Patient-important upper gastrointestinal bleeding in the ICU: A mixed-methods study of patient and family perspectives.

INTRODUCTION: The objective of this study was to create a definition of patient-important upper gastrointestinal bleeding during critical illness as an outcome for a randomized trial. DESIGN: This was a sequential mixed-methods qualitative-dominant multi-center study with an instrument-building aim. In semi-structured individual interviews or focus groups we elicited views from survivors of critical illness and family members of patients in the intensive care unit (ICU) regarding which features indicate important gastrointestinal bleeding. Quantitative demographic characteristics were collected. We analyzed qualitative data using inductive content analysis to develop a definition for patient-important upper gastrointestinal bleeding. SETTING: Canada and the United States. PARTICIPANTS: 51 ICU survivors and family members of ICU patients. RESULTS: Participants considered gastrointestinal bleeding to be important if it resulted in death, disability, or prolonged hospitalization. The following also signaled patient-important upper gastrointestinal bleeding: blood transfusion, vasopressors, endoscopy, CT-angiography, or surgery. Whether an intervention evinced concern depended on its effectiveness, side-effects, invasiveness and accessibility; contextual influences included participant familiarity and knowledge of interventions and trust in the clinical team. CONCLUSIONS: Survivors of critical illness and family members described patient-important upper gastrointestinal bleeding differently than current definitions of clinically-important upper gastrointestinal bleeding.

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer's lactate.

OBJECTIVES: Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids used for fluid therapy. Despite evidence of possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function and death), few large multi-centre randomised trials have evaluated the effect of these fluids on clinically important outcomes. We conducted a pilot trial to explore the feasibility of a large trial powered for clinically important outcomes. DESIGN: FLUID was a pragmatic pilot cluster randomised cross-over trial. SETTING: Four hospitals in the province of Ontario, Canada PARTICIPANTS: All hospitalised adult and paediatric patients with an incident admission to the hospital over the course of each study period. INTERVENTIONS: A hospital wide policy/strategy which stocked either NS or RL throughout the hospital for 12 weeks before crossing over to the alternate fluid for the subsequent 12 weeks. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary feasibility outcome was study fluid protocol adherence. Secondary feasibility outcomes included time to Research Ethics Board (REB) approval and trial initiation. Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes were analysed descriptively. RESULTS: Among 24 905 included patients, mean age 59.1 (SD 20.5); 13 977 (56.1%) were female and 21 150 (85.0%) had medical or surgical admitting diagnoses. Overall, 96 821 L were administered in the NS arm, and 78 348 L in the RL arm. Study fluid adherence to NS and RL was 93.7% (site range: 91.6%-98.0%) and 79.8% (site range: 72.5%-83.9%), respectively. Time to REB approval ranged from 2 to 48 days and readiness for trial initiation from 51 to 331 days. 5544 (22.3%) patients died or required hospital re-admission in the first 90 days. CONCLUSIONS: The future large trial is feasible. Anticipating and addressing logistical challenges during the planning stages will be imperative. TRIAL REGISTRATION NUMBER: NCT02721485.

Prognostic Factors Associated With Development of Venous Thromboembolism in Critically Ill Patients-A Systematic Review and Meta-Analysis.

OBJECTIVE: To identify prognostic factors for the development of venous thromboembolism in the ICU. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception to March 1, 2021. STUDY SELECTION: We included English-language studies describing prognostic factors associated with the development of venous thromboembolism among critically ill patients. DATA EXTRACTION: Two authors performed data extraction and risk-of-bias assessment. We pooled adjusted odds ratios and adjusted hazard ratios for prognostic factors using random-effects model. We assessed risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. DATA SYNTHESIS: We included 39 observational cohort studies involving 729,477 patients. Patient factors with high or moderate certainty of association with increased odds of venous thromboembolism include older age (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29 per 10 yr), obesity (adjusted odds ratio, 1.25; 95% CI, 1.18-1.32), active malignancy (adjusted odds ratio, 1.70; 95% CI, 1.18-2.44), history of venous thromboembolism (adjusted odds ratio, 4.77; 95% CI, 3.42-6.65), and history of recent surgery (adjusted odds ratio, 1.77; 95% CI, 1.26-2.47). ICU-specific factors with high or moderate certainty of association with increased risk of venous thromboembolism include sepsis (adjusted odds ratio, 1.41; 95% CI, 1.12-1.78), lack of pharmacologic venous thromboembolism prophylaxis (adjusted odds ratio, 1.80; 95% CI, 1.14-2.84), central venous catheter (adjusted odds ratio, 2.93; 95% CI, 1.98-4.34), invasive mechanical ventilation (adjusted odds ratio, 1.74; 95% CI, 1.36-2.24), and use of vasoactive medication (adjusted odds ratio, 1.86; 95% CI, 1.23-2.81). CONCLUSIONS: This meta-analysis provides quantitative summaries of the association between patient-specific and ICU-related prognostic factors and the risk of venous thromboembolism in the ICU. These findings provide the foundation for the development of a venous thromboembolism risk stratification tool for critically ill patients.

