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. 2020 Dec;48(12):e1300-e1305.
doi: 10.1097/CCM.0000000000004569.

Late Ventilator-Induced Diaphragmatic Dysfunction After Extubation

Haikel Dridi  1   2 , Boris Jung  1   3 , Mohamad Yehya  1 , Aurelien Daurat  4   5 , Steven Reiken  2 , Johan Moreau  1 , Andrew R Marks  2 , Stefan Matecki  1   5 , Alain Lacampagne  1 , Samir Jaber  1   4
Affiliations

Late Ventilator-Induced Diaphragmatic Dysfunction After Extubation

Haikel Dridi et al. Crit Care Med. 2020 Dec.

Abstract

Objectives: Mechanical ventilation is associated with primary diaphragmatic dysfunction, also termed ventilator-induced diaphragmatic dysfunction. Studies evaluating diaphragmatic function recovery after extubation are lacking. We evaluated early and late recoveries from ventilator-induced diaphragmatic dysfunction in a mouse model.

Design: Experimental randomized study.

Setting: Research laboratory.

Subjects: C57/BL6 mice.

Interventions: Six groups of C57/BL6 mice. Mice were ventilated for 6 hours and then euthanatized immediately (n = 18), or 1 (n = 18) or 10 days after extubation with (n = 5) and without S107 (n = 16) treatment. Mice euthanatized immediately after 6 hours of anesthesia (n = 15) or after 6 hours of anesthesia and 10 days of recovery (n = 5) served as controls.

Measurements and main results: For each group, diaphragm force production, posttranslational modification of ryanodine receptor, oxidative stress, proteolysis, and cross-sectional areas were evaluated. After 6 hours of mechanical ventilation, diaphragm force production was decreased by 25-30%, restored to the control levels 1 day after extubation, and secondarily decreased by 20% 10 days after extubation compared with controls. Ryanodine receptor was protein kinase A-hyperphosphorylated, S-nitrosylated, oxidized, and depleted of its stabilizing subunit calstabin-1 6 hours after the onset of the mechanical ventilation, 1 and 10 days after extubation. Post extubation treatment with S107, a Rycal drug that stabilizes the ryanodine complex, did reverse the loss of diaphragmatic force associated with mechanical ventilation. Total protein oxidation was restored to the control levels 1 day after extubation. Markers of proteolysis including calpain 1 and calpain 2 remained activated 10 days after extubation without significant changes in cross-sectional areas.

Conclusions: We report that mechanical ventilation is associated with a late diaphragmatic dysfunction related to a structural alteration of the ryanodine complex that is reversed with the S107 treatment.

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References

    1. Demoule A, Jung B, Prodanovic H, et al. Diaphragm dysfunction on admission to the intensive care unit. Prevalence, risk factors, and prognostic impact-a prospective study. Am J Respir Crit Care Med. 2013;188:213–219.
    1. Supinski GS, Callahan LA. Diaphragm weakness in mechanically ventilated critically ill patients. Crit Care. 2013;17:R120.
    1. Dres M, Dubé BP, Mayaux J, et al. Coexistence and impact of limb muscle and diaphragm weakness at time of liberation from mechanical ventilation in medical intensive care unit patients. Am J Respir Crit Care Med. 2017;195:57–66.
    1. Jung B, Moury PH, Mahul M, et al. Diaphragmatic dysfunction in patients with ICU-acquired weakness and its impact on extubation failure. Intensive Care Med. 2016;42:853–861.
    1. Dres M, Schmidt M, Ferre A, et al. Diaphragm electromyographic activity as a predictor of weaning failure. Intensive Care Med. 2012;38:2017–2025.

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