Lung and diaphragm protective ventilation: a synthesis of recent data

References

• Bates JHT, Smith BJ. Ventilator-induced lung injury and lung mechanics. Ann Transl Med. 2018;6:377–378.
   PubMed Web of Science ®Google Scholar
• Gaver DP, Nieman GF, Gatto LA, et al. The POOR get POORer: a hypothesis for the pathogenesis of ventilator-induced lung injury. Am J Respir Crit Care Med. 2020;202:1081–1087.
   PubMed Web of Science ®Google Scholar
• Marini JJ, Rocco PRM, Gattinoni L. Static and dynamic contributors to ventilator-induced lung injury in clinical practice pressure, energy, and power. Am J Respir Crit Care Med. 2020;201:767–774.
   PubMed Web of Science ®Google Scholar
• Chiumello D, Carlesso E, Cadringher P, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Respir Crit Care Med. 2008;178:346–355.
   PubMed Web of Science ®Google Scholar
• Cressoni M, Cadringher P, Chiurazzi C, et al. Lung inhomogeneity in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2014;189:149–158.
   PubMed Web of Science ®Google Scholar
• Gattinoni L, Tonetti T, Quintel M. Regional physiology of ARDS. Crit Care. 2017;21:21.
   PubMed Web of Science ®Google Scholar
• Froese AB, Bryan AC. Effects of anesthesia and paralysis on diaphragmatic mechanics in man. Anesthesiology. 1974;41:242–255.
   PubMed Web of Science ®Google Scholar
• Goligher EC, Jonkman AH, Dianti J, et al. Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and excessive effort. Intensive Care Med. 2020;46:2314–2326.
   PubMed Web of Science ®Google Scholar
• Costa ELV, Slutsky AS, Brochard LJ, et al. Ventilatory variables and mechanical power in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2021;204:303–311.
   PubMed Web of Science ®Google Scholar
• Vaporidi K, Voloudakis G, Priniannakis G, et al. Effects of respiratory rate on ventilator-induced lung injury at a constant Paco2 in a mouse model of normal lung. Crit Care Med. 2008;36:1277–1283.
   PubMed Web of Science ®Google Scholar
• Gattinoni L, Tonetti T, Cressoni M, et al. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016;42:1567–1575.
   PubMed Web of Science ®Google Scholar
• Serpa Neto A, Deliberato RO, Johnson AEW, et al. Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts. Intensive Care Med. 2018;44:1914–1922.
   PubMed Web of Science ®Google Scholar
• Amato MBP, Meade MO, Slutsky AS, et al. Driving Pressure and Survival in the Acute Respiratory Distress Syndrome. N Engl J Med. 2015;372:747–755.
   PubMed Web of Science ®Google Scholar
• Neto AS, Hemmes SNT, Barbas CSV, et al. Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data. Lancet Respir Med. 2016;4:272–280.
   PubMed Web of Science ®Google Scholar
• Williams EC, Motta-Ribeiro GC, Melo MFV. Driving Pressure and Transpulmonary Pressure: how Do We Guide Safe Mechanical Ventilation? Anesthesiology. Anesthesiology. 2019;131:155–163.
   PubMed Web of Science ®Google Scholar
• Yehya N, Hodgson CL, Amato MBP, et al. Response to ventilator adjustments for predicting acute respiratory distress syndrome mortality: driving pressure versus oxygenation. Ann Am Thorac Soc. 2021;18:857–864.
   PubMed Web of Science ®Google Scholar
• Leatherman JW, Ravenscraft SA. Low measured auto-positive end-expiratory pressure during mechanical ventilation of patients with severe asthma: hidden auto-positive end-expiratory pressure. Crit Care Med. 1996;24:541–546.
   PubMed Web of Science ®Google Scholar
• Coudroy R, Vimpere D, Aissaoui N, et al. Prevalence of complete airway closure according to body mass index in acute respiratory distress syndrome: pooled cohort analysis. Anesthesiology. 2020;133:867–878.