End-of-life transitions for family member on the solid tumour oncology ward: the 3 Wishes Project.

OBJECTIVES: Although death is not uncommon for hospitalised patients with cancer, there are few interventions in oncology that are designed to create a dignified, compassionate end-of-life (EOL) experience for patients and families. The 3 Wishes Project (3WP), a programme in which clinicians elicit and implement final wishes for dying patients, has been shown effective in intensive care units (ICUs) at improving the EOL experience. The objective was to initiate 3WP on an oncology ward and evaluate its effect on family member experiences of their loved one's EOL. We hypothesised that the 3WP can be implemented in the non-ICU setting and help oncological patients and their families with transition to the EOL. METHODS: When the patient's probability of dying is greater than 95%, patients and families were invited to participate in the 3WP. Wishes were elicited, implemented and categorised. Audiorecorded, semistructured interviews were conducted with family members, transcribed and analysed using content analysis. RESULTS: 175 wishes were implemented for 52 patients with cancer (average cost of US$34). The most common wish (66%) was to personalise the environment. Qualitative analysis of 11 family member interviews revealed that the 3WP facilitates three transitions at the EOL: (1) the transition from multiple admissions to the final admission, (2) the transition of a predominantly caregiver role to a family member role and (3) the transition from a focus on the present to a focus on legacy. CONCLUSION: The 3WP can be implemented on the oncology ward and enhance the EOL experience for hospitalised patients with cancer.

Community implementation of the 3 Wishes Project: an observational study of a compassionate end-of-life care initiative for critically ill patients.

BACKGROUND: The 3 Wishes Project (3WP) promotes a personalized dying experience by eliciting and facilitating individualized terminal wishes for patients, families and the clinicians caring for them. We aimed to evaluate the adaptability of the 3WP to a community intensive care unit (ICU), and to describe the patients cared for with this palliative approach, as well as local implementation strategies. METHODS: The 3WP was implemented in a 15-bed community hospital ICU in southern Ontario from 2017 to 2019. In this observational, descriptive study, we invited adult patients (≥ 18 yr) whose risk of death was deemed to be 95% or greater by the attending physician, or patients undergoing withdrawal of life-support to participate. We abstracted patient data from medical records, as well as the type, timing and cost of each wish, which person or service made and facilitated each wish, and if and why wishes were completed or not. We summarized data both narratively and quantitatively. RESULTS: The 3WP helped to realize 479 (99.2%) of 483 terminal wishes for 101 dying patients. This initiative was introduced as an interprofessional intervention and championed by nursing staff who were responsible for most patient enrolment and wish facilitation. Wishes included humanizing the ICU environment for the patient with belongings and blankets, musical performances, smudging and bathing ceremonies, and keepsakes. The cost was $5.39 per patient (standard deviation $22.40), with 430 (89.8%) wishes incurring no cost. Wishes made directly by patients accounted for 30 (6.2%) of wishes; those from family members and ICU staff accounted for 236 (48.9%) and 238 (49.3%) of wishes, respectively. The program comforted patients and their loved ones, motivating clinicians to sustain this end-of-life intervention. INTERPRETATION: We documented successful implementation of the 3WP in a community hospital, showing program adaptability and uptake outside of academic centres at relatively low cost. The lack of strict protocolization and personalized design of this intervention underscores its inherent flexibility, with potential to promote individualized end-of-life care in nonacademic hospital wards, homes or hospice.

Lung-Protective Ventilation and Associated Outcomes and Costs Among Patients Receiving Invasive Mechanical Ventilation in the ED.

