Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome*

O’Neal, Hollis R.; Koyama, Tatasuki; Koehler, Elizabeth; Siew, Edward D.; Curtis, Blake R; Fremont, Richard D.; May, Addison K.; Bernard, Gordon R.; Ware, Lorraine B.

doi:10.1097/ccm.0b013e3182120992

Cited by 167 publications

(115 citation statements)

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“…Various experimental studies of ARDS have shown a beneficial effect of aspirin on reducing pulmonary inflammation 11. Similarly, in observational studies, patients on aspirin therapy prior to hospitalisation had a reduced incidence of ARDS12 13 and organ dysfunction14. In contrast, the recent LIPS-A study, which prospectively treated patients at risk of developing ARDS with aspirin, showed no reduction in incidence of ARDS 15.…”

Section: Introductionmentioning

confidence: 99%

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS

Hamid

Krasnodembskaya

Fitzgerald

et al. 2017

Thorax

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Rationale Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin’s antiplatelet and immunomodulatory effects may be beneficial in ARDS. Objective To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Methods Healthy volunteers were randomised to receive placebo or aspirin 75 or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 μg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. Results In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. Conclusions These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the prevention and treatment of ARDS. Trial registration number NCT01659307 Results.

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Section: Introductionmentioning

confidence: 99%

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS

Hamid

Krasnodembskaya

Fitzgerald

et al. 2017

Thorax

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“…Our group reported in a prior study of 575 patients in the Validating Acute Lung Injury Markers for Diagnosis (VALID) cohort, that concurrent statin and aspirin use, but not aspirin alone, was associated with reduced risk of ARDS (19). However, this study was likely underpowered to show an independent association between prehospital aspirin use and reduced risk of ARDS, given the large proportion of patients who were receiving both prehospital statin and prehospital aspirin therapy.…”

Section: Introductionmentioning

confidence: 99%

“…This analysis included the previously studied 575 patients as well as patients who were enrolled in the VALID cohort after our previous study was published (19). The aim of the study was to investigate the association between prehospital aspirin therapy and development of ARDS in a heterogeneous group of critically ill patients at high risk for ARDS as well as in the subgroup of patients with sepsis, adjusting for propensity to receive aspirin.…”

Section: Introductionmentioning

confidence: 99%

Prehospital Aspirin Use Is Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Patients

Chen

Janz

Bastarache

et al. 2015

Critical Care Medicine

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102

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Objectives Platelet activation plays an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). In our prior study of 575 patients at high risk for ARDS, concurrent statin and aspirin use was associated with reduced ARDS. However, the largest study (n=3855) to date found no significant benefit of prehospital aspirin in a lower risk population when adjusted for the propensity for aspirin use. We aimed to determine whether prehospital aspirin use is associated with decreased ARDS in patients at high risk for ARDS after adjusting for the propensity to receive aspirin. Design Secondary analysis of patients enrolled prospectively in the Validating Acute Lung Injury Markers for Diagnosis (VALID) study. Patients A total of 1149 critically ill patients (age ≥ 40) admitted to the medical or surgical intensive care units of an academic tertiary care hospital including 575 previously reported patients as well as additional patients who were enrolled after completion of the prior statin and aspirin study. Intervention None Measurements and Results Of 1149 patients, 368 (32%) developed ARDS during the first four ICU days and 287 (25%) patients had prehospital aspirin use. Patients with prehospital aspirin had significantly lower incidence of ARDS (27% vs. 34%, p=0.034). In a multivariable, propensity-adjusted analysis including age, gender, race, sepsis and APACHE II, prehospital aspirin use was associated with a decreased risk of ARDS (OR 0.66, 95% CI 0.46-0.94) in the entire cohort and in a subgroup of 725 patients with sepsis (OR 0.60, 95% CI 0.41-0.90). Conclusions In this selected cohort of critically ill patients, prehospital aspirin use was independently associated with a decreased risk of ARDS even after adjusting for the propensity of pre-hospital aspirin use. These findings support the need for prospective clinical trials to determine whether aspirin may be beneficial for the prevention of clinical ARDS.

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“…Примечательно, что обусловлен ное диетой повышение ТГ в плазме здоровых добровольцев сопровождается усилением выработки ок сида азота [6] и может способствовать развитию хрониче ских воспалительных заболеваний воспаления дыхатель ных путей и паренхимы легких [10]. Следует также отметить, что модификация липидного обмена при помо щи симвастатина может оказывать влияние как на тече ние, так и само развитие ОПЛ у пациентов ОИТ [20,21].…”

Section: таблица 1 основные характеристики пациентов в исследованных unclassified

The Relationship between the Plasma Triglyceride Concentration and the Severity of Acute Respiratory Distress Syndrome

Kuzkov¹,

Fot²,

Смёткин³

et al. 2012

rmt

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На сегодняшний день изменения жирового обмена при критических состояниях, а также роль эндогенных липидов в развитии полиорганной недостаточности изу чены крайне ограниченно. Известно, что перекисное окисление липидов является неотъемлемым компонен том каскада патофизиологических реакций, развертыва ющихся при повреждении тканей и системном воспали тельном ответе. Этот каскад может сопровождаться высвобождением триглицеридов (ТГ) и жирных кислот, играющих важную регуляторную и трофическую роль [1][2][3][4][5]. В последнее время внимание исследователей в большей мере обращено на роль холестерина при крити ческих состояниях [6][7][8], тогда как сведения о потенци альном значении ТГ носят фрагментарный характер.Продукты жирового обмена могут играть немало важную роль при тяжелой травме, сепсисе и остром по вреждении легких (ОПЛ) [3,[6][7][8]. Как в норме, так и при критических состояниях, легкие, обладающие об ширной сосудистой поверхностью, активно участвуют в жировом обмене [9,10]. Экспериментальные исследова ния подтверждают, что ОПЛ ведет к подавлению мета болизма липидов клетками эндотелия легочных сосудов [11]. С другой стороны, хорошо известно повреждающее действие экзогенных жиров на ткань легких, что широко используется в эксперименте для воспроизведения мо дели обратимого острого повреждения легких при помо щи олеиновой кислоты [12].Цель исследования -изучить взаимосвязь плаз менной концентрации триглицеридов с клиническим ис Triglycerides (TG) may be involved in the pathogenesis of critical impairments. Objective: to study the relationship between the plasma concentration of TG, the outcome of the disease, and the markers of its severity in intensive care unit patients with early stage acute respiratory distress syndrome (ARDS). Subjects and methods. The prospective study included 18 patients with acute lung injury (ALI), who needed respiratory support. For further analysis, all the patients were divided into groups with TG < 1.00 mmol/l (TG low ; n=7) and 1.00 mmol/l (TG high ; n=11). Results. A negative cor relation was found between plasma TG concentration and oxygenation index (PaO 2 /FiO 2 ). In the TG high group, extravas cular lung water index was significantly higher and cardiac index was lower than those in the TG low group. Among the deceased patients, there was a 1.03 mmol/l reduction in TG concentration by day 4 of the study whereas in the survivors, TG concentration increased by an average of 0.15 mmol/l (p=0.02). Conclusion. In the patients with ALI, the plasma con centration of TG is related to oxygenation impairments and the degree of pulmonary edema, as well as with the outcome of the disease. Key words: triglycerides, acute lung injury, extravascular lung water index, pulmonary edema.

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Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome*

Cited by 167 publications

References 50 publications

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS

Prehospital Aspirin Use Is Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Patients

The Relationship between the Plasma Triglyceride Concentration and the Severity of Acute Respiratory Distress Syndrome

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