized clinical trials involving patients in an acute or nonacute care setting. SUBJECTS AND INTERVENTIONS We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. MEASUREMENTS AND MAIN RESULTS Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. CONCLUSIONS Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.

CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients

Abstract: Introduction Early exercise with in-bed cycling as part of an intensive care unit (ICU) rehabilitation programme has the potential to improve physical and functional outcomes following critical illness. The objective of this study is to determine the feasibility of enrolling adults in a multicentre pilot randomised clinical trial (RCT) of early in-bed cycling versus routine physiotherapy to inform a larger RCT. Methods and analysis 60-patient parallel group pilot RCT in 7 Canadian medical-surgical ICUs. We will include all previously ambulatory adult patients within the first 0–4 days of mechanical ventilation, without exclusion criteria. After informed consent, patients will be randomised using a web-based, centralised electronic system, to 30 min of in-bed leg cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay (28 days maximum) or routine physiotherapy alone. We will measure patients9 muscle strength (Medical Research Council Sum Score, quadriceps force) and function (Physical Function in ICU Test (scored), 30 s sit-to-stand, 2 min walk test) at ICU awakening, ICU discharge and hospital discharge. Our 4 feasibility outcomes are: (1) patient accrual of 1–2 patients per month per centre, (2) protocol violation rate 80% at the 3 time points and (4) blinded outcomes ascertainment >80% at hospital discharge. Hospital outcome assessors are blinded to group assignment, whereas participants, ICU physiotherapists, ICU caregivers, research coordinators and ICU outcome assessors are not blinded to group assignment. We will analyse feasibility outcomes with descriptive statistics. Ethics and dissemination Each participating centre will obtain local ethics approval, and results of the study will be published to inform the design and conduct of a future multicentre RCT of in-bed cycling to improve physical outcomes in ICU survivors. Trial registration number NCT02377830; Pre-results.

Stress ulcer prophylaxis in critical illness: a Canadian survey

Abstract: 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.

Resident reflections on end-of-life education: a mixed-methods study of the 3 Wishes Project

Abstract: Objective The objectives of this study were to describe residents9 experiences with end-of-life (EOL) education during a rotation in the intensive care unit (ICU), and to understand the possible influence of the 3 Wishes Project. Design We enrolled dying patients, their families and 1–3 of their clinicians in the 3 Wishes Project, eliciting and honouring a set of 3 wishes to bring peace to the final days of a critically ill patient9s life, and ease the grieving process for families. We conducted semistructured interviews with 33 residents who had cared for 50 dying patients to understand their experiences with the project. Interviews were recorded, transcribed verbatim, then analysed using a qualitative descriptive approach. Setting 21-bed medical surgical ICU in a tertiary care, university-affiliated hospital. Results 33 residents participated from internal medicine (24, 72.7%), anaesthesia (8, 24.2%) and laboratory medicine (1, 3.0%) programmes in postgraduate years 1–3. 3 categories and associated themes emerged. (1) EOL care is a challenging component of training in that (a) death in the ICU can invoke helplessness, (b) EOL education is inadequate, (c) personal connections with dying patients is difficult in the ICU and (d) EOL skills are valued by residents. (2) The project reframes the dying process for residents by (a) humanising this aspect of practice, (b) identifying that family engagement is central to the dying process, (c) increasing emotional responsiveness and (d) showing that care shifts, not stops. (3) The project offers experiential education by (a) intentional role modelling, (b) facilitating EOL dialogue, (c) empowering residents to care in a tangible way and (d) encouraging reflection. Conclusions For residents, the 3 Wishes Project integrated many forms of active learning for residents. Practice-based rather than classroom-based programmes may engage trainees to develop EOL skills transferable to other settings.