BACKGROUND: Invasive mechanical ventilation is often initiated in the ED, and mechanically ventilated patients may be kept in the ED for hours before ICU transfer. Although lung-protective ventilation is beneficial, particularly in ARDS, it remains uncertain how often lung-protective tidal volumes are used in the ED, and whether lung-protective ventilation in this setting impacts patient outcomes. RESEARCH QUESTION: What is the association between the use of lung-protective ventilation in the ED and outcomes among invasively ventilated patients? STUDY DESIGN AND METHODS: A retrospective analysis (2011-2017) of a prospective registry from eight EDs enrolling consecutive adult patients (≥ 18 years) who received invasive mechanical ventilation in the ED was performed. Lung-protective ventilation was defined by use of tidal volumes ≤ 8 mL/kg predicted body weight. The primary outcome was hospital mortality. Secondary outcomes included development of ARDS, hospital length of stay, and total hospital costs. RESULTS: The study included 4,174 patients, of whom 2,437 (58.4%) received lung-protective ventilation in the ED. Use of lung-protective ventilation was associated with decreased odds of hospital death (adjusted OR [aOR], 0.91; 95% CI, 0.84-0.96) and development of ARDS (aOR, 0.87; 95% CI, 0.81-0.92). Patients who received lung-protective ventilation in the ED had shorter median duration of mechanical ventilation (4 vs 5 days; P < 0.01), shorter median hospital length of stay (11 vs 14 days; P < .001), and reduced total hospital costs (Can$44,348 vs Can$52,484 [US$34,153 vs US$40,418]; P = .03) compared with patients who received higher tidal volumes. INTERPRETATION: Use of lung-protective ventilation in the ED was associated with important patient- and system-centered outcomes, including lower hospital mortality, decreased incidence of ARDS, lower hospital length of stay, and decreased total costs. Protocol development promoting the regular use of lung-protective ventilation in the ED may be of value.

Keepsakes at the End of Life.

CONTEXT: Keepsakes are a relatively unexplored form of bereavement support that is frequently provided as part of the 3 Wishes Project (3WP). The 3WP is a palliative care intervention in which individualized wishes are implemented in the adult intensive care unit for dying patients and their families. OBJECTIVES: We aimed to characterize and enumerate the keepsakes that were created as part of the 3WP and to understand their value from the perspective of bereaved family members. METHODS: We performed a secondary analysis of family interviews during a multicenter study on the 3WP and characterized all wishes that involved keepsakes. Sixty interviews with family members regarding the 3WP were reanalyzed using qualitative analysis to identify substantive themes related to keepsakes. RESULTS: Of 730 patients, 345 (47%) received keepsakes as part of their participation in 3WP. Most keepsakes were either tangible items that served as reminders of the patient's presence (thumbprints and locks of hair) or technology-assisted items (photographs and word clouds). The median cost per keepsake wish was $8.50 (interquartile range $2.00-$25.00). Qualitative analysis revealed two major themes: keepsakes are tangible items that are highly valued by family members; and the creation of the keepsake with clinical staff is valued and viewed as a gesture of compassion. CONCLUSION: Keepsakes are common wishes that clinicians in the intensive care unit are able to provide and sometimes cocreate with families when patients are dying. Both the offering to create the keepsake and receipt of the final product are perceived by family members as helpful.

Definitions of post-coronary artery bypass grafting myocardial infarction: variations in incidence and prognostic significance.

OBJECTIVES: Using data from the CORONARY trial (n = 4752), we evaluated the incidence and prognostic significance of myocardial infarction (MI) applying different definitions based on peak postoperative creatine kinase-MB isoenzyme and cardiac troponin levels. We then aimed to identify the peak cardiac troponin during the first 3 postoperative days that was independently associated with a 2-fold increase in 30-day mortality. METHODS: To combine different assays, we analysed cardiac troponins in multiples of their respective upper limit of normal (ULN). We identified the lowest threshold with a hazard ratio (HR) >2 for 30-day mortality independent of EuroSCORE and on- versus off-pump surgery. RESULTS: Depending on the definition used based on creatine kinase-MB, the incidence of MI after coronary artery bypass grafting (CABG) ranged from 0.6% to 19% and the associated HRs for 30-day mortality ranged from 2.7 to 6.9. Using cardiac troponin (1528 patients), the incidence of MI ranged from 1.7% to 13% depending on the definition used with HRs for 30-day mortality ranging from 5.1 to 7.2. The first cardiac troponin threshold we evaluated, 180xULN, was associated with an adjusted HR for 30-day mortality of 7.6 [95% confidence interval (CI) 3.4-17.1] when compared to <130xULN. The next independent threshold was 130xULN with an adjusted HR for 30-day mortality of 7.8 (95% CI 2.3-26.1). The next cardiac troponin tested threshold (70xULN) did not meet criteria for significance. CONCLUSIONS: Our results illustrate that the incidence and prognosis of a post-CABG MI varies based on the definition used. Validated post-CABG MI diagnostic criteria formulated from their independent association with important clinical outcomes are needed.

