No increase in the incidence of acute kidney injury in a population-based annual temporal trends epidemiology study.

Recent literature suggests an increase in the incidence of acute kidney injury (AKI). We evaluated population-based trends of AKI over the course of nine years, using a validated electronic health record tool to detect AKI. All adult residents (18 years of age and older) of Olmsted County, Minnesota (MN), admitted to the Mayo Clinic Hospital between 2006 and 2014 were included. The incidence rate of AKI was calculated and temporal trends in the annual AKI incident rates assessed. During the nine-year study period, 10,283, and 41,847 patients were admitted to the intensive care unit or general ward, with 1,740 and 2,811 developing AKI, respectively. The unadjusted incidence rates were 186 and 287 per 100,000 person years in 2006 and reached 179 and 317 per 100,000 person years in 2014. Following adjustment for age and sex, there was no significant change in the annual AKI incidence rate during the study period with a Relative Risk of 0.99 per year (95% confidence interval 0.97-1.01) for intensive care unit patients and 0.993 per year (0.98-1.01) for the general ward patients. Similar results were obtained when the ICD-9 codes or administrative data for dialysis-requiring AKI was utilized to determine incident cases. Thus, despite the current literature that suggests an epidemic of AKI, we found that after adjusting for age and sex the incidence of AKI in the general population remained relatively stable over the last decade.

Development and validation of severe hypoxemia associated risk prediction model in 1,000 mechanically ventilated patients*.

OBJECTIVES: Patients with severe, persistent hypoxemic respiratory failure have a higher mortality. Early identification is critical for informing clinical decisions, using rescue strategies, and enrollment in clinical trials. The objective of this investigation was to develop and validate a prediction model to accurately and timely identify patients with severe hypoxemic respiratory failure at high risk of death, in whom novel rescue strategies can be efficiently evaluated. DESIGN: Electronic medical record analysis. SETTING: Medical, surgical, and mixed ICU setting at a tertiary care institution. PATIENTS: Mechanically-ventilated ICU patients. MEASUREMENTS AND MAIN RESULTS: Mechanically ventilated ICU patients were screened for severe hypoxemic respiratory failure (Murray lung injury score of ≥ 3). Survival to hospital discharge was the dependent variable. Clinical predictors within 24 hours of onset of severe hypoxemia were considered as the independent variables. An area under the curve and a Hosmer-Lemeshow goodness-of-fit test were used to assess discrimination and calibration. A logistic regression model was developed in the derivation cohort (2005-2007). The model was validated in an independent cohort (2008-2010). Among 79,341 screened patients, 1,032 met inclusion criteria. Mortality was 41% in the derivation cohort (n = 464) and 35% in the validation cohort (n = 568). The final model included hematologic malignancy, cirrhosis, aspiration, estimated dead space, oxygenation index, pH, and vasopressor use. The area under the curve of the model was 0.85 (0.82-0.89) and 0.79 (0.75-0.82) in the derivation and validation cohorts, respectively, and showed good calibration. A modified model, including only physiologic variables, performed similarly. It had comparable performance in patients with acute respiratory distress syndrome and outperformed previous prognostic models. CONCLUSIONS: A model using comorbid conditions and physiologic variables on the day of developing severe hypoxemic respiratory failure can predict hospital mortality.

Six-month quality-of-life and functional status of acute respiratory distress syndrome survivors compared to patients at risk: a population-based study.

