Physiological and Pathophysiological Consequences of Mechanical Ventilation

Abstract

Mechanical ventilation is a life-support system used to ensure blood gas exchange and to assist the respiratory muscles in ventilating the lung during the acute phase of lung disease or following surgery. Positive-pressure mechanical ventilation differs considerably from normal physiologic breathing. This may lead to several negative physiological consequences, both on the lungs and on peripheral organs. First, hemodynamic changes can affect cardiovascular performance, cerebral perfusion pressure (CPP), and drainage of renal veins. Second, the negative effect of mechanical ventilation (compression stress) on the alveolar-capillary membrane and extracellular matrix may cause local and systemic inflammation, promoting lung and peripheral-organ injury. Third, intra-abdominal hypertension may further impair lung and peripheral-organ function during controlled and assisted ventilation. Mechanical ventilation should be optimized and personalized in each patient according to individual clinical needs. Multiple parameters must be adjusted appropriately to minimize ventilator-induced lung injury (VILI), including: inspiratory stress (the respiratory system inspiratory plateau pressure); dynamic strain (the ratio between tidal volume and the end-expiratory lung volume, or inspiratory capacity); static strain (the end-expiratory lung volume determined by positive end-expiratory pressure [PEEP]); driving pressure (the difference between the respiratory system inspiratory plateau pressure and PEEP); and mechanical power (the amount of mechanical energy imparted as a function of respiratory rate). More recently, patient self-inflicted lung injury (P-SILI) has been proposed as a potential mechanism promoting VILI. In the present chapter, we will discuss the physiological and pathophysiological consequences of mechanical ventilation and how to personalize mechanical ventilation parameters.

Keywords

mechanical ventilation - cardiopulmonary interaction - lung mechanics - ventilator-induced lung injury - alveolar-capillary membrane - ventilatory variables

Publication History

Article published online:
19 April 2022

• References

• 1 Mitchell JR, Whitelaw WA, Sas R, Smith ER, Tyberg JV, Belenkie I. RV filling modulates LV function by direct ventricular interaction during mechanical ventilation. Am J Physiol Heart Circ Physiol 2005; 289 (02) H549-H557
• 2 Pelosi P, Ferguson ND, Frutos-Vivar F. et al. Ventila Study Group. Management and outcome of mechanically ventilated neurologic patients. Crit Care Med 2011; 39 (06) 1482-1492
• 3 Husain-Syed F, Slutsky AS, Ronco C. Lung-kidney cross-talk in the critically ill patient. Am J Respir Crit Care Med 2016; 194 (04) 402-414
• 4 Kredel M, Muellenbach RM, Johannes A, Brederlau J, Roewer N, Wunder C. Hepatic effects of lung-protective pressure-controlled ventilation and a combination of high-frequency oscillatory ventilation and extracorporeal lung assist in experimental lung injury. Med Sci Monit 2011; 17 (10) BR275-BR281
• 5 Kirkpatrick AW, Roberts DJ, De Waele J. et al. Pediatric Guidelines Sub-Committee for the World Society of the Abdominal Compartment Syndrome. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med 2013; 39 (07) 1190-1206
• 6 Regli A, Hockings LE, Musk GC. et al. Commonly applied positive end-expiratory pressures do not prevent functional residual capacity decline in the setting of intra-abdominal hypertension: a pig model. Crit Care 2010; 14 (04) R128
