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We evaluated characteristics associated with neuromuscular blockade (NMB) use, center-level variation, and whether NMB mediated excess mortality among patients assigned to high-frequency oscillatory ventilation (HFOV) in the OSCILLATE trial.NMB exposure was defined as receipt after randomization; the primary outcome was hospital mortality. Descriptive analyses compared NMB-exposed vs unexposed patients. Multivariable analyses included patients not on baseline NMB. Cox regression evaluated associations of patient- and center-level variables with NMB use. A log-normal frailty model evaluated center effects. Mediation analysis examined the effect of NMB in HFOV-assigned patients.376/548 patients (39 centers) received post-randomization NMB, of whom 165 received baseline NMB. Patients receiving post-randomization NMB (vs. not) had worse lung mechanics and gas exchange, received more sedation and vasopressors (p 0.05), and had higher hospital mortality (44% vs. 34%, p = 0.03). Mean airway pressure ≥ 24 cmHIn OSCILLATE, receipt of post-randomization NMB was associated with worse outcomes, but NMB use did not mediate HFOV-associated higher mortality.

Purpose Severe acute kidney injury (AKI) is associated with a significant risk of mortality and persistent renal replacement therapy (RRT) dependence. The objective of this study was to develop prediction models for mortality at 90-day and 1-year following RRT initiation in critically ill patients with AKI. Methods All patients who commenced RRT in the intensive care unit for AKI at a tertiary care hospital between 2007 and 2014 constituted the development cohort. We evaluated the external validity of our mortality models using data from the multicentre OPTIMAL-AKI study. Results The development cohort consisted of 594 patients, of whom 320(54%) died and 40 (15% of surviving patients) remained RRT-dependent at 90-day Eleven variables were included in the model to predict 90-day mortality (AUC:0.79, 95%CI:0.76–0.82). The performance of the 90-day mortality model declined upon validation in the OPTIMAL-AKI cohort (AUC:0.61, 95%CI:0.54–0.69) and showed modest calibration. Similar results were obtained for mortality model at 1-year. Conclusions Routinely collected variables at the time of RRT initiation have limited ability to predict mortality in critically ill patients with AKI who commence RRT.

Background Sustained low efficiency dialysis (SLED) has emerged as an alternative to continuous renal replacement therapy (CRRT) for the treatment of acute kidney injury (AKI) in critically ill patients. However, there is limited information on the short- and long-term outcomes of SLED compared to CRRT. Methods We conducted a retrospective cohort study of patients with AKI who commenced either SLED or CRRT in ICUs at a tertiary care hospital in Toronto, Canada. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at one year, and dialysis dependence at 90 days and one year. All outcomes were ascertained by linkage to provincial datasets. Results We identified 284 patients, of whom 95 and 189 commenced SLED and CRRT, respectively. Compared to SLED recipients, more CRRT recipients were mechanically ventilated (96% vs 86%, p = 0.002) and receiving vasopressors (94% vs 84%, p = 0.01) at the time of RRT initiation. At 90 days following RRT initiation, 52 (55%) and 126 (67%) SLED and CRRT recipients, respectively, died (adjusted risk ratio (RR) 0.91, 95% CI 0.75–1.11). There was no inter-modality difference in time to death through 90 days (adjusted hazard ratio 0.90, 95% CI 0.64–1.27). Among patients surviving to Day 90, a higher proportion of SLED recipients remained RRT dependent (10 (23%) vs 6 (10%) CRRT recipients, adjusted RR 2.82, 95% CI 1.02–7.81). At one year, there was no difference in mortality or dialysis dependence. Conclusions Among critically ill patients with acute kidney injury, mortality at 90 days and one year was not different among patients initiating SLED as compared to CRRT.

