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      Severe but reversible impaired diaphragm function in septic mechanically ventilated patients

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          Abstract

          Background

          Whether sepsis-associated diaphragm dysfunction may improve despite the exposure of mechanical ventilation in critically ill patients is unclear. This study aims at describing the diaphragm function time course of septic and non-septic mechanically ventilated patients.

          Methods

          Secondary analysis of two prospective observational studies of mechanically ventilated patients in whom diaphragm function was assessed twice: within the 24 h after intubation and when patients were switched to pressure support mode, by measuring the endotracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Change in diaphragm function was expressed as the difference between Ptr,stim measured under pressure support mode and Ptr,stim measured within the 24 h after intubation. Sepsis was defined according to the Sepsis-3 international guidelines upon inclusion. In a sub-group of patients, the right hemidiaphragm thickness was measured by ultrasound.

          Results

          Ninety-two patients were enrolled in the study. Sepsis upon intubation was present in 51 (55%) patients. In septic patients, primary reason for ventilation was acute respiratory failure related to pneumonia (37/51; 73%). In non-septic patients, main reasons for ventilation were acute respiratory failure not related to pneumonia (16/41; 39%), coma (13/41; 32%) and cardiac arrest (6/41; 15%). Ptr,stim within 24 h after intubation was lower in septic patients as compared to non-septic patients: 6.3 (4.9–8.7) cmH 2O vs. 9.8 (7.0–14.2) cmH 2O ( p = 0.004), respectively. The median (interquartile) duration of mechanical ventilation between first and second diaphragm evaluation was 4 (2–6) days in septic patients and 3 (2–4) days in non-septic patients ( p = 0.073). Between first and second measurements, the change in Ptr,stim was + 19% (− 13–61) in septic patients and − 7% (− 40–12) in non-septic patients ( p = 0.005). In the sub-group of patients with ultrasound measurements, end-expiratory diaphragm thickness decreased in both, septic and non-septic patients. The 28-day mortality was higher in patients with decrease or no change in diaphragm function.

          Conclusion

          Septic patients were associated with a more severe but reversible impaired diaphragm function as compared to non-septic patients. Increase in diaphragm function was associated with a better survival.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13613-022-01005-9.

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          Most cited references40

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans.

            Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in a rapid loss of diaphragmatic strength in animals. However, very little is known about the time course or mechanistic basis for such a phenomenon in humans. To determine in a prospective fashion the time course for development of diaphragmatic weakness during MV; and the relationship between MV duration and diaphragmatic injury or atrophy, and the status of candidate cellular pathways implicated in these phenomena. Airway occlusion pressure (TwPtr) generated by the diaphragm during phrenic nerve stimulation was measured in short-term (0.5 h; n = 6) and long-term (>5 d; n = 6) MV groups. Diaphragmatic biopsies obtained during thoracic surgery (MV for 2-3 h; n = 10) and from brain-dead organ donors (MV for 24-249 h; n = 15) were analyzed for ultrastructural injury, atrophy, and expression of proteolysis-related proteins (ubiquitin, nuclear factor-κB, and calpains). TwPtr decreased progressively during MV, with a mean reduction of 32 ± 6% after 6 days. Longer periods of MV were associated with significantly greater ultrastructural fiber injury (26.2 ± 4.8 vs. 4.7 ± 0.6% area), decreased cross-sectional area of muscle fibers (1,904 ± 220 vs. 3,100 ± 329 μm²), an increase of ubiquitinated proteins (+19%), higher expression of p65 nuclear factor-κB (+77%), and greater levels of the calcium-activated proteases calpain-1, -2, and -3 (+104%, +432%, and +266%, respectively) in the diaphragm. Diaphragmatic weakness, injury, and atrophy occur rapidly in critically ill patients during MV, and are significantly correlated with the duration of ventilator support.
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              Mechanical Ventilation-induced Diaphragm Atrophy Strongly Impacts Clinical Outcomes.

              Diaphragm dysfunction worsens outcomes in mechanically ventilated patients, but the clinical impact of potentially preventable changes in diaphragm structure and function caused by mechanical ventilation is unknown.
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                Author and article information

                Contributors
                lecronier.marie@gmail.com
                Journal
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                2110-5820
                11 April 2022
                11 April 2022
                2022
                : 12
                : 34
                Affiliations
                [1 ]GRID grid.411439.a, ISNI 0000 0001 2150 9058, Médecine Intensive - Réanimation (Département “R3S”), , APHP. Sorbonne Université, Hôpital Pitié-Salpêtrière, ; Paris, France
                [2 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, Neurophysiologie Respiratoire Expérimentale et Clinique, INSERM-UMR S 1158, Sorbonne Université, ; Paris, France
                [3 ]GRID grid.157868.5, ISNI 0000 0000 9961 060X, Département de Médecine Intensive - Réanimation, , CHU Montpellier, ; Montpellier, France
                [4 ]GRID grid.121334.6, ISNI 0000 0001 2097 0141, Laboratoire de Physiologie et Médecine Expérimentale du cœur et des Muscles, INSERM U1046-CNRS UMR 9214, , Université de Montpellier, ; Montpellier, France
                [5 ]Department of Medical Information, Hôpital Arnaud de Villeneuve, IMAG U5149, Université de Montpellier, Montpellier, France
                Author information
                http://orcid.org/0000-0002-5543-5074
                Article
                1005
                10.1186/s13613-022-01005-9
                9001790
                35403916
                ff0211d5-5025-4436-833f-42968ae7e151
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 17 January 2022
                : 18 March 2022
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Emergency medicine & Trauma
                diaphragm dysfunction,sepsis,mechanical ventilation,sepsis-associated diaphragm dysfunction

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