• 7 Regli A, Mahendran R, Fysh ET. et al. Matching positive end-expiratory pressure to intra-abdominal pressure improves oxygenation in a porcine sick lung model of intra-abdominal hypertension. Crit Care 2012; 16 (05) R208
• 8 Regli A, Chakera J, De Keulenaer BL. et al. Matching positive end-expiratory pressure to intra-abdominal pressure prevents end-expiratory lung volume decline in a pig model of intra-abdominal hypertension. Crit Care Med 2012; 40 (06) 1879-1886
• 9 Cortes-Puentes GA, Keenan JC, Adams AB, Parker ED, Dries DJ, Marini JJ. Impact of chest wall modifications and lung injury on the correspondence between airway and transpulmonary driving pressures. Crit Care Med 2015; 43 (08) e287-e295
• 10 Tobin MJ, Mador MJ, Guenther SM, Lodato RF, Sackner MA. Variability of resting respiratory drive and timing in healthy subjects. J Appl Physiol (1985) 1988; 65 (01) 309-317
• 11 Brower R, Wise RA, Hassapoyannes C, Bromberger-Barnea B, Permutt S. Effect of lung inflation on lung blood volume and pulmonary venous flow. J Appl Physiol (1985) 1985; 58 (03) 954-963
• 12 Hakim TS, Michel RP, Chang HK. Effect of lung inflation on pulmonary vascular resistance by arterial and venous occlusion. J Appl Physiol 1982; 53 (05) 1110-1115
• 13 Simmons D, Linde L, Miller J, O'Reilly R. Relation between lung volume and pulmonary vascular resistance. Circ Res 1961; 9: 465-471
• 14 Mahjoub Y, Lejeune V, Muller L. et al. Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study. Br J Anaesth 2014; 112 (04) 681-685
• 15 Pinsky MR. Functional haemodynamic monitoring. Curr Opin Crit Care 2014; 20 (03) 288-293
• 16 Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest 2002; 121 (06) 2000-2008
• 17 Michard F, Boussat S, Chemla D. et al. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med 2000; 162 (01) 134-138
• 18 Kimmoun A, Baux E, Das V. et al. Outcomes of patients admitted to intensive care units for acute manifestation of small-vessel vasculitis: a multicenter, retrospective study. Crit Care 2016; 20: 27
• 19 He H, Long Y, Liu D, Wang X, Tang B. The prognostic value of central venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio in septic shock patients with central venous O2 saturation ≥80. Shock 2017; 48 (05) 551-557
• 20 Dumas G, Lavillegrand JR, Joffre J. et al. Mottling score is a strong predictor of 14-day mortality in septic patients whatever vasopressor doses and other tissue perfusion parameters. Crit Care 2019; 23 (01) 211
• 21 The Brain Trauma Foundation. The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Guidelines for cerebral perfusion pressure. J Neurotrauma 2000; 17 (6-7): 507-511
• 22 Brian Jr JE. Carbon dioxide and the cerebral circulation. Anesthesiology 1998; 88 (05) 1365-1386
• 23 Cold GE. Cerebral blood flow in acute head injury. The regulation of cerebral blood flow and metabolism during the acute phase of head injury, and its significance for therapy. Acta Neurochir Suppl (Wien) 1990; 49: 1-64
• 24 Robba C, Ball L, Battaglini D. et al. Early effects of ventilatory rescue therapies on systemic and cerebral oxygenation in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: a prospective observational study. Crit Care 2021; 25 (01) 111
• 25 Robba C, Poole D, McNett M. et al. Mechanical ventilation in patients with acute brain injury: recommendations of the European Society of Intensive Care Medicine consensus. Intensive Care Med 2020; 46 (12) 2397-2410
