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Erschienen in: Intensive Care Medicine 4/2019

21.02.2019 | Original

Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation

verfasst von: J. Marin-Corral, I. Dot, M. Boguña, L. Cecchini, A. Zapatero, M. P. Gracia, S. Pascual-Guardia, C. Vilà, A. Castellví, P. Pérez-Terán, J. Gea, J. R. Masclans

Erschienen in: Intensive Care Medicine | Ausgabe 4/2019

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Abstract

Purpose

Ventilator-induced diaphragm dysfunction or damage (VIDD) is highly prevalent in patients under mechanical ventilation (MV), but its analysis is limited by the difficulty of obtaining histological samples. In this study we compared diaphragm histological characteristics in Maastricht III (MSIII) and brain-dead (BD) organ donors and in control subjects undergoing thoracic surgery (CTL) after a period of either controlled or spontaneous MV (CMV or SMV).

Methods

In this prospective study, biopsies were obtained from diaphragm and quadriceps. Demographic variables, comorbidities, severity on admission, treatment, and ventilatory variables were evaluated. Immunohistochemical analysis (fiber size and type percentages) and quantification of abnormal fibers (a surrogate of muscle damage) were performed.

Results

Muscle samples were obtained from 35 patients. MSIII (n = 16) had more hours on MV (either CMV or SMV) than BD (n = 14) and also spent more hours and a greater percentage of time with diaphragm stimuli (time in assisted and spontaneous modalities). Cross-sectional area (CSA) was significantly reduced in the diaphragm and quadriceps in both groups in comparison with CTL (n = 5). Quadriceps CSA was significantly decreased in MSIII compared to BD but there were no differences in the diaphragm CSA between the two groups. Those MSIII who spent 100 h or more without diaphragm stimuli presented reduced diaphragm CSA without changes in their quadriceps CSA. The proportion of internal nuclei in MSIII diaphragms tended to be higher than in BD diaphragms, and their proportion of lipofuscin deposits tended to be lower, though there were no differences in the quadriceps fiber evaluation.