Fostering humanism: a mixed methods evaluation of the Footprints Project in critical care.

OBJECTIVES: The objectives of this mixed-methods study were to assess the uptake, sustainability and influence of the Footprints Project. SETTING: Twenty-two-bed university-affiliated ICU in Hamilton, Canada. PARTICIPANTS: ICU patients admitted and their families, as well as clinicians. INTERVENTIONS: We developed a personalised patient Footprints Form and Whiteboard to facilitate holistic, patient-centred care, to inform clinical encounters, and to create deeper connections among patients, families and clinicians. OUTCOME MEASURES: We conducted 3 audits to examine uptake and sustainability. We conducted semi-structured interviews with 10 clinicians, and held 5 focus groups with 25 clinicians; and we interviewed 5 patients and 13 family representatives of 5 patients who survived and 5 who died in the ICU. Transcripts were analysed using qualitative content analysis. RESULTS: The Footprints Project facilitated holistic, patient-centred care by setting the stage for patient and family experience, motivating the patient and humanising the patient for clinicians. Through informing clinical encounters, Footprints helped clinicians initiate more personal conversations, foster deeper connections and guide treatment. Professional practice influences included more focused attention on the patient, enhanced interdisciplinary communication and changes in community culture. Initially used in 15.8% of patients (audit A), uptake increased to 51.4% in audit B, and was sustained at 57.8% in audit C. CONCLUSIONS: By sharing valuable personal information about patients before and beyond their illness on individualised whiteboards at each bedside, the Footprints Project fosters humanism in critical care practice.

Improving End-of-Life Care in the Intensive Care Unit: Clinicians' Experiences with the 3 Wishes Project.

Background: End-of-life (EOL) care is an important aspect of practice in the intensive care unit (ICU), where approximately one of every five patients may die. Objective: The objective of this study was to describe clinicians' experiences with the 3 Wishes Project (3WP) and understand the influence of the project on care in the ICU. Design: The 3WP is a palliative care intervention in which clinicians elicit and implement final wishes for patients dying in the ICU; it had been implemented for seven months at the time of this study. This mixed-methods study includes quantitative data from clinician surveys and qualitative data from clinician focus groups. Setting: A 24-bed medical ICU in a tertiary academic center. Subjects: Perspectives of 97 clinicians working in the ICU during the study period were obtained by self-administered surveys. Five focus groups with 25 nurses and 5 physicians were held, digitally recorded, transcribed, and analyzed. Measurements and Results: During the 7-month period, 67 decedents and their families participated in the 3WP. The overarching concept identified through analysis of the survey and focus group data is that the 3WP improves EOL care in the ICU, which was supported by three main themes: (1) The 3WP facilitates meaningful EOL care; (2) The 3WP has a positive impact on nurses and physicians; and (3) clinicians observe a positive influence of the 3WP on families. Conclusions: This patient-centered and family-partnered intervention facilitates meaningful EOL care, favorably impacting the ICU team and positively influencing family members.

Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial.

INTRODUCTION: There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial. METHODS: We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression. RESULTS: In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant. CONCLUSIONS: In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone.

Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery.

Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a multicenter factorial trial. Computerized Internet randomization was done between 2010 and 2013. Patients, clinicians, data collectors, and outcome adjudicators were blinded to treatment assignment. (ClinicalTrials.gov: NCT01082874). Setting: 135 centers in 23 countries. Patients: Adults aged 45 years or older who had or were at risk for atherosclerotic disease and were having noncardiac surgery. Exclusions were placement of a bare-metal stent within 6 weeks, placement of a drug-eluting stent within 1 year, or receipt of nonstudy aspirin within 72 hours before surgery. Intervention: Aspirin therapy (overall trial, n = 4998; subgroup, n = 234) or placebo (overall trial, n = 5012; subgroup, n = 236) initiated within 4 hours before surgery and continued throughout the perioperative period. Of the 470 subgroup patients, 99.9% completed follow-up. Measurements: The 30-day primary outcome was death or nonfatal myocardial infarction; bleeding was a secondary outcome. Results: In patients with prior PCI, aspirin reduced the risk for the primary outcome (absolute risk reduction, 5.5% [95% CI, 0.4% to 10.5%]; hazard ratio [HR], 0.50 [CI, 0.26 to 0.95]; P for interaction = 0.036) and for myocardial infarction (absolute risk reduction, 5.9% [CI, 1.0% to 10.8%]; HR, 0.44 [CI, 0.22 to 0.87]; P for interaction = 0.021). The effect on the composite of major and life-threatening bleeding in patients with prior PCI was uncertain (absolute risk increase, 1.3% [CI, -2.6% to 5.2%]). In the overall population, aspirin increased the risk for major bleeding (absolute risk increase, 0.8% [CI, 0.1% to 1.6%]; HR, 1.22 [CI, 1.01 to 1.48]; P for interaction = 0.50). Limitation: Nonprespecified subgroup analysis with small sample. Conclusion: Perioperative aspirin may be more likely to benefit rather than harm patients with prior PCI. Primary Funding Source: Canadian Institutes of Health Research.

