Lipoxin A4 ameliorates renal ischaemia-reperfusion-induced acute lung injury in rats.

Lipoxin A4 (LA4), a bioactive product of arachidonic acid, has been shown to exert strong anti-inflammatory activity. By contrast, the anti-inflammatory action of LA4 in a renal ischaemia-reperfusion (RIR)-mediated acute lung inflammation (ALI) model and the potential pathogenesis of the condition is still unclear. The aim of the current research was to investigate the effect of LA4 on RIR-induced ALI. The rat ALI model was induced by RIR. LA4 was injected via the tail vein immediately after RIR. The results indicate that LA4 markedly inhibits inflammatory cells infiltration, attenuates myeloperoxidase activity, and reduces the concentration of inflammatory mediators and Toll-like receptor 4 (TLR4) in RIR-induced ALI. Furthermore, LA4 suppressed nuclear factor kappa B (NF-κB) p65 and mitogen-activated protein kinase (MAPK) activation. The protective effect of LA4 in RIR-stimulated ALI was reversed by BOC-2 (an antagonist of the LA4 receptor). These results indicate that LA4 exerts powerful anti-inflammatory functions in RIR-induced ALI by attenuating TLR4 expression via MAPK and NF-κB signalling. Accordingly, LA4 might be an underlying treatment drug for RIR-induced ALI.

Cost of Critically Ill Surgical Patients in Thailand: A Prospective Analysis of a Multicenter THAI-SICU Study.

Objective: To quantify the total cost per admission and daily cost of critically ill surgical patients and cost attributable to Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score, invasive mechanical ventilation and major complications in surgical intensive care unit (SICU) including sepsis, acute respiratory distress syndrome (ARDS), acute lung injury (ALI), acute kidney injury (AKI), cardiac arrest, and myocardial infarction. Material and Method: A multicentre, prospective, observational, cost analysis study was carried out in SICU of five university hospitals in Thailand. Patients of age over 18 admitted to SICU (more than 6 hours) from 18 April 2011 to 30 November 2012 were recruited.The total SICU cost per admission (in Thai baht currency year 2011-2012) were recorded using hospital accounting database. Average daily SICU cost was calculated from total ICU cost divided by the ICU length of stay. The occurrence of sepsis, major cardiac and respiratory complications and duration of invasive mechanical ventilation were studied. Results: A total of 3,055 patients with 12,592 ICU-days admitted to SICU during the study period. The median (IQR) ICU- length of stay was 2 (1, 4) days. The median (IQR) total SICU cost per admission was 44,055 (29,950-73,694) Thai baht. The median (IQR) daily cost was 18,777 (13,650-22,790) Thai baht. There was a variation of total and daily SICU cost across ICUs. For each of APACHE II score increases, cost increases with a median (IQR) of 1,731.755 (1,507.418-1,956.093) Thai baht. Invasive mechanically ventilated patients had higher cost than non-ventilated patients with a median (IQR) 15,873.4 (15,631.13-16,115.67) Thai baht. The patient with any complications listed here (sepsis, ARDS, ALI, AKI, myocardial infarction) had higher costs of care than ones who had none. Conclusion: Cost of critically ill surgical patients in the public university hospital in Thailand was varied. The complications occurred in ICU increased the cost. To quantify the resource consumption of individual patient admitted to SICU, the costing method and cost components must be verified.

Health care resource use and costs of two-year survivors of acute lung injury. An observational cohort study.

RATIONALE: Survivors of acute lung injury (ALI) require ongoing health care resources after hospital discharge. The extent of such resource use, and associated costs, are not fully understood. OBJECTIVES: For patients surviving at least 2 years after ALI, we evaluated cumulative 2-year inpatient admissions and related costs, and the association of patient- and intensive care unit-related exposures with these costs. METHODS: Multisite observational cohort study in 13 intensive care units at four academic teaching hospitals evaluating 138 two-year survivors of ALI. MEASUREMENTS AND MAIN RESULTS: Two-year inpatient health care use data (i.e., admissions to hospitals, and skilled nursing and rehabilitation facilities) were collected for patients surviving at least 2 years, via (1) one-time retrospective structured interview with patient and/or proxy, (2) systematic medical record review for nonfederal study site hospitals, and (3) inpatient medical record review for non-study site hospitals, as needed for clarifying patient/proxy reports. Costs are reported in 2013 U.S. dollars. A total of 138 of 142 (97%) 2-year survivors completed the interview, with 111 (80%) reporting at least one inpatient admission during follow-up, for median (interquartile range [IQR]) estimated costs of $35,259 ($10,565-$81,166). Hospital readmissions accounted for 76% of costs. Among 12 patient- and intensive care unit-related exposures evaluated, baseline comorbidity and intensive care unit length of stay were associated with increased odds of incurring any follow-up inpatient costs. Having Medicare or Medicaid (vs. private insurance) was associated with median estimated costs that were 85% higher (relative median, 1.85; 95% confidence interval, 1.01-3.45; P=0.045). CONCLUSIONS: In this multisite study of 138 two-year survivors of ALI, 80% had one or more inpatient admission, representing a median (IQR) estimated cost $35,259 ($10,565-$81,166) per patient and $6,598,766 for the entire cohort. Hospital readmissions represented 76% of total inpatient costs, and having Medicare or Medicaid before ALI was associated with increased costs. With the aging population and increasing comorbidity, these findings have important health policy implications for the care of critically ill patients.

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial: study protocol for a randomized controlled trial.

BACKGROUND: Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI. METHODS/DESIGN: Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1:1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms by which simvastatin might act to improve clinical outcomes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88244364.

The effect of pulmonary artery catheter use on costs and long-term outcomes of acute lung injury.

BACKGROUND: The pulmonary artery catheter (PAC) remains widely used in acute lung injury (ALI) despite known complications and little evidence of improved short-term mortality. Concurrent with NHLBI ARDS Clinical Trials Network Fluid and Catheters Treatment Trial (FACTT), we conducted a prospectively-defined comparison of healthcare costs and long-term outcomes for care with a PAC vs. central venous catheter (CVC). We explored if use of the PAC in ALI is justified by a beneficial cost-effectiveness profile. METHODS: We obtained detailed bills for the initial hospitalization. We interviewed survivors using the Health Utilities Index Mark 2 questionnaire at 2, 6, 9 and 12 m to determine quality of life (QOL) and post-discharge resource use. Outcomes beyond 12 m were estimated from federal databases. Incremental costs and outcomes were generated using MonteCarlo simulation. RESULTS: Of 1001 subjects enrolled in FACTT, 774 (86%) were eligible for long-term follow-up and 655 (85%) consented. Hospital costs were similar for the PAC and CVC groups ($96.8k vs. $89.2k, p = 0.38). Post-discharge to 12 m costs were higher for PAC subjects ($61.1k vs. 45.4k, p = 0.03). One-year mortality and QOL among survivors were similar in PAC and CVC groups (mortality: 35.6% vs. 31.9%, p = 0.33; QOL [scale: 0-1]: 0.61 vs. 0.66, p = 0.49). MonteCarlo simulation showed PAC use had a 75.2% probability of being more expensive and less effective (mean cost increase of $14.4k and mean loss of 0.3 quality-adjusted life years (QALYs)) and a 94.2% probability of being higher than the $100k/QALY willingness-to-pay threshold. CONCLUSION: PAC use increased costs with no patient benefit and thus appears unjustified for routine use in ALI. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00234767.