Narrative medicine and death in the ICU: word clouds as a visual legacy

Abstract: Objective The Word Cloud is a frequent wish in the 3 Wishes Project developed to nurture peace and ease the grieving process for dying critically ill patients. The objective was to examine whether Word Clouds can act as a heuristic approach to encourage a narrative orientation to medicine. Narrative medicine is an approach which can strengthen relationships, compassion and resilience. Design Word Clouds were created for 42 dying patients, and we interviewed 37 family members and 73 clinicians about their impact. We conducted a directed qualitative content analysis, using the 3 stages of narrative medicine (attention, representation, affiliation) to examine the narrative medicine potential of Word Clouds. Results The elicitation of stories for the Word Cloud promotes narrative attention to the patient as a whole person. The distillation of these stories into a list of words and the prioritisation of those words for arrangement in the collage encourages a representation that did not enforce a beginning, middle or end to the story of the patient9s life. Strong affiliative connections were achieved through the honouring of patients, caring for families and sharing of memories encouraged through the creation, sharing and discussion of Word Clouds. Conclusions In the 3 Wishes Project, Word Clouds are 1 way that families and clinicians honour a dying patient. Engaging in the process of making a Word Cloud can promote a narrative orientation to medicine, forging connections, making meaning through reminiscence and leaving a legacy of a loved one. Documenting and displaying words to remember someone in death reaffirms their life.

The Impact of Clinical Trials Conducted by Research Networks in Pediatric Critical Care.

Abstract: OBJECTIVES Research networks in adult and neonatal critical care have demonstrated collaborative and successful execution of clinical trials. Such networks appear to have been relatively recently established in the field of pediatric critical care. The objective of this study was to evaluate the productivity and impact of randomized controlled trials conducted by pediatric critical care research networks, compared with nonnetwork trials. DATA SOURCES, STUDY SELECTION, AND DATA ABSTRACTION We searched multiple online databases including MEDLINE, reference lists of randomized controlled trials, and relevant systematic reviews. Independent pairs of reviewers identified published randomized controlled trials administering any intervention to children in a PICU and abstracted data. A research network was defined as a formal consortium or collaborative research group established for the purpose of conducting clinical research. Data were independently abstracted in duplicate. MAIN RESULTS There were 288 pediatric critical care randomized controlled trials published in English between 1986 and July 2015, of which 15 randomized controlled trials (5.2%) were conducted by a total of five research networks. Network randomized controlled trials were more often multicentered, multinational, and larger in size (p < 0.001), compared with nonnetwork randomized controlled trials. Accordingly, their trials took longer to complete (median, 36 vs 21 mo; p < 0.001). Early stopping occurred in 46.7% of network randomized controlled trials (46.7%) and 27% of nonnetwork randomized controlled trials (p = 0.14), most commonly for futility. None of the network, but 45% of the nonnetwork trials found a significant difference in their primary outcome (p < 0.001). Network trials were more frequently cited (median, 6 vs 2 citations per year) and published in higher impact journals (median impact factor, 21.8 vs 3; p < 0.001). CONCLUSIONS Research networks have conducted a minority of randomized controlled trials in pediatric critical care. They infrequently demonstrate significant differences in their primary outcomes. Despite this, network trials are cited more frequently and appear to have greater impact. There are important lessons to learn from both individual researchers as well as research networks that may guide the successful conduct of collaborative, high-quality randomized controlled trials in critically ill children.

β-Blockers in sepsis: protocol for a systematic review and meta-analysis of randomised control trials.

Abstract: Introduction Sepsis is a common and deadly complication of infection. As part of the host response, sympathetic stimulation can result in septic myocardial depression, and metabolic, haematological and immunological dysfunction. Administration of β-blockers may attenuate this pathophysiological response to infection, but the effects on clinical outcomes are unknown. The objective of this systematic review is to determine the efficacy and safety of β-blockers in adults with sepsis using data from randomised control trials. Methods and analysis We will identify randomised control trials comparing treatment with β-blockers, versus placebo or standard care in adults with sepsis. Data sources will include MEDLINE, EMBASE, CENTRAL, clinical trial registries and conference proceedings. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, risk of bias assessment and evaluation of the quality of the evidence using the GRADE approach. Ethics and dissemination Our systematic review will evaluate the effects of β-blockers in adults with sepsis, comprehensively summarising and appraising the available evidence from randomised control trials. The results of this systematic review will help clinicians treating patients with sepsis to understand the potential role of β-blockade, and inform future research on this topic. Our findings will be disseminated through conference presentation and publication in a peer-reviewed journal. Trial registration number CRD42016036933.

