Personalized medicine for ARDS: the 2035 research agenda

Beitler, Jeremy R.; Goligher, Ewan C.; Schmidt, Matthieu; Spieth, Peter M.; Zanella, Alberto; Martín‐Loeches, Ignacio; Calfee, Carolyn S.; Cavalcanti, Alexandre Biasi

doi:10.1007/s00134-016-4331-6

Cited by 64 publications

(49 citation statements)

References 77 publications

(99 reference statements)

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“…

Despite the attempt to homogenize its definition following the publication of the Berlin criteria, there is still a high heterogeneity in the epidemiology of ARDS across the world [3].

…”

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confidence: 99%

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Focus on ARDS

2017

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Since 1967, when first described, ARDS has been widely recognized as a major health problem worldwide, carrying a high morbidity and mortality [1][2][3]. This focus editorial summarizes recent advances about the incidence, pathophysiology, right ventricular dysfunction, and mortality of ARDS.Despite the attempt to homogenize its definition following the publication of the Berlin criteria, there is still a high heterogeneity in the epidemiology of ARDS across the world [3]. Indeed, estimates of the incidence of ARDS are highly variable, ranging from less than 2 to more than 70 cases per 100,000 person-years, with the most recent study on the topic suggesting a higher incidence in Europe, North America, and Oceania compared to South America, Asia, and Africa [2,3]. However, it is important to emphasize that this scenario could only reflect the under-recognition of this syndrome [3]. Recent reports suggest a progressive decline of the incidence of ARDS. In a study conducted in Rochester, cases fell by half between 2001 and 2008 while mortality remained stable [4]. Nearly all of the reduction in the incidence was observed in hospital-acquired ARDS, suggesting that ARDS could be prevented through strategies addressing its related risk factors [4,5]. However, in some instances, patients meeting the Berlin criteria for ARDS lack exposure to common risk factors [6]. It was recently reported that the prevalence of patients with ARDS but without common risk factors was as high as 7.5% [6]. According to medical history, bronchoalveolar lavage fluid cytology, and chest computed tomography (CT) scan patterns, four etiological categories were identified in this group of patients: immune, drug-induced, malignant, and idiopathic [6]. The overall ICU mortality rate was higher in patients lacking common risk factors as compared to their counterparts, even after adjustment for potential confounding factors [6].It is already well known that ventilator-induced lung injury contributes to ARDS-associated mortality [2,3]. Recently, some biological markers have been proposed as potential biomarkers of ARDS, such as the soluble form of the receptor for advanced glycation end-products (sRAGE). This biomarker is a transmembrane receptor that can bind multiple ligands resulting in intracellular signaling, leading to activation of the proinflammatory transcription factor nuclear factor κB [7]. Plasma levels of sRAGE could change according to ventilator settings in ARDS patients, as recently suggested by a study describing a significant decrease of sRAGE 1 h after a recruitment maneuver followed by an increase toward baseline values 4 h after the maneuver [7]. It has also been shown that sRAGE is higher in non-survivors than survivors in early pediatric ARDS and strongly correlated with number of non-pulmonary organ failures [8]. Other biomarkers of endothelial injury are also investigated in ARDS patients. Higher levels of circulating endothelial cells were found in the blood of patients with moderate-to-severe ARDS as compared to those with...

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“…

Despite the attempt to homogenize its definition following the publication of the Berlin criteria, there is still a high heterogeneity in the epidemiology of ARDS across the world [3].

…”

mentioning

confidence: 99%

“…Since 1967, when first described, ARDS has been widely recognized as a major health problem worldwide, carrying a high morbidity and mortality [1][2][3]. This focus editorial summarizes recent advances about the incidence, pathophysiology, right ventricular dysfunction, and mortality of ARDS.…”

mentioning

confidence: 99%

Focus on ARDS

2017

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“…Based on these general recommendations clinicians should individualize the therapy for their patients, especially regarding the presented conditional recommendations. Personalizing mechanical ventilation to patient-specific physiology to further enhance lung protection will be a top research priority for the years ahead, as stated by the ARDSne(x)t investigators (25). Profound understanding of the heterogeneous pathophysiological processes leading to the development of ARDS is needed to tailor ventilatory and other therapeutic strategies to the individual patient.…”

mentioning

confidence: 99%

“…Profound understanding of the heterogeneous pathophysiological processes leading to the development of ARDS is needed to tailor ventilatory and other therapeutic strategies to the individual patient. The next 20 years of ARDS research require that we ask not just whether novel preventive or therapeutic interventions work but also in whom (25).…”

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confidence: 99%

Preventing ventilator-induced lung injury—what does the evidence say?

