Citations

Introduction Acute lung injury (ALI) is a devastating condition that places a heavy burden on public health resources. Although the need for effective ALI prevention strategies is increasingly recognised, no effective preventative strategies exist. The Lung Injury Prevention Study with Aspirin (LIPS-A) aims to test whether aspirin (ASA) could prevent and/or mitigate the development of ALI. Methods and analysis LIPS-A is a multicentre, double-blind, randomised clinical trial testing the hypothesis that the early administration of ASA will result in a reduced incidence of ALI in adult patients at high risk. This investigation will enrol 400 study participants from 14 hospitals across the USA. Conditional logistic regression will be used to test the primary hypothesis that early ASA administration will decrease the incidence of ALI. Ethics and dissemination Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approval of both the protocol and informed consent documents were also obtained from the institutional review board of each participating institution prior to enrolling study participants at the respective site. In addition to providing important clinical and mechanistic information, this investigation will inform the scientific merit and feasibility of a phase III trial on ASA as an ALI prevention agent. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to Pub Med Central in accordance with the National Institute of Health Public Access Policy.

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.

Abstract 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 (ΔPaO2/FiO2). 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 ΔPaO2/FiO2 (difference between the mean ΔPaO2/FiO2 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).

AbstractTransfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti–human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.

BACKGROUND: An increasing number of patients require prolonged mechanical ventilation (PMV), which is associated with high morbidity and poor long-term survival, but there are few data regarding the incidence and outcome of PMV patients from a community perspective. METHODS: We retrospectively reviewed the electronic medical records of adult Olmsted county, Minnesota, residents admitted to the intensive care units at the 2 Mayo Clinic Rochester hospitals from January 1, 2003, to December 31, 2007, who underwent tracheostomy for PMV. RESULTS: Sixty-five patients, median age 68 years (interquartile range [IQR] 49–80 y), 39 male, underwent tracheostomy for PMV, resulting in an age-adjusted incidence of 13 (95% CI 10–17) per 100,000 patient-years at risk. The median number of days on mechanical ventilation was 24 days (IQR 18–37 d). Forty-six patients (71%) survived to hospital discharge, and 36 (55%) were alive at 1-year follow-up. After adjusting for age and baseline severity of illness, the presence of COPD was independently associated with 1-year mortality (hazard ratio 3.4, 95% CI 1.4–8.2%). CONCLUSIONS: There was a considerable incidence of tracheostomy for PMV. The presence of COPD was an independent predictor of 1-year mortality.

The outcome of critical illness depends not only on life threatening pathophysiologic disturbances, but also on several complex “system” dimensions: health care providers’ performance, organizational factors, environmental factors, family preferences and the interactions between each component. Systems engineering tools offer a novel approach which can facilitate a “systems understanding” of patient-environment interactions enabling advances in the science of healthcare delivery. Due to the complexity of operations in critical care medicine, certain assumptions are needed in order to understand system behavior. Patient variation and uncertainties underlying these assumptions present a challenge to investigators wishing to model and improve health care delivery processes. In this chapter we present a systems engineering approach to modeling critical care delivery using sepsis resuscitation as an example condition.

Acute lung injury affects a subset of hospitalized patients but is not universal. This syndrome can substantially delay ventilator liberation, prolong intensive care unit (ICU) stay, and increase mortality. As with many critical illness syndromes, the available treatment options are limited in number and impact. Once a patient develops lung injury, the best known strategy is supportive care. Observational studies have identified potential risk factors and have suggested that the use and timing of certain critical care interventions may influence the likelihood of developing lung injury. These findings suggest that a well designed screening tool and the systematic application of best practices in critical care may limit the risk of lung injury. An effective prediction score may also facilitate enrollment in pharmacopreventive trials. Development of such tools is accelerated by multicenter collaboration.

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.