Conclusions

This study provides the first evidence in humans regarding the effects of different modes of MV (controlled, assisted, and spontaneous) on diaphragm myofiber damage, and shows that diaphragm inactivity during mechanical ventilation is associated with the development of VIDD.
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Literatur
1.
Zurück zum Zitat Dres M, Goligher EC, Heunks LMA, Brochard LJ (2017) Critical illness-associated diaphragm weakness. Intensive Care Med 43(10):1441–1452CrossRefPubMed Dres M, Goligher EC, Heunks LMA, Brochard LJ (2017) Critical illness-associated diaphragm weakness. Intensive Care Med 43(10):1441–1452CrossRefPubMed
3.
Zurück zum Zitat Li LF, Tien ML, Leung SY, Lin MC (2011) High tidal volume mechanical ventilation elicits increased activity in protein kinase B and c-Jun NH2-terminal kinase pathways in mouse diaphragm. Intensive Care Med 37:2015–2022CrossRefPubMed Li LF, Tien ML, Leung SY, Lin MC (2011) High tidal volume mechanical ventilation elicits increased activity in protein kinase B and c-Jun NH2-terminal kinase pathways in mouse diaphragm. Intensive Care Med 37:2015–2022CrossRefPubMed
4.
Zurück zum Zitat Vassilakopoulos T, Petrof BJ (2004) Ventilator-induced diaphragmatic dysfunction. Am J Respir Crit Care Med 169:336–341CrossRefPubMed Vassilakopoulos T, Petrof BJ (2004) Ventilator-induced diaphragmatic dysfunction. Am J Respir Crit Care Med 169:336–341CrossRefPubMed
5.
Zurück zum Zitat Jaber S, Petrof BJ, Jung B, Chanques G, Berthet JP, Rabuel C et al (2011) Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. Am J Respir Crit Care Med 183(3):364–371CrossRefPubMed Jaber S, Petrof BJ, Jung B, Chanques G, Berthet JP, Rabuel C et al (2011) Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. Am J Respir Crit Care Med 183(3):364–371CrossRefPubMed
6.
Zurück zum Zitat Petrof B, Hussain S (2016) Ventilator-induced diaphragmatic dysfunction: what have we learned? Curr Opin Crit Care 22(1):67–72CrossRefPubMed Petrof B, Hussain S (2016) Ventilator-induced diaphragmatic dysfunction: what have we learned? Curr Opin Crit Care 22(1):67–72CrossRefPubMed
8.
Zurück zum Zitat Herridge MS, Tansey C, Matté A, Tomlinson G, Diaz-Granados N, Cooper A et al (2009) Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 364(14):123–134 Herridge MS, Tansey C, Matté A, Tomlinson G, Diaz-Granados N, Cooper A et al (2009) Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 364(14):123–134
9.
Zurück zum Zitat Smuder AJ, Nelson WB, Hudson MB, Kavazis AN, Powers SK (2010) Inhibition of the ubiquitin-proteasome pathway does not protect against ventilator-induced accelerated proteolysis or atrophy in the diaphragm. Surg Clin North Am 90(5):955–968CrossRef Smuder AJ, Nelson WB, Hudson MB, Kavazis AN, Powers SK (2010) Inhibition of the ubiquitin-proteasome pathway does not protect against ventilator-induced accelerated proteolysis or atrophy in the diaphragm. Surg Clin North Am 90(5):955–968CrossRef
10.
Zurück zum Zitat Smuder AJ, Hudson MB, Nelson WB, Kavazis AN, Powers SK (2012) Nuclear factor-κB signaling contributes to mechanical ventilation-induced diaphragm weakness. Crit Care Med 40(3):927–934CrossRefPubMedPubMedCentral Smuder AJ, Hudson MB, Nelson WB, Kavazis AN, Powers SK (2012) Nuclear factor-κB signaling contributes to mechanical ventilation-induced diaphragm weakness. Crit Care Med 40(3):927–934CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Smuder AJ, Sollanek KJ, Min K, Nelson WB, Powers SK (2015) Inhibition of forkhead boxO-specific transcription prevents mechanical ventilation-induced diaphragm dysfunction. Crit Care Med 43(5):e133–e142CrossRefPubMedPubMedCentral Smuder AJ, Sollanek KJ, Min