Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults: A Secondary Exploratory Analysis of the BaSICS Clinical Trial.

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).

Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial.

IMPORTANCE: Intravenous fluids are used for almost all intensive care unit (ICU) patients. Clinical and laboratory studies have questioned whether specific fluid types result in improved outcomes, including mortality and acute kidney injury. OBJECTIVE: To determine the effect of a balanced solution vs saline solution (0.9% sodium chloride) on 90-day survival in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Patients who were admitted to the ICU with at least 1 risk factor for worse outcomes, who required at least 1 fluid expansion, and who were expected to remain in the ICU for more than 24 hours were randomized between May 29, 2017, and March 2, 2020; follow-up concluded on October 29, 2020. Patients were randomized to 2 different fluid types (a balanced solution vs saline solution reported in this article) and 2 different infusion rates (reported separately). INTERVENTIONS: Patients were randomly assigned 1:1 to receive either a balanced solution (n = 5522) or 0.9% saline solution (n = 5530) for all intravenous fluids. MAIN OUTCOMES AND MEASURES: The primary outcome was 90-day survival. RESULTS: Among 11 052 patients who were randomized, 10 520 (95.2%) were available for the analysis (mean age, 61.1 [SD, 17] years; 44.2% were women). There was no significant interaction between the 2 interventions (fluid type and infusion speed; P = .98). Planned surgical admissions represented 48.4% of all patients. Of all the patients, 60.6% had hypotension or vasopressor use and 44.3% required mechanical ventilation at enrollment. Patients in both groups received a median of 1.5 L of fluid during the first day after enrollment. By day 90, 1381 of 5230 patients (26.4%) assigned to a balanced solution died vs 1439 of 5290 patients (27.2%) assigned to saline solution (adjusted hazard ratio, 0.97 [95% CI, 0.90-1.05]; P = .47). There were no unexpected treatment-related severe adverse events in either group. CONCLUSION AND RELEVANCE: Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02875873.

Effect of a Multifaceted Quality Improvement Intervention on the Prescription of Evidence-Based Treatment in Patients at High Cardiovascular Risk in Brazil: The BRIDGE Cardiovascular Prevention Cluster Randomized Clinical Trial.

Importance: Studies have found that patients at high cardiovascular risk often fail to receive evidence-based therapies in community practice. Objective: To evaluate whether a multifaceted quality improvement intervention can improve the prescription of evidence-based therapies. Design, Setting, and Participants: In this 2-arm cluster randomized clinical trial, patients with established atherothrombotic disease from 40 public and private outpatient clinics (clusters) in Brazil were studied. Patients were recruited from August 2016 to August 2017, with follow-up to August 2018. Data were analyzed in September 2018. Interventions: Case management, audit and feedback reports, and distribution of educational materials (to health care professionals and patients) vs routine practice. Main Outcomes and Measures: The primary end point was prescription of evidence-based therapies (ie, statins, antiplatelet therapy, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) using the all-or-none approach at 12 months after the intervention period in patients without contraindications. Results: Of the 1619 included patients, 1029 (63.6%) were male, 1327 (82.0%) had coronary artery disease (843 [52.1%] with prior acute myocardial infarction), 355 (21.9%) had prior ischemic stroke or transient ischemic attack, and 197 (12.2%) had peripheral vascular disease, and the mean (SD) age was 65.6 (10.5) years. Among randomized clusters, 30 (75%) were cardiology sites, 6 (15%) were primary care units, and 26 (65%) were teaching institutions. Among eligible patients, those in intervention clusters were more likely to receive a prescription of evidence-based therapies than those in control clusters (73.5% [515 of 701] vs 58.7% [493 of 840]; odds ratio, 2.30; 95% CI, 1.14-4.65). There were no differences between the intervention and control groups with regards to risk factor control (ie, hyperlipidemia, hypertension, or diabetes). Rates of education for smoking cessation were higher among current smokers in the intervention group than in the control group (51.9% [364 of 701] vs 18.2% [153 of 840]; odds ratio, 11.24; 95% CI, 2.20-57.43). The rate of cardiovascular mortality, acute myocardial infarction, and stroke was 2.6% for patients from intervention clusters and 3.4% for those in the control group (hazard ratio, 0.76; 95% CI, 0.43-1.34). Conclusions and Relevance: Among Brazilian patients at high cardiovascular risk, a quality improvement intervention resulted in improved prescription of evidence-based therapies. Trial Registration: ClinicalTrials.gov identifier: NCT02851732.

Rationale and design for a cluster randomized quality-improvement trial to increase the uptake of evidence-based therapies for patients at high cardiovascular risk: The BRIDGE-Cardiovascular Prevention trial.

