Recent advances in understanding and treating acute respiratory distress syndrome [version 1; referees: 2 approved]

Acute respiratory distress syndrome (ARDS) is a clinically and biologically heterogeneous disorder associated with many disease processes that injure the lung, culminating in increased non-hydrostatic extravascular lung water, reduced compliance, and severe hypoxemia. Despite enhanced understanding of molecular mechanisms, advances in ventilatory strategies, and general care of the critically ill patient, mortality remains unacceptably high. The Berlin definition of ARDS has now replaced the American-European Consensus Conference definition. The recently concluded Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) provided worldwide epidemiological data of ARDS including prevalence, geographic variability, mortality, and patterns of mechanical ventilation use. Failure of clinical therapeutic trials prompted the investigation and subsequent discovery of two distinct phenotypes of ARDS (hyper-inflammatory and hypo-inflammatory) that have different biomarker profiles and clinical courses and respond differently to the random application of positive end expiratory pressure (PEEP) and fluid management strategies. Low tidal volume ventilation remains the predominant mainstay of the ventilatory strategy in ARDS. High-frequency oscillatory ventilation, application of recruitment maneuvers, higher PEEP, extracorporeal membrane oxygenation, and alternate modes of mechanical ventilation have failed to show benefit. Similarly, most pharmacological therapies including keratinocyte growth factor, beta-2 agonists, and aspirin did not improve outcomes. Prone positioning and early neuromuscular blockade have demonstrated mortality benefit, and clinical guidelines now recommend their use. Current ongoing trials include the use of mesenchymal stem cells, vitamin C, re-evaluation of neuromuscular blockade, and extracorporeal carbon dioxide removal. In this article, we describe advances in the diagnosis, epidemiology, and treatment of ARDS over the past decade

Effect of Rosuvastatin on Acute Kidney Injury in Sepsis-Associated Acute Respiratory Distress Syndrome.

Background:Acute kidney injury (AKI) commonly occurs in patients with sepsis and acute respiratory distress syndrome (ARDS). Objective:To investigate whether statin treatment is protective against AKI in sepsis-associated ARDS. Design:Secondary analysis of data from Statins for Acutely Injured Lungs in Sepsis (SAILS), a randomized controlled trial that tested the impact of rosuvastatin therapy on mortality in patients with sepsis-associated ARDS. Setting:44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Patients:644 of 745 participants in SAILS who had available baseline serum creatinine data and who were not on chronic dialysis. Measurements:Our primary outcome was AKI defined using the Kidney Disease Improving Global Outcomes creatinine criteria. Randomization to rosuvastatin vs placebo was the primary predictor. Additional covariates include demographics, ARDS etiology, and severity of illness. Methods:We used multivariable logistic regression to analyze AKI outcomes in 511 individuals without AKI at randomization, and 93 with stage 1 AKI at randomization. Results:Among individuals without AKI at randomization, rosuvastatin treatment did not change the risk of AKI (adjusted odds ratio: 0.99, 95% confidence interval [CI]: 0.67-1.44). Among those with preexisting stage 1 AKI, rosuvastatin treatment was associated with an increased risk of worsening AKI (adjusted odds ratio: 3.06, 95% CI: 1.14-8.22). When serum creatinine was adjusted for cumulative fluid balance among those with preexisting stage 1 AKI, rosuvastatin was no longer associated worsening AKI (adjusted odds ratio: 1.85, 95% CI: 0.70-4.84). Limitations:Sample size, lack of urine output data, and prehospitalization baseline creatinine. Conclusion:Treatment with rosuvastatin in patients with sepsis-associated ARDS did not protect against de novo AKI or worsening of preexisting AKI

A Comparison of Administrative and Physiologic Predictive Models in Determining Risk Adjusted Mortality Rates in Critically Ill Patients

Hospitals are increasingly compared based on clinical outcomes adjusted for severity of illness. Multiple methods exist to adjust for differences between patients. The challenge for consumers of this information, both the public and healthcare providers, is interpreting differences in risk adjustment models particularly when models differ in their use of administrative and physiologic data. We set to examine how administrative and physiologic models compare to each when applied to critically ill patients.We prospectively abstracted variables for a physiologic and administrative model of mortality from two intensive care units in the United States. Predicted mortality was compared through the Pearsons Product coefficient and Bland-Altman analysis. A subgroup of patients admitted directly from the emergency department was analyzed to remove potential confounding changes in condition prior to ICU admission.We included 556 patients from two academic medical centers in this analysis. The administrative model and physiologic models predicted mortalities for the combined cohort were 15.3% (95% CI 13.7%, 16.8%) and 24.6% (95% CI 22.7%, 26.5%) (t-test p-value<0.001). The r(2) for these models was 0.297. The Bland-Atlman plot suggests that at low predicted mortality there was good agreement; however, as mortality increased the models diverged. Similar results were found when analyzing a subgroup of patients admitted directly from the emergency department. When comparing the two hospitals, there was a statistical difference when using the administrative model but not the physiologic model. Unexplained mortality, defined as those patients who died who had a predicted mortality less than 10%, was a rare event by either model.In conclusion, while it has been shown that administrative models provide estimates of mortality that are similar to physiologic models in non-critically ill patients with pneumonia, our results suggest this finding can not be applied globally to patients admitted to intensive care units. As patients and providers increasingly use publicly reported information in making health care decisions and referrals, it is critical that the provided information be understood. Our results suggest that severity of illness may influence the mortality index in administrative models. We suggest that when interpreting "report cards" or metrics, health care providers determine how the risk adjustment was made and compares to other risk adjustment models

