Timothy R. Watkins

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).

Prediction of Critical Illness During Out-of-Hospital Emergency Care

CONTEXT Early identification of nontrauma patients in need of critical care services in the emergency setting may improve triage decisions and facilitate regionalization of critical care. OBJECTIVES To determine the out-of-hospital clinical predictors of critical illness and to characterize the performance of a simple score for out-of-hospital prediction of development of critical illness during hospitalization. DESIGN AND SETTING Population-based cohort study of an emergency medical services (EMS) system in greater King County, Washington (excluding metropolitan Seattle), that transports to 16 receiving facilities. PATIENTS Nontrauma, non-cardiac arrest adult patients transported to a hospital by King County EMS from 2002 through 2006. Eligible records with complete data (N = 144,913) were linked to hospital discharge data and randomly split into development (n = 87,266 [60%]) and validation (n = 57,647 [40%]) cohorts. MAIN OUTCOME MEASURE Development of critical illness, defined as severe sepsis, delivery of mechanical ventilation, or death during hospitalization. RESULTS Critical illness occurred during hospitalization in 5% of the development (n = 4835) and validation (n = 3121) cohorts. Multivariable predictors of critical illness included older age, lower systolic blood pressure, abnormal respiratory rate, lower Glasgow Coma Scale score, lower pulse oximetry, and nursing home residence during out-of-hospital care (P < .01 for all). When applying a summary critical illness prediction score to the validation cohort (range, 0-8), the area under the receiver operating characteristic curve was 0.77 (95% confidence interval [CI], 0.76-0.78), with satisfactory calibration slope (1.0). Using a score threshold of 4 or higher, sensitivity was 0.22 (95% CI, 0.20-0.23), specificity was 0.98 (95% CI, 0.98-0.98), positive likelihood ratio was 9.8 (95% CI, 8.9-10.6), and negative likelihood ratio was 0.80 (95% CI, 0.79- 0.82). A threshold of 1 or greater for critical illness improved sensitivity (0.98; 95% CI, 0.97-0.98) but reduced specificity (0.17; 95% CI, 0.17-0.17). CONCLUSIONS In a population-based cohort, the score on a prediction rule using out-of-hospital factors was significantly associated with the development of critical illness during hospitalization. This score requires external validation in an independent population.

A Phase II Randomized Placebo-Controlled Trial of Omega-3 Fatty Acids for the Treatment of Acute Lung Injury

Objectives:Administration of eicosapentaenoic acid and docosahexanoic acid, omega-3 fatty acids in fish oil, has been associated with improved patient outcomes in acute lung injury when studied in a commercial enteral formula. However, fish oil has not been tested independently in acute lung injury. We therefore sought to determine whether enteral fish oil alone would reduce pulmonary and systemic inflammation in patients with acute lung injury. Design:Phase II randomized controlled trial. Setting:Five North American medical centers. Patients:Mechanically ventilated patients with acute lung injury ≥18 yrs of age. Interventions:Subjects were randomized to receive enteral fish oil (9.75 g eicosapentaenoic acid and 6.75 g docosahexanoic acid daily) or saline placebo for up to 14 days. Measurements and Main Results:Bronchoalveolar lavage fluid and blood were collected at baseline (day 0), day 4 ± 1, and day 8 ± 1. The primary end point was bronchoalveolar lavage fluid interleukin-8 levels. Forty-one participants received fish oil and 49 received placebo. Enteral fish oil administration was associated with increased serum eicosapentaenoic acid concentration (p < .0001). However, there was no significant difference in the change in bronchoalveolar lavage fluid interleukin-8 from baseline to day 4 (p = .37) or day 8 (p = .55) between treatment arms. There were no appreciable improvements in other bronchoalveolar lavage fluid or plasma biomarkers in the fish oil group compared with the control group. Similarly, organ failure score, ventilator-free days, intensive care unit-free days, and 60-day mortality did not differ between the groups. Conclusions:Fish oil did not reduce biomarkers of pulmonary or systemic inflammation in patients with acute lung injury, and the results do not support the conduct of a larger clinical trial in this population with this agent. This experimental approach is feasible for proof-of-concept studies evaluating new treatments for acute lung injury.

Anemia in critical illness: insights into etiology, consequences, and management.

Anemia is common in the intensive care unit, and may be associated with adverse consequences. However, current options for correcting anemia are not without problems and presently lack convincing efficacy for improving survival in critically ill patients. In this article we review normal red blood cell physiology; etiologies of anemia in the intensive care unit; its association with adverse outcomes; and the risks, benefits, and efficacy of various management strategies, including blood transfusion, erythropoietin, blood substitutes, iron therapy, and minimization of diagnostic phlebotomy.