BACKGROUND: Translating evidence into clinical practice in the management of high cardiovascular risk patients is challenging. Few quality improvement interventions have rigorously evaluated their impact on both patient care and clinical outcomes. OBJECTIVES: The main objectives are to evaluate the impact of a multifaceted educational intervention on adherence to local guidelines for the prescription of statins, antiplatelets and angiotensin converting enzyme inhibitors or angiotensin II receptor blockers for high cardiovascular risk patients, as well as on the incidence of major cardiovascular events. DESIGN: We designed a pragmatic two arm cluster randomized trial involving 40 clusters. Clusters are randomized to receive a multifaceted quality improvement intervention or to routine practice (control). The multifaceted intervention includes: reminders, care algorithms, training of a case manager, audit and feedback reports, and distribution of educational materials to health care providers. The primary endpoint is the adherence to combined evidence-based therapies (statins, antiplatelet therapy and angiotensin converting enzyme inhibitors or angiotensin receptor blockers) at 12 months after the intervention period in patients without contra-indications for these medications. All analyses follow the intention-to-treat principle and take the cluster design into account using linear mixed logistic regression modeling. SUMMARY: If proven effective, this multifaceted intervention would have wide utility as a means of promoting optimal usage of evidence-based interventions for the management of high cardiovascular risk patients.

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.

Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients: A Randomized Clinical Trial.

IMPORTANCE: The effectiveness of checklists, daily goal assessments, and clinician prompts as quality improvement interventions in intensive care units (ICUs) is uncertain. OBJECTIVE: To determine whether a multifaceted quality improvement intervention reduces the mortality of critically ill adults. DESIGN, SETTING, AND PARTICIPANTS: This study had 2 phases. Phase 1 was an observational study to assess baseline data on work climate, care processes, and clinical outcomes, conducted between August 2013 and March 2014 in 118 Brazilian ICUs. Phase 2 was a cluster randomized trial conducted between April and November 2014 with the same ICUs. The first 60 admissions of longer than 48 hours per ICU were enrolled in each phase. INTERVENTIONS: Intensive care units were randomized to a quality improvement intervention, including a daily checklist and goal setting during multidisciplinary rounds with follow-up clinician prompting for 11 care processes, or to routine care. MAIN OUTCOMES AND MEASURES: In-hospital mortality truncated at 60 days (primary outcome) was analyzed using a random-effects logistic regression model, adjusted for patients' severity and the ICU's baseline standardized mortality ratio. Exploratory secondary outcomes included adherence to care processes, safety climate, and clinical events. RESULTS: A total of 6877 patients (mean age, 59.7 years; 3218 [46.8%] women) were enrolled in the baseline (observational) phase and 6761 (mean age, 59.6 years; 3098 [45.8%] women) in the randomized phase, with 3327 patients enrolled in ICUs (n = 59) assigned to the intervention group and 3434 patients in ICUs (n = 59) assigned to routine care. There was no significant difference in in-hospital mortality between the intervention group and the usual care group, with 1096 deaths (32.9%) and 1196 deaths (34.8%), respectively (odds ratio, 1.02; 95% CI, 0.82-1.26; P = .88). Among 20 prespecified secondary outcomes not adjusted for multiple comparisons, 6 were significantly improved in the intervention group (use of low tidal volumes, avoidance of heavy sedation, use of central venous catheters, use of urinary catheters, perception of team work, and perception of patient safety climate), whereas there were no significant differences between the intervention group and the control group for 14 outcomes (ICU mortality, central line-associated bloodstream infection, ventilator-associated pneumonia, urinary tract infection, mean ventilator-free days, mean ICU length of stay, mean hospital length of stay, bed elevation to ≥30°, venous thromboembolism prophylaxis, diet administration, job satisfaction, stress reduction, perception of management, and perception of working conditions). CONCLUSIONS AND RELEVANCE: Among critically ill patients treated in ICUs in Brazil, implementation of a multifaceted quality improvement intervention with daily checklists, goal setting, and clinician prompting did not reduce in-hospital mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01785966.

Direct examination and cultures of bronchoalveolar lavage in pneumonia diagnosis: a comparative experimental study.

OBJECTIVE: To assess the accuracy of direct examination and quantitative cultures of BAL to diagnose pneumonia with or without antibiotic treatment. DESIGN: Experimental rat models. INTERVENTIONS: Pneumonia was induced by intratracheal inoculation of S. pneumoniae (10(9) cfu/ml) or P. aeruginosa (10(8)cfu/ml). Controls (n = 10) received sterile inoculum. Study animals received penicillin (n = 19) or saline (n = 18) (pneumococcal model); amikacin (n = 13), ceftazidime (n = 11), or saline (n = 13) (Pseudomonas model). BAL was assessed 48 h after infection. The animals were killed for histopathological analysis. RESULTS: All study animals developed pneumonia, which was more extensive in the pneumococcal than in the Pseudomonas model. In pneumococcal pneumonia the sensitivity of BAL cultures (10(3) cfu/ml or higher) was 77.8% with saline and 21.0% with penicillin. In the Pseudomonas ceftazidime group all specimens were negative, precluding diagnosis. The sensitivity of cultures with amikacin was 23.1% vs. 30.8% with saline. In the pneumococcal model intracellular organism (ICO) count of 2% or higher had a sensitivity of 100% for detecting pneumonia with saline and 57.9% with penicillin. In the Pseudomonas model the sensitivity of ICO was 69.2% with both amikacin and saline and 36.3% with ceftazidime. The sensitivity of neutrophil count above 50% in pneumococcal pneumonia was 77.8% and 64.7% with saline and penicillin, respectively, and 69.2%, 61.5%, and 81.8% with saline, amikacin, and ceftazidime, respectively, in Pseudomonas pneumonia. CONCLUSIONS: BAL-positive intracellular organisms were more accurate than cultures for the diagnosis of recent pneumonia, and were less affected by antibiotic treatment.