Multicountry survey of emergency and critical care medicine physicians’ fluid resuscitation practices for adult patients with early septic shock

Abstract: Objectives Evidence to guide fluid resuscitation evidence in sepsis continues to evolve. We conducted a multicountry survey of emergency and critical care physicians to describe current stated practice and practice variation related to the quantity, rapidity and type of resuscitation fluid administered in early septic shock to inform the design of future septic shock fluid resuscitation trials. Methods Using a web-based survey tool, we invited critical care and emergency physicians in Canada, the UK, Scandinavia and Saudi Arabia to complete a self-administered electronic survey. Results A total of 1097 physicians’ responses were included. 1 L was the most frequent quantity of resuscitation fluid physicians indicated they would administer at a time (46.9%, n=499). Most (63.0%, n=671) stated that they would administer the fluid challenges as quickly as possible. Overall, normal saline and Ringer9s solutions were the preferred crystalloid fluids used ‘often’ or ‘always’ in 53.1% (n=556) and 60.5% (n=632) of instances, respectively. However, emergency physicians indicated that they would use normal saline ‘often’ or ‘always’ in 83.9% (n=376) of instances, while critical care physicians said that they would use saline ‘often’ or ‘always’ in 27.9% (n=150) of instances. Only 1.0% (n=10) of respondents indicated that they would use hydroxyethyl starch ‘often’ or ‘always’; use of 5% (5.6% (n=59)) or 20–25% albumin (1.3% (n=14)) was also infrequent. The majority (88.4%, n=896) of respondents indicated that a large randomised controlled trial comparing 5% albumin to a crystalloid fluid in early septic shock was important to conduct. Conclusions Critical care and emergency physicians stated that they rapidly infuse volumes of 500–1000 mL of resuscitation fluid in early septic shock. Colloid use, specifically the use of albumin, was infrequently reported. Our survey identifies the need to conduct a trial on the efficacy of albumin and crystalloids on 90-day mortality in patients with early septic shock.

Variation in diurnal sedation in mechanically ventilated patients who are managed with a sedation protocol alone or a sedation protocol and daily interruption.

Abstract: Mechanically ventilated patients may receive more sedation during the night than during the day, potentially delaying extubation. We compared nighttime and daytime benzodiazepine and opioid administration in adult patients enrolled in a multicenter sedation trial comparing protocolized sedation alone or protocolized sedation combined with daily sedation interruption; and we evaluated whether nighttime and daytime doses were associated with liberation from mechanical ventilation. This is a secondary analysis of a randomized trial which was conducted in 16 North American medical-surgical ICUs. In all 423 patients, nurses applied a validated sedation scale hourly to titrate benzodiazepine and opioid infusions to achieve a light level of sedation. Using fentanyl equivalents and midazolam equivalents, we compared dosages administered during night (19:00 to 07:00) and day (07:00 to 19:00) shifts. Using multivariable logistic regression we evaluated the association between nighttime and daytime opioid and sedative doses, and spontaneous breathing trial (SBT) conduct, SBT success, and extubation. Nighttime benzodiazepine and opioid doses were significantly higher than daytime doses (mean difference midazolam equivalents 23.3 mg, 95 % CI 12.9, 33.8, p < 0.0001; mean difference fentanyl equivalents 356 mcg, 95 % CI 130, 582, p = 0.0021). Mean Sedation Agitation Scale score was similar between night and day, and was at target (3.2 vs 3.3, 95 % CI −0.05, 0.02, p = 0.35). Self-reported nurse workload was similar during the night and day. Patients were more often restrained during day shifts (76.3 % vs 73.7 %, p < 0.0001), and there were more unintentional device removals during the day compared with night (15.9 % vs 9.1 %, p < 0.0001). Increases in nighttime drug doses were independently associated with failure to meet SBT screening criteria, SBT failure, and the decision not to extubate the patient despite successful SBT. Patients received higher doses of opioids and benzodiazepines at night. Higher nighttime doses were associated with SBT failure and delayed extubation. ClinicalTrials.gov NCT00675363 . Registered 7 May 2008.

Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS

Abstract: Objectives A recent individual patient data (IPD) meta-analysis suggested that patients with moderate or severe acute respiratory distress syndrome (ARDS) benefit from higher positive end-expiratory pressure (PEEP) ventilation strategies. However, thresholds for continuous variables (eg, hypoxaemia) are often arbitrary and linearity assumptions in regression approaches may not hold; the multivariable fractional polynomial interaction (MFPI) approach can address both problems. The objective of this study was to apply the MFPI approach to investigate interactions between four continuous patient baseline variables and higher versus lower PEEP on clinical outcomes. Setting Pooled data from three randomised trials in intensive care identified by a systematic review. Participants 2299 patients with acute lung injury requiring mechanical ventilation. Interventions Higher (N=1136) versus lower PEEP (N=1163) ventilation strategy. Outcome measures Prespecified outcomes included mortality, time to death and time-to-unassisted breathing. We examined the following continuous baseline characteristics as potential effect modifiers using MFPI: PaO 2 /FiO 2 (arterial partial oxygen pressure/ fraction of inspired oxygen), oxygenation index, respiratory system compliance (tidal volume/(inspiratory plateau pressure−PEEP)) and body mass index (BMI). Results We found that for patients with PaO 2 /FiO 2 below 150 mm Hg, but above 100 mm Hg or an oxygenation index above 12 (moderate ARDS), higher PEEP reduces hospital mortality, but the beneficial effect appears to level off for patients with very severe ARDS. Patients with mild ARDS (PaO 2 /FiO 2 above 200 mm Hg or an oxygenation index below 10) do not seem to benefit from higher PEEP and might even be harmed. For patients with a respiratory system compliance above 40 mL/cm H 2 O or patients with a BMI above 35 kg/m 2 , we found a trend towards reduced mortality with higher PEEP, but there is very weak statistical confidence in these findings. Conclusions MFPI analyses suggest a nonlinear effect modification of higher PEEP ventilation by PaO 2 /FiO 2 and oxygenation index with reduced mortality for some patients suffering from moderate ARDS. Study registration number CRD42012003129.

Assessment of Postresuscitation Volume Status by Bioimpedance Analysis in Patients with Sepsis in the Intensive Care Unit: A Pilot Observational Study

Abstract: Background. Bioimpedance analysis (BIA) is a novel method of assessing a patient's volume status. Objective. We sought to determine the feasibility of using vector length (VL), derived from bioimpedance analysis (BIA), in the assessment of postresuscitation volume status in intensive care unit (ICU) patients with sepsis. Method. This was a prospective observational single-center study. Our primary outcome was feasibility. Secondary clinical outcomes included ventilator status and acute kidney injury. Proof of concept was sought by correlating baseline VL measurements with other known measures of volume status. Results. BIA was feasible to perform in the ICU. We screened 655 patients, identified 78 eligible patients, and approached 64 for consent. We enrolled 60 patients (consent rate of 93.8%) over 12 months. For each 50-unit increase in VL, there was an associated 22% increase in the probability of not requiring invasive mechanical ventilation (IMV) (p = 0.13). Baseline VL correlated with other measures of volume expansion including serum pro-BNP levels, peripheral edema, and central venous pressure (CVP). Conclusion. It is feasible to use BIA to predict postresuscitation volume status and patient-important outcomes in septic ICU patients. Trial Registration. This trial is registered with clinicaltrials.gov NCT01379404 registered on June 7, 2011.