Variable mechanical ventilation

Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini, Luiz Alberto; Friedman, Gilberto

doi:10.5935/0103-507X.20170012

Paula Caitano Fontela

Postgraduate Program in Penumological Sciences, Universidade Federal do Rio Grande do Sul - Porto Alegre (RS), Brazil.

Renata Bernardy Prestes

Master Course in Biosciences and Rehabilitation, Centro Universitário Metodista IPA - Porto Alegre (RS), Brazil.

Luiz Alberto Forgiarini Jr.

Postgraduate Program in Biosciences and Rehabilitation, and Rehabilitation and Inclusion, Centro Universitário Metodista IPA - Porto Alegre (RS), Brazil.

Gilberto Friedman Corresponding author: Gilberto Friedman, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Pneumológicas da Universidade Federal do Rio Grande do Sul, Rua Fernandes Vieira, 181 - Bom Fim, Zip code: 90035-091 - Porto Alegre (RS), Brazil, E-mail: gfriedman@hcpa.edu.br

Postgraduate Program in Pneumological Sciences, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul - Porto Alegre (RS), Brazil.

Corresponding author: Gilberto Friedman, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Pneumológicas da Universidade Federal do Rio Grande do Sul, Rua Fernandes Vieira, 181 - Bom Fim, Zip code: 90035-091 - Porto Alegre (RS), Brazil, E-mail: gfriedman@hcpa.edu.br

Conflicts of interest: None.

