High energy dissipation is associated with ventilator-induced lung injury (VILI)
Conventional mechanical ventilation, even when applied for only a few hours, has been shown to be a source of lung injury, so-called ‘ventilator-induced lung injury’ (VILI) 4,5. In combination with previously existing inflammatory responses, which are present in more than 90% of intensive care unit (ICU) patients1, this extra burden plays an important role in the morbidity and mortality of these patients 2,3. Thus, it is of utmost importance to minimize the risk of ventilation hampering recovery or, even worse, leading to a lethal outcome 2,8-15.
Over the last decades, innovative ‘lung-protective ventilation’ approaches have been developed to reduce VILI in the context of the two current golden standard ventilation techniques Pressure Controlled Ventilation (PCV) and Volume Controlled Ventilation (VCV). Up to now, these strategies are limited to suggested values for tidal volume settings (6 mL/kg of body mass), positive end expiratory pressure (PEEP) and plateau pressure in a “one size fits all” fashion 3,6. In fact, the ‘golden standard’ of 6 mL/kg of body mass is based on one large randomized controlled trial focusing on a specific patient group, namely patients suffering from the relatively rare lung disease Acute Respiratory Distress Syndrome (ARDS) 3. The study showed a statistically significant reduction in mortality from 39.8% in the control group to 31.0% in the intervention group. However, later studies aiming to reduce ICU mortality of ARDS patients by setting high or low PEEP failed to show significant effects and reported unchanged high mortality rates of 22–40% 16-19. A similarly high mortality rate of 35% was confirmed in the LUNG SAFE study analyzing data from 29,144 ICU patients in 50 countries 20. Also, a recent study revealed no difference in ICU stay, mortality and morbidity between patients ventilated with low (4–6 mL/kg) versus intermediate (8–10 mL/kg) tidal volumes, raising further doubts as to whether low tidal volume ventilation represents the actual ‘holy grail’ 21.
The literature describes effects of mechanical power as well as mechanical energy during ventilation, where the energy dissipation is the overall power dissipation per unit of time. Mechanical power/energy derives from flow/volume and pressures provided by the ventilator in relation to the compliance and resistance of the patient’s thoracic wall and lungs. In general, more power is generated than is needed to induce inspiration and expiration. The net overspill of energy is dissipated in the lungs, which has been shown to have deleterious effects 2 and is increasingly accepted as one of the causes for VILI 7,8. While current ‘protective’ ventilation strategies mainly focus on optimizing inspiratory ventilation, the passive and abrupt expiration that occurs with conventional methods is considerably relevant 22 and potentially a key factor in inducing lung damage 23. Moreover, controlling expiration has been shown to reduce lung damage in porcine ARDS 24. Of note, a recent study revealed that mechanical power is associated with worse outcomes in critically ill patients receiving mechanical ventilation for more than 48 hours 9. As energy dissipation can be calculated based on factors such as pressures, flow and respiratory rate, independent top leaders in the field postulated that the ideal ventilator should monitor and display energy dissipation in order to really apply ‘safe’ ventilation 10.
FCV® results in lower energy dissipation
FCV® is based on the generation of a constant flow into and out of the lungs, resulting in linear increases and decreases of intratracheal pressures that are just high or low enough to facilitate mechanical breathing with efficient gas exchange. The sudden alveolar pressure drop during passive expiration with conventional ventilation is prevented. In other words, the amount of energy generated by the ventilator is just enough to facilitate respiration. Thereby, the impact on the lung tissue by dissipated energy is kept to a minimum, enabling ventilation with a markedly reduced risk of lung damage.
Figure 1. Left: Idealized PV loops (the enclosed area of each loop is the dissipated energy) during PCV (red line), VCV (blue line) and FCV® (blue line during inspiration, green line during expiration). The dashed line is the static compliance curve of the lung/chest system in this example. Right: Real-time measured PV loops of a patient ventilated with FCV®, demonstrating minimized hysteresis area of the PV loops (=energy dissipation) 26.