• 26 Robba C, Ball L, Nogas S. et al. Effects of positive end-expiratory pressure on lung recruitment, respiratory mechanics, and intracranial pressure in mechanically ventilated brain-injured patients. Front Physiol 2021; 12: 711273
• 27 Ott L, McClain CJ, Gillespie M, Young B. Cytokines and metabolic dysfunction after severe head injury. J Neurotrauma 1994; 11 (05) 447-472
• 28 Waikar SS, Liu KD, Chertow GM. The incidence and prognostic significance of acute kidney injury. Curr Opin Nephrol Hypertens 2007; 16 (03) 227-236
• 29 Uchino S, Kellum JA, Bellomo R. et al. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 294 (07) 813-818
• 30 Walcher A, Faubel S, Keniston A, Dennen P. In critically ill patients requiring CRRT, AKI is associated with increased respiratory failure and death versus ESRD. Ren Fail 2011; 33 (10) 935-942
• 31 Annat G, Viale JP, Bui Xuan B. et al. Effect of PEEP ventilation on renal function, plasma renin, aldosterone, neurophysins and urinary ADH, and prostaglandins. Anesthesiology 1983; 58 (02) 136-141
• 32 Verbrugge FH, Dupont M, Steels P. et al. Abdominal contributions to cardiorenal dysfunction in congestive heart failure. J Am Coll Cardiol 2013; 62 (06) 485-495
• 33 Uhlig S, Ranieri M, Slutsky AS. Biotrauma hypothesis of ventilator-induced lung injury. Am J Respir Crit Care Med 2004; 169 (02) 314-315
• 34 Gurkan OU, O'Donnell C, Brower R, Ruckdeschel E, Becker PM. Differential effects of mechanical ventilatory strategy on lung injury and systemic organ inflammation in mice. Am J Physiol Lung Cell Mol Physiol 2003; 285 (03) L710-L718
• 35 Imai Y, Parodo J, Kajikawa O. et al. Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome. JAMA 2003; 289 (16) 2104-2112
• 36 Kuiper JW, Groeneveld AB, Slutsky AS, Plötz FB. Mechanical ventilation and acute renal failure. Crit Care Med 2005; 33 (06) 1408-1415
• 37 Ortiz A, Lorz C, Egido J. The Fas ligand/Fas system in renal injury. Nephrol Dial Transplant 1999; 14 (08) 1831-1834
• 38 Wu B, Iwakiri R, Ootani A, Fujise T, Tsunada S, Fujimoto K. Platelet-activating factor promotes mucosal apoptosis via FasL-mediating caspase-9 active pathway in rat small intestine after ischemia-reperfusion. FASEB J 2003; 17 (09) 1156-1158
• 39 van den Akker JP, Egal M, Groeneveld AB. Invasive mechanical ventilation as a risk factor for acute kidney injury in the critically ill: a systematic review and meta-analysis. Crit Care 2013; 17 (03) R98
• 40 Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Acute Respiratory Distress Syndrome Network. 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 (18) 1301-1308
• 41 Mercat A, Richard JC, Vielle B. et al. Expiratory Pressure (Express) Study Group. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2008; 299 (06) 646-655
• 42 Audimoolam VK, McPhail MJ, Wendon JA. et al. Lung injury and its prognostic significance in acute liver failure. Crit Care Med 2014; 42 (03) 592-600
• 43 Levesque E, Saliba F, Ichaï P, Samuel D. Outcome of patients with cirrhosis requiring mechanical ventilation in ICU. J Hepatol 2014; 60 (03) 570-578
• 44 Gacouin A, Locufier M, Uhel F. et al. Liver cirrhosis is independently associated with 90-day mortality in ARDS patients. Shock 2016; 45 (01) 16-21
• 45 Quintel M, Pelosi P, Caironi P. et al. An increase of abdominal pressure increases pulmonary edema in oleic acid-induced lung injury. Am J Respir Crit Care Med 2004; 169 (04) 534-541
• 46 Santos CL, Moraes L, Santos RS. et al. Effects of different tidal volumes in pulmonary and extrapulmonary lung injury with or without intraabdominal hypertension. Intensive Care Med 2012; 38 (03) 499-508
