Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients

Soßdorf, Maik; Otto, Gordon P.; Boettel, Janina; Winning, Johannes; Lösche, Wolfgang

doi:10.1186/cc11886

Cited by 50 publications

(35 citation statements)

References 5 publications

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“…In addition, we are the first to report a meta-analysis of clinical studies demonstrating an association between ASA and diminished risk of ARDS in critically-ill patients at risk for acute lung injury. Although our results are in line with data from studies with ASA in other inflammatory conditions, (54–56) the results of this meta-analysis should be interpreted with caution. General limitations of the clinical studies include lack of information regarding ASA dose, lack of control of prehospital vs. in hospital ASA use and the bias or confounding inherent to observational studies.…”

Section: Discussionsupporting

confidence: 84%

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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Section: Discussionsupporting

confidence: 84%

Prevention or Treatment of Ards With Aspirin

Panka

Grooth

Man

et al. 2017

Shock

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“…A retrospective study of 979 septic patients (mean APACHE II score 22–23, p=0.16) showed mortality benefit from aspirin 44. Logistic regression analysis determined that being on aspirin or a non-steroidal anti-inflammatory agent (NSAID; ibuprofen, diclofenac, or indomethacin) was associated with decreased mortality (aspirin (ASA) OR 0.57, 95% CI 0.39 to 0.83, NSAID OR 0.5, CI 0.26 to 0.94); however, being on both agents eliminated the benefit of either agent (ASA and NSAID OR 1.12, CI 0.55 to 2.25), indicating that NSAID use must be considered in clinical trials.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of β Blocker, Aspirin, and Statin in Critically Ill Patients: Importance of Severity of Illness and Cardiac Troponin

Rothenberg

Clay²,

Jamali

et al. 2017

Journal of Investigative Medicine

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Non-cardiac critically ill patients with type II myocardial infarction (MI) have a high risk of mortality. There are no evidence-based interventions to mitigate this risk. We systematically reviewed the literature regarding the use of medications known to reduce mortality in patients with cardiac troponin (cTn) elevation due to type I MI (β blockers, statin, and aspirin) in studies of critically ill patients without Type I MI. All PubMed publications between 1976-2/19/16 were reviewed. Search terms included: β blocker or aspirin or statin and intensive care unit (ICU) or critically ill or sepsis; 497 primary references were obtained. Inclusion criteria were as follows: (1) study population consisted of critically ill patients in the ICU with non-cardiovascular illnesses, (2) mortality end point, (3) severity of illness (or injury) was measured, and (4) the antiplatelet agent was primarily aspirin. Retrospective investigations, prospective observational studies, meta-analysis, systematic review, and randomized controlled trials were included; case reports were excluded. 25 primary references were obtained. The data were extracted and tabulated using data collection headings as follows: article title, first author/year/reference number, study type/design, population studied, outcome and intervention, and study question addressed. Evidence was not graded as the majority of studies were non-randomized (low-to-moderate quality). 11 studies were found through bibliography reviews for a total of 36 references. In conclusion, β blockers, statins, and aspirin may play a role in reducing mortality in non-cardiac critically ill patients. Benefit appears to be related to severity of illness, for which cTn may be a marker.

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“…Most studies provided individual-level data on aspirin use, allowing this exposure variable to be used for the primary analysis (7–9, 11, 12, 14, 15, 17, 19, 21). In one study, it was not possible to disaggregate aspirin use from that of other antiplatelets in the hospital-based cohort (13).…”

Section: Methodsmentioning

confidence: 99%

Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching*

Trauer

Muhi

McBryde

et al. 2017

Critical Care Medicine

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Objective The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. Study Selection Studies which reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. Data sources Fifteen studies described hospital-based cohorts (n=17,065), while one was a large insurance-based database (n=683,421). Individual-level patient data were incorporated from all selected studies. Data Extraction Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. Data Synthesis Use of aspirin was associated with a 7% (95%CI, 2% to 12%, p=0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity (I2=61.6%). Conclusions These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.

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Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients

Cited by 50 publications

References 5 publications

Prevention or Treatment of Ards With Aspirin

Prevention or Treatment of Ards With Aspirin

Systematic Review of β Blocker, Aspirin, and Statin in Critically Ill Patients: Importance of Severity of Illness and Cardiac Troponin

Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching*

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