INTRODUCTION: The long-term attributable burden related to acute respiratory distress syndrome (ARDS) is not fully investigated. The aim of this study is to evaluate the quality of life (QOL) and functional status at 6 months after hospitalization in patients at risk for ARDS who did and did not develop the syndrome. METHOD: This is a population-based prospective cohort study of adult patients from Olmsted County, Minnesota, with or at risk for ARDS hospitalized from October 2008 to July 2011. The primary outcomes were changes in QOL and functional status, measured through 12-Item Short Form Survey (SF-12) and Barthel Index (BI) respectively, from baseline to 6 months, compared between survivors who did and did not develop ARDS. RESULTS: Of 410 patients with or at risk for ARDS, 98 had baseline surveys collected and 67 responded to a 6-month survey (26 ARDS, 41 non-ARDS). Both ARDS and non-ARDS groups had lower physical component of SF-12 at baseline compared to general population (P < 0.001 for both). ARDS patients had poorer baseline functional status compared to non-ARDS (mean BI 80 ± 25 vs. 88 ± 22, P = 0.03). No significant differences were observed for the change between 6 months and baseline BI (delta 2.3 for ARDS vs. 2.0 for non-ARDS, P = 0.5), or mental (delta 2.7 vs. 2.4, P = 0.9) or physical (delta -3 vs. -3.3, P = 0.9) component of SF-12 between survivors with and without ARDS. CONCLUSION: In this population-based study, decreased QOL and functional status 6 months after hospitalization were largely explained by baseline condition, with similar recovery in survivors who did and did not develop ARDS.

The role of potentially preventable hospital exposures in the development of acute respiratory distress syndrome: a population-based study.

OBJECTIVE: Acute respiratory distress syndrome is a common complication of critical illness, with high mortality and limited treatment options. Preliminary studies suggest that potentially preventable hospital exposures contribute to acute respiratory distress syndrome development. We aimed to determine the association between specific hospital exposures and the rate of acute respiratory distress syndrome development among at-risk patients. DESIGN: Population-based, nested, Matched case-control study. PATIENTS: Consecutive adults who developed acute respiratory distress syndrome from January 2001 through December 2010 during their hospital stay (cases) were matched to similar-risk patients without acute respiratory distress syndrome (controls). They were matched for 6 baseline characteristics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Trained investigators blinded to outcome of interest reviewed medical records for evidence of specific exposures, including medical and surgical adverse events, inadequate empirical antimicrobial treatment, hospital-acquired aspiration, injurious mechanical ventilation, transfusion, and fluid and medication administration. Conditional logistic regression was used to calculate the risk associated with individual exposures. During the 10-year period, 414 patients with hospital-acquired acute respiratory distress syndrome were identified and matched to 414 at-risk, acute respiratory distress syndrome-free controls. Adverse events were highly associated with acute respiratory distress syndrome development (odds ratio, 6.2; 95% CI, 4.0-9.7), as were inadequate antimicrobial therapy, mechanical ventilation with injurious tidal volumes, hospital-acquired aspiration, and volume of blood products transfused and fluids administered. Exposure to antiplatelet agents during the at-risk period was associated with a decreased risk of acute respiratory distress syndrome. Rate of adverse hospital exposures and prevalence of acute respiratory distress syndrome decreased during the study period. CONCLUSIONS: Prevention of adverse hospital exposures in at-risk patients may limit the development of acute respiratory distress syndrome.

Impact of SARS-CoV-2 Vaccine Rollout on Hispanic and Non-Hispanic Admission and Mortality Trends: An Interrupted Time Series Analysis.

BACKGROUND: Challenges with SARS-CoV-2 vaccine prioritization, access, and hesitancy have influenced vaccination uptake. RESEARCH QUESTION: Was the impact of SARS-CoV-2 vaccine rollout on COVID-19 monthly admission and mortality trends different between Hispanic and non-Hispanic populations? STUDY DESIGN AND METHODS: We used interrupted time series analysis to conduct an ancillary study of the Viral Infection and Respiratory Illness Universal Study registry supplemented by electronic health record data from five participating Mayo Clinic sites in Florida, Arizona, Minnesota, and Wisconsin. We included hospitalized patients with COVID-19 admitted between April 2020 and December 2021. Our primary outcome was the impact of vaccine rollout on admission trends. Our secondary outcome was the impact of vaccine rollout on mortality trends. RESULTS: This interrupted time series analysis includes 6,442 patients. Vaccine rollout was associated with improved monthly hospital admission trends among both Hispanic and non-Hispanic patients. Among Hispanic patients, pre-vaccine rollout, monthly admissions increased by 12.9% (95% CI, 8.1%-17.9%). Immediately after vaccine rollout, patient admissions declined by -66.3% (95% CI, -75.6% to -53.9%). Post-vaccine rollout, monthly admissions increased by 3.7% (95% CI, 0.2%-7.3%). Among non-Hispanic patients, pre-vaccine rollout, monthly admissions increased by 35.8% (95% CI, 33.4%-38.1%). Immediately after vaccine rollout, patient admissions declined by -75.2% (95% CI, -77.6% to -72.7%). Post-vaccine rollout, monthly admissions increased by 5.6% (95% CI, 4.5%-6.7%). These pre-vaccine rollout admission trends were significantly different (P < .001). Post-vaccine rollout, the change in admission trend was significantly different (P < .001). The associated beneficial impact from vaccine rollout on monthly hospital admission trends among Hispanic patients was significantly lower. The trend in monthly mortality rate was fourfold greater (worse) among Hispanic patients (8.3%; 95% CI, 3.6%-13.4%) vs non-Hispanic patients (2.2%; 95% CI, 0.6%-3.8%), but this was not shown to be related to vaccine rollout. INTERPRETATION: SARS-CoV-2 vaccine rollout was associated with improved COVID-19 admission trends among non-Hispanic vs Hispanic patients. Vaccine rollout was not shown to influence mortality trends in either group, which were four times higher among Hispanic patients. Improved vaccine rollout may have reduced disparities in admission trends for Hispanic patients, but other factors influenced their mortality trends.