Author	Sample (N)	Sample characteristics	Objective	Intervention	Conclusion
Thammanomai et al.⁽⁹9 Thammanomai A, Hueser LE, Majumdar A, Bartolák-Suki E, Suki B. Design of a new variable-ventilation method optimized for lung recruitment in mice. J Appl Physiol (1995). 2008;104(5):1329-40.⁾	G1, G2, G3, and G4 = 8 animals in each group with ARDS and 8 animals without ARDS	Mice (22 - 26g) with and without ARDS ventilated for 60 minutes	To investigate the physiological effects of VV and test the hypothesis that the beneficial effects of VV are due to the variability in TV considering its distribution and not simply the presence of large ventilation volumes	G1: CV (TV of 8mL/kg; RR of 240rpm; PEEP of 3cmH₂O) G2: Original VV (variable RR and TV to maintain the V_min of CV) G3: CV with sighs (large breaths, two ventilations per minute) G4: New VV (variable RR and TV - minimum, peak, and maximum volumes - to keep the same V_min)	The new VV and CV with sighs led to stable dynamic equilibrium in alveolar recruitment that significantly outperformed the CV and the original VV. During the new VV, this balance improved pulmonary mechanics
Berry et al.⁽¹⁰10 Berry CA, Suki B, Polglase GR, Pillow JJ. Variable ventilation enhances ventilation without exacerbating injury in preterm lambs with respiratory distress syndrome. Pediatr Res. 2012;72(4):384-92.⁾	G1 = 6 animals G2 = 8 animals G3 = 8 animals	Premature lambs (3.2 kg) with 129 days of gestation, ventilated for 3 hours	To assess whether VV is effective for achieving permissive hypercapnia without increasing injury markers or pulmonary inflammation compared with CV	G1: CG (without the use of MV) G2: CV (TV to achieve a PaCO₂ of 40 - 50mmHg) G3: VV (variable TV and RR to maintain the V_min of CV)	VV promoted recruitment and increased ventilatory efficiency without increasing pulmonary inflammation or injury
Bellardine et al.⁽¹¹11 Bellardine CL, Hoffman AM, Tsai L, Ingenito EP, Arold SP, Lutchen KR, et al. Comparison of variable and conventional ventilation in a sheep saline lavage lung injury model. Crit Care Med. 2006;34(2):439-45.⁾	G1 = 6 animals G2 = 7 animals	Sheep (59.8 ± 10.5kg) with ARDS ventilated for 4 hours	To compare VV with CV in terms of gas exchange, hemodynamics, and lung mechanics	G1: CV (TV of 10mL/kg; RR of 16bpm; PEEP of 7.5cmH₂O; FiO₂ of 1.0) G2: VV (variable RR and TV to maintain the V_min of CV; PEEP of 7.5cmH₂O; FiO₂ of 1.0)	VV provided continuous improvement in oxygenation and ventilation pressures and overall better pulmonary mechanics while minimizing pulmonary damage
Mutch et al.⁽¹²12 Mutch WA, Eschun GM, Kowalski SE, Graham MR, Girling LG, Lefevre GR. Biologically variable ventilation prevents deterioration of gas exchange during prolonged anaesthesia. Br J Anaesth. 2000;84(2):197-203.⁾	G1 = 10 animals G2 = 10 animals	Pigs (20 - 30kg) ventilated for 7 hours	To compare gas exchange and respiratory mechanics in CV and VV during prolonged anesthesia	G1: CV (RR of 15rpm; V_min adjusted to deliver a TV of approximately 10mL/kg) G2: VV (variable TV and RR to maintain the V_min of CV)	Deterioration of gas exchange and respiratory mechanics occurred with CV but not in VV
Mutch et al.⁽¹³13 Mutch WA, Harms S, Lefevre GR, Graham MR, Girling LG, Kowalski SE. Biologically variable ventilation increases arterial oxygenation over that seen with positive end-expiratory pressure alone in a porcine model of acute respiratory distress syndrome. Crit Care Med. 2000;28(7):2457-64.⁾	G1 = 9 animals G2 = 8 animals	Pigs (20 - 30kg) with ARDS ventilated for 4 hours	To assess whether VV had positive effects when used with PEEP	G1: CV (RR of 15rpm; PEEP of 10cmH₂O) G2: VV (variable RR with reciprocal changes of TV; PEEP of 10cmH₂O)	VV with PEEP of 10cmH₂O improved arterial oxygenation compared with CV with the same PEEP value
Arold et al.⁽¹⁴14 Arold SP, Mora R, Lutchen KR, Ingenito EP, Suki B. Variable tidal volume ventilation improves lung mechanics and gas exchange in a rodent model of acute lung injury. Am J Respir Crit Care Med. 2002;165(3):366-71.⁾	G1 = 4 animals G2 = 10 animals	Guinea pigs (500 - 600g) with ARDS ventilated for 3 hours	To test whether the ability of VV to improve oxygenation and pulmonary mechanics depends on the amount of variability added to TV	G1: CV (RR of 60bpm; TV of 5.1mL/kg, PEEP of 3cmH₂O) G2: VV (different variations of VT - 10%, 20%, 40%, and 60% of the average - adjustment of RR to maintain the V_min of CV)	VV was effective in improving lung function and gas exchange in an ARDS model
