Statins in patients with sepsis and ARDS: is it over? We are not sure

McAuley, Daniel F.; Charles, Pierre‐Emmanuel; Papazian, Laurent

doi:10.1007/s00134-016-4454-9

Cited by 9 publications

(7 citation statements)

References 15 publications

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“…(2) Are statins more appropriate for the prevention or for the treatment of sepsis-associated ARDS [68] ? (3) What is the adequate statin and statin dose associated with better outcomes in sepsis/ARDS [71] ?…”

Section: Ards Epidemiologymentioning

confidence: 99%

Update of Sepsis in the Intensive Care Unit

Genga¹,

Russell²

2017

J Innate Immun

116

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Sepsis, the most common cause of admission to an intensive care unit (ICU), has had an increased incidence and prevalence over the last years with a simultaneous decrease in its short-term mortality. Sepsis survivors are more frequently discharged from hospital and often experience long-term outcomes such as late mortality, immune dysfunction, secondary infections, impaired quality of life, and unplanned readmissions. Early recognition and management of sepsis have challenged emergency care and critical care physicians and nurses. New sepsis definitions were produced and the Surviving Sepsis Campaign (SSC) 2016 was updated recently. Although hospital readmissions after sepsis are common, associated risk factors and how to manage patients who survive an episode of sepsis still need clarification. The immune dysfunction caused by sepsis/septic shock is complex, persistent, affects inflammatory and anti-inflammatory systems, and might be associated with long-term outcomes of sepsis. Several randomized controlled trials (RCT) that analyzed new (and old) interventions in sepsis/septic shock are discussed in this review in parallel with the SSC 2016 recommendations and other guidelines when relevant. RCTs addressing incidence, treatment, and prevention of important sepsis-associated organ dysfunction such as the acute respiratory distress syndrome, acute kidney injury, and brain dysfunction are highlighted. Finally, we briefly discuss the need for novel targets, predictive biomarkers, and new designs of RCTs in sepsis.

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Section: Ards Epidemiologymentioning

confidence: 99%

Update of Sepsis in the Intensive Care Unit

Genga¹,

Russell²

2017

J Innate Immun

116

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“…In these regions, circulating statins interact directly with endothelial cell layers, raising the possibility that statin inhibition of an invasion would limit the progression of endovascular infection. McAuley et al maintain that patients with underlying endovascular disease may benefit from statin therapy in an infection setting [ 37 ]. However, epidemiological and medical research using observational studies on cardiac implant infection in patient populations on a statin regimen is minimal, but at least one study suggests that statin therapy offers protection against infection.…”

Section: Settings Where Biology Suggests Statins May Offer Protection...mentioning

confidence: 99%

Innovations in Evaluating Statin Benefit and Efficacy in Staphylococcus aureus Intracellular Infection Management

Nesson

McDowell²

2022

IJMS

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An emerging therapeutic approach in the treatment of infectious disease is to augment the host response through repurposing of well-tolerated, non-antibiotic, host-directed therapeutics. Earlier retrospective studies identify a positive association between statin use and a decreased risk of death due to sepsis or bacteremia. However, more recent randomized control trials fail to detect a therapeutic benefit in these complex infection settings. It is postulated that unrecognized biases in certain observational studies may have led to an overestimation of benefit and that statin use is instead a marker for health status, wealth, and demographic characteristics which may separately affect death due to infection. What remains unresolved is that in vitro and in vivo evidence reproducibly indicates that statin pharmacology limits infection and augments immunomodulatory responses, suggesting that therapeutic benefits may be attainable in certain infection settings, such as intracellular infection by S. aureus. Carefully considering the biological mechanisms capable of driving the relationship between statins and infections and constructing a methodology to avoid potential biases in observational studies would enable the examination of protective effects against infection and limit the risk of underestimating statin efficacy. Such an approach would rely on the examination of statin use in defined infection settings based on an underlying mode-of-action and pharmacology, where the inhibition of HMG-CoA-reductase at the rate-limiting step in cholesterol biosynthesis diminishes not only cholesterol levels but also isoprenoid intermediates central to host cell invasion by S. aureus. Therapeutic benefit in such settings, if existent, may be of clinical importance.

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“…Statins, traditionally administered to lower serum cholesterol, have been considered an attractive class of drugs in the setting of COVID-19 [ 2 , 3 ] due to their pleiotropic effects, including anti-inflammatory, immunomodulatory, antithrombotic, and antimicrobial properties [ 4 , 5 ]. Previously studies have evaluated the use of statins in the treatment of pneumonia and ARDS (Acute Respiratory Distress Syndrome) [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Particularly, an analysis of 540 individuals from the HARP-2 (hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction-2) trial demonstrated improved survival upon statin treatment in patients with a hyperinflammatory phenotype [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Phenotypical and Functional Alteration of γδ T Lymphocytes in COVID-19 Patients: Reversal by Statins

Simone

Corsale

Presti

et al. 2022

Cells

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(1) Background: statins have been considered an attractive class of drugs in the pharmacological setting of COVID-19 due to their pleiotropic properties and their use correlates with decreased mortality in hospitalized COVID-19 patients. Furthermore, it is well known that statins, which block the mevalonate pathway, affect γδ T lymphocyte activation. As γδ T cells participate in the inflammatory process of COVID-19, we have investigated the therapeutical potential of statins as a tool to inhibit γδ T cell pro-inflammatory activities; (2) Methods: we harvested peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild clinical manifestations, COVID-19 recovered patients, and healthy controls. We performed ex vivo flow cytometry analysis to study γδ T cell frequency, phenotype, and exhaustion status. PBMCs were treated with Atorvastatin followed by non-specific and specific stimulation, to evaluate the expression of pro-inflammatory cytokines; (3) Results: COVID-19 patients had a lower frequency of circulating Vδ2+ T lymphocytes but showed a pronounced pro-inflammatory profile, which was inhibited by in vitro treatment with statins; (4) Conclusions: the in vitro capacity of statins to inhibit Vδ2+ T lymphocytes in COVID-19 patients highlights a new potential biological function of these drugs and supports their therapeutical use in these patients.

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Statins in patients with sepsis and ARDS: is it over? We are not sure

Abstract: International audienceno abstrac

Cited by 9 publications

References 15 publications

Update of Sepsis in the Intensive Care Unit

Update of Sepsis in the Intensive Care Unit

Innovations in Evaluating Statin Benefit and Efficacy in Staphylococcus aureus Intracellular Infection Management

Phenotypical and Functional Alteration of γδ T Lymphocytes in COVID-19 Patients: Reversal by Statins

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