K, Nelson WB, Powers SK (2015) Inhibition of forkhead boxO-specific transcription prevents mechanical ventilation-induced diaphragm dysfunction. Crit Care Med 43(5):e133–e142CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Azuelos I, Jung B, Picard M, Liang F, Li T, Lemaire C et al (2015) Relationship between autophagy and ventilator-induced diaphragmatic dysfunction. Anesthesiology 122(6):1349–1361CrossRefPubMed Azuelos I, Jung B, Picard M, Liang F, Li T, Lemaire C et al (2015) Relationship between autophagy and ventilator-induced diaphragmatic dysfunction. Anesthesiology 122(6):1349–1361CrossRefPubMed
13.
Zurück zum Zitat Matecki S, Dridi H, Jung B, Saint N, Reiken SR, Scheuermann V et al (2016) Leaky ryanodine receptors contribute to diaphragmatic weakness during mechanical ventilation. Proc Natl Acad Sci 113(32):9069–9074CrossRefPubMed Matecki S, Dridi H, Jung B, Saint N, Reiken SR, Scheuermann V et al (2016) Leaky ryanodine receptors contribute to diaphragmatic weakness during mechanical ventilation. Proc Natl Acad Sci 113(32):9069–9074CrossRefPubMed
14.
Zurück zum Zitat Matecki S, Jung B, Saint N, Scheuermann V, Jaber S, Lacampagne A (2017) Respiratory muscle contractile inactivity induced by mechanical ventilation in piglets leads to leaky ryanodine receptors and diaphragm weakness. J Muscle Res Cell Motil 38:17–24CrossRefPubMed Matecki S, Jung B, Saint N, Scheuermann V, Jaber S, Lacampagne A (2017) Respiratory muscle contractile inactivity induced by mechanical ventilation in piglets leads to leaky ryanodine receptors and diaphragm weakness. J Muscle Res Cell Motil 38:17–24CrossRefPubMed
15.
Zurück zum Zitat Jaber S, Sebbane M, Koechlin C, Hayot M, Capdevila X, EledJam J et al (2005) Effects of short vs prolonged mechanical ventilation on antioxidant systems in piglet diaphragm. Intensive Care Med 31:1427–1433CrossRefPubMed Jaber S, Sebbane M, Koechlin C, Hayot M, Capdevila X, EledJam J et al (2005) Effects of short vs prolonged mechanical ventilation on antioxidant systems in piglet diaphragm. Intensive Care Med 31:1427–1433CrossRefPubMed
16.
Zurück zum Zitat Hussain SNA, Mofarrahi M, Sigala I, Kim HC, Vassilakopoulos T, Maltais F et al (2010) Mechanical ventilation-induced diaphragm disuse in humans triggers autophagy. Am J Respir Crit Care Med 182(11):1377–1386CrossRefPubMed Hussain SNA, Mofarrahi M, Sigala I, Kim HC, Vassilakopoulos T, Maltais F et al (2010) Mechanical ventilation-induced diaphragm disuse in humans triggers autophagy. Am J Respir Crit Care Med 182(11):1377–1386CrossRefPubMed
17.
Zurück zum Zitat Levine S, Biswas C, Dierov J, Barsotti R, Shrager JB, Nguyen T et al (2011) Increased proteolysis, myosin depletion, and atrophic AKT-FOXO signaling in human diaphragm disuse. Am J Respir Crit Care Med 183(4):483–490CrossRefPubMed Levine S, Biswas C, Dierov J, Barsotti R, Shrager JB, Nguyen T et al (2011) Increased proteolysis, myosin depletion, and atrophic AKT-FOXO signaling in human diaphragm disuse. Am J Respir Crit Care Med 183(4):483–490CrossRefPubMed
18.
Zurück zum Zitat Picard M, Jung B, Liang F, Azuelos I, Hussain S, Goldberg P et al (2012) Mitochondrial dysfunction and lipid accumulation in the human diaphragm during mechanical ventilation. Am J Respir Crit Care Med 186(11):1140–1149CrossRefPubMed Picard M, Jung B, Liang F, Azuelos I, Hussain S, Goldberg P et al (2012) Mitochondrial dysfunction and lipid accumulation in the human diaphragm during mechanical ventilation. Am J Respir Crit Care Med 186(11):1140–1149CrossRefPubMed
19.