Boker et al.⁽¹⁵15 Boker A, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, et al. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002;165(4):456-62.⁾	G1 = 8 animals G2 = 9 animals	Pigs with ARDS mechanically ventilated for 5 hours	To measure changes in PaO₂, lung compliance, and proinflammatory cytokines in MV with and without biological variability using an ARDSnet protocol⁽¹⁶16 Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-8.⁾	G1: CV (RR of 30bpm; TV of 6mL/kg) G2: VV (variable RR and TV in the same average)	The variability added to the ARDSnet protocol improved oxygenation and reduced the shunting fraction, peak airway pressure, and IL-8 concentrations in the tracheal aspirate
Arold et al.⁽¹⁷17 Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003;285(2):L370-5.⁾	G1 = 6 animals G2 = 5 animals G3 = 5 animals	Guinea pigs (500 - 600g) ventilated for 3 hours	To test whether VV promoted the release of surfactant in vivo	G1: CV (RR of 60rpm; TV of 5mL/kg, PEEP of 3cmH₂O) G2: VV (variable RR and TV to maintain the V_min of CV) G3: CG (Without the use of MV)	VV promoted the release of surfactant, reduced lung damage, and improved blood oxygenation
Funk et al.⁽¹⁸18 Funk DJ, Graham MR, Girling LG, Thliveris JA, McManus BM, Walker EK, et al. A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury. Respir Res. 2004;5:22.⁾	G1 = 8 animals G2 = 8 animals G3 = 8 animals	Pigs (20 - 30kg) with ARDS ventilated for 5 hours	To compare three ventilation strategies in terms of gas exchange, respiratory mechanics, inflammatory levels, and surfactant function	G1: CV (TV of 7mL/kg; RR of 30bpm; PEEP of 10cmH₂O) G2: CV with ARM (40cmH₂O for 40 seconds every hour) G3: VV (variable TV; RR of 30bpm; PEEP of 10cmH₂O)	VV with a human variability file was greater than CV, and CV with ARM was used for the sustained improvement of gas exchange and respiratory mechanics
Mutch et al.⁽¹⁹19 Mutch WA, Graham MR, Girling LG, Brewster JF. Fractal ventilation enhances respiratory sinus arrhythmia. Respir Res. 2005;6:41.⁾	10 animals	Pigs (30 - 40kg) initially with healthy lungs and then with ARDS	To test whether the imposition of a variable respiratory signal with the addition of physiological noise affected cardiorespiratory oscillators	The animals were subjected to MV for 4 to 5 minutes for each ventilation mode - CV and VV (variable RR and TV to maintain the V_min of CV) - before and after ARDS	The increase of respiratory sinus arrhythmia by VV may be used to improve the recoupling of organic systems
McMullen et al.⁽²⁰20 McMullen MC, Girling LG, Graham MR, Mutch WA. Biologically variable ventilation improves oxygenation and respiratory mechanics during one-lung ventilation. Anesthesiology. 2006;105(1):91-7.⁾	G1 = 8 animals G2 = 8 animals	Pigs (25 - 30kg) subjected to selective MV in the dependent lung for 90 minutes and for another 60 minutes after the restoration of ventilation in both lungs	To compare VV with CV in terms of gas exchange and pulmonary mechanics during selective ventilation and after ARM and the reestablishment of ventilation in both lungs	G1: CV (TV of 12mL/kg; RR of 20rpm; PEEP of 5cmH₂O) G2: VV (algorithm of variability of RR and TV to ensure the V_min of CV)	In the selective ventilation model, VV improved gas exchange and respiratory mechanics compared with CV. A better static compliance in VV persisted with the restoration of ventilation in both lungs
Mutch et al.⁽²¹21 Mutch WA, Buchman TG, Girling LG, Walker EK, McManus BM, Graham MR. Biologically variable ventilation improves gas exchange and respiratory mechanics in a model of severe bronchospasm. Crit Care Med. 2007;35(7):1749-55.⁾	G1 = 9 animals G2 = 9 animals	Pigs (25 - 30kg) with bronchospasm ventilated for 4 hours	To compare VV with CV in terms of gas exchange, respiratory mechanics, CO₂ exhalation, and inflammatory cytokines in the bronchoalveolar lavage fluid	G1: CV (TV of 10mL/kg) G2: VV (variable RR and TV to maintain a constant V_min)	VV performed better than CV in terms of gas exchange and respiratory mechanics during severe bronchospasm but without significant differences regarding inflammatory cytokines
