Ellen Caldwell

Incidence and outcomes of pediatric acute lung injury.

OBJECTIVE: This population-based, prospective, cohort study was designed to determine the population incidence and outcomes of pediatric acute lung injury. METHODS: Between 1999 and 2000, 1 year of screening was performed at all hospitals admitting critically ill children in King County, Washington. County residents 0.5 to 15 years of age who required invasive (through endotracheal tube or tracheostomy) or noninvasive (through full face mask) mechanical ventilation, regardless of the duration of mechanical ventilation, were screened. From this population, children meeting North American-European Consensus Conference acute lung injury criteria were eligible for enrollment. Postoperative patients who received mechanical ventilation for <24 hours were excluded. Data collected included the presence of predefined cardiac conditions, demographic and physiological data, duration of mechanical ventilation, and deaths. US Census population figures were used to estimate incidence. Associations between outcomes and subgroups identified a priori were assessed. RESULTS: Thirty-nine children met the criteria for acute lung injury, resulting in a calculated incidence of 12.8 cases per 100000 person-years. Severe sepsis (with pneumonia as the infection focus) was the most common risk factor. The median 24-hour Pediatric Risk of Mortality III score was 9.0, and the mean ± SD was 11.7 ± 7.5. The hospital mortality rate was 18%, lower than that reported previously for pediatric acute lung injury. There were no statistically significant associations between age, gender, or risk factors and outcomes. CONCLUSIONS: We present the first population-based estimate of pediatric acute lung injury incidence in the United States. Population incidence and mortality rates are lower than those for adult acute lung injury. Low mortality rates in pediatric acute lung injury may necessitate clinical trial outcome measures other than death.

Effect of acute lung injury and acute respiratory distress syndrome on outcome in critically ill trauma patients

ObjectiveAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are known to be associated with increased mortality and costs in trauma patients. We estimated the independent impact of these conditions on mortality and cost, beyond the severity of injury with which they are correlated. DesignOne-year prospective cohort. Patients and SettingAll trauma patients admitted to the intensive care unit in a level I center were evaluated daily for ALI/ARDS using the American-European Consensus Conference definition. Measurements and Main ResultsThe main outcome measures were hospital mortality and costs. Logistic regression was used to model hospital mortality in relation to the presence of ALI and ARDS, adjusting for trauma severity (Injury Severity Score), Acute Physiology Score, and age. Hospital costs were modeled using multivariable linear regression. Of the 1,296 trauma patients surviving beyond the first day, 4% experienced ALI (defined as Pao2/Fio2 of 201–300 mm Hg) and 12% had ARDS (Pao2/Fio2 ≤ 200 mm Hg). The crude relative risk of mortality was 2.24 (95% confidence interval, 0.92–5.45) in patients with ALI and 3.84 (95% confidence interval, 2.41–6.13) in patients with ARDS compared with those without ALI/ARDS. However, there was no association of mortality with ALI (relative risk, 0.99; 95% confidence interval, 0.29–3.36) or with ARDS (relative risk, 1.23; 95% confidence interval, 0.63–2.43) after adjustment for age, Injury Severity Score, and Acute Physiology Score. Among patients of comparable age, severity score, and length of stay, median cost was 20% to 30% higher for those with ALI/ARDS. ConclusionsThere is no additional mortality associated with ALI/ARDS above and beyond the factors that can be measured at intensive care unit admission. Therefore, mortality in trauma patients is explained by injury severity at admission and is not affected by the subsequent occurrence of ALI/ARDS. Nonetheless, ALI/ARDS was associated with increased intensive care unit stay and hospital cost, independent of trauma severity.

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.

Predictors of hospital mortality in a population-based cohort of patients with acute lung injury

Objective:Studies describing predictors of mortality in patients with acute lung injury were primarily derived from selected academic centers. We sought to determine the predictors of mortality in a population-based cohort of patients with acute lung injury and to characterize the performance of current severity of illness scores in this population. Design:Secondary analysis of a prospective, multicenter, population-based cohort. Setting:Twenty-one hospitals in Washington State. Patients:The cohort included 1,113 patients with acute lung injury identified during the year 1999–2000. Interventions:None. Measurements and Main Results:We evaluated physiology, comorbidities, risk factors for acute lung injury, and other variables for their association with death at hospital discharge. Bivariate predictors of death were entered into a multiple logistic regression model. We compared Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, and Simplified Acute Physiology Score II to the multivariable model using area under the receiver operating characteristic curve. The model was validated in an independent cohort of 886 patients with acute lung injury. Modified acute physiology score, age, comorbidities, arterial pH, minute ventilation, Paco2, Pao2/Fio2 ratio, intensive care unit admission source, and intensive care unit days before onset of acute lung injury were independently predictive of in-hospital death (p < .05). The area under the receiver operating characteristic curve for the multivariable model was superior to that of APACHE III (.81 vs. .77, p < .001) but was no different after external validation (.71 vs. .70, p = .64). Conclusions:The predictors of mortality in patients with acute lung injury are similar to those predictive of mortality in the general intensive care unit population, indicating disease heterogeneity within this cohort. Accordingly, APACHE III predicts mortality in acute lung injury as well as a model using variables selected specifically for patients with acute lung injury.