   PubMed Web of Science ®Google Scholar
• Chen L, Del Sorbo L, Luca Grieco D, et al. Airway closure in acute respiratory distress syndrome: an underestimated and misinterpreted phenomenon. Am J Respir Crit Care Med. 2018;197:132–136.
   PubMed Web of Science ®Google Scholar
• Soundoulounaki S, Akoumianaki E, Kondili E, et al. Airway pressure morphology and respiratory muscle activity during end-inspiratory occlusions in pressure support ventilation. Crit Care. 2020;24:467.
   PubMed Web of Science ®Google Scholar
• Younes M, Webster K, Kun J, et al. A method for measuring passive elastance during proportional assist ventilation. Am J Respir Crit Care Med. 2001;164(1):50–60.
   PubMed Web of Science ®Google Scholar
• Goligher EC, Dres M, Patel BK, et al. Lung- and diaphragm-protective ventilation. Am J Respir Crit Care Med. 2020;202(7):950–961.
   PubMed Web of Science ®Google Scholar
• Goligher E, Jonkman A, Dianti J, et al. Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and excessive effort. Intensive Care Medicine. 2020;46(12):2314–2326.
   PubMed Web of Science ®Google Scholar
• Protti A, Cressoni M, Santini A, et al. Lung stress and strain during mechanical ventilation: any safe threshold? Am J Respir Crit Care Med. 2011;183:1354–1362.
   PubMed Web of Science ®Google Scholar
• Fumagalli J, Berra L, Zhang C, et al. Transpulmonary pressure describes lung morphology during decremental positive end-expiratory pressure trials in obesity. Crit Care Med. 2017;45:1374–1381.
   PubMed Web of Science ®Google Scholar
• Yoshida T, Amato MBP, Grieco DL, et al. Esophageal manometry and regional transpulmonary pressure in lung injury. Am J Respir Crit Care Med. 2018;197:1018–1026.
   PubMed Web of Science ®Google Scholar
• Sarge T, Baedorf-Kassis E, Banner-Goodspeed V, et al. Effect of Esophageal Pressure-guided Positive End-Expiratory Pressure on Survival from Acute Respiratory Distress Syndrome: a Risk-based and Mechanistic Reanalysis of the EPVent-2 Trial. Am J Respir Crit Care Med. 2021;204:1153–1163.
   PubMed Web of Science ®Google Scholar
• Sheard S, Rao P, Devaraj A. Imaging of acute respiratory distress syndrome. Respir Care. 2012;57:607–612.
   PubMed Web of Science ®Google Scholar
• Frerichs I, Amato MBP, Van Kaam AH, et al. Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group. Thorax. 2017;72:83–93.
   PubMed Web of Science ®Google Scholar
• Somhorst P, Gommers D, Endeman H. Advanced respiratory monitoring in mechanically ventilated patients with coronavirus disease 2019-associated acute respiratory distress syndrome. Curr Opin Crit Care. 2022;28:66–73.
   PubMed Web of Science ®Google Scholar
• Rozé H, Boisselier C, Bonnardel E, et al. Electrical Impedance Tomography to Detect Airway Closure Heterogeneity in Asymmetrical Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2021;203:511–515.
   PubMed Web of Science ®Google Scholar
• Vasques F, Sanderson B, Barrett NA, et al. Monitoring of regional lung ventilation using electrical impedance tomography. Minerva Anestesiol. 2019;85:1231–1241.
   PubMed Web of Science ®Google Scholar
• Gattinoni L, Carlesso E, Brazzi L, et al. Positive end-expiratory pressure. Curr Opin Crit Care Curr Opin Crit Care. 2010;16:39–44.
   PubMed Web of Science ®Google Scholar
• Brower R, Lanken P, MacIntyre N, et al. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med. 2004;351:327–336.
   PubMed Web of Science ®Google Scholar
• Algera AG, Pisani L, Serpa Neto A, et al. Effect of a lower vs higher positive end-expiratory pressure strategy on ventilator-free days in ICU patients without ARDS: a randomized clinical trial. J Am Med Assoc. 2020;324:2509–2520.