Perioperative Corticosteroids Reduce Short-Term Edema and Ecchymosis in Rhinoplasty: A Meta-Analysis.

BACKGROUND: A number of randomized controlled trials (RCTs) have investigated the role of perioperative corticosteroids in rhinoplasty. Each of these trials however has an insufficient sample sizes to reach definitive conclusions and detect harms. Three recent reviews have analyzed edema and ecchymosis outcomes following rhinoplasty; each arrived at a different conclusion and recommendation. OBJECTIVE: To estimate the effectiveness of systemic perioperative corticosteroid treatment compared to placebo for clinical outcomes in rhinoplasty using a methodologically rigorous meta-analysis. METHODS: Electronic databases were searched without language restriction. Included trials were randomized controlled trials of systemic perioperative corticosteroid treatment vs placebo in rhinoplasty evaluating at least one of: edema, ecchymosis, bleeding, cosmetic outcome, and patient satisfaction. The Cochrane risk of bias tool was applied to included trials, and the quality of evidence for each outcome was assessed using the GRADE approach. RESULTS: Analyses included 336 patients from eight trials. Perioperative corticosteroids reduced the worst edema (SMD: -1.03, 95%CI -1.30 to -0.76, P < .001) and ecchymosis (SMD: -0.78, 95%CI -1.09 to 0.47, P < .001) after rhinoplasty. At one day postoperative, a single dose of perioperative corticosteroid reduced edema (SMD -1.15, 95%CI -1.42 to -0.87, P < .001) and ecchymosis (SMD -0.79, 95%CI -1.05 to -0.52, P < .001). No clinical benefit in edema or ecchymosis was found seven days postoperatively, nor did intraoperative bleeding increase. CONCLUSIONS: There is high quality evidence to support perioperative systemic corticosteroid treatment in rhinoplasty to reduce short-term edema and ecchymosis without increased intraoperative bleeding. These findings are not present at seven days. For future trials, we suggest evaluation of patient satisfaction, and correlation with long-term cosmetic outcome. LEVEL OF EVIDENCE 2: Therapeutic.

Competing Risk Analysis for Evaluation of Dalteparin Versus Unfractionated Heparin for Venous Thromboembolism in Medical-Surgical Critically Ill Patients.

Failure to recognize the presence of competing risk or to account for it may result in misleading conclusions. We aimed to perform a competing risk analysis to assess the efficacy of the low molecular weight heparin dalteparin versus unfractionated heparin (UFH) in venous thromboembolism (VTE) in medical-surgical critically ill patients, taking death as a competing risk.This was a secondary analysis of a prospective randomized study of the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT) database. A total of 3746 medical-surgical critically ill patients from 67 intensive care units (ICUs) in 6 countries receiving either subcutaneous UFH 5000 IU twice daily (n = 1873) or dalteparin 5000 IU once daily plus once-daily placebo (n = 1873) were included for analysis.A total of 205 incident proximal leg deep vein thromboses (PLDVT) were reported during follow-up, among which 96 were in the dalteparin group and 109 were in the UFH group. No significant treatment effect of dalteparin on PLDVT compared with UFH was observed in either the competing risk analysis or standard survival analysis (also known as cause-specific analysis) using multivariable models adjusted for APACHE II score, history of VTE, need for vasopressors, and end-stage renal disease: sub-hazard ratio (SHR) = 0.92, 95% confidence interval (CI): 0.70-1.21, P-value = 0.56 for the competing risk analysis; hazard ratio (HR) = 0.92, 95% CI: 0.68-1.23, P-value = 0.57 for cause-specific analysis. Dalteparin was associated with a significant reduction in risk of pulmonary embolism (PE): SHR = 0.54, 95% CI: 0.31-0.94, P-value = 0.02 for the competing risk analysis; HR = 0.51, 95% CI: 0.30-0.88, P-value = 0.01 for the cause-specific analysis. Two additional sensitivity analyses using the treatment variable as a time-dependent covariate and using as-treated and per-protocol approaches demonstrated similar findings.This competing risk analysis yields no significant treatment effect on PLDVT but a superior effect of dalteparin on PE compared with UFH in medical-surgical critically ill patients. The findings from the competing risk method are in accordance with results from the cause-specific analysis.clinicaltrials.gov Identifier: NCT00182143.