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.

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

IntroductionLittle is known about the mechanisms through which intensivist physician staffing influences patient outcomes. We aimed to assess the effect of closed-model intensive care on evidence-based ventilatory practice in patients with acute lung injury (ALI).MethodsWe conducted a secondary analysis of a prospective population-based cohort of 759 patients with ALI who were alive and ventilated on day three of ALI, and were cared for in 23 intensive care units (ICUs) in King County, Washington.ResultsWe compared day three tidal volume (VT) in open versus closed ICUs adjusting for potential patient and ICU confounders. In 13 closed model ICUs, 429 (63%) patients were cared for. Adjusted mean VT (mL/Kg predicted body weight (PBW) or measured body weight if height not recorded) for patients in closed ICUs was 1.40 mL/Kg PBW (95% confidence interval (CI) = 0.57 to 2.24 mL/Kg PBW) lower than patients in open model ICUs. Patients in closed ICUs were more likely (odds ratio (OR) = 2.23, 95% CI = 1.09 to 4.56) to receive lower VT (≤ 6.5 mL/Kg PBW) and were less likely (OR = 0.30, 95% CI = 0.17 to 0.55) to receive a potentially injurious VT (≥ 12 mL/Kg PBW) compared with patients cared for in open ICUs, independent of other covariates. The effect of closed ICUs on hospital mortality was not changed after accounting for delivered VT.ConclusionsPatients with ALI cared for in closed model ICUs are more likely to receive lower VT and less likely to receive higher VT, but there were no other differences in measured processes of care. Moreover, the difference in delivered VT did not completely account for the improved mortality observed in closed model ICUs.

Point Prevalence Study of Mobilization Practices for Acute Respiratory Failure Patients in the United States

Objective: Early mobility in mechanically ventilated patients is safe, feasible, and may improve functional outcomes. We sought to determine the prevalence and character of mobility for ICU patients with acute respiratory failure in U.S. ICUs. Design: Two-day cross-sectional point prevalence study. Setting: Forty-two ICUs across 17 Acute Respiratory Distress Syndrome Network hospitals. Patients: Adult patients (≥ 18 yr old) with acute respiratory failure requiring mechanical ventilation. Interventions: We defined therapist-provided mobility as the proportion of patient-days with any physical or occupational therapy–provided mobility event. Hierarchical regression models were used to identify predictors of out-of-bed mobility. Measurements and Main Results: Hospitals contributed 770 patient-days of data. Patients received mechanical ventilation on 73% of the patient-days mostly (n = 432; 56%) ventilated via an endotracheal tube. The prevalence of physical therapy/occupational therapy–provided mobility was 32% (247/770), with a significantly higher proportion of nonmechanically ventilated patients receiving physical therapy/occupational therapy (48% vs 26%; p ⩽ 0.001). Patients on mechanical ventilation achieved out-of-bed mobility on 16% (n = 90) of the total patient-days. Physical therapy/occupational therapy involvement in mobility events was strongly associated with progression to out-of-bed mobility (odds ratio, 29.1; CI, 15.1–56.3; p ⩽ 0.001). Presence of an endotracheal tube and delirium were negatively associated with out-of-bed mobility. Conclusions: In a cohort of hospitals caring for acute respiratory failure patients, physical therapy/occupational therapy–provided mobility was infrequent. Physical therapy/occupational therapy involvement in mobility was strongly predictive of achieving greater mobility levels in patients with respiratory failure. Mechanical ventilation via an endotracheal tube and delirium are important predictors of mobility progression.

Volume Overload: Prevalence, Risk Factors, and Functional Outcome in Survivors of Septic Shock