Zurück zum Zitat Tang H, Smith IJ, Hussain SN, Goldberg P, Lee M, Sugiarto S et al (2014) The JAK-STAT pathway is critical in ventilator-induced diaphragm dysfunction. Mol Med 20(36):579–589CrossRef Tang H, Smith IJ, Hussain SN, Goldberg P, Lee M, Sugiarto S et al (2014) The JAK-STAT pathway is critical in ventilator-induced diaphragm dysfunction. Mol Med 20(36):579–589CrossRef
20.
Zurück zum Zitat Hooijman PE, Beishuizen A, Witt CC, de Waard MC, Girbes ARJ, Spoelstra-de Man AME et al (2015) Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients. Am J Respir Crit Care Med 191(10):1126–1138CrossRefPubMedPubMedCentral Hooijman PE, Beishuizen A, Witt CC, de Waard MC, Girbes ARJ, Spoelstra-de Man AME et al (2015) Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients. Am J Respir Crit Care Med 191(10):1126–1138CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Bruells CS, Bergs I, Rossaint R, Du J, Bleilevens C, Goetzenich A et al (2014) Recovery of diaphragm function following mechanical ventilation in a rodent model. PLoS One 9(1):3–10CrossRef Bruells CS, Bergs I, Rossaint R, Du J, Bleilevens C, Goetzenich A et al (2014) Recovery of diaphragm function following mechanical ventilation in a rodent model. PLoS One 9(1):3–10CrossRef
22.
Zurück zum Zitat Callahan LA, Supinski GS (2013) Rapid and complete recovery in ventilator-induced diaphragm weakness-problem solved? J Appl Physiol 115(6):773–774CrossRefPubMedPubMedCentral Callahan LA, Supinski GS (2013) Rapid and complete recovery in ventilator-induced diaphragm weakness-problem solved? J Appl Physiol 115(6):773–774CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Futier E, Constantin JM, Combaret L, Mosoni L, Roszyk L, Sapin V et al (2008) Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm. Crit Care 12(5):R116CrossRefPubMedPubMedCentral Futier E, Constantin JM, Combaret L, Mosoni L, Roszyk L, Sapin V et al (2008) Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm. Crit Care 12(5):R116CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Sassoon CS, Zhu E, Caiozzo VJ (2004) Assist-control mechanical ventilation attenuates ventilator-induced diaphragmatic dysfunction. Am J Respir Crit Care Med 170(6):626–632CrossRefPubMed Sassoon CS, Zhu E, Caiozzo VJ (2004) Assist-control mechanical ventilation attenuates ventilator-induced diaphragmatic dysfunction. Am J Respir Crit Care Med 170(6):626–632CrossRefPubMed
25.
Zurück zum Zitat Hudson MB, Smuder AJ, Nelson WB, Wiggs MP, Shimkus KL, Fluckey JD et al (2015) Partial support ventilation and mitochondrial targeted antioxidants protect against ventilator-induced decreases in diaphragm muscle protein synthesis. PLoS One 10(9):e0137693CrossRefPubMedPubMedCentral Hudson MB, Smuder AJ, Nelson WB, Wiggs MP, Shimkus KL, Fluckey JD et al (2015) Partial support ventilation and mitochondrial targeted antioxidants protect against ventilator-induced decreases in diaphragm muscle protein synthesis. PLoS One 10(9):e0137693CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Jung B, Constantin JM, Rossel N, Le Goff C, Sebbane M, Coisel Y et al (2010) Adaptive support ventilation prevents ventilator-induced diaphragmatic dysfunction in piglet: an in vivo and in vitro study. Anesthesiology 112(6):1435–1443CrossRefPubMed Jung B, Constantin JM, Rossel N, Le Goff C, Sebbane M, Coisel Y et al (2010) Adaptive support ventilation prevents ventilator-induced diaphragmatic dysfunction in piglet: an in vivo and in vitro study. Anesthesiology 112(6):1435–1443CrossRefPubMed
27.