Association Between Ethnicity and Mortality Outcomes in Patients with COVID-19: A Mayo Clinic VIRUS Registry Cohort Study.

Hispanic populations face significant disparities in health and healthcare. The COVID-19 pandemic highlighted and sometimes further exacerbated these disparities. We conducted a multisite, retrospective cohort study of 6494 hospitalized adult patients admitted between March 2020 and January 2022 with a diagnosis of COVID-19 from five sites including academic hospitals in MN, AZ, and FL and community hospitals in MN and WI. This is an ancillary project of the Viral Infection and Respiratory illness Universal Study (VIRUS) registry, supplemented by electronic health record data. We compared in-hospital mortality and length of stay outcomes between Hispanic and non-Hispanic populations admitted with COVID-19 using propensity matched scores to account for imbalances in demographic and clinical covariables. Among a total of 6494 patients, 512 (7.9%) patients were reported deceased and 5982 (92.1%) alive at discharge. We did not find a statistically significant difference between in-hospital mortality nor length of stay between the two groups.

Electronic health record surveillance algorithms facilitate the detection of transfusion-related pulmonary complications.

BACKGROUND: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are leading causes of transfusion-related mortality. Notably, poor syndrome recognition and underreporting likely result in an underestimate of their true attributable burden. We aimed to develop accurate electronic health record-based screening algorithms for improved detection of TRALI/transfused acute lung injury (ALI) and TACO. STUDY DESIGN AND METHODS: This was a retrospective observational study. The study cohort, identified from a previous National Institutes of Health-sponsored prospective investigation, included 223 transfused patients with TRALI, transfused ALI, TACO, or complication-free controls. Optimal case detection algorithms were identified using classification and regression tree (CART) analyses. Algorithm performance was evaluated with sensitivities, specificities, likelihood ratios, and overall misclassification rates. RESULTS: For TRALI/transfused ALI detection, CART analysis achieved a sensitivity and specificity of 83.9% (95% confidence interval [CI], 74.4%-90.4%) and 89.7% (95% CI, 80.3%-95.2%), respectively. For TACO, the sensitivity and specificity were 86.5% (95% CI, 73.6%-94.0%) and 92.3% (95% CI, 83.4%-96.8%), respectively. Reduced PaO2 /FiO2 ratios and the acquisition of posttransfusion chest radiographs were the primary determinants of case versus control status for both syndromes. Of true-positive cases identified using the screening algorithms (TRALI/transfused ALI, n = 78; TACO, n = 45), only 11 (14.1%) and five (11.1%) were reported to the blood bank by physicians, respectively. CONCLUSIONS: Electronic screening algorithms have shown good sensitivity and specificity for identifying patients with TRALI/transfused ALI and TACO at our institution. This supports the notion that active electronic surveillance may improve case identification, thereby providing a more accurate understanding of TRALI/transfused ALI and TACO epidemiology.