Hoegl

Zwißler

2017

J. Thorac. Dis.

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“…It is concluded that the combination of ECCO 2 -R with renal replacement therapy allows a safe and adequate blood 'purification' of renal-and pulmonary-associated substances together while enhancing lung protective ventilation in critically ill patients. The trend towards a 'personalised medicine' has reached intensive care medicine and the management of ARDS patients should be revisited accordingly [5]. ECCO 2 -R could become an important part of such a project in a 'balanced' portfolio of extracorporeal lung support.…”

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confidence: 99%

Focus on ECMO and ECCO2R in ARDS patients

Bein

Aubron²,

Papazian

2017

Intensive Care Med

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The technical aspects of veno-venous extracorporeal membrane oxygenation (vv-ECMO) are still improving, permitting the treatment of ARDS patients with very severe hypoxaemia. A recent German survey showed that the incidence of vv-ECMO in the population increased from 1.0:100,000 inhabitants/year in 2007 to a maximum of 3.0:100,000 in 2012, and then stabilised at 2.4:100,000 in 2014 [1]. The in-hospital mortality slightly decreased over time but remained high, at 58.1% in 2014. This real-life mortality rates in an unselected population of patients undergoing ECMO for ARDS is even higher than previously reported. The extracorporeal CO 2 -removal (ECCO 2 -R) is a modification of ECMO characterised by a reduction in extracorporeal blood and sweep gas flow. The aims of ECCO 2 -R are: (1) the management of acute 'isolated' hypercapnic respiratory failure, (2) the reduction of tidal volume (3-4 ml/kg) and the control of hypercapnia, and (3) the avoidance of intubation in exacerbated chronic obstructive lung disease. While in the latter situation a number of small observational studies or case reports exerted promising results, the scientific evidence for the use and benefit of ECCO 2 -R in ARDS patients is limited [2].The prospective observational study by Hermann et al. [3], investigating the efficacy and safety of a novel pumpdriven ECCO2-R-system demonstrated a significant, but 'intensity'-dependent, amount of CO 2 removal between 40 and 70 ml/min. The CO 2 transfer was dependent on the amount of blood flow (0.5-2.0 l/min) and sweep gas flow. A rapid normalisation of hypercapnia secondary to higher blood flows (>1.0 l/min) and a moderate increase in oxygenation were found. However, very high sweep gas flows (higher than 10 l/min) were associated with a deterioration in O 2 and CO 2 transfer. Based on these study results, it is recommended to use ECCO 2 -R settings that combine moderate blood flow (1-1.5 l/min) and sweep gas flow (2-8 l/min) to achieve the best clinical effect and to avoid adverse effects. The combination of ECCO 2 -R and renal replacement therapy was investigated in 11 patients with ARDS and acute renal failure [4]. A membrane oxygenator was inserted in a continuous RRT system, resulting in an average CO 2 removal rate of 80 ml/ min (corresponds to a reduction of ≈20% of the arterial PaCO 2 level). Consequently, the tidal volume was lowered from 6 to 4 ml/kg and the plateau pressure could be reduced from 25 to 21 cm H 2 O (p < 0.01); no adverse events were reported. It is concluded that the combination of ECCO 2 -R with renal replacement therapy allows a safe and adequate blood 'purification' of renal-and pulmonary-associated substances together while enhancing lung protective ventilation in critically ill patients. The trend towards a 'personalised medicine' has reached intensive care medicine and the management of ARDS patients should be revisited accordingly [5]. ECCO 2 -R could become an important part of such a project in a 'balanced' portfolio of extracorporeal lung support. Although vv-ECMO r...

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Personalized medicine for ARDS: the 2035 research agenda

Cited by 64 publications

References 77 publications

Focus on ARDS

Focus on ARDS

Preventing ventilator-induced lung injury—what does the evidence say?

Focus on ECMO and ECCO2R in ARDS patients

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