IntroductionIn the setting of early acute kidney injury (AKI), no test has been shown to definitively predict the progression to more severe stages.MethodsWe investigated the ability of a furosemide stress test (FST) (one-time dose of 1.0 or 1.5 mg/kg depending on prior furosemide-exposure) to predict the development of AKIN Stage-III in 2 cohorts of critically ill subjects with early AKI. Cohort 1 was a retrospective cohort who received a FST in the setting of AKI in critically ill patients as part of Southern AKI Network. Cohort 2 was a prospective multicenter group of critically ill patients who received their FST in the setting of early AKI.ResultsWe studied 77 subjects; 23 from cohort 1 and 54 from cohort 2; 25 (32.4%) met the primary endpoint of progression to AKIN-III. Subjects with progressive AKI had significantly lower urine output following FST in each of the first 6 hours (p<0.001). The area under the receiver operator characteristic curves for the total urine output over the first 2 hours following FST to predict progression to AKIN-III was 0.87 (p = 0.001). The ideal-cutoff for predicting AKI progression during the first 2 hours following FST was a urine volume of less than 200mls(100ml/hr) with a sensitivity of 87.1% and specificity 84.1%.ConclusionsThe FST in subjects with early AKI serves as a novel assessment of tubular function with robust predictive capacity to identify those patients with severe and progressive AKI. Future studies to validate these findings are warranted.
A 72-hr, continuous intravenous infusion of rhIL-1ra failed to demonstrate a statistically significant reduction in mortality when compared with standard therapy in this multicenter clinical trial. If rhIL-1ra treatment has any therapeutic activity in severe sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial.
Clinicians have access to limited tools that predict which patients with early AKI will progress to more severe stages. In early AKI, urine output after a furosemide stress test (FST), which involves intravenous administration of furosemide (1.0 or 1.5 mg/kg), can predict the development of stage 3 AKI. We measured several AKI biomarkers in our previously published cohort of 77 patients with early AKI who received an FST and evaluated the ability of FST urine output and biomarkers to predict the development of stage 3 AKI (n=25 [32.5%]), receipt of RRT (n=11 [14.2%]), or inpatient mortality (n=16 [20.7%]). With an area under the curve (AUC)6SEM of 0.8760.09 (P,0.0001), 2-hour urine output after FST was significantly better than each urinary biomarker tested in predicting progression to stage 3 (P,0.05). FST urine output was the only biomarker to significantly predict RRT (0.8660.08; P=0.001). Regardless of the end point, combining FST urine output with individual biomarkers using logistic regression did not significantly improve risk stratification (DAUC, P.0.10 for all). When FST urine output was assessed in patients with increased biomarker levels, the AUC for progression to stage 3 improved to 0.9060.06 and the AUC for receipt of RRT improved to 0.9160.08. Overall, in the setting of early AKI, FST urine output outperformed biochemical biomarkers for prediction of progressive AKI, need for RRT, and inpatient mortality. Using a FST in patients with increased biomarker levels improves risk stratification, although further research is needed.
IntroductionPatients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown.MethodsIn total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N =10) or placebo (N =10) plus standard of care. ATII was started at a dose of 20 ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65 mmHg. The infusion (either ATII or placebo) was continued for 6 hours then titrated off. The primary endpoint was the effect of ATII on the standing dose of norepinephrine required to maintain a MAP of 65 mmHg.ResultsATII resulted in marked reduction in norepinephrine dosing in all patients. The mean hour 1 norepinephrine dose for the placebo cohort was 27.6 ± 29.3 mcg/min versus 7.4 ± 12.4 mcg/min for the ATII cohort (P =0.06). The most common adverse event attributable to ATII was hypertension, which occurred in 20% of patients receiving ATII. 30-day mortality for the ATII cohort and the placebo cohort was similar (50% versus 60%, P =1.00).ConclusionAngiotensin II is an effective rescue vasopressor agent in patients with distributive shock requiring multiple vasopressors. The initial dose range of ATII that appears to be appropriate for patients with distributive shock is 2 to 10 ng/kg/min.Trial registrationClinicaltrials.gov NCT01393782. Registered 12 July 2011.
Acute kidney injury (AKI) is common in critically ill patients with severe sepsis (SS), and the predictors of AKI in this population have not been well characterized. The study group was the placebo group of the Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) data set. PROWESS is a prospective, randomized, controlled study of the use of drotrecogin ␣ (activated) for the treatment of SS. Placebo patients who had an admission renal sepsis organ failure score of 2 or more were excluded. AKI was defined as an increase in serum creatinine of 25% or 0.3 mg/dl during the first week postbaseline. The incidence of relevant parameters was then compared in patients with and without AKI. Half of the patients were randomly assigned to a model-building data set, and multivariable Cox regression was used to determine risk factors. Factors that remained significant in the remaining "model validation" data set were considered significant. Of the 840 patients in the placebo group, 547 met inclusion criteria. Of the 547 patients, 127 (23.2%) patients met criteria for AKI. The mean age of the 547 patients was 59.8 ؎ 17.0, and 43.3% of the cohort were female. The ethnicity breakdown was as follows: White 83.2%, black 5.9%, and other 11%. Univariate analyses indicated that patients with AKI had a higher incidence of a dependence on the basis of activity of daily living scale (38.6 versus 26.7%; P ؍ 0.01), a lower baseline platelet count (193,000 versus 222,000; P ؍ 0.02), a higher baseline respiratory Sepsis Organ Failure Assessment score (2.9 versus 2.7; P ؍ 0.02), higher preinfusion Acute Physiology and Chronic Health Evaluation II (APACHE II) score (24.8 versus 22.0; P ؍ 0.0002), older age (63.7 versus 58.7 yr; P ؍ 0.008), and higher log IL-6 (6.6 versus 5.8; P ؍ 0.0006). In a multivariable Cox regression, the predictors of AKI were log IL-6 (P < 0.0001) and APACHE II (P ؍ 0.0008). Increased log IL-6 and APACHE II score are significant risk factors of AKI in patients with SS. IL-6 data and the absence of correlation with measures of hypotension (e.g., mean arterial pressure, dosage of vasopressors) support the notion that inflammation is a significant component of AKI in SS.
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