Spieth et al.⁽²²22 Spieth PM, Carvalho AR, Pelosi P, Hoehn C, Meissner C, Kasper M, et al. Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury. Am J Respir Crit Care Med. 2009;179(8):684-93.⁾	G1 = 9 animals G2 = 9 animals G3 = 9 animals G4 = 9 animals	Pigs (23.8 - 37kg) with ARDS ventilated for 6 hours	To determine the impact of VV on pulmonary function and its effect on pulmonary parenchyma compared with conventional protective MV strategies	G1: CV - ARDSnet⁽¹⁶16 Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-8.⁾ G2: VV - ARDSnet⁽¹⁶16 Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-8.⁾ (variable TV) G3: CV - OLA⁽²³23 Amato MB, Barbas CS, Medeiros DM, Schettino GP, Lorenzi Filho G, Kairalla RA, et al. Beneficial effects of the ''open lung approach'' with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med. 1995;152(6 Pt 1):1835-46.⁾ G4: VV - OLA⁽²³23 Amato MB, Barbas CS, Medeiros DM, Schettino GP, Lorenzi Filho G, Kairalla RA, et al. Beneficial effects of the ''open lung approach'' with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med. 1995;152(6 Pt 1):1835-46.⁾ (variable TV)	The use of variable TV improved respiratory function and reduced histologic damage during MV according to ARDSnet and OLA protocols without increasing pulmonary inflammation and mechanical stress
Spieth et al.⁽²⁴24 Spieth PM, Carvalho AR, Güldner A, Kasper M, Schubert R, Carvalho NC, et al. Pressure support improves oxygenation and lung protection compared to pressure-controlled ventilation and is further improved by random variation of pressure support. Crit Care Med. 2011;39(4):746-55.⁾	G1 = 8 animals G2 = 8 animals G3 = 8 animals	Pigs (27.2 - 37kg) with ARDS ventilated for 6 hours	To test whether PAV and variable PSV improved oxygenation and reduced the lung damage associated with MV compared with PCV and whether variable PSV further improved oxygenation and reduced lung lesions compared with conventional PSV	G1: CV - (PCV; RR to achieve a pH > 7.25; TV of approximately 6mL/kg, PEEP of 8cmH₂O) G2: CV - (PSV - free RR, TV of approximately 6mL/kg, PEEP of 8cmH₂O) G3: VV - (variable PSV - support pressure with a variation of 30% to achieve a TV of approximately 6mL/kg)	PSV and variable PSV reduced lung injury and inflammation and improved gas exchange in relation to protective PCV. Variable PSV further improved oxygenation and reduced inspiratory effort with less alveolar edema and inflammatory infiltration compared to conventional PSV
Ruth Graham et al.⁽²⁵25 Ruth Graham M, Goertzen AL, Girling LG, Friedman T, Pauls RJ, Dickson T, et al. Quantitative computed tomography in porcine lung injury with variable versus conventional ventilation: Recruitment and surfactant replacement. Crit Care Med. 2011;39(7):1721-30.⁾	G1 = 6 animals G2 = 8 animals G3 = 6 animals G4 = 8 animals	Pigs (10 - 15kg) with ARDS ventilated for 4 hours	To test whether aeration, gas exchange, and pulmonary mechanics were improved when administration of the surfactant was combined with VV	G1: CV (RR of 30rpm; TV of 7.5mL/kg, PEEP of 10cmH₂O) G2: CV with surfactant replacement G3: VV (variable RR and TV) G4: VV with surfactant replacement	Isolated VV was more effective in reestablishing gas exchange and pulmonary mechanics and had a positive effect on lung recruitment
Graham et al.⁽²⁶26 Graham MR, Gulati H, Kha L, Girling LG, Goertzen A, Mutch WA. Resolution of pulmonary edema with variable mechanical ventilation in a porcine model of acute lung injury. Can J Anesth. 2011;58(8):740-50.⁾	G1 = 8 animals G2 = 8 animals	Pigs (22 - 30kg) with ARDS ventilated for 4 hours	To test whether alveolar recruitment and periodic breathing with low TV, as observed with VV, increased the resolution of edema in ARDS	G1: CV (TV < 7.5mL/kg, PEEP of 10cmH₂O; fixed V_min) G2: VV (variable RR with reciprocal changes in TV to maintain a V_min; PEEP of 10cmH₂O)	The CT suggested that the beneficial redistribution and enhanced clearance of pulmonary edema contributed to the beneficial effects of VV