   PubMed Web of Science ®Google Scholar
• McNamee JJ, Gillies MA, Barrett NA, et al. Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients with Acute Hypoxemic Respiratory Failure: the REST Randomized Clinical Trial. J Am Med Assoc. 2021;326:1013–1023.
   PubMed Web of Science ®Google Scholar
• Nestler C, Simon P, Petroff D, et al. Individualized positive end-expiratory pressure in obese patients during general anaesthesia: a randomized controlled clinical trial using electrical impedance tomography. Br JAnaesth. 2017;119:1194–1205.
   PubMed Web of Science ®Google Scholar
• Pereira SM, Tucci MR, Morais CCA, et al. Individual positive end-expiratory pressure settings optimize intraoperative mechanical ventilation and reduce postoperative atelectasis. Anesthesiology. 2018;129:1070–1081.
   PubMed Web of Science ®Google Scholar
• Sella N, Zarantonello F, Andreatta G, et al. Positive end-expiratory pressure titration in COVID-19 acute respiratory failure: electrical impedance tomography vs. PEEP/FiO 2 tables. Crit Care. 2020;24:24.
   PubMed Web of Science ®Google Scholar
• Gibot S, Conrad M, Courte G, et al. Positive end-expiratory pressure setting in covid-19-related acute respiratory distress syndrome: comparison between electrical impedance tomography, peep/fio 2 tables, and transpulmonary pressure. Front Med. 2021;8:720920.
   Web of Science ®Google Scholar
• Zadek F, Rubin J, Grassi L, et al. Individualized Multimodal physiologic approach to mechanical ventilation in patients with obesity and severe acute respiratory distress syndrome reduced venovenous extracorporeal membrane oxygenation utilization. Crit Care Explor. 2021;3:e0461.
   PubMedGoogle Scholar
• Beitler J, Sarge T, Banner-Goodspeed V, et al. Effect of titrating positive end-expiratory pressure (peep) with an esophageal pressure-guided strategy vs an empirical high peep-fio2 strategy on death and days free from mechanical ventilation among patients with acute respiratory distress syndrome: a R. JAMA. 2019;321:846–857.
   PubMed Web of Science ®Google Scholar
• Der Zee P V, Somhorst P, Endeman H, et al. Electrical impedance tomography for positive end-expiratory pressure titration in COVID-19-related acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;202:280–284.
   PubMed Web of Science ®Google Scholar
• Turbil E, Terzi N, Cour M, et al. Positive end-expiratory pressure-induced recruited lung volume measured by volume-pressure curves in acute respiratory distress syndrome: a physiologic systematic review and meta-analysis. Intensive Care Med. 2020;46:2212–2225.
   PubMed Web of Science ®Google Scholar
• Kallet RH, Lipnick MS, Burns GD. The nature of recruitment and de-recruitment and its implications for management of ards. Respir Care. 2021;66:510–530.
   PubMed Web of Science ®Google Scholar
• Cavalcanti AB, Suzumura ÉA, Laranjeira LN, et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome - A randomized clinical trial. J Am Med Assoc. 2017;318:1335–1345.
   PubMed Web of Science ®Google Scholar
• Johnson NJ, Luks AM, Glenny RW. Gas exchange in the prone posture. Respir Care. 2017;62:1097–1110.
   PubMed Web of Science ®Google Scholar
• Athota KP, Millar D, Branson RD, et al. A practical approach to the use of prone therapy in acute respiratory distress syndrome. Expert Rev Respir Med. 2014;8:453–463.
   PubMed Web of Science ®Google Scholar
• Katira BH, Osada K, Engelberts D, et al. Positive end-expiratory pressure, pleural pressure, and regional compliance during pronation an experimental study. Am J Respir Crit Care Med. 2021;203:1266–1274.
   PubMed Web of Science ®Google Scholar
• Mentzelopoulos SD, Roussos C, Zakynthinos SG. Prone position reduces lung stress and strain in severe acute respiratory distress syndrome. Eur Respir J. 2005;25:534–544.