Zurück zum Zitat Hudson MB, Smuder AJ, Nelson WB, Bruells CS, Levine S, Powers SK (2012) Both high level pressure support ventilation and controlled mechanical ventilation induce diaphragm dysfunction and atrophy. Crit Care Med 40(4):1254–1260CrossRefPubMedPubMedCentral Hudson MB, Smuder AJ, Nelson WB, Bruells CS, Levine S, Powers SK (2012) Both high level pressure support ventilation and controlled mechanical ventilation induce diaphragm dysfunction and atrophy. Crit Care Med 40(4):1254–1260CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Gayan-Ramirez G, Testelmans D, Maes K, Rácz GZ, Cadot P, Zádor E et al (2005) Intermittent spontaneous breathing protects the rat diaphragm from mechanical ventilation effects. Crit Care Med 33(12):2804–2809CrossRefPubMed Gayan-Ramirez G, Testelmans D, Maes K, Rácz GZ, Cadot P, Zádor E et al (2005) Intermittent spontaneous breathing protects the rat diaphragm from mechanical ventilation effects. Crit Care Med 33(12):2804–2809CrossRefPubMed
29.
Zurück zum Zitat Macgowan NA, Evans KG, Road JD, Reid WD (2001) Diaphragm injury in individuals with airflow obstruction. Am J Respir Crit Care Med 163(7):1654–1659CrossRefPubMed Macgowan NA, Evans KG, Road JD, Reid WD (2001) Diaphragm injury in individuals with airflow obstruction. Am J Respir Crit Care Med 163(7):1654–1659CrossRefPubMed
30.
Zurück zum Zitat Pascual-Guardia S, Wodja E, Gorostiza A, López de Santamaría E, Gea J, Gáldiz JB et al (2013) Improvement in quality of life and exercise capacity without muscular biology changes after general training in patients with severe chronic obstructive pulmonary disease. Med Clin 140(5):200–206CrossRef Pascual-Guardia S, Wodja E, Gorostiza A, López de Santamaría E, Gea J, Gáldiz JB et al (2013) Improvement in quality of life and exercise capacity without muscular biology changes after general training in patients with severe chronic obstructive pulmonary disease. Med Clin 140(5):200–206CrossRef
31.
Zurück zum Zitat Levine S, Nguyen T, Taylor N, Friscia M, Budak MT, Rothenberg P et al (2007) Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med 358(13):1327–1335CrossRef Levine S, Nguyen T, Taylor N, Friscia M, Budak MT, Rothenberg P et al (2007) Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med 358(13):1327–1335CrossRef
32.
Zurück zum Zitat Belperio JA, Keane MP, Lynch JP, Strieter RM (2006) The role of cytokines during the pathogenesis of ventilator-associated and ventilator-induced lung injury. Semin Respir Crit Care Med 27:350–364CrossRefPubMed Belperio JA, Keane MP, Lynch JP, Strieter RM (2006) The role of cytokines during the pathogenesis of ventilator-associated and ventilator-induced lung injury. Semin Respir Crit Care Med 27:350–364CrossRefPubMed
33.
Zurück zum Zitat Amado JA, López-Espadas F, Vázquez-Barquero A, Salas E, Riancho JA, López-Cordovilla JJ et al (1995) Blood levels of cytokines in brain-dead patients: relationship with circulating hormones and acute-phase reactants. Metabolism 44:812–816CrossRefPubMed Amado JA, López-Espadas F, Vázquez-Barquero A, Salas E, Riancho JA, López-Cordovilla JJ et al (1995) Blood levels of cytokines in brain-dead patients: relationship with circulating hormones and acute-phase reactants. Metabolism 44:812–816CrossRefPubMed
34.
Zurück zum Zitat Auraen H, Molines TE, Bjortuft O, Bakkan PA, Geiran O, Kongerud J et al (2013) Multiorgan procurement increases systemic inflammation in brain dead donors. Clin Transplant 27(4):613–618CrossRefPubMed Auraen H, Molines TE, Bjortuft O, Bakkan PA, Geiran O, Kongerud J et al (2013) Multiorgan procurement increases systemic inflammation in brain dead donors. Clin Transplant 27(4):613–618CrossRefPubMed
35.
Zurück zum Zitat Barklin A (2009) Systemic inflammation in the brain-dead organ donor. Acta Anaesthesiol Scand 53:425–435CrossRefPubMed Barklin A (2009) Systemic inflammation in the brain-dead organ donor. Acta Anaesthesiol Scand 53:425–435CrossRefPubMed
36.