Fresh red blood cell transfusion and short-term pulmonary, immunologic, and coagulation status: a randomized clinical trial.

RATIONALE: Transfusion-related pulmonary complications are leading causes of morbidity and mortality attributed to transfusion. Observational studies suggest an important role for red blood cell (RBC) storage duration in these adverse outcomes. OBJECTIVES: To evaluate the impact of RBC storage duration on short-term pulmonary function as well as immunologic and coagulation status in mechanically ventilated patients receiving RBC transfusion. METHODS: This is a double-blind, randomized, clinical trial comparing fresh (≤5 d of storage) versus standard issue single-unit RBC transfusion in adult intubated and mechanically ventilated patients. The primary outcome is the change in pulmonary gas exchange as assessed by the partial pressure of arterial oxygen to fraction of inspired oxygen concentration ratio (ΔPa(O(2))/Fi(O(2))). Secondary outcomes include changes in immune and coagulation status. MEASUREMENTS AND MAIN RESULTS: Fifty patients were randomized to receive fresh RBCs and an additional 50 patients to standard issue RBCs. Median storage age was 4.0 days (interquartile range, 3.0-5.0) and 26.5 days (interquartile range, 21.0-36.0) in the fresh RBC group and standard issue RBC group, respectively. No differences were noted in the primary outcome of ΔPa(O(2))/Fi(O(2)) (difference between the mean ΔPa(O(2))/Fi(O(2)) in the standard issue RBC group vs. the fresh RBC group, -11.5; 95% confidence interval, -35.3 to 12.3; P = 0.22). Similarly, no significant differences were noted in markers of immunologic or coagulation status. CONCLUSIONS: In this randomized clinical trial, no differences were noted in early measures of pulmonary function or in immunologic or coagulation status when comparing fresh versus standard issue single-unit RBC transfusion. Clinical trial registered with ClinicalTrials.gov (NCT00751322).

CHARACTERISTICS AND PREDICTORS OF PATIENTS WITH SEPSIS WHO ARE CANDIDATES FOR MINIMALLY INVASIVE APPROACH OUTSIDE OF INTENSIVE CARE UNIT.

ABSTRACT: Objective: To identify and describe characteristics of patients with sepsis who could be treated with minimally invasive sepsis (MIS) approach without intensive care unit (ICU) admission and to develop a prediction model to select candidates for MIS approach. Methods: A secondary analysis of the electronic database of patients with sepsis at Mayo Clinic, Rochester, MN. Candidates for the MIS approach were adults with septic shock and less than 48 hours of ICU stay, who did not require advanced respiratory support and were alive at hospital discharge. Comparison group consisted of septic shock patients with an ICU stay of more than 48 hours without advanced respiratory support at the time of ICU admission. Results: Of 1795 medical ICU admissions, 106 patients (6%) met MIS approach criteria. Predictive variables (age >65 years, oxygen flow >4 L/min, temperature <37°C, creatinine >1.6 mg/dL, lactate >3 mmol/L, white blood cells >15 × 10 9 /L, heart rate >100 beats/min, and respiration rate >25 breaths/min) selected through logistic regression were translated into an 8-point score. Model discrimination yielded the area under the receiver operating characteristic curve of 79% and was well fitted (Hosmer-Lemeshow P = 0.94) and calibrated. The MIS score cutoff of 3 resulted in a model odds ratio of 0.15 (95% confidence interval, 0.08-0.28) and a negative predictive value of 91% (95% confidence interval, 88.69-92.92). Conclusions: This study identifies a subset of low-risk septic shock patients who can potentially be managed outside the ICU. Once validated in an independent, prospective sample our prediction model can be used to identify candidates for MIS approach.

Development and Validation of an Acute Respiratory Distress Syndrome Prediction Model in Coronavirus Disease 2019: Updated Lung Injury Prediction Score.