Recently, clear theoretical evidence was provided for lower energy dissipation in the lungs by FCV® as compared to VCV or PCV. A relatively simple analysis and numerical calculations indicated that energy dissipation is minimized by controlling the ventilation flow to be constant and continuous during both inspiration and expiration, and by ventilating at an I:E ratio close to 1:1. In other words, by using FCV® 25. Energy dissipation can be calculated from the hysteresis area of pressure-volume loops obtained during ventilation. PV loops calculated based on routine ventilation protocols showed a 53% reduction in energy dissipation by FCV® as compared to PCV and a 32% reduction as compared to VCV 25. Additionally, it was emphasized that accurate measurement of intratracheal pressures is crucial for calculating energy dissipation. Where other VCV and PCV ventilators rely on calculated airway pressures, Evone is the only device that actually measures intratracheal pressures and is thus capable of measuring energy dissipation accurately.
This theory was further validated on a patient. Pressure-volume (PV) loops were recorded in real time, and the energy dissipated in the patient’s lungs was calculated from the hysteresis area of the PV loops. Strikingly, the energy dissipation was just 0.17 J/L, which is even lower than values reported for spontaneous breathing (0.2–0.7 J/L) 26. Figure 1 outlines schematic PV loops obtained for PCV, VCV and FCV® and the PV loops obtained during FCV® ventilation of a patient.
In porcine ARDS, FCV® ventilation had a higher efficiency as compared to VCV with similar tidal volumes and PEEP, resulting in a 46% increased oxygenation (P=0.035) while using a 26% lower minute volume (P<0.001) 27. Moreover, FCV® resulted in lower mechanical power 26. Strikingly, histologic results demonstrated a significantly increased alveolar wall thickness in the control group as compared to the FCV® group (7.8±0.2 μm vs. 5.5±0.1 μm; P<0.001), which was indicative of a worsened lung condition (Figure 2). Also, cell infiltrates, a marker for inflammation, were much less in the FCV group (32±2 vs 20±2/field; P<0.001). The authors state that they herewith provided evidence for attenuated lung injury after FCV® 27.
- Lord J et al. The Systemic Immune Response to Trauma: An Overview of Pathophysiology and Treatment. The Lancet 2014 ;1455-465
- Cressoni M et al. Mechanical Power and Development of Ventilator-induced Lung Injury. Anaesthesiology 2016;124(5):1100-8
- Brower R 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(18):1301-8
- Wolthuis E et al. Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice. Crit Care. 2009;13(1): R1
- Woods S et al. Kinetic profiling of in vivo lung cellular inflammatory responses to mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 2015;308:L912–L921
- Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2014 Mar 6;370(10):980
- Marini JJ et al. Dissipation of energy during the respiratory cycle: conditional importance of ergotrauama to structural lung damage. Curr Opin Crit Care. 2018; 24(1):16-22
- Gattinoni L et at. New insights in mechanical ventilation. Med Klin Intensivmed Notfmed. 2018 Jan 9. EPub ahead of print
- Tonetti T et al. Volutrauma, Atelectrauma, and Mechanical Power. Crit Care Med. 2017;45(3):e327-e328
- Gattinoni L et al. Intensive care medicin in 2050: ventilator-induced lung injury. Intensive Care Med Published online: 22 March 2017
- Nieman GF. Lung stress, strain, and energy load: engineering concepts to understand the mechanism of ventilator-induced lung injury (VILI). Intensive Care Med Exp. 2016;4(1):16
- Tonetti T. Driving pressure and mechanical power: new targets for VILI prevention. Ann Transl Med. 2017;5(14):286
- Gattinoni L et al. Ventilator-related causes of lung injury: the mechanical power. Intesive Care Med. 2016;42(10):1567-1575
- Protti A et al. Lung anatomy, energy load, and ventilator-induced lung injury. Intensive Care Med Exp. 2015;3(1):34
- Marini J et al. A few of our favorite unconfirmed ideas. Crit Care. 2015;19(Suppl 3): S1
- Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; 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(4):327-36
- Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, Austin P, Lapinsky S, Baxter A, Russell J, Skrobik Y, Ronco JJ, Stewart TE; 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(6):637-45
- Mercat A, Richard JC, Vielle B, Jaber S, Osman D, Diehl JL, Lefrant JY, Prat G, Richecoeur J, Nieszkowska A, Gervais C, Baudot J, Bouadma L, Brochard L; 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(6):646-55
- Kacmarek RM, Villar J, Sulemanji D, Montiel R, Ferrando C, Blanco J, Koh Y, Soler JA, Martinez D, Hernández M, Tucci M, Borges JB, Lubillo S, Santos A, Araujo JB, Amato MB, Suárez-Sipmann F; Open Lung Approach Network. Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial. Crit Care Med. 2016;44(1):32-42
- Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291
- PReVENT Investigators, Simonis FD, Serpa Neto A, Binnekade JM, Braber A, Bruin KCM, Determann RM, Goekoop GJ, Heidt J, Horn J, Innemee G, de Jonge E, Juffermans NP, Spronk PE, Steuten LM, Tuinman PR, de Wilde RBP, Vriends M, Gama de Abreu M, Pelosi P, Schultz MJ.Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial.JAMA. 2018 Nov 13;320(18):1872-1880
- Marini JJ, Gattinoni L. Protecting the Ventilated Lung: Vascular Surge and Deflation Energetics. Am J Respir Crit Care Med. 2018 Nov 1;198(9):1112-1114
- Katira BH, Engelberts D, Otulakowski G, Giesinger RE, Yoshida T, Post M, Kuebler WM, Connelly KA, Kavanagh BP. Abrupt Deflation after Sustained Inflation Causes Lung Injury. Am J Respir Crit Care Med. 2018 Nov 1;198(9):1165-1176
- Goebel U, Haberstroh J, Foerster K, Dassow C, Priebe HJ, Guttmann J, Schumann Flow-controlled expiration: a novel ventilation mode to attenuate experimental porcine lung injury. Br J Anaesth. 2014 Sep;113(3):474-83. doi: 10.1093/bja/aeu058. Epub 2014 Apr 2. PubMed PMID: 24694683
- Barnes T, van Asseldonk D, Enk D. Minimisation of dissipated energy in the airways during mechanical ventilation by using constant inspiratory and expiratory flows – flow controlled ventilation. Medical Hypotheses 2018 Dec;121:167-176
- Barnes T, Enk D. Ventilation for low dissipated energy achieved using flow control during both inspiration and expiration. Trends in Anaesthesia and Critical Care 2018, Trends in Anaesthesia and Critical Care 24 (2019); 5-12
- Schmidt J, Wenzel C, Spassov S, Wirth S, Schumann S. Expiratory Ventilation Assistance during mandatory ventilation in porcine ARDS improves arterial oxygenation – a randomised controlled animal study [Abstract]. Eur J Anaesthesiol 2018; 35 e-supplement 56: 7
- Schmidt J, Wenzel C, Mahn M, Spassov S, Schmitz HC, Borgmann S, Lin Z, Haberstroh J, Meckel S, Eiden S, Wirth S, Buerkle H, Schumann S. Improved lung recruitment and oxygenation during mandatory ventilation with a new expiratory ventilation assistance device: A controlled interventional trial in healthy pigs. Eur J Anaesthesiol. 2018 Oct 35(10):736-744
What a fantastic closing of a great year!: Ventinova has been awarded ‘Company of the Year 2019’ by MedTech Outlook. The US-based Medical Technology Magazine annually selects the ‘Top 10 MedTech Solution Providers in Europe". Ventinova was selected as Company...