Aspirin effect on early and late changes in acute lung injury in sheep

Chelucci, Gian Luca; Boncinelli, S; Marsili, M; Lorenzi, P.; Allegra, Andrea Gaetano; Linden, Matthew D.; Chelucci, A.; Merciai, V.; Cresci, F; Rostagno, Carlo; Gensini, Gian Franco; Lockhart, A; Milic-Emili, J

doi:10.1007/bf01709272

Cited by 21 publications

(21 citation statements)

References 29 publications

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“…The finding that prehospital aspirin use is associated with a decreased risk of ARDS in critically ill patients is consistent with the known beneficial effects of aspirin in both clinical and experimental acute lung injury (13, 26, 27). In addition, aspirin also has potent effects on treatment and prevention of sepsis via anti-platelet and anti-inflammatory effects in preclinical and clinical studies (28-30).…”

Section: Discussionsupporting

confidence: 82%

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

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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Section: Discussionsupporting

confidence: 82%

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

102

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“…No benefit was observed in one study (28) and in one study (29) worsening of inflammation was demonstrated.…”

Section: Resultsmentioning

confidence: 89%

“…In 10 studies the antiplatelet drug was ASA (26–31, 35–38) in three studies ASA-triggered lipoxin (32, 33, 38) , and in three studies ASA-triggered resolving D 1 (34, 39, 40) were studied. In 12 preclinical studies (29–33, 35–40) a mouse model was used, in two preclinical studies a sheep model (27, 28) and in one study a dog model (26). Both direct and indirect models of acute lung injury were tested (table 1).…”

Section: Resultsmentioning

confidence: 99%

“…All models induced lung injury, evidenced by an increase in lung edema and the appearance of neutrophils, proteins and inflammatory mediators in broncho-alveolar lavage fluid. In two studies respiratory mechanics (27, 28) and in three studies pulmonary and systemic hemodynamics were measured (26–28). …”

Section: Resultsmentioning

confidence: 99%

“…In the study of Chelucci et al, ASA pretreatment reduced early pulmonary vasoconstriction, airway resistance, and early pulmonary gas exchange (28). However, the late increase in pulmonary artery pressure and airway resistance was not inhibited by ASA and the late severe deterioration of gas exchange was even exaggerated compared to controls.…”

Section: Resultsmentioning

confidence: 99%

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Prevention or Treatment of Ards With Aspirin

Panka

Grooth

Man

et al. 2017

Shock

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Background The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions directed at lung injury itself, have proven effective in improving outcome of patients with ARDS. Platelet activation was identified as a key component in ARDS pathophysiology and may provide an opportunity for preventive and therapeutic strategies. We hypothesize that use of acetyl salicylic acid (ASA) may prevent and/or attenuate lung injury. Methods We conducted a systematic review of preclinical studies and meta-analysis of clinical studies investigating the efficacy of ASA in the setting of lung injury. MEDLINE, EMBASE AND COCHRANE databases were searched. Results The literature search yielded 1314 unique articles. Fifteen pre-clinical studies and eight clinical studies fulfilled the in- and exclusion criteria. In the animal studies, the overall effect of ASA was positive, e.g. ASA improved survival and attenuated inflammation and pulmonary edema. Mechanisms of actions involved, among others, are interference with the neutrophil-platelets interaction, reduction of leukotrienes, neutrophil extracellular traps and prostaglandins. High dose ASA may be the drug of choice. A meta-analysis of 3 clinical studies showed an association between ASA use and a reduced incidence of ARDS (OR 0.59, 95% CI 0.36–0.98), albeit with substantial between-study heterogeneity. All studies had their own shortcomings in methodological quality. Conclusion This systematic review of preclinical studies and meta-analysis of clinical studies suggests a beneficial role for ASA in ARDS prevention and treatment. However, the currently available data is insufficient to justify an indication for ASA in ARDS. The body of literature does support further studies in humans. We suggest clinical trials in which the mechanisms of action of ASA in lung injury models is being evaluated to guide optimal timing and dose, before prospective randomized trials.

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Meconium aspiration induces ARDS-like pulmonary response in lungs of ten-week-old pigs

et al. 1997

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To investigate whether aspiration of meconium induces a hemodynamic and histologic pulmonary response similar to that frequently seen in experimental acute respiratory distress syndrome, twelve 10‐week‐old pigs with postnatally adapted lungs were studied. Six 10‐week‐old pigs received 3 ml/kg 20% human meconium via the endotracheal tube. Six control pigs of the same age were given sterile saline. Ventilator settings were adjusted to keep PaO2 above 8 kPa and PaCO2 below 5 kPa. The pulmonary hemodynamic response to aspiration consisted of two separate hypertensive components. An initial peak in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) was followed by a progressive increase in PAP and PVR in the meconium group, whereas in the saline group these parameters returned to baseline levels. The distribution of PVR, determined by pulmonary artery occlusion, was characterized by an increase in the postarterial resistance immediately after meconium aspiration and a progressive increase in both arterial and postarterial resistances during the later phase. On histological examination, marked neutrophil sequestration was seen in the meconium lungs. In addition, lung edema formation was significantly enhanced in the meconium group, as shown by an increased lung wet/dry weight ratio. Thus, meconium aspiration resulted in a biphasic pulmonary pressor response and severe pulmonary inflammation. This response resembled that of models of experimental acute respiratory distress syndrome following diverse types of precipitating insults; this suggests that similar pathophysiologic mechanisms are elicited and cause similar pulmonary dysfunction following different forms of lung injury. Pediatr. Pulmonol. 1997; 23:205–211 © 1997 Wiley‐Liss, Inc.

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Aspirin effect on early and late changes in acute lung injury in sheep

Cited by 21 publications

References 29 publications

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

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

Prevention or Treatment of Ards With Aspirin

Meconium aspiration induces ARDS-like pulmonary response in lungs of ten-week-old pigs

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