OBJECTIVE: To develop and validate an updated lung injury prediction score for coronavirus disease 2019 (COVID-19) (c-LIPS) tailored for predicting acute respiratory distress syndrome (ARDS) in COVID-19. PATIENTS AND METHODS: This was a registry-based cohort study using the Viral Infection and Respiratory Illness Universal Study. Hospitalized adult patients between January 2020 and January 2022 were screened. Patients who qualified for ARDS within the first day of admission were excluded. Development cohort consisted of patients enrolled from participating Mayo Clinic sites. The validation analyses were performed on remaining patients enrolled from more than 120 hospitals in 15 countries. The original lung injury prediction score (LIPS) was calculated and enhanced using reported COVID-19-specific laboratory risk factors, constituting c-LIPS. The main outcome was ARDS development and secondary outcomes included hospital mortality, invasive mechanical ventilation, and progression in WHO ordinal scale. RESULTS: The derivation cohort consisted of 3710 patients, of whom 1041 (28.1%) developed ARDS. The c-LIPS discriminated COVID-19 patients who developed ARDS with an area under the curve (AUC) of 0.79 compared with original LIPS (AUC, 0.74; P<.001) with good calibration accuracy (Hosmer-Lemeshow P=.50). Despite different characteristics of the two cohorts, the c-LIPS's performance was comparable in the validation cohort of 5426 patients (15.9% ARDS), with an AUC of 0.74; and its discriminatory performance was significantly higher than the LIPS (AUC, 0.68; P<.001). The c-LIPS's performance in predicting the requirement for invasive mechanical ventilation in derivation and validation cohorts had an AUC of 0.74 and 0.72, respectively. CONCLUSION: In this large patient sample c-LIPS was successfully tailored to predict ARDS in COVID-19 patients.

Eight-year trend of acute respiratory distress syndrome: a population-based study in Olmsted County, Minnesota.

RATIONALE: significant progress has been made in understanding the pathogenesis of acute respiratory distress syndrome (ARDS). Recent advances in hospital practice may have reduced the incidence of this lethal syndrome. OBJECTIVES: to observe incidence trends and associated outcomes of ARDS. METHODS: this population-based cohort study was conducted in Olmsted County, Minnesota. Using a validated screening protocol, investigators identified intensive care patients with acute hypoxemia and bilateral pulmonary infiltrates. The presence of ARDS was independently confirmed according to American-European Consensus Conference criteria. The incidence of ARDS and associated outcomes were compared over the 8-year study period (2001-2008). MEASUREMENTS AND MAIN RESULTS: over the 8-year period, critically ill Olmsted County residents presented with increasing severity of acute illness, a greater number of comorbidities, and a higher prevalence of major predisposing conditions for ARDS. The ARDS incidence decreased significantly from 82.4 to 38.9 per 100,000 person-years during the study period (P < 0.001). A decline in hospital-acquired ARDS (P < 0.001) was responsible for the fall in the incidence density with no change on admission (P = 0.877). Overall, mortality and hospital and intensive care unit lengths of stay decreased over time (P < 0.001), whereas the ARDS case-fatality did not change significantly. CONCLUSIONS: despite an increase in patients' severity of illness, number of comorbidities, and prevalence of major ARDS risk factors, the incidence of ARDS in this suburban community decreased by more than half. Correlation of the observed findings with changes in health care delivery may have important implications for the planning of acute care services in other regions.

Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study.

RATIONALE: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. OBJECTIVES: To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). METHODS: In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. MEASUREMENTS AND MAIN RESULTS: Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1-4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78-0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9-5.7). CONCLUSIONS: ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772).

Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury.