   PubMed Web of Science ®Google Scholar
• Guérin C, Albert RK, Beitler J, et al. Prone position in ARDS patients: why, when, how and for whom Intensive Care Med. 2020;46:2385–2396.
   PubMed Web of Science ®Google Scholar
• Beitler JR, Shaefi S, Montesi SB, et al. Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis. Intensive Care Med. 2014;40:332–341.
   PubMed Web of Science ®Google Scholar
• Sud S, Friedrich JO, Adhikari NKJ, et al. Comparative effectiveness of protective ventilation strategies for moderate and severe acute respiratory distress syndrome a network meta-analysis. Am J Respir Crit Care Med. 2021;203:1366–1377.
   PubMed Web of Science ®Google Scholar
• Shelhamer MC, Wesson PD, Solari IL, et al. Prone Positioning in moderate to severe acute respiratory distress syndrome due to COVID-19: a cohort study and analysis of physiology. J Intensive Care Med. 2021;36:241–252.
   PubMed Web of Science ®Google Scholar
• Carsetti A, Paciarini AD, Marini B, et al. Prolonged prone position ventilation for SARS-CoV-2 patients is feasible and effective. Crit Care. 2020;24:24.
   PubMed Web of Science ®Google Scholar
• Parker EM, Bittner EA, Berra L, et al. Efficiency of prolonged prone positioning for mechanically ventilated patients infected with COVID-19. J Clin Med. 2021;10:2969.
   PubMed Web of Science ®Google Scholar
• Schmidt M, Hajage D, Demoule A, et al. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2021;47:60–73.
   PubMed Web of Science ®Google Scholar
• Ehrmann S, Li J, Ibarra-Estrada M, et al. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. Lancet Respir Med. 2021;9:1387–1395.
   PubMed Web of Science ®Google Scholar
• Putensen C, Zech S, Wrigge H, et al. Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury. Am J Respir Crit Care Med. 2001;164:43–49.
   PubMed Web of Science ®Google Scholar
• Putensen C, Mutz NJ, Putensen-Himmer G, et al. Spontaneous breathing during ventilatory support improves ventilation- perfusion distributions in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999;159:1241–1248.
   PubMed Web of Science ®Google Scholar
• Rohrs EC, Bassi TG, Fernandez KC, et al. Diaphragm neurostimulation during mechanical ventilation reduces atelectasis and transpulmonary plateau pressure, preserving lung homogeneity and PaO2/FIO2. J Appl Physiol. 2021;131:290–301.
   PubMed Web of Science ®Google Scholar
• Yoshida T, Fujino Y, Amato MBP, et al. Fifty years of research in ards spontaneous breathing during mechanical ventilation risks, mechanisms, and management. Am J Respir Crit Care Med. 2017;195:985–992.
   PubMedGoogle Scholar
• Brower R, Matthay M, Morris A, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–1308.
   PubMed Web of Science ®Google Scholar
• Sahetya SK, Mancebo J, Brower RG. Fifty years of research in ARDS VT selection in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;196:1519–1525.
   PubMed Web of Science ®Google Scholar
• Goligher EC, Costa ELV, Yarnell CJ, et al. Effect of lowering vt on mortality in acute respiratory distress syndrome varies with respiratory system elastance. Am J Respir Crit Care Med. 2021;203:1378–1385.
   PubMed Web of Science ®Google Scholar
• Vaporidi K, Psarologakis C, Proklou A, et al. Driving pressure during proportional assist ventilation: an observational study. Ann Intensive Care. 2019;9. https://doi.org/10.1186/s13613-018-0477-4.
   Google Scholar
• Richard JC, Marque S, Gros A, et al. Feasibility and safety of ultra-low tidal volume ventilation without extracorporeal circulation in moderately severe and severe ARDS patients. Intensive Care Med. 2019;45:1590–1598.
   PubMed Web of Science ®Google Scholar
• Regunath H, Moulton N, Woolery D, et al. Ultra-protective mechanical ventilation without extra-corporeal carbon dioxide removal for acute respiratory distress syndrome. J Intensive Care Soc. 2019;20:40–45.