Purpose Gram stains of endotracheal aspirates (EA) and bronchoalveolar lavages (BAL) may guide empiric antibiotic therapy in critically ill patients with suspected ventilator-associated pneumonia (VAP). Previous studies differ regarding the ability of the Gram stain to predict final culture results. The aim of the present study was to evaluate the relationship between EA or BAL Gram stains and final culture results in intensive care unit patients with a suspected VAP. Material and Methods We retrospectively analyzed data from the Canadian multicenter VAP study to correlate EA or BAL Gram stain and final culture results. We categorized Gram stains as Gram positive (GP) and Gram negative (GN) if any GP or GN organisms respectively were seen on staining. Cultures were considered "positive" if they yielded pathogenic organisms on final results. Results Seven hundred forty patients were enrolled in the study; 35 did not have a Gram stain done leaving 350 BALs and 355 EAs from 705 patients. Pooling BAL and EA results, we found the overall agreement between Gram stain class and pathogenic bacteria culture results to be poor ( κ = 0.36; 95% CI, 0.31-0.40). Among specimens with Gram stains showing no organisms, 99 (30%) of 331 grew pathogenic organisms. Among specimens with Gram stains showing no GN organisms, 113 (25%) of 452 grew pathogenic GN organisms. Among specimens with Gram stains showing no GP organisms, 45 (11%) of 428 grew pathogenic GP organisms. Conclusions Gram stains performed for clinically suspected VAP poorly predict the final culture result and thus have a limited role in guiding initial empiric antibiotic therapy in such patients.

Purpose To examine the predictive validity of prior cultures at predicting the microorganism isolated at the time of suspicion of ventilator-associated pneumonia (VAP). Materials and Methods We performed a retrospective analysis of a randomized controlled trial of different diagnostic and antibiotic strategies. In a subset of patients with pre-enrollment cultures, we examined agreement between cultures 1 to 3 days before suspicion of VAP and enrollment cultures performed on the day of suspicion of VAP and potential antibiotic error rates (estimated using the equation 1 − crude agreement). Results Two hundred eighty-one (39%) of 739 patients had pre-enrollment culture. One hundred thirty (46%) of 281 yielded a pathogenic microorganism. In patients with positive pre-enrollment cultures, crude agreement was 0.63 (95% confidence interval, 0.55-0.71) for organism, 0.84 (0.77-0.89) for Gram class, and 0.61 (0.52-0.69) for species with sensitivity. Potential antibiotic error rates ranged from 16% (11%-33%) to 39% (31%-48%). Better agreement ( P = .033) occurred in isolates from patients receiving new antibiotics during the surveillance period (0.78 [0.64-0.87]) compared to those not on antibiotics (0.58 [0.45-0.69]), or on no new antibiotics (0.50 [0.32-0.68]). Conclusions There is poor agreement between prior cultures and cultures performed at time of suspicion of VAP. Prior cultures should not be used to narrow the spectrum of empiric antibiotics.

Our objective was to describe the current practice for initiation of RRT in this population. There is uncertainty regarding the optimal time to initiate renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI).Prospective study of patients receiving RRT in 6 intensive care units (ICUs) at 3 hospitals from July 2007 to August 2008. We characterized factors associated with start of RRT and evaluated their relationship with mortality.We included 234 patients. RRT was initiated 1 day (0-4) after ICU admission (median [interquartile range]). Median creatinine was 331 μmol/L (225-446 μmol/L), urea 22.9 mmol/L (13.9-32.9 mmol/L), and RIFLE-Failure in 76.9%. Of traditional indications, Pao(2)/Fio(2)200 (54.5%) and oliguria (32.9%) were most common. ICU and hospital mortality were 45.3% and 51.9%, respectively. In adjusted analysis, mortality at RRT initiation was associated with creatinine332 μmol/L (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.5-5.4), change in urea from admission8.9 mmol/L (OR 1.8; 95% CI, 1.0-3.4), urine output82 mL/24 hours (OR 3.0; 95% CI, 1.4-6.5), fluid balance3.0 L/24 hours (OR 2.3; 95% CI, 1.2-4.5), percentage of fluid overload5% (OR 2.3; 95% CI, 1.2-4.7), 3 or more failing organs (OR 4.5; 95% CI, 1.2-4.2), Sequential Organ Failure Assessment score14 (OR 2.3; 95% CI, 1.3-4.3), and start 4 days or more after admission (OR 4.3; 95% CI, 1.9-9.5). Mortality was higher as factors accumulated.In ICU patients requiring RRT, there was marked variation in factors that influence start of RRT. RRT initiation with fewer clinical triggers was associated with lower mortality. Timing of RRT may modify survival but requires appraisal in a randomized trial.