BACKGROUND: Optimal titration of inspired oxygen is important to prevent hyperoxia in mechanically ventilated patients in ICUs. There is mounting evidence of the deleterious effects of hyperoxia; however, there is a paucity of data about F(IO(2)) practice and oxygen exposure among patients in ICUs. We therefore sought to assess excessive F(IO(2)) exposure in mechanically ventilated patients with acute lung injury and to evaluate the effect on pulmonary outcomes. METHODS: From a database of ICU patients with acute lung injury identified by prospective electronic medical record screening, we identified those who underwent invasive mechanical ventilation for > 48 hours from January 1 to December 31, 2008. Ventilator settings, including F(IO(2)) and corresponding S(pO(2)), were collected from the electronic medical record at 15-min intervals for the first 48 hours. Excessive F(IO(2)) was defined as F(IO(2)) > 0.5 despite S(pO(2)) > 92%. The association between the duration of excessive exposure and pulmonary outcomes was assessed by change in oxygenation index from baseline to 48 hours and was analyzed by univariate and multivariate linear regression analysis. RESULTS: Of 210 patients who met the inclusion criteria, 155 (74%) were exposed to excessive F(IO(2)) for a median duration of 17 hours (interquartile range 7.5-33 h). Prolonged exposure to excessive F(IO(2)) correlated with worse oxygenation index at 48 hours in a dose-response manner (P < .001.). Both exposure to higher F(IO(2)) and longer duration of exposure were associated with worsening oxygenation index at 48 hours (P < .001), more days on mechanical ventilation, longer ICU stay, and longer hospital stay (P = .004). No mortality difference was noted. CONCLUSIONS: Excessive oxygen supplementation is common in mechanically ventilated patients with ALI and may be associated with worsening lung function.

Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Intensive Care Unit Admission Diagnosis: A Prospective Cohort Study.

Background: Acute kidney injury (AKI) is most commonly caused by tubular injury and is associated with a wide variety of critical illnesses. It is well known that urinary biomarkers can lead to the early identification of AKI. However, the ability of urinary biomarkers to distinguish between different types of critical illness has been less studied. Methods: In this prospective cohort study, urinary neutrophil gelatinase-associated lipocalin (uNGAL) was measured in 107 patients consecutively admitted to the ICUs in our tertiary medical center. uNGAL samples were collected within 3-6 hours of admission to an ICU and measured by ELISA. All data were analyzed using R statistical software, and univariate analysis was used to determine the correlations of uNGAL levels with AKI stage, admission diagnoses, and ICU course. Results: uNGAL level increased by a mean of 24-fold (SD 10-59) in ICU patients with AKI and demonstrated a significant correlation with the different AKI stages. uNGAL predicted the need for RRT, with values increased by more than 15-fold (P<0.05) in patients needing RRT, and remained a useful tool to predict AKI in ICU patients with a urinary tract infection. uNGAL level was correlated with certain ICU admitting diagnoses whereby uNGAL levels were lower in ICU patients with cardiogenic shock compared with other admission diagnoses (ß=-1.92, P<0.05). Conclusions: uNGAL can be used as an early predictor of AKI and its severity in patients admitted to the ICU, including the need for RRT. uNGAL may also help in distinguishing patients with cardiogenic shock from those with other critical illnesses and identifying those at risk for poor outcomes irrespective of the presence of AKI.

Incidence and risk factors of recurrent acute lung injury.

OBJECTIVE: To determine risk factors for development of recurrent acute lung injury. DESIGN: A population-based case-control study. SETTING: The study was conducted in Olmsted County, MN, from 1999 to 2008. PATIENTS: Using a validated electronic screening protocol, investigators identified intensive care patients with acute hypoxemia and bilateral pulmonary infiltrates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The presence of acute lung injury was independently confirmed according to American-European Consensus Conference criteria. Recurrent acute lung injury cases were subsequently matched (1:1:1) with two controls (single acute lung injury and no acute lung injury) on age, gender, duration of follow-up, and predisposing conditions. Risk factors evaluated included gastroesophageal reflux disease, alcohol consumption, smoking, chronic opioid use, and transfusions. We identified 917 patients with acute lung injury, 19 of which developed a second episode, yielding a frequency of 2.02 (95% confidence interval 1.10-2.93) per 100,000 person years. The median time to development of the second episode was 264 days (interquartile range 80-460 days), with a mortality of 47% during the episode. The history of gastroesophageal reflux disease was highly prevalent in patients who developed recurrent acute lung injury: 15 of 19 patients (79%) compared to 5 of 19 (26%) matches with a single episode of acute lung injury (p = .006) and 8 of 19 (42%) matches without acute lung injury (p = .016). Other exposures were similar between the cases and the two matched controls. CONCLUSIONS: Recurrent acute lung injury is not a rare phenomenon in the intensive care unit and may continue to increase with improvements in survival following acute lung injury. Gastroesophageal reflux disease was identified as an important risk factor for recurrent acute lung injury and may suggest an important role of gastric aspiration in the development of this syndrome.

Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients.

OBJECTIVE: To evaluate the association between prehospitalization aspirin therapy and incident acute lung injury in a heterogeneous cohort of at-risk medical patients. DESIGN: This is a secondary analysis of a prospective multicenter international cohort investigation. SETTING: Multicenter observational study including 20 US hospitals and two hospitals in Turkey. PATIENTS: Consecutive, adult, nonsurgical patients admitted to the hospital with at least one major risk factor for acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics and acute lung injury risk factors/modifiers were identified. The presence of aspirin therapy and the propensity to receive this therapy were determined. The primary outcome was acute lung injury during hospitalization. Secondary outcomes included intensive care unit and hospital mortality and intensive care unit and hospital length of stay. Twenty-two hospitals enrolled 3855 at-risk patients over a 6-month period. Nine hundred seventy-six (25.3%) were receiving aspirin at the time of hospitalization. Two hundred forty (6.2%) patients developed acute lung injury. Univariate analysis noted a reduced incidence of acute lung injury in those receiving aspirin therapy (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.46-0.90; p = .010). This association was attenuated in a stratified analysis based on deciles of aspirin propensity scores (Cochran-Mantel-Haenszel pooled OR, 0.70; 95% CI, 0.48-1.03; p = .072). CONCLUSIONS: After adjusting for the propensity to receive aspirin therapy, no statistically significant associations between prehospitalization aspirin therapy and acute lung injury were identified; however, a prospective clinical trial to further evaluate this association appears warranted.

Incidence and transfusion risk factors for transfusion-associated circulatory overload among medical intensive care unit patients.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is a frequent complication of blood transfusion. Investigations identifying risk factors for TACO in critically ill patients are lacking. STUDY DESIGN AND METHODS: We performed a 2-year prospective cohort study of consecutive patients receiving blood product transfusion in the medical intensive care unit (ICU) of the tertiary care institution. Patients were followed for development of transfusion-related complications. TACO was defined as acute hydrostatic pulmonary edema occurring within 6 hours of transfusion. In a nested case-control design, transfusion characteristics were compared between cases (TACO) and controls after matching by age, sex, and ICU admission diagnostic category. In a secondary analysis, patient characteristics before transfusion were compared between cases (TACO) and randomly selected controls. RESULTS: Fifty-one of 901 (6%) transfused patients developed TACO. Compared with matched controls, TACO cases had a more positive fluid balance (1.4 L vs. 0.8 L, p = 0.003), larger amount of plasma transfused (0.4 L vs. 0.07 L, p = 0.007), and faster rate of blood component transfusion (225 mL/hr vs. 168 mL/hr, p = 0.031). In a secondary analysis comparing TACO cases and random controls, left ventricular dysfunction before transfusion (odds ratio [OR], 8.23; 95% confidence interval [CI], 3.36-21.97) and plasma ordered for the reversal of anticoagulant (OR, 4.31; 95% CI, 1.45-14.30) were significantly related to the development of TACO. CONCLUSION: Volume of transfused plasma and the rate of transfusion were identified as transfusion-specific risk factors for TACO. Left ventricular dysfunction and fresh-frozen plasma ordered for the reversal of anticoagulant were strong predictors of TACO before the onset of transfusion.

Derivation and diagnostic accuracy of the surgical lung injury prediction model.

BACKGROUND: Acute lung injury (ALI) is a serious postoperative complication with limited treatment options. A preoperative risk-prediction model would assist clinicians and scientists interested in ALI. The objective of this investigation was to develop a surgical lung injury prediction (SLIP) model to predict risk of postoperative ALI based on readily available preoperative risk factors. METHODS: Secondary analysis of a prospective cohort investigation including adult patients undergoing high-risk surgery. Preoperative risk factors for postoperative ALI were identified and evaluated for inclusion in the SLIP model. Multivariate logistic regression was used to develop the model. Model performance was assessed with the area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: Out of 4,366 patients, 113 (2.6%) developed early postoperative ALI. Predictors of postoperative ALI in multivariate analysis that were maintained in the final SLIP model included high-risk cardiac, vascular, or thoracic surgery, diabetes mellitus, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and alcohol abuse. The SLIP score distinguished patients who developed early postoperative ALI from those who did not with an area under the receiver operating characteristic curve (95% CI) of 0.82 (0.78-0.86). The model was well calibrated (Hosmer-Lemeshow, P = 0.55). Internal validation using 10-fold cross-validation noted minimal loss of diagnostic accuracy with a mean ± SD area under the receiver operating characteristic curve of 0.79 ± 0.08. CONCLUSIONS: Using readily available preoperative risk factors, we developed the SLIP scoring system to predict risk of early postoperative ALI.