   PubMedGoogle Scholar
• Fanelli V, V RM, Mancebo J, et al. Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome. Crit Care. 2016;20:20.
   PubMed Web of Science ®Google Scholar
• Kassis EB, Su HK, Graham AR, et al. Reverse Trigger Phenotypes in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2021;203:67–77.
   PubMedGoogle Scholar
• de HC, López-Aguilar J, Magrans R, et al. Double cycling during mechanical ventilation: frequency, mechanisms, and physiologic implications*. Crit Care Med. 2018;46:1385–1392.
   PubMed Web of Science ®Google Scholar
• Pham T, Montanya J, Telias I, et al. Automated detection and quantification of reverse triggering effort under mechanical ventilation. Crit Care. 2021;25:60.
   PubMed Web of Science ®Google Scholar
• Rodriguez PO, Tiribelli N, Gogniat E, et al. Automatic detection of reverse-triggering related asynchronies during mechanical ventilation in ARDS patients using flow and pressure signals. J Clin Monit Comput. 2020;34:1239–1246.
   PubMed Web of Science ®Google Scholar
• Vaporidi K. NAVA and PAV+ for lung and diaphragm protection. Curr Opin Crit Care Curr Opin Crit Care. 2020;26:41–46.
   PubMed Web of Science ®Google Scholar
• Vaporidi K, Akoumianaki E, Telias I, et al., Respiratory drive in critically Ill patients pathophysiology and clinical implications. Am J Respir Crit Care Med. 201(1): 20–32. 2020;
   PubMed Web of Science ®Google Scholar
• Akoumianaki E, Lyazidi A, Rey N, et al. Mechanical ventilation-induced reverse-triggered breaths: a frequently unrecognized form of neuromechanical coupling. Chest. 2013;143:927–938.
   PubMed Web of Science ®Google Scholar
• Torbic H, Krishnan S, Harnegie MP, et al. Neuromuscular blocking agents for ARDS: a systematic review and meta-analysis. Respir Care. 2021;66:120–128.
   PubMed Web of Science ®Google Scholar
• Park S, Schmidt M. Early neuromuscular blockade in moderate to severe acute respiratory distress syndrome: do not throw the baby out with the bathwater! J Thorac Dis. 2019;11:E231–E234.
   PubMed Web of Science ®Google Scholar
• Slutsky AS, Villar J. Early paralytic agents for ARDS? Yes, No, and Sometimes. N Engl J Med. 2019;380:2061–2063.
   PubMed Web of Science ®Google Scholar
• Moss M, Huang DT, Brower RG, et al. Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med. 2019;380:1997–2008.
   PubMed Web of Science ®Google Scholar
• Papazian L, Forel J-M, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107–1116.
   PubMed Web of Science ®Google Scholar
• Brochard L. Ventilation-induced lung injury exists in spontaneously breathing patients with acute respiratory failure: yes. Intensive Care Med. 2017;43:250–252.
   PubMed Web of Science ®Google Scholar
• Carteaux G, Parfait M, Combet M, et al. Patient-Self Inflicted Lung Injury: a Practical Review. J Clin Med. 2021;10:2738.
   PubMed Web of Science ®Google Scholar
• Vieillard-Baron A, Prin S, Augarde R, et al. Increasing respiratory rate to improve CO2 clearance during mechanical ventilation is not a panacea in acute respiratory failure. Crit Care Med. 2002;30:1407–1412.
   PubMed Web of Science ®Google Scholar
• Barnes T, Zochios V, Parhar K. Re-examining Permissive Hypercapnia in ARDS: a Narrative Review. Chest Chest. 2018;154:185–195.
   PubMed Web of Science ®Google Scholar
• Levine S, Nguyen T, Taylor N, et al. Rapid Disuse Atrophy of Diaphragm Fibers in Mechanically Ventilated Humans. N Engl J Med. 2008;358:1327–1335.
   PubMed Web of Science ®Google Scholar
• Jaber S, Petrof BJ, Jung B, et al. Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. Am J Respir Crit Care Med. 2011;183:364–371.
