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Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial

Author(s): Constantin JM, Jabaudon M, Lefrant JY, Jaber S, Quenot JP, Langeron O, Ferrandière M, Grelon F, Seguin P, Ichai C, Veber B, Souweine B, Uberti T, Lasocki S, Legay F, Leone M, Eisenmann N, Dahyot-Fizelier C, Dupont H, Asehnoune K, Sossou A, Chanques G, Muller L, Bazin JE, Monsel A, Borao L, Garcier JM, Rouby JJ, Pereira B, Futier E; AZUREA Network

Lancet Respir Med 2019 . pii: S2213-2600(19)30138-9

Respiratory critical care

Digest Author(s): Silvia Mongodi / 2 September, 2019

In the last years, several studies showed that protective mechanical ventilation with low tidal volume, reduced inspiratory plateau pressure and low driving pressure improves ARDS (Acute Respiratory Distress Syndrome) outcome in terms of mortality, ventilator free-days and major complication. Nevertheless, some aspects of ventilatory strategy remain debated, as for PEEP-setting and recruitments manoeuvres (1). The most recent evidence suggests that ARDS is an heterogenous syndrome with different sub-phenotypes (i.e. focal vs. non-focal; hyper-inflammatory vs. hypo-inflammatory) with different clinical needs and prognoses (2).

In the paper by Constantin and colleagues, the authors aimed to test whether a ventilator setting personalized on patient’s lung morphology - as assessed by imaging techniques (focal vs. non focal-ARDS) - would improve survival in comparison with conventional management (ARDSnet guidelines). In the personalized group, focal ARDS were treated by low PEEP setting, tidal-volume of 8 mL/kg of ideal body weight and early pronation while non-focal ARDS received 6 mL/kg, recruitment manoeuvres and high PEEP. The control group received 6 mL/kg and the ventilator was set on the basis of the low PEEP/FiO2 table. This multicentre French randomised controlled trial didn’t show any difference in 90-day mortality between personalized and control group (HR 1.01; 0.61-1.66; p = 0.98). Although this is a negative study, some additional considerations deserve to be done:

  • Misclassification of lung morphology was the major concern of the study; it occurred in 21% of patients of the personalized group, hiding the potential benefits of this strategy. The amount of misclassification could be explained by methodological issues: ability of each investigator after training program and inter-investigator agreement was not tested.
  • Misclassified patients of the personalized group received a ventilation-strategy not aligned with their lung morphology and had a significantly higher mortality rate than those correctly classified, both in focal and non-focal ARDS subgroups (p < 0.001).
  • When excluding misclassified patients from the personalized group, 90-day mortality was significantly lower for the personalized ventilation strategy (17% vs. 27%; HR 0.6: 95%CI 0.36-0.99, p = 0.045).
  • Non quantitative CT-scan is per protocol the reference imaging technique for morphology assessment; CXR±lung ultrasound was also allowed in case of high-risk transportation to radiology department. However, CT-scan was performed in 39% and 29% of control and intervention group, respectively. The majority of patients was assessed by CXR, which has limited performance in aeration assessment. No patient was studied with lung ultrasound score, which is strongly associated to lung tissue density as assessed by quantitative CT scan (3). Finally, interaction with other bedside monitoring tool for personalized ventilation of ARDS patients was not allowed in the protocol (for example, esophageal pressure) (4).

    Key points:

  • Personalized ventilation tailored to lung morphology may improve ARDS outcome, if the patients are correctly classified
  • Characterization of lung morphology requires trained physicians. In addition to CT-scan, further techniques as lung ultrasound may be useful for non-invasive and bedside assessment of lung morphology.
  • Further studies are needed to correctly assign the best ventilation strategy for each ARDS phenotype.
  • Integration with other bedside tool to assess and monitor ARDS patient may further improve personalized strategies.

    References

    1. Meade MO, Cook DJ, Guyatt GH, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome. JAMA 2008;299:637-45.
    2. Calfee CS, Delucchi KL, Sinha P, et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med 2018;6:691-8.
    3. Chiumello D, Mongodi S, Algieri I, et al. Assessment of lung aeration and recruitment by CT scan and ultrasound in acute respiratory distress syndrome patients. Crit Care Med 2018;46:1761-8.
    4. Mauri T, Yoshida T, Bellani G, et al. Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives. Intensive Care Med 2016;42:1360-73.

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