• 47 Pelosi P, Luecke T, Rocco PR. Chest wall mechanics and abdominal pressure during general anaesthesia in normal and obese individuals and in acute lung injury. Curr Opin Crit Care 2011; 17 (01) 72-79
• 48 Ranieri VM, Brienza N, Santostasi S. et al. Impairment of lung and chest wall mechanics in patients with acute respiratory distress syndrome: role of abdominal distension. Am J Respir Crit Care Med 1997; 156 (4 Pt 1): 1082-1091
• 49 Santos CL, Moraes L, Santos RS. et al. The biological effects of higher and lower positive end-expiratory pressure in pulmonary and extrapulmonary acute lung injury with intra-abdominal hypertension. Crit Care 2014; 18 (03) R121
• 50 Regli A, Pelosi P, Malbrain MLNG. Ventilation in patients with intra-abdominal hypertension: what every critical care physician needs to know. Ann Intensive Care 2019; 9 (01) 52
• 51 Ball L, Pelosi P. How I ventilate an obese patient. Crit Care 2019; 23 (01) 176
• 52 Amato MB, Meade MO, Slutsky AS. et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 2015; 372 (08) 747-755
• 53 Neto AS, Hemmes SN, Barbas CS. et al. PROVE Network Investigators. 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 (04) 272-280
• 54 Silva PL, Gama de Abreu M. Regional distribution of transpulmonary pressure. Ann Transl Med 2018; 6 (19) 385
• 55 Pelosi P, D'Andrea L, Vitale G, Pesenti A, Gattinoni L. Vertical gradient of regional lung inflation in adult respiratory distress syndrome. Am J Respir Crit Care Med 1994; 149 (01) 8-13
• 56 Guay J, Ochroch EA. Intraoperative use of low volume ventilation to decrease postoperative mortality, mechanical ventilation, lengths of stay and lung injury in patients without acute lung injury. Cochrane Database Syst Rev 2015; (12) CD011151
• 57 Futier E, Pereira B, Jaber S. Intraoperative low-tidal-volume ventilation. N Engl J Med 2013; 369 (19) 1862-1863
• 58 Felix NS, Samary CS, Cruz FF, Rocha NN, Fernandes MVS, Machado JA, Bose-Madureira RL, Capelozzi VL, Pelosi P, Silva PL, Marini JJ, Rocco PRM. Gradually Increasing Tidal Volume May Mitigate Experimental Lung Injury in Rats. Anesthesiology 2019; May; 130 (05) 767-777
• 59 Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ. PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet 2014; 384 (9942): 495-503
• 60 Brower RG, Lanken PN, MacIntyre N. et al. National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004; 351 (04) 327-336
• 61 Meade MO, Cook DJ, Guyatt GH. et al. Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2008; 299 (06) 637-645
• 62 Pelosi P, Ball L, Barbas CSV. et al. Personalized mechanical ventilation in acute respiratory distress syndrome. Crit Care 2021; 25 (01) 250
• 63 Ball L, Serpa Neto A, Trifiletti V. et al. PROVE Network: PROtective Ventilation Network. Effects of higher PEEP and recruitment manoeuvres on mortality in patients with ARDS: a systematic review, meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials. Intensive Care Med Exp 2020; 8 (Suppl. 01) 39
• 64 Pelosi P, Rocco PRM, Gama de Abreu M. Close down the lungs and keep them resting to minimize ventilator-induced lung injury. Crit Care 2018; 22 (01) 72
• 65 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 (07) 1407-1412
• 66 Goligher EC, Hodgson CL, Adhikari NKJ, Meade MO, Wunsch H, Uleryk E, Gajic O, Amato MPB, Ferguson ND, Rubenfeld GD, Fan E. Lung Recruitment Maneuvers for Adult Patients with Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc 2017; Oct;14(Supplement_4): S304-S311 DOI: 10.1513/AnnalsATS.201704-340OT.