   PubMed Web of Science ®Google Scholar
• Goligher EC, Dres M, Fan E, et al. Mechanical ventilation-induced diaphragm atrophy strongly impacts clinical outcomes. Am J Respir Crit Care Med. 2018;197:204–213.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Dridi H, Jung B, Yehya M, et al. Late ventilator-induced diaphragmatic dysfunction after extubation. Crit Care Med. 2020;48:e1300–e1305.
   PubMed Web of Science ®Google Scholar
• Gayan-Ramirez G, Decramer M. Effects of mechanical ventilation on diaphragm function and biology. Eur Respir J. 2002;20:1579–1586.
   PubMed Web of Science ®Google Scholar
• Lin MC, Leung SY, Fang WF, et al. Down-regulation of insulin-like growth factor I (IGF-I) in the mouse diaphragm during sepsis. Chang Gung Med J. 2010;33:501–508.
   PubMedGoogle Scholar
• Zhu X, van Hees HWH, Heunks L, et al. The role of calpains in ventilator-induced diaphragm atrophy. Intensive Care Med Exp. 2017;5. DOI:https://doi.org/10.1186/s40635-017-0127-4.
   Google Scholar
• Whidden MA, Smuder AJ, Wu M, et al. Oxidative stress is required for mechanical ventilation-induced protease activation in the diaphragm. J Appl Physiol. 2010;108:1376–1382.
   PubMed Web of Science ®Google Scholar
• Hooijman PE, Beishuizen A, Witt CC, et al. Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients. Am J Respir Crit Care Med. 2015;191:1126–1138.
   PubMed Web of Science ®Google Scholar
• Morton AB, Smuder AJ, Wiggs MP, et al. Increased SOD2 in the diaphragm contributes to exercise-induced protection against ventilator-induced diaphragm dysfunction. Redox Biol. 2019;20:402–413.
   PubMed Web of Science ®Google Scholar
• Der Pijl RJ V, Granzier HL, Ottenheijm CAC. Diaphragm contractile weakness due to reduced mechanical loading: role of titin. Am J Physiol Cell Physiol. 2019;317:C167–C176.
   PubMed Web of Science ®Google Scholar
• Goligher EC, Fan E, Herridge MS, et al. Evolution of diaphragm thickness during mechanical ventilation: impact of inspiratory effort. Am J Respir Crit Care Med. 2015;192:1080–1088.
   PubMed Web of Science ®Google Scholar
• Hudson MB, Smuder AJ, Nelson WB, et al. Both high level pressure support ventilation and controlled mechanical ventilation induce diaphragm dysfunction and atrophy. Crit Care Med. 2012;40:1254–1260.
   PubMed Web of Science ®Google Scholar
• Urner M, Mitsakakis N, Vorona S, et al. Identifying subjects at risk for diaphragm atrophy during mechanical ventilation using routinely available clinical data. Respir Care. 2021;66:551–558.
   PubMed Web of Science ®Google Scholar
• Marin-Corral J, Dot I, Boguña M, et al. Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation. Intensive Care Med. 2019;45:488–500.
   PubMed Web of Science ®Google Scholar
• Akoumianaki E, Vaporidi K, Georgopoulos D. The injurious effects of elevated or non elevated respiratory rate during mechanical ventilation. Am J Respir Crit Care Med. 2019;199:149–157.
   PubMedGoogle Scholar
• Baumert P, Lake MJ, Stewart CE, et al. Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing. Eur J Appl Physiol. 2016;116:1595–1625.
   PubMed Web of Science ®Google Scholar
• Orozco-Levi M, Lloreta J, Minguella J, et al. Injury of the human diaphragm associated with exertion and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;164:1734–1739.
   PubMed Web of Science ®Google Scholar
• Kayser B, Sliwinski P, Yan S, et al. Respiratory effort sensation during exercise with induced expiratory- flow limitation in healthy humans. J Appl Physiol. 1997;83:936–947.
   PubMed Web of Science ®Google Scholar
• El-Manshawi A, Killian KJ, Summers E, et al. Breathlessness during exercise with and without resistive loading. J Appl Physiol. 1986;61:896–905.