Pillow et al.⁽²⁷27 Pillow JJ, Musk GC, McLean CM, Polglase GR, Dalton RG, Jobe AH, et al. Variable ventilation improves ventilation and lung compliance in preterm lambs. Intensive Care Med. 2011;37(8):1352-9.⁾	G1 = 7 animals G2 = 9 animals G3 = 9 animals	Premature lambs with 129 days of gestation ventilated for 2 hours	To test whether VV improved arterial oxygenation, ventilatory efficiency, and lung compliance	G1: CV (PRVC - TV of 11mL/kg; RR of 50rpm; maximum peak inspiratory pressure of 40cmH₂O) G2: VV (variable TV and RR to maintain the V_min of CV) G3: CG (without the use of MV)	VV improved lung compliance and ventilatory efficiency compared with CV
Carvalho et al.⁽²⁸28 Carvalho AR, Spieth PM, Güldner A, Cuevas M, Carvalho NC, Beda A, et al. Distribution of regional lung aeration and perfusion during conventional and noisy pressure support ventilation in experimental lung injury. J Appl Physiol (1985). 2011;110(4):1083-92.⁾	12 animals	Pigs (33.1 - 46.6Kg) with ARDS ventilated for 1 hour in each mode	To evaluate the effect of PSV and variable PSV compared to PCV in the regional distribution of aeration, reaeration, and current hyperinflation, and the distribution of ventilation and pulmonary blood flow	CV - (PCV - TV ≈ 6mL/kg; RR to maintain pH > 7.3; PEEP of 8cmH₂O) CV - (PSV - TV ≈ 6mL/kg; free RR; PEEP of 8cmH₂O) VV - (variable PSV - support pressure with 20% variation to achieve a TV of ≈ 6mL/kg)	PSV and variable PSV improved oxygenation and intrapulmonary shunting compared with PCV. Compared with PSV, variable PSV redistributed the perfusion of caudal to cranial zones, further improving oxygenation
Spieth et al.⁽²⁹29 Spieth PM, Güldner A, Beda A, Carvalho N, Nowack T, Krause A, et al. Comparative effects of proportional assist and variable pressure support ventilation on lung function and damage in experimental lung injury. Crit Care Med. 2012;40(9):2654-61.⁾	G1 = 8 animals G2 = 8 animals G3 = 8 animals	Pigs (26.8 - 34.4kg) with ARDS ventilated for 6 hours	To determine the effect of PAV, variable PSV, and conventional PSV on lung function, respiratory pattern, and lung damage	G1: CV - (PAV - assisted flux of 60%; assisted TV adjusted to achieve a target TV of ≈ 6mL/kg) G2: CV - (PSV - support pressure configured to reach a TV of ≈ 6mLkg) G3: VV - (variable PSV - support pressure with a variation of 30% to achieve a TV of approximately 6mL/kg)	PAV and variable PSV increased the variability of TV and improved the oxygenation and venous mixture without affecting the patient-ventilator synchrony or lung injury compared with conventional PSV. PSV and variable PSV reduced the inspiratory effort compared with PAV
Thammanomai et al.⁽³⁰30 Thammanomai A, Hamakawa H, Bartolák-Suki E, Suki B. Combined effects of ventilation mode and positive end-expiratory pressure on mechanics, gas exchange and the epithelium in mice with acute lung injury. PLoS One. 2013;8(1):e53934.⁾	G1 = 8 animals G2 = 8 animals G3 = 8 animals G4 = 8 animals	Rats (22 - 26g) with ARDS	To investigate the combined effects of ventilation modes and PEEP on pulmonary mechanics, gas exchange, and lung biology, including surfactant and epithelial cell integrity, at two PEEP levels	G1: CV (TV of 8mL/kg; RR of 240rpm) with PEEP of 3 and 6cmH₂O. G2: CV with sighs (large ventilations, two every minute) with PEEP of 3 and 6cmH₂O G3: New VV (variable RR and TV - minimum, peak, and maximum volumes - to maintain the V_min of CV) with PEEP of 3 and 6cmH₂O G4: CG (received only the initial ventilation after lung injury) with PEEP of 3 and 6cmH₂O	PEEP had a significant effect on the performance of all the ventilation modes. The higher PEEP protected the lung from collapse and reduced tissue heterogeneity. However, the lower PEEP better protected the epithelium and had a positive effect on the surfactant, particularly during VV
Samary et al.⁽³¹1 Ivanov PC, Amaral LA, Goldberger AL, Havlin S, Rosenblum MG, Struzik ZR, et al. Multifractality in human heartbeat dynamics. Nature. 1999;399(6735):461-5.⁾	G1 = 12 animals G2 = 12 animals	Wistar rats (365 ± 55g) with pulmonary and extrapulmonary ARDS ventilated for 1 hour	To compare VV with CV	G1: CV (VCV - TV 6mL/kg, PEEP of 5cmH₂O) G2: VV (VCV - variable TV, coefficient of variation of 30%; PEEP of 5cmH₂O)	VV improved lung function in both groups. However, VV had further beneficial effects on biological markers in pulmonary ARDS than in extrapulmonary ARDS