Oxygen saturation target range for extremely preterm infants: a systematic review and meta-analysis.

IMPORTANCE: The optimal oxygen saturation (SpO2) target for extremely preterm infants is unknown. OBJECTIVE: To systematically review evidence evaluating the effect of restricted vs liberal oxygen exposure on morbidity and mortality in extremely preterm infants. DATA SOURCES: MEDLINE, PubMed, CENTRAL, and CINAHL databases from their inception to March 31, 2014, and abstracts submitted to Pediatric Academic Societies from 2000 to 2014. STUDY SELECTION: All published randomized trials evaluating the effect of restricted (SpO2, 85%-89%) vs liberal (SpO2, 91%-95%) oxygen exposure in preterm infants (<28 weeks' gestation at birth). DATA EXTRACTION AND SYNTHESIS: All meta-analyses were performed using Review Manager 5.2. The Cochrane risk-of-bias tool was used to assess study quality. The summary of the findings and the level of confidence in the estimate of effect were assessed using GRADEpro. Treatment effect was analyzed using a random-effects model. MAIN OUTCOMES AND MEASURES: Death before hospital discharge, death or severe disability before 24 months, death before 24 months, neurodevelopmental outcomes, hearing loss, bronchopulmonary dysplasia, necrotizing enterocolitis, and severe retinopathy of prematurity. RESULTS: Five trials were included in the final synthesis. These studies had a similar design with a prespecified composite outcome of death/disability at 18 to 24 months corrected for prematurity; however, this outcome has not been reported for 2 of the 5 trials. There was no difference in the outcome of death/disability before 24 months (risk ratio [RR], 1.02 [95% CI, 0.92-1.14]). Mortality before 24 months was not different (RR, 1.13 [95% CI, 0.97-1.33]); however, a significant increase in mortality before hospital discharge was found in the restricted oxygen group (RR, 1.18 [95% CI, 1.03-1.36]). The rates of bronchopulmonary dysplasia, neurodevelopmental outcomes, hearing loss, and retinopathy of prematurity were similar between the 2 groups. Necrotizing enterocolitis occurred more frequently in infants on restricted oxygen (RR, 1.24 [95% CI, 1.05-1.47]). Using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria, we found that the quality of evidence for these outcomes was moderate to low. CONCLUSIONS AND RELEVANCE: Although infants cared for with a liberal oxygen target had significantly lower mortality before hospital discharge than infants cared for with a restricted oxygen target, the quality of evidence for this estimate of effect is low. Necrotizing enterocolitis occurred less frequently in the liberal oxygen group. We found no significant differences in death or disability at 24 months, bronchopulmonary dysplasia, retinopathy of prematurity, neurodevelopmental outcomes, or hearing loss at 24 months.

Laparoscopic versus open repair of recto-bladderneck and recto-prostatic anorectal malformations: a systematic review and meta-analysis.

OBJECTIVE: The laparoscopically-assisted anorectal pull-through (LAARP) for recto-bladderneck and recto-prostatic anorectal malformations (RB/RP-ARMs) is believed to improve patient outcomes. We performed a systematic review of the effect of LAARP on postoperative mucosal prolapse and defecation dysfunction. METHODS: A comprehensive search of MEDLINE, EMBASE, CENTRAL, and grey literature was performed (2000-2014). Full-text screening, data abstraction and quality appraisal were conducted in duplicate. Included studies reported a primary diagnosis of RB/RP-ARM and compared LAARP versus open repair (OPEN). RESULTS: From 3681 retrieved articles, 7 studies enrolling 187 patients were analyzed. One was a randomized control trial, 6 were retrospective observational studies, and all were single-centre. The majority were of poor-moderate quality (MINORS scores: mean 16.42 (SD 2.225) out of 24). Mucosal prolapse was not significantly different after LAARP versus OPEN (p = 0.18). Defecation outcomes were inconsistently reported but were no different between LAARP and OPEN for either children >3 years old (p = 0.84), or all ages combined (p = 0.11). CONCLUSION: We found no significant difference in rates of mucosal prolapse or defecation scores for LAARP compared to OPEN for children with RB/RP-ARMs. However, studies are small and of poor-moderate quality and results are heterogeneous. Comprehensive, standardized, reliable reporting is necessary to guide practice and inform postoperative guidelines. LEVEL OF EVIDENCE: 1c.