   PubMed Web of Science ®Google Scholar
• Jelinčić V, Van Diest I, Torta DM, et al. The breathing brain: the potential of neural oscillations for the understanding of respiratory perception in health and disease. Psychophysiology. 2021; DOI:https://doi.org/10.1111/psyp.13844.
   Google Scholar
• von Leupoldt A, Ashoori M, Jelinčić V, et al. The impact of unpredictability of dyspnea offset on dyspnea perception, fear, and respiratory neural gating. Psychophysiology. 2021;58:e13807.
   PubMed Web of Science ®Google Scholar
• Raux M, Navarro-Sune X, Wattiez N, et al. Adjusting ventilator settings to relieve dyspnoea modifies brain activity in critically ill patients: an electroencephalogram pilot study. Sci Rep 2019;9DOI:https://doi.org/10.1038/s41598-019-53152-y.
   Google Scholar
• Yoshida T, Torsani V, Gomes S, et al. Spontaneous effort causes occult pendelluft during mechanical ventilation. Am J Respir Crit Care Med. 2013;188:1420–1427.
   PubMed Web of Science ®Google Scholar
• Alzahrany M, Banerjee A. A biomechanical model of pendelluft induced lung injury. J Biomech. 2015;48:1804–1810.
   PubMed Web of Science ®Google Scholar
• Shimatani T, Shime N, Nakamura T, et al. Neurally adjusted ventilatory assist mitigates ventilator-induced diaphragm injury in rabbits. Respir Res. 2019;20:20.
   PubMed Web of Science ®Google Scholar
• Jansen D, Jonkman AH, de VHJ, et al. Positive end-expiratory pressure affects geometry and function of the human diaphragm. J Appl Physiol. 2021;131:1328–1339.
   PubMed Web of Science ®Google Scholar
• Lindqvist J, Van Den Berg M, Van Der Pijl R, et al. Positive end-expiratory pressure ventilation induces longitudinal atrophy in diaphragm fibers. Am J Respir Crit Care Med. 2018;198:472–485.
   PubMed Web of Science ®Google Scholar
• Horn AG, Baumfalk DR, Schulze KM, et al. Effects of elevated positive end-expiratory pressure on diaphragmatic blood flow and vascular resistance during mechanical ventilation. J Appl Physiol. 2020;129:626–635.
   PubMed Web of Science ®Google Scholar
• de Vries H, Jonkman A, Shi Z-H, et al. Assessing breathing effort in mechanical ventilation: physiology and clinical implications. Ann Transl Med. 2018;6:386–387.
   PubMed Web of Science ®Google Scholar
• Vassilakopoulos T, Zakynthinos S, Roussos C. The tension-time index and the frequency/tidal volume ratio are the major pathophysiologic determinants of weaning failure and success. Am J Respir Crit Care Med. 1998;158:378–385.
   PubMed Web of Science ®Google Scholar
• Lilitsis E, Stamatopoulou V, Andrianakis E, et al. Inspiratory effort and breathing pattern change in response to varying the assist level: a physiological study. Respir Physiol Neurobiol. 2020;280:103474.
   PubMed Web of Science ®Google Scholar
• Mancebo J, Isabey D, Lorino H, et al. Comparative effects of pressure support ventilation and intermittent positive pressure breathing (IPPB) in non-intubated healthy subjects. Eur Respir J. 1995;8:1901–1909.
   PubMed Web of Science ®Google Scholar
• Vaporidi K, Soundoulounaki S, Papadakis E, et al. Esophageal and transdiaphragmatic pressure swings as indices of inspiratory effort. Respir Physiol Neurobiol. 2021;284:103561.
   PubMed Web of Science ®Google Scholar
• Umbrello M, Formenti P, Lusardi AC, et al. Oesophageal pressure and respiratory muscle ultrasonographic measurements indicate inspiratory effort during pressure support ventilation. Br J Anaesth. 2020;125:e148–e157.
   PubMed Web of Science ®Google Scholar
• Jubran A, Grant BJB, Laghi F, et al. Weaning prediction esophageal pressure monitoring complements readiness testing. Am J Respir Crit Care Med. 2005;171:1252–1259.