Author	Sample (N)	Sample characteristics	Objective	Intervention	Conclusion
Boker et al.⁽³²32 Boker A, Haberman CJ, Girling L, Guzman RP, Louridas G, Tanner JR, et al. Variable ventilation improves perioperative lung function in patients undergoing abdominal aortic aneurysmectomy. Anesthesiology. 2004;100(3):608-16.⁾	G1 = 21 patients G2 = 20 patients	Patients who underwent elective aneurysmectomy of the abdominal aorta	To compare CV with VV for pulmonary gas exchange, respiratory mechanics, and radiological evidence of atelectasis	G1: CV (TV of 10mL/kg; RR of 10rpm; PEEP of 0cmH₂O; FiO₂ of 0.6). G2: VV (mode with a volume divider - changes in RR resulted in reciprocal changes in TV to maintain the V_min of CV)	VV significantly improved lung function compared with CV
Spieth et al.⁽³³33 Spieth PM, Güldner A, Huhle R, Beda A, Bluth T, Schreiter D, et al. Short-term effects of noisy pressure support ventilation in patients with acute hypoxemic respiratory failure. Crit Care. 2013;17(5):R261.⁾	13 patients	Patients with acute hypoxemic respiratory failure who underwent ventilation with conventional PSV and variable PSV for 1 hour each, at random	To compare variable PSV with conventional PSV in terms of pulmonary function and improved patient comfort	Conventional PSV - spontaneous RR; support pressure to achieve a TV of ≈ 8mL/kg; PEEP and FiO₂ in accordance with current therapy. Variable PSV - support pressure with a variation of 30% to achieve a TV of ≈ 8mL/kg	Variable PSV proved to be safe and feasible compared with conventional PSV; it increased the variability of TV and improved patient-ventilator synchrony, but the rate of gas exchange was similar for the two techniques.
Wang et al.⁽³⁴34 Wang R, Chen J, Wu G. Variable lung protective mechanical ventilation decreases incidence of postoperative delirium and cognitive dysfunction during open abdominal surgery. Int J Clin Exp Med. 2015;8(11):21208-14.⁾	G1 = 83 patients G2 = 79 patients	Older patients subjected to elective resection of gastrointestinal tumor via laparotomy lasting more than 2 hours	To compare two protective MV strategies for cognitive dysfunction during the postoperative period in elderly patients 1 week after open abdominal surgery	G1: CV (VCV - TV of 8mL/kg; RR to reach normocapnia; PEEP of 5cmH₂O; FiO₂ of 0.35). G2: VV (VCV - TV of ≈ 8mL/kg with random cycle-to-cycle variation of 30%).	VV versus protective CV decreased the incidence of delirium and cognitive dysfunction in the postoperative period by reducing the systemic proinflammatory response

