clinicaltrials.gov Identifier: ACTRN12613001370796.

Many animal studies have shown that high peak inspiratory pressures (PIP) during mechanical ventilation can induce acute lung injury with hyaline membranes. Since 1984 we have limited PIP in patients with ARDS by reducing tidal volume, allowing spontaneous breathing with SIMV and disregarding hypercapnia. Since 1987 50 patients with severe ARDS with a "lung injury score" greater than or equal to 2.5 and a mean PaO2/FiO2 ratio of 94 were managed in this manner. The mean maximum PaCO2 was 62 mmHg, the highest being 129 mmHg. The hospital mortality was significantly lower than that predicted by Apache II (16% vs. 39.6%, chi 2 = 11.64, p less than 0.001). Only one death was due to respiratory failure, caused by pneumocystis pneumonia. 10 patients had a "ventilator score" greater than 80, which has previously predicted 100% mortality from respiratory failure. Only 2 died, neither from respiratory failure. There was no significant difference in lung injury score, ventilator score, PaO2/FiO2 or maximum PaCO2 between survivors and non-survivors. We suggest that this ventilatory management may substantially reduce mortality in ARDS, particularly from respiratory failure.

To better understand the diagnostic and predictive performance of urinary biomarkers of kidney injury, we evaluated γ-glutamyltranspeptidase (GGT), alkaline phosphatase (AP), neutrophil-gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in a prospective observational study of 529 patients in 2 general intensive care units (ICUs). Comparisons were made using the area under the receiver operator characteristic curve (AUC) for diagnosis or prediction of acute kidney injury (AKI), dialysis, or death, and reassessed after patient stratification by baseline renal function (estimated glomerular filtration rate, eGFR) and time after renal insult. On ICU entry, no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI. Several biomarkers (NGAL, CysC, and IL-18) predicted dialysis (AUC over 0.7), and all except KIM-1 predicted death at 7 days (AUC between 0.61 and 0.69). Performance was improved by stratification for eGFR or time or both. With eGFR <60ml/min, CysC and KIM-1 had AUCs of 0.69 and 0.73, respectively, within 6 h of injury, and between 12 and 36 h, CysC (0.88), NGAL (0.85), and IL-18 (0.94) had utility. With eGFR >60 ml/min, GGT (0.73), CysC (0.68), and NGAL (0.68) had the highest AUCs within 6h of injury, and between 6 and 12 h, all AUCs except AP were between 0.68 and 0.78. Beyond 12 h, NGAL (0.71) and KIM-1 (0.66) performed best. Thus, the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI.

ART-123 is a safe intervention in critically ill patients with sepsis and suspected disseminated intravascular coagulation. The study provided evidence suggestive of efficacy supporting further development of this drug in sepsis-associated coagulopathy including disseminated intravascular coagulation. Future study should focus on using ART-123 in the subgroup of patients most likely to respond to this agent.

No abstract

We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes gamma-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

No abstract

We have assessed a range of high volume, low pressure (HVLP) cuffed tracheal tubes in a benchtop model, for leakage of fluid from above the cuff to the model trachea below, during various ventilatory modes. Rapid leakage occurred in the model during all modes of ventilation, unless tracheal pressure was greater than the height of fluid in the column above the cuff. This leakage occurred preferentially down longitudinal folds that occur in the HVLP cuff wall. This model suggests that, if a longitudinal fold within the cuff wall is patent, then the possibility exists of subglottic to tracheal leakage.