   PubMed Web of Science ®Google Scholar
• Whitelaw WA, Derenne JP, Milic-Emili J. Occlusion pressure as a measure of respiratory center output cm conscious man. Respir Physiol. 1975;23:181–199.
   PubMedGoogle Scholar
• Telias I, Junhasavasdikul D, Rittayamai N, et al. Airway occlusion pressure as an estimate of respiratory drive and inspiratory effort during assisted ventilation. Am J Respir Crit Care Med. 2020;201:1086–1098.
   PubMed Web of Science ®Google Scholar
• Bertoni M, Telias I, Urner M, et al. A novel non-invasive method to detect excessively high respiratory effort and dynamic transpulmonary driving pressure during mechanical ventilation. Crit Care. 2019;23(1):346.
   PubMed Web of Science ®Google Scholar
• Roesthuis L, van den Berg M, van der Hoeven H. Non-invasive method to detect high respiratory effort and transpulmonary driving pressures in COVID-19 patients during mechanical ventilation. Ann Intensive Care. 2021;11:11.
   PubMed Web of Science ®Google Scholar
• Umbrello M, Formenti P, Longhi D, et al. Diaphragm ultrasound as indicator of respiratory effort in critically ill patients undergoing assisted mechanical ventilation: a pilot clinical study. Crit Care. 2015;19. DOI:https://doi.org/10.1186/s13054-015-0894-9.
   Google Scholar
• Mauri T, Grasselli G, Suriano G, et al. Control of respiratory drive and effort in extracorporeal membrane oxygenation patients recovering from severe acute respiratory distress syndrome. Anesthesiology. 2016;125:159–167.
   PubMed Web of Science ®Google Scholar
• Blanch L, Villagra A, Sales B, et al. Asynchronies during mechanical ventilation are associated with mortality. Intensive Care Med. 2015;41:633–641.
   PubMed Web of Science ®Google Scholar
• Vaporidi K, Babalis D, Chytas A, et al. Clusters of ineffective efforts during mechanical ventilation: impact on outcome. Intensive Care Med. 2017;43:184–191.
   PubMed Web of Science ®Google Scholar
• Georgopoulos D, Prinianakis G, Kondili E. Bedside waveforms interpretation as a tool to identify patient-ventilator asynchronies. Intensive Care Med Intensive Care Med. 2006;32:34–47.
   PubMed Web of Science ®Google Scholar
• De Wit M, Miller KB, Green DA, et al. Ineffective triggering predicts increased duration of mechanical ventilation. Crit Care Med. 2009;37:2740–2745.
   PubMed Web of Science ®Google Scholar
• Prinianakis G, Kondili E, Georgopolous D. Patient-ventilator interaction: an overview. Respir Care Clin N Am Respir Care Clin N Am. 2005;11:201–224.
   PubMedGoogle Scholar
• Esperanza JA, Sarlabous L, de Haro C, et al. Monitoring asynchrony during invasive mechanical ventilation. Respir Care. 2020;65:847–869.
   PubMedGoogle Scholar
• Chiumello D, Pelosi P, Calvi E, et al. Different modes of assisted ventilation in patients with acute respiratory failure. Eur Respir J. 2002;20:925–933.
   PubMed Web of Science ®Google Scholar
• Kondili E, Prinianakis G, Georgopoulos D. Patient-ventilator interaction. Br J Anaesth. 2003;91:106–119.
   PubMed Web of Science ®Google Scholar
• Di Mussi R, Spadaro S, Mirabella L, et al. Impact of prolonged assisted ventilation on diaphragmatic efficiency: NAVA versus PSV. Crit Care. 2016;20:20.
   PubMed Web of Science ®Google Scholar
• Schmidt M, Kindler F, Cecchini J, et al. Neurally adjusted ventilatory assist and proportional assist ventilation both improve patient-ventilator interaction. Crit Care. 2015;19. https://doi.org/10.1186/s13054-015-0763-6.
   Google Scholar