Ventilator-Associated Pneumonia: Diagnosis, Treatment, and Prevention

While critically ill patients experience a life-threatening illness, they commonly contract ventilator-associated pneumonia. This nosocomial infection increases morbidity and likely mortality as well as the cost of health care. This article reviews the literature with regard to diagnosis, treatment, and prevention. It provides conclusions that can be implemented in practice as well as an algorithm for the bedside clinician and also focuses on the controversies with regard to diagnostic tools and approaches, treatment plans, and prevention strategies

Effect of Rosuvastatin on Acute Kidney Injury in Sepsis-Associated Acute Respiratory Distress Syndrome.

BackgroundAcute kidney injury (AKI) commonly occurs in patients with sepsis and acute respiratory distress syndrome (ARDS).ObjectiveTo investigate whether statin treatment is protective against AKI in sepsis-associated ARDS.DesignSecondary analysis of data from Statins for Acutely Injured Lungs in Sepsis (SAILS), a randomized controlled trial that tested the impact of rosuvastatin therapy on mortality in patients with sepsis-associated ARDS.Setting44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network.Patients644 of 745 participants in SAILS who had available baseline serum creatinine data and who were not on chronic dialysis.MeasurementsOur primary outcome was AKI defined using the Kidney Disease Improving Global Outcomes creatinine criteria. Randomization to rosuvastatin vs placebo was the primary predictor. Additional covariates include demographics, ARDS etiology, and severity of illness.MethodsWe used multivariable logistic regression to analyze AKI outcomes in 511 individuals without AKI at randomization, and 93 with stage 1 AKI at randomization.ResultsAmong individuals without AKI at randomization, rosuvastatin treatment did not change the risk of AKI (adjusted odds ratio: 0.99, 95% confidence interval [CI]: 0.67-1.44). Among those with preexisting stage 1 AKI, rosuvastatin treatment was associated with an increased risk of worsening AKI (adjusted odds ratio: 3.06, 95% CI: 1.14-8.22). When serum creatinine was adjusted for cumulative fluid balance among those with preexisting stage 1 AKI, rosuvastatin was no longer associated worsening AKI (adjusted odds ratio: 1.85, 95% CI: 0.70-4.84).LimitationsSample size, lack of urine output data, and prehospitalization baseline creatinine.ConclusionTreatment with rosuvastatin in patients with sepsis-associated ARDS did not protect against de novo AKI or worsening of preexisting AKI

Effect of Rosuvastatin on Acute Kidney Injury in Sepsis-Associated Acute Respiratory Distress Syndrome

Background: Acute kidney injury (AKI) commonly occurs in patients with sepsis and acute respiratory distress syndrome (ARDS). Objective: To investigate whether statin treatment is protective against AKI in sepsis-associated ARDS. Design: Secondary analysis of data from Statins for Acutely Injured Lungs in Sepsis (SAILS), a randomized controlled trial that tested the impact of rosuvastatin therapy on mortality in patients with sepsis-associated ARDS. Setting: 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Patients: 644 of 745 participants in SAILS who had available baseline serum creatinine data and who were not on chronic dialysis. Measurements: Our primary outcome was AKI defined using the Kidney Disease Improving Global Outcomes creatinine criteria. Randomization to rosuvastatin vs placebo was the primary predictor. Additional covariates include demographics, ARDS etiology, and severity of illness. Methods: We used multivariable logistic regression to analyze AKI outcomes in 511 individuals without AKI at randomization, and 93 with stage 1 AKI at randomization. Results: Among individuals without AKI at randomization, rosuvastatin treatment did not change the risk of AKI (adjusted odds ratio: 0.99, 95% confidence interval [CI]: 0.67-1.44). Among those with preexisting stage 1 AKI, rosuvastatin treatment was associated with an increased risk of worsening AKI (adjusted odds ratio: 3.06, 95% CI: 1.14-8.22). When serum creatinine was adjusted for cumulative fluid balance among those with preexisting stage 1 AKI, rosuvastatin was no longer associated worsening AKI (adjusted odds ratio: 1.85, 95% CI: 0.70-4.84). Limitations: Sample size, lack of urine output data, and prehospitalization baseline creatinine. Conclusion: Treatment with rosuvastatin in patients with sepsis-associated ARDS did not protect against de novo AKI or worsening of preexisting AKI