Failure of anticoagulant thromboprophylaxis: risk factors in medical-surgical critically ill patients*.

OBJECTIVES: To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU. DESIGN: Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial. SETTING: Sixty-seven medical-surgical ICUs in six countries. PATIENTS: Three thousand seven hundred forty-six medical-surgical critically ill patients. INTERVENTIONS: All patients received anticoagulant thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin at standard doses. MEASUREMENTS AND MAIN RESULTS: Independent predictors for venous thromboembolism, proximal leg deep vein thrombosis, and pulmonary embolism developing during critical illness were assessed. A total of 289 patients (7.7%) developed venous thromboembolism. Predictors of thromboprophylaxis failure as measured by development of venous thromboembolism included a personal or family history of venous thromboembolism (hazard ratio, 1.64; 95% CI, 1.03-2.59; p = 0.04) and body mass index (hazard ratio, 1.18 per 10-point increase; 95% CI, 1.04-1.35; p = 0.01). Increasing body mass index was also a predictor for developing proximal leg deep vein thrombosis (hazard ratio, 1.25; 95% CI, 1.06-1.46; p = 0.007), which occurred in 182 patients (4.9%). Pulmonary embolism occurred in 47 patients (1.3%) and was associated with body mass index (hazard ratio, 1.37; 95% CI, 1.02-1.83; p = 0.035) and vasopressor use (hazard ratio, 1.84; 95% CI, 1.01-3.35; p = 0.046). Low-molecular-weight heparin (in comparison to unfractionated heparin) thromboprophylaxis lowered pulmonary embolism risk (hazard ratio, 0.51; 95% CI, 0.27-0.95; p = 0.034) while statin use in the preceding week lowered the risk of proximal leg deep vein thrombosis (hazard ratio, 0.46; 95% CI, 0.27-0.77; p = 0.004). CONCLUSIONS: Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparin is more likely in ICU patients with elevated body mass index, those with a personal or family history of venous thromboembolism, and those receiving vasopressors. Alternate management or incremental risk reduction strategies may be needed in such patients.

Nonleg venous thrombosis in critically ill adults: a nested prospective cohort study.

IMPORTANCE: Critically ill patients are at risk of venous thrombosis, and therefore guidelines recommend daily thromboprophylaxis. Deep vein thrombosis (DVT) commonly occurs in the lower extremities but can occur in other sites including the head and neck, trunk, and upper extremities. The risk of nonleg deep venous thromboses (NLDVTs), predisposing factors, and the association between NLDVTs and pulmonary embolism (PE) or death are unclear. OBJECTIVE: To describe the frequency, anatomical location, risk factors, management, and consequences of NLDVTs in a large cohort of medical-surgical critically ill adults. DESIGN, SETTING, AND PARTICIPANTS: A nested prospective cohort study in the setting of secondary and tertiary care intensive care units (ICUs). The study population comprised 3746 patients, who were expected to remain in the ICU for at least 3 days and were enrolled in a randomized clinical trial of dalteparin vs standard heparin for thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The proportion of patients who had NLDVTs, the mean number per patient, and the anatomical location. We characterized NLDVTs as prevalent or incident (identified within 72 hours of ICU admission or thereafter) and whether they were catheter related or not. We used multivariable regression models to evaluate risk factors for NLDVT and to examine subsequent anticoagulant therapy, associated PE, and death. RESULTS Of 3746 trial patients, 84 (2.2%) developed 1 or more non-leg vein thromboses (superficial or deep, proximal or distal). Thromboses were more commonly incident (n = 75 [2.0%]) than prevalent (n = 9 [0.2%]) (P < .001) and more often deep (n = 67 [1.8%]) than superficial (n = 31 [0.8%]) (P < .001). Cancer was the only independent predictor of incident NLDVT (hazard ratio [HR], 2.22; 95% CI, 1.06-4.65). After adjusting for Acute Physiology and Chronic Health Evaluation (APACHE) II scores, personal or family history of venous thromboembolism, body mass index, vasopressor use, type of thromboprophylaxis, and presence of leg DVT, NLDVTs were associated with an increased risk of PE (HR, 11.83; 95% CI, 4.80-29.18). Nonleg DVTs were not associated with ICU mortality (HR, 1.09; 95% CI, 0.62-1.92) in a model adjusting for age, APACHE II, vasopressor use, mechanical ventilation, renal replacement therapy, and platelet count below 50 × 10(9)/L. CONCLUSIONS AND RELEVANCE Despite universal heparin thromboprophylaxis, nonleg thromboses are found in 2.2% of medical-surgical critically ill patients, primarily in deep veins and proximal veins. Patients who have a malignant condition may have a significantly higher risk of developing NLDVT, and patients with NLDVT, compared with those without, appeared to be at higher risk of PE but not higher risk of death. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00182143.