RATIONALE Survivors of septic shock have impaired functional status. Volume overload is associated with poor outcomes in patients with septic shock, but the impact of volume overload on functional outcome and discharge destination of survivors is unknown. OBJECTIVES This study describes patterns of fluid management both during and after septic shock. We examined factors associated with volume overload upon intensive care unit (ICU) discharge. We then examined associations between volume overload upon ICU discharge, mobility limitation, and discharge to a healthcare facility in septic shock survivors, with the hypothesis that volume overload is associated with increased odds of these outcomes. METHODS We retrospectively reviewed the medical records of 247 patients admitted with septic shock to an academic county hospital between June 2009 and April 2012 who survived to ICU discharge. We defined volume overload as a fluid balance expected to increase the subjects admission weight by 10%. Statistical methods included unadjusted analyses and multivariable logistic regression. MEASUREMENTS AND MAIN RESULTS Eighty-six percent of patients had a positive fluid balance, and 35% had volume overload upon ICU discharge. Factors associated with volume overload in unadjusted analyses included more severe illness, cirrhosis, blood transfusion during shock, and higher volumes of fluid administration both during and after shock. Blood transfusion during shock was independently associated with increased odds of volume overload (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.33-5.27; P = 0.01) after adjusting for preexisting conditions and severity of illness. Only 42% of patients received at least one dose of a diuretic during their hospitalization. Volume overload upon ICU discharge was independently associated with inability to ambulate upon hospital discharge (OR, 2.29; 95% CI, 1.24-4.25; P = 0.01) and, in patients admitted from home, upon discharge to a healthcare facility (OR, 2.34; 95% CI, 1.1-4.98; P = 0.03). CONCLUSIONS Volume overload is independently associated with impaired mobility and discharge to a healthcare facility in survivors of septic shock. Prevention and treatment of volume overload in patients with septic shock warrants further investigation.

Ventilator-associated pneumonia: bacteremia and death after traumatic injury.

BACKGROUND: The implications of bacteremia in critically ill patients are uncertain. Some reports suggest bacteremia is linked to higher mortality whereas others do not. These differences may, in part, be because of differences in patient cohorts. To address the potential independent relationship between bacteremia and outcome, we focused on critically ill trauma patients with ventilator-associated pneumonia (VAP), of whom a significant proportion had concomitant bacteremia. We tested the hypothesis that bacteremia was associated with death in trauma patients who developed VAP. METHODS: In this retrospective cohort study, we measured the incidence of bacteremia associated with VAP and compared the case-fatality rates between patients with and without bacteremia. We adjusted for other mortality risk factors and possible confounders in two ways. First, using forward conditional logistic regression and second, we calculated propensity scores and then adjusted for this score in a regression model. RESULTS: There were 554 with VAP. Patients with bacteremia had a 26% case-fatality rate (19 of 74 patients). Patients with VAP alone had a case-fatality rate of 12% (56 of 480 patients). The unadjusted relative risk (RR) for death associated with bacteremia was 2.2 (95% confidence interval = 1.4–3.5). After adjusting for age, acute physiology score, and severity of injury, patients with bacteremia had an increased risk of death compared with patients with VAP alone (adjusted odds ratio = 2.65, 95% confidence interval = 1.36–5.17). Our propensity score analysis resulted in a similar association between bacteremia and mortality. CONCLUSIONS: VAP with bacteremia is associated with an increased mortality in comparison with VAP alone after severe traumatic injury.

Factors Associated With Receipt of Physical Therapy Consultation in Patients Requiring Prolonged Mechanical Ventilation

Background/Introduction:Mobilization of critically ill patients in the intensive care unit is associated with improved function at hospital discharge and reduced duration of mechanical ventilation (MV). Few studies, however, focus on physical therapy (PT) in patients on prolonged mechanical ventilation (PMV) despite their high risk of immobility and poor outcomes. Objective/Aims:The objective of this study was to identify factors associated with the receipt of PT consultation among patients requiring PMV. We hypothesized that key factors including age, severity of illness, and presence of a tracheostomy are associated with PT consultation. MethodsThis was a retrospective cohort study of adults on MV for 14 days or longer for acute respiratory failure at an academic medical center. Primary outcome was PT consultation by day 14 of MV. We examined associations between the following key predictors chosen a priori and PT consultation: age, tracheostomy, illness severity, oxygenation status, shock, hemodialysis, and medical service using multivariable logistic regression. Wilcoxon rank sum testing was used to test relationship between sedation and PT. Results:We identified 175 patients requiring PMV at our institution. Most were middle-aged (mean, 49.7 [SD, 18.5] years old) men (65%) with high illness severity (mean Acute Physiology and Chronic Health Evaluation III score, 86 [SD, 40]). Less than half of all patients requiring PMV (78/175, 45%) received PT consultation in the intensive care unit, and most failed to progress with therapy beyond range-of-motion exercises (85%). Failure to progress was associated with level of sedation (med Ramsay score 4.5 [interquartile range, 3-6] vs 3.5 [interquartile range, 3-5]; P = .01). Presence of a tracheostomy and prehospital nonambulatory status were associated with receipt of PT by day 14 of MV (odds ratio, 6.94 and 3.42, respectively; P ⩽ .05). Conclusions:In our study, we found that PT for PMV patients occurs infrequently and is generally of low intensity. Level of sedation, presence of a tracheostomy, and prehospital nonambulatory status were associated with receipt of PT consultation by day 14 of MV.