• 67 Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT. Wheeler AAcute Respiratory Distress Syndrome Network. Ventilationwith 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 (18) 1301-1308
• 68 Parhar KKS, Zjadewicz K, Soo A. et al. Epidemiology, mechanical power, and 3-year outcomes in acute respiratory distress syndrome patients using standardized screening. an observational cohort study. Ann Am Thorac Soc 2019; 16 (10) 1263-1272
• 69 Koh SO. Mode of mechanical ventilation: volume controlled mode. Crit Care Clin 2007; 23 (02) 161-167, viii
• 70 Smith RA, Venus B. Cardiopulmonary effect of various inspiratory flow profiles during controlled mechanical ventilation in a porcine lung model. Crit Care Med 1988; 16 (08) 769-772
• 71 Al-Saady N, Bennett ED. Decelerating inspiratory flow waveform improves lung mechanics and gas exchange in patients on intermittent positive-pressure ventilation. Intensive Care Med 1985; 11 (02) 68-75
• 72 Terragni PP, Rosboch G, Tealdi A. et al. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 2007; 175 (02) 160-166
• 73 Villar J, Ambrós A, Soler JA. et al. Stratification and Outcome of Acute Respiratory Distress Syndrome (STANDARDS) Network. Age, PaO2/FIO2, and plateau pressure score: a proposal for a simple outcome score in patients with the acute respiratory distress syndrome. Crit Care Med 2016; 44 (07) 1361-1369
• 74 Gattinoni L, Tonetti T, Cressoni M. et al. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med 2016; 42 (10) 1567-1575
• 75 Otis AB, Fenn WO, Rahn H. Mechanics of breathing in man. J Appl Physiol 1950; 2 (11) 592-607
• 76 Giosa L, Busana M, Pasticci I. et al. Mechanical power at a glance: a simple surrogate for volume-controlled ventilation. Intensive Care Med Exp 2019; 7 (01) 61
• 77 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 (03) 303-311
• 78 Camporota L, Busana M, Marini JJ, Gattinoni L. The 4DPRR index and mechanical power: a step ahead or four steps backward?. Am J Respir Crit Care Med 2021; 204 (04) 491-492
• 79 Cressoni M, Gotti M, Chiurazzi C. et al. Mechanical power and development of ventilator-induced lung injury. Anesthesiology 2016; 124 (05) 1100-1108
• 80 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 (10) 1354-1362
• 81 Yoshida T, Fujino Y, Amato MB, Kavanagh BP. Fifty years of research in ARDS. Spontaneous breathing during mechanical ventilation. risks, mechanisms, and management. Am J Respir Crit Care Med 2017; 195 (08) 985-992
• 82 Pelosi P, Rocco PR. Effects of mechanical ventilation on the extracellular matrix. Intensive Care Med 2008; 34 (04) 631-639
• 83 Brochard L, Slutsky AS, Pesenti A. Reply: “A Word of Caution Regarding Patient Self-inflicted Lung Injury and Prophylactic Intubation” and “Hyperventilation (Not Ventilator)-Induced Lung Injury”. Am J Respir Crit Care Med 2017; 196 (07) 937-938
• 84 Yoshida T, Torsani V, Gomes S. et al. Spontaneous effort causes occult pendelluft during mechanical ventilation. Am J Respir Crit Care Med 2013; 188 (12) 1420-1427
• 85 Kallet RH, Alonso JA, Luce JM, Matthay MA. Exacerbation of acute pulmonary edema during assisted mechanical ventilation using a low-tidal volume, lung-protective ventilator strategy. Chest 1999; 116 (06) 1826-1832
• 86 Pinto EF, Santos RS, Antunes MA. et al. Static and dynamic transpulmonary driving pressures affect lung and diaphragm injury during pressure-controlled versus pressure-support ventilation in experimental mild lung injury in rats. Anesthesiology 2020; 132 (02) 307-320
• 87 Bellani G, Grasselli G, Teggia-Droghi M. et al. Do spontaneous and mechanical breathing have similar effects on average transpulmonary and alveolar pressure? A clinical crossover study. Crit Care 2016; 20 (01) 142
• 88 Busana M, Giosa L, Cressoni M. et al. The impact of ventilation-perfusion inequality in COVID-19: a computational model. J Appl Physiol (1985) 2021; 130 (03) 865-876
• 89 Blanch L, Villagra A, Sales B. et al. Asynchronies during mechanical ventilation are associated with mortality. Intensive Care Med 2015; 41 (04) 633-641
• 90 Crapo JD, Crapo RO, Jensen RL, Mercer RR, Weibel ER. Evaluation of lung diffusing capacity by physiological and morphometric techniques. J Appl Physiol (1985) 1988; 64 (05) 2083-2091
• 91 Roan E, Wilhelm K, Bada A. et al. Hyperoxia alters the mechanical properties of alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 2012; 302 (12) L1235-L1241
• 92 Ding N, Wang F, Xiao H, Xu L, She S. Mechanical ventilation enhances HMGB1 expression in an LPS-induced lung injury model. PLoS One 2013; 8 (09) e74633