Zurück zum Zitat Rubio JJ, Palacios D (2016) Reflections upon donation after controlled cardiac death (Maastricht type III donors). Med Intensiva 40(7):431–433CrossRefPubMed Rubio JJ, Palacios D (2016) Reflections upon donation after controlled cardiac death (Maastricht type III donors). Med Intensiva 40(7):431–433CrossRefPubMed
37.
Zurück zum Zitat Vassilakopoudos T (2008) Ventilator-induced diaphragm dysfunction: the clinical relevance of animal models. Intensive Care Med 34:7–16CrossRef Vassilakopoudos T (2008) Ventilator-induced diaphragm dysfunction: the clinical relevance of animal models. Intensive Care Med 34:7–16CrossRef
38.
Zurück zum Zitat Latronico N, Herridge M, Hopkins R, Angus D, Hart N, Hermans G et al (2017) The ICM research agenda on intensive care unit-acquired weakness. Intensive Care Med 43(9):1270–1281CrossRefPubMed Latronico N, Herridge M, Hopkins R, Angus D, Hart N, Hermans G et al (2017) The ICM research agenda on intensive care unit-acquired weakness. Intensive Care Med 43(9):1270–1281CrossRefPubMed
39.
Zurück zum Zitat Powers SK, Smuder AJ, Fuller D, Levine S (2013) Crosstalk proposal: mechanical ventilation-induced diaphragm atrophy is primarily due to inactivity. J Physiol 591(21):5255–5257CrossRefPubMedPubMedCentral Powers SK, Smuder AJ, Fuller D, Levine S (2013) Crosstalk proposal: mechanical ventilation-induced diaphragm atrophy is primarily due to inactivity. J Physiol 591(21):5255–5257CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Barreiro E, Ferrer D, Sanchez F, Minguella J, Marin-Corral J, Martinez-Llorens J et al (2011) Inflammatory cells and apoptosis in respiratory and limb muscles of patients with COPD. J Appl Physiol 111(3):808–817CrossRefPubMed Barreiro E, Ferrer D, Sanchez F, Minguella J, Marin-Corral J, Martinez-Llorens J et al (2011) Inflammatory cells and apoptosis in respiratory and limb muscles of patients with COPD. J Appl Physiol 111(3):808–817CrossRefPubMed
42.
Zurück zum Zitat Latronico N, Fenzi F, Recupero D, Guarneri B, Tomelleri G, Tonin P et al (1996) Critical illness myopathy and neuropathy. Lancet 347(9015):1579–1582CrossRefPubMed Latronico N, Fenzi F, Recupero D, Guarneri B, Tomelleri G, Tonin P et al (1996) Critical illness myopathy and neuropathy. Lancet 347(9015):1579–1582CrossRefPubMed
43.
Zurück zum Zitat Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P et al (2013) Acute skeletal muscle wasting in critically illness. JAMA 310(15):1591–1600CrossRefPubMed Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P et al (2013) Acute skeletal muscle wasting in critically illness. JAMA 310(15):1591–1600CrossRefPubMed
44.
Zurück zum Zitat Pettenuzzo T, Fan E (2017) 2016 year in review: mechanical ventilation. Respir Care 62(5):629–635CrossRefPubMed Pettenuzzo T, Fan E (2017) 2016 year in review: mechanical ventilation. Respir Care 62(5):629–635CrossRefPubMed
45.
Zurück zum Zitat Zambon M, Greco M, Bocchino S, Cabrini L, Beccaria PF, Zangrillo A (2017) Assessment of diaphragmatic dysfunction in the critically ill patient with ultrasound: a systematic review. Intensive Care Med 43(1):29–38CrossRefPubMed Zambon M, Greco M, Bocchino S, Cabrini L, Beccaria PF, Zangrillo A (2017) Assessment of diaphragmatic dysfunction in the critically ill patient with ultrasound: a systematic review. Intensive Care Med 43(1):29–38CrossRefPubMed
Metadaten
Titel
Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation
verfasst von
J. Marin-Corral
I. Dot
M. Boguña
L. Cecchini
A. Zapatero
M. P. Gracia
S. Pascual-Guardia
C. Vilà
A. Castellví
P. Pérez-Terán
J. Gea
J. R. Masclans
Publikationsdatum
21.02.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Intensive Care Medicine / Ausgabe 4/2019
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-019-05566-5

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