Variable mechanical ventilation
Benefits
Improved gas exchange (experimental evidence⁽⁹9 Thammanomai A, Hueser LE, Majumdar A, Bartolák-Suki E, Suki B. Design of a new variable-ventilation method optimized for lung recruitment in mice. J Appl Physiol (1995). 2008;104(5):1329-40.^,¹¹11 Bellardine CL, Hoffman AM, Tsai L, Ingenito EP, Arold SP, Lutchen KR, et al. Comparison of variable and conventional ventilation in a sheep saline lavage lung injury model. Crit Care Med. 2006;34(2):439-45. 12 Mutch WA, Eschun GM, Kowalski SE, Graham MR, Girling LG, Lefevre GR. Biologically variable ventilation prevents deterioration of gas exchange during prolonged anaesthesia. Br J Anaesth. 2000;84(2):197-203. 13 Mutch WA, Harms S, Lefevre GR, Graham MR, Girling LG, Kowalski SE. Biologically variable ventilation increases arterial oxygenation over that seen with positive end-expiratory pressure alone in a porcine model of acute respiratory distress syndrome. Crit Care Med. 2000;28(7):2457-64. 14 Arold SP, Mora R, Lutchen KR, Ingenito EP, Suki B. Variable tidal volume ventilation improves lung mechanics and gas exchange in a rodent model of acute lung injury. Am J Respir Crit Care Med. 2002;165(3):366-71.^-¹⁵15 Boker A, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, et al. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002;165(4):456-62.^,¹⁷17 Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003;285(2):L370-5.^,¹⁸18 Funk DJ, Graham MR, Girling LG, Thliveris JA, McManus BM, Walker EK, et al. A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury. Respir Res. 2004;5:22.^,²⁰20 McMullen MC, Girling LG, Graham MR, Mutch WA. Biologically variable ventilation improves oxygenation and respiratory mechanics during one-lung ventilation. Anesthesiology. 2006;105(1):91-7. 21 Mutch WA, Buchman TG, Girling LG, Walker EK, McManus BM, Graham MR. Biologically variable ventilation improves gas exchange and respiratory mechanics in a model of severe bronchospasm. Crit Care Med. 2007;35(7):1749-55.^-²²22 Spieth PM, Carvalho AR, Pelosi P, Hoehn C, Meissner C, Kasper M, et al. Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury. Am J Respir Crit Care Med. 2009;179(8):684-93.^,²⁴24 Spieth PM, Carvalho AR, Güldner A, Kasper M, Schubert R, Carvalho NC, et al. Pressure support improves oxygenation and lung protection compared to pressure-controlled ventilation and is further improved by random variation of pressure support. Crit Care Med. 2011;39(4):746-55.^,²⁵25 Ruth Graham M, Goertzen AL, Girling LG, Friedman T, Pauls RJ, Dickson T, et al. Quantitative computed tomography in porcine lung injury with variable versus conventional ventilation: Recruitment and surfactant replacement. Crit Care Med. 2011;39(7):1721-30.^,²⁸28 Carvalho AR, Spieth PM, Güldner A, Cuevas M, Carvalho NC, Beda A, et al. Distribution of regional lung aeration and perfusion during conventional and noisy pressure support ventilation in experimental lung injury. J Appl Physiol (1985). 2011;110(4):1083-92. 29 Spieth PM, Güldner A, Beda A, Carvalho N, Nowack T, Krause A, et al. Comparative effects of proportional assist and variable pressure support ventilation on lung function and damage in experimental lung injury. Crit Care Med. 2012;40(9):2654-61. 30 Thammanomai A, Hamakawa H, Bartolák-Suki E, Suki B. Combined effects of ventilation mode and positive end-expiratory pressure on mechanics, gas exchange and the epithelium in mice with acute lung injury. PLoS One. 2013;8(1):e53934.^-³¹31 Samary CS, Moraes L, Santos CL, Huhle R, Santos RS, Ornellas DS, et al. Lung Functional and Biologic Responses to Variable Ventilation in Experimental Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome. Crit Care Med. 2016;44(7):e553-62.⁾ and clinical evidence⁽³²32 Boker A, Haberman CJ, Girling L, Guzman RP, Louridas G, Tanner JR, et al. Variable ventilation improves perioperative lung function in patients undergoing abdominal aortic aneurysmectomy. Anesthesiology. 2004;100(3):608-16.⁾)
Improved respiratory mechanics (experimental evidence⁽⁹9 Thammanomai A, Hueser LE, Majumdar A, Bartolák-Suki E, Suki B. Design of a new variable-ventilation method optimized for lung recruitment in mice. J Appl Physiol (1995). 2008;104(5):1329-40.^,¹¹11 Bellardine CL, Hoffman AM, Tsai L, Ingenito EP, Arold SP, Lutchen KR, et al. Comparison of variable and conventional ventilation in a sheep saline lavage lung injury model. Crit Care Med. 2006;34(2):439-45.^,¹³13 Mutch WA, Harms S, Lefevre GR, Graham MR, Girling LG, Kowalski SE. Biologically variable ventilation increases arterial oxygenation over that seen with positive end-expiratory pressure alone in a porcine model of acute respiratory distress syndrome. Crit Care Med. 2000;28(7):2457-64. 14 Arold SP, Mora R, Lutchen KR, Ingenito EP, Suki B. Variable tidal volume ventilation improves lung mechanics and gas exchange in a rodent model of acute lung injury. Am J Respir Crit Care Med. 2002;165(3):366-71.^-¹⁵15 Boker A, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, et al. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002;165(4):456-62.^,¹⁸18 Funk DJ, Graham MR, Girling LG, Thliveris JA, McManus BM, Walker EK, et al. A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury. Respir Res. 2004;5:22.^,¹⁹19 Mutch WA, Graham MR, Girling LG, Brewster JF. Fractal ventilation enhances respiratory sinus arrhythmia. Respir Res. 2005;6:41.^,²²22 Spieth PM, Carvalho AR, Pelosi P, Hoehn C, Meissner C, Kasper M, et al. Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury. Am J Respir Crit Care Med. 2009;179(8):684-93.^,²⁴24 Spieth PM, Carvalho AR, Güldner A, