Faculty Bibliography

OBJECTIVE: The Lung Injury Prediction Score identifies patients at risk for acute respiratory distress syndrome in the emergency department, but it has not been validated in non-emergency department hospitalized patients. We aimed to evaluate whether Lung Injury Prediction Score identifies non-emergency department hospitalized patients at risk of developing acute respiratory distress syndrome at the time of critical care contact. DESIGN: Retrospective study. SETTING: Five academic medical centers. PATIENTS: Nine hundred consecutive patients (>/= 18 yr old) with at least one acute respiratory distress syndrome risk factor at the time of critical care contact. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Lung Injury Prediction Score was calculated using the worst values within the 12 hours before initial critical care contact. Patients with acute respiratory distress syndrome at the time of initial contact were excluded. Acute respiratory distress syndrome developed in 124 patients (13.7%) a median of 2 days (interquartile range, 2-3) after critical care contact. Hospital mortality was 22% and was significantly higher in acute respiratory distress syndrome than non-acute respiratory distress syndrome patients (48% vs 18%; p < 0.001). Increasing Lung Injury Prediction Score was significantly associated with development of acute respiratory distress syndrome (odds ratio, 1.31; 95% CI, 1.21-1.42) and the composite outcome of acute respiratory distress syndrome or death (odds ratio, 1.26; 95% CI, 1.18-1.34). A Lung Injury Prediction Score greater than or equal to 4 was associated with the development of acute respiratory distress syndrome (odds ratio, 4.17; 95% CI, 2.26-7.72), composite outcome of acute respiratory distress syndrome or death (odds ratio, 2.43; 95% CI, 1.68-3.49), and acute respiratory distress syndrome after accounting for the competing risk of death (hazard ratio, 3.71; 95% CI, 2.05-6.72). For acute respiratory distress syndrome development, the Lung Injury Prediction Score has an area under the receiver operating characteristic curve of 0.70 and a Lung Injury Prediction Score greater than or equal to 4 has 90% sensitivity (misses only 10% of acute respiratory distress syndrome cases), 31% specificity, 17% positive predictive value, and 95% negative predictive value. CONCLUSIONS: In a cohort of non-emergency department hospitalized patients, the Lung Injury Prediction Score and Lung Injury Prediction Score greater than or equal to 4 can identify patients at increased risk of acute respiratory distress syndrome and/or death at the time of critical care contact but it does not perform as well as in the original emergency department cohort.

IMPORTANCE: Management of acute respiratory distress syndrome (ARDS) remains largely supportive. Whether early intervention can prevent development of ARDS remains unclear. OBJECTIVE: To evaluate the efficacy and safety of early aspirin administration for the prevention of ARDS. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 16 US academic hospitals. Between January 2, 2012, and November 17, 2014, 7673 patients at risk for ARDS (Lung Injury Prediction Score >/=4) in the emergency department were screened and 400 were randomized. Ten patients were excluded, leaving 390 in the final modified intention-to-treat analysis cohort. INTERVENTIONS: Administration of aspirin, 325-mg loading dose followed by 81 mg/d (n = 195) or placebo (n = 195) within 24 hours of emergency department presentation and continued to hospital day 7, discharge, or death. MAIN OUTCOMES AND MEASURES: The primary outcome was the development of ARDS by study day 7. Secondary measures included ventilator-free days, hospital and intensive care unit length of stay, 28-day and 1-year survival, and change in serum biomarkers associated with ARDS. A final alpha level of .0737 (alpha = .10 overall) was required for statistical significance of the primary outcome. RESULTS: Among 390 analyzed patients (median age, 57 years; 187 [48%] women), the median (IQR) hospital length of stay was 6 3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (10.3% vs 8.7%, respectively; odds ratio, 1.24 [92.6% CI, 0.67 to 2.31], P = .53). No significant differences were seen in secondary outcomes: ventilator-free to day 28, mean (SD), 24.9 (7.4) days vs 25.2 (7.0) days (mean [90% CI] difference, -0.26 [-1.46 to 0.94] days; P = .72); ICU length of stay, mean (SD), 5.2 (7.0) days vs 5.4 (7.0) days (mean [90% CI] difference, -0.16 [-1.75 to 1.43] days; P = .87); hospital length of stay, mean (SD), 8.8 (10.3) days vs 9.0 (9.9) days (mean [90% CI] difference, -0.27 [-1.96 to 1.42] days; P = .79); or 28-day survival, 90% vs 90% (hazard ratio [90% CI], 1.03 [0.60 to 1.79]; P = .92) or 1-year survival, 73% vs 75% (hazard ratio [90% CI], 1.06 [0.75 to 1.50]; P = .79). Bleeding-related adverse events were infrequent in both groups (aspirin vs placebo, 5.6% vs 2.6%; odds ratio [90% CI], 2.27 [0.92 to 5.61]; P = .13). RESULTS: Among 390 analyzed patients (median age, 57 years; 187 [48%] women), median (IQR) hospital length of stay was 6 (3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (OR, 1.24; 92.6%CI, 0.67-2.31). No significant differences were seen in secondary outcomes or adverse events. [table: see text] CONCLUSIONS AND RELEVANCE: Among at-risk patients presenting to the ED, the use of aspirin compared with placebo did not reduce the risk of ARDS at 7 days. The findings of this phase 2b trial do not support continuation to a larger phase 3 trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01504867.

The intensive care unit (ICU) was initially developed in the 1950s to treat patients who required invasive respiratory support and hemodynamic resuscitation. Since the beginning, ICU medicine has focused on maintaining sufficient arterial blood flow and oxygenation to provide adequate tissue oxygen delivery to forestall or reverse organ failure. Over time, ICU medicine became more intensive, with the administration of many diagnostic tests and monitors, invasive procedures, and treatments, often with scant evidence of benefit associated with them. An alternative perspective holds that ICU patients may represent a group of patients that is especially vulnerable to iatrogenic harm. We outline a case that presents common ICU dilemmas and discusses current data that propose that "less is more" when making key diagnostic or therapeutic choices in the ICU. Further, we assert that providers should skeptically consider common ICU interventions, trying to account for the potential unintended consequences of interventions. Finally, we suggest that the guiding principle of ICU medicine should be primum non nocere: in delicate situations, it may be better not to do something, or even to do nothing, rather than risk causing harm.

Dead space fraction (V d/V t) measurement performed using volumetric capnography requires arterial blood gas (ABG) sampling to estimate the partial pressure of carbon dioxide (PaCO2). In recent years, transcutaneous capnography (PtcCO2) has emerged as a noninvasive method of estimating PaCO2. We hypothesized that PtcCO2 can be used as a substitute for PaCO2 in the calculation of V d/V t. In this prospective pilot comparison study, 30 consecutive postcardiac surgery mechanically ventilated patients had V d/V t calculated separately using volumetric capnography by substituting PtcCO2 for PaCO2. The mean V d/V t calculated using PaCO2 and PtcCO2 was 0.48 +/- 0.09 and 0.53 +/- 0.08, respectively, with a strong positive correlation between the two methods of calculation (Pearson's correlation = 0.87, p < 0.05). Bland-Altman analysis showed a mean difference of -0.05 (95% CI: -0.01 to -0.09) between the two methods. PtcCO2 measurements can provide a noninvasive means to measure V d/V t, thus accessing important physiologic information and prognostic assessment in patients receiving mechanical ventilation.