Randomized controlled trials in pediatric critical care: a scoping review.

INTRODUCTION: Evidence from randomized controlled trials (RCTs) is required to guide treatment of critically ill children, but the number of RCTs available is limited and the publications are often difficult to find. The objectives of this review were to systematically identify RCTs in pediatric critical care and describe their methods and reporting. METHODS: We searched MEDLINE, EMBASE, LILACS and CENTRAL (from inception to April 16, 2013) and reference lists of included RCTs and relevant systematic reviews. We included published RCTs administering any intervention to children in a pediatric ICU. We excluded trials conducted in neonatal ICUs, those enrolling exclusively preterm infants, and individual patient crossover trials. Pairs of reviewers independently screened studies for eligibility, assessed risk of bias, and abstracted data. Discrepancies were resolved by consensus. RESULTS: We included 248 RCTs: 45 (18%) were multicentered and 14 (6%) were multinational. Trials most frequently enrolled both medical and surgical patients (43%) but postoperative cardiac surgery was the single largest population studied (19%). The most frequently evaluated types of intervention were medications (63%), devices (11%) and nutrition (8%). Laboratory or physiological measurements were the most frequent type of primary outcomes (18%). Half of these trials (50%) reported blinding. Of the 107 (43%) trials that reported an a priori sample size, 34 (32%) were stopped early. The median number of children randomized per trial was 49 and ranged from 6 to 4,947. The frequency of RCT publications increased at a mean rate of 0.7 RCTs per year (P<0.001) from 1 to 20 trials per year. CONCLUSIONS: This scoping review identified the available RCTs in pediatric critical care and made them accessible to clinicians and researchers (http://epicc.mcmaster.ca). Most focused on medications and intermediate or surrogate outcomes, were single-centered and were conducted in North America and Western Europe. The results of this review underscore the need for trials with rigorous methodology, appropriate outcome measures, and improved quality of reporting to ensure that high quality evidence exists to support clinical decision-making in this vulnerable population.

Corticosteroid use in the intensive care unit: a survey of intensivists.

OBJECTIVE: The efficacy of systemic corticosteroids in many critical illnesses remains uncertain. Our primary objective was to survey intensivists in North America about their perceived use of corticosteroids in clinical practice. DESIGN: Self-administered paper survey. POPULATION: Intensivists in academic hospitals with clinical trial expertise in critical illness. MEASUREMENTS: We generated questionnaire items in focus groups and refined them after assessments of clinical sensibility and test-retest reliability and pilot testing. We administered the survey to experienced intensivists practicing in selected North American centres actively enrolling patients in the multicentre Oscillation for ARDS Treated Early (OSCILLATE) Trial (ISRCTN87124254). Respondents used a four-point scale to grade how frequently they would administer corticosteroids in 14 clinical settings. They also reported their opinions on 16 potential near-absolute indications or contraindications for the use of corticosteroids. MAIN RESULTS: Our response rate was 82% (103/125). Respondents were general internists (50%), respirologists (22%), anesthesiologists (21%), and surgeons (7%) who practiced in mixed medical-surgical units. A majority of respondents reported almost always prescribing corticosteroids in the setting of significant bronchospasm in a mechanically ventilated patient (94%), recent corticosteroid use and low blood pressure (93%), and vasopressor-refractory septic shock (52%). Although more than half of respondents stated they would almost never prescribe corticosteroids in severe community-acquired pneumonia (81%), acute lung injury (ALI, 76%), acute respiratory distress syndrome (ARDS, 65%), and severe ARDS (51%), variability increased with severity of acute lung injury. Near-absolute indications selected by most respondents included known adrenal insufficiency (99%) and suspicion of cryptogenic organizing pneumonia (89%), connective tissue disease (85%), or other potentially corticosteroid-responsive illnesses (85%). CONCLUSIONS: Respondents reported rarely prescribing corticosteroids for ALI, but accepted them for bronchospasm, suspected adrenal insufficiency due to previous corticosteroid use, and vasopressor-refractory septic shock. These competing indications will complicate the design and interpretation of any future large-scale trial of corticosteroids in critical illness.