Towards the prevention of acute lung injury: a population based cohort study protocol.

BACKGROUND: Acute lung injury (ALI) is an example of a critical care syndrome with limited treatment options once the condition is fully established. Despite improved understanding of pathophysiology of ALI, the clinical impact has been limited to improvements in supportive treatment. On the other hand, little has been done on the prevention of ALI. Olmsted County, MN, geographically isolated from other urban areas offers the opportunity to study clinical pathogenesis of ALI in a search for potential prevention targets. METHODS/DESIGN: In this population-based observational cohort study, the investigators identify patients at high risk of ALI using the prediction model applied within the first six hours of hospital admission. Using a validated system-wide electronic surveillance, Olmsted County patients at risk are followed until ALI, death or hospital discharge. Detailed in-hospital (second hit) exposures and meaningful short and long term outcomes (quality-adjusted survival) are compared between ALI cases and high risk controls matched by age, gender and probability of developing ALI. Time sensitive biospecimens are collected for collaborative research studies. Nested case control comparison of 500 patients who developed ALI with 500 matched controls will provide an adequate power to determine significant differences in common hospital exposures and outcomes between the two groups. DISCUSSION: This population-based observational cohort study will identify patients at high risk early in the course of disease, the burden of ALI in the community, and the potential targets for future prevention trials.

The Stability and Workload Index for Transfer score predicts unplanned intensive care unit patient readmission: initial development and validation.

OBJECTIVE: Unplanned readmission of hospitalized patients to an intensive care unit (ICU) is associated with a worse outcome, but our ability to identify who is likely to deteriorate after ICU dismissal is limited. The objective of this study is to develop and validate a numerical index, named the Stability and Workload Index for Transfer, to predict ICU readmission. DESIGN: In this prospective cohort study, risk factors for ICU readmission were identified from a broad range of patients' admission and discharge characteristics, specific ICU interventions, and in-patient workload measurements. The prediction score was validated in two independent ICUs. SETTING: One medical and one mixed medical-surgical ICU in two tertiary centers. PATIENTS: Consecutive patients requiring >24 hrs of ICU care. INTERVENTIONS: None. MEASUREMENTS: Unplanned ICU readmission or unexpected death following ICU dismissal. RESULTS: In a derivation cohort of 1,131 medical ICU patients, 100 patients had unplanned readmissions, and five died unexpectedly in the hospital following ICU discharge. Predictors of readmission/unexpected death identified in a logistic regression analysis were ICU admission source, ICU length of stay, and day of discharge neurologic (Glasgow Coma Scale) and respiratory (hypoxemia, hypercapnia, or nursing requirements for complex respiratory care) impairment. The Stability and Workload Index for Transfer score predicted readmission more precisely (area under the curve [AUC], 0.75; 95% confidence interval [CI], 0.70-0.80) than the day of discharge Acute Physiology and Chronic Health Evaluation III score (AUC, 0.62; 95% CI, 0.56-0.68). In the two validation cohorts, the Stability and Workload Index for Transfer score predicted readmission similarly in a North American medical ICU (AUC, 0.74; 95% CI, 0.67-0.80) and a European medical-surgical ICU (AUC, 0.70; 95% CI, 0.64-0.76), but was less well calibrated in the medical-surgical ICU. CONCLUSION: The Stability and Workload Index for Transfer score is derived from information readily available at the time of ICU dismissal and acceptably predicts ICU readmission. It is not known if discharge decisions based on this prediction score will decrease the number of ICU readmissions and/or improve outcome.