Effects of leukoreduced blood on acute lung injury after trauma : A randomized controlled trial

Objective:The requirement for a blood transfusion after trauma is associated with an increased risk of acute lung injury. Residual leukocytes contaminating red cells are potential mediators of this syndrome. The goal of this trial was to test our hypothesis that prestorage leukoreduction of blood would reduce rates of posttraumatic lung injury. Design:Double blind, randomized, controlled clinical trial. Setting:University-affiliated level I trauma center in King County, Seattle, WA. Patients:Two hundred sixty-eight injured patients requiring red blood cell transfusion within 24 hrs of injury. Interventions:Prestorage leukoreduced vs. standard allogeneic blood transfusions. Measurements and Main Results:We compared the incidence of acute lung injury and acute respiratory distress syndrome at early (≤72 hrs) and late (>72 hrs) time points after injury. In a subset, we compared plasma levels of surfactant protein-D and von Willebrand factor antigen between intervention arms. Rates of acute lung injury (relative risk [RR] 1.06, 95% confidence interval [CI] .69–1.640) and acute respiratory distress syndrome (RR .96, 95% CI 0.48–1.91) were not statistically different between intervention arms early after injury. Similarly, no statistically significant effect of leukoreduced transfusion on rates of acute lung injury (RR .88, 95% CI .54–1.44) or acute respiratory distress syndrome (RR .95, 95% CI .58–1.57) was observed to occur late after injury. There was no significant difference in the number of ventilator-free days or in other ventilator parameters between intervention arms. No statistically significant effect of leukoreduced blood on plasma levels of surfactant protein-D or von Willebrand factor antigen was identified. Conclusions:Prestorage leukoreduction had no effect on the incidence or timing of lung injury or on plasma measures of systemic alveolar and endothelial inflammation in a population of trauma patients requiring transfusion. The relationship between transfusion and lung injury is not obviously explained by mechanistic pathways involving the presence of transfused leukocytes.

Traumatic Brain Injury-Associated Coagulopathy

Traumatic injury is a common cause of coagulopathy, primarily due to blood loss and hemodilution secondary to fluid resuscitation. Traumatic injury-associated coagulopathy often follows a course of transition from hyper- to hypocoagulable state exemplified in disseminated intravascular coagulation. The incidence of coagulopathy is significantly higher in patients with traumatic brain injury (TBI), especially those with penetrating trauma compared to injury to the trunk and limbs. This occurs despite the fact that patients with isolated TBI bleed less and receive restricted volume load of fluids. TBI-associated coagulopathy is extensively documented to associate with poor clinical outcomes, but its pathophysiology remains poorly understood. Studies in the past have shown that brain tissue is highly enriched in key procoagulant molecules. This review focuses on the biochemical and cellular characteristics of these molecules and pathways that could make brain uniquely procoagulant and prone to coagulopathy. Understanding this unique procoagulant environment will help to identify new therapeutic targets that could reverse a state of coagulopathy with minimal impacts on hemostasis, a critical requirement for neurosurgical treatments of TBI.

Cost-effectiveness of implementing low-tidal volume ventilation in patients with acute lung injury.

BACKGROUND Despite widespread guidelines recommending the use of lung-protective ventilation (LPV) in patients with acute lung injury (ALI), many patients do not receive this lifesaving therapy. We sought to estimate the incremental clinical and economic outcomes associated with LPV and determined the maximum cost of a hypothetical intervention to improve adherence with LPV that remained cost-effective. METHODS Adopting a societal perspective, we developed a theoretical decision model to determine the cost-effectiveness of LPV compared to non-LPV care. Model inputs were derived from the literature and a large population-based cohort of patients with ALI. Cost-effectiveness was determined as the cost per life saved and the cost per quality-adjusted life-years (QALYs) gained. RESULTS Application of LPV resulted in an increase in QALYs gained by 15% (4.21 years for non-LPV vs 4.83 years for LPV), and an increase in lifetime costs of

Acute respiratory distress syndrome after trauma: Development and validation of a predictive model

7,233 per patient with ALI (

An international normalized ratio-based definition of acute traumatic coagulopathy is associated with mortality, venous thromboembolism, and multiple organ failure after injury

99,588 for non-LPV vs

The effect of an intensive care unit staffing model on tidal volume in patients with acute lung injury

106,821 for LPV). The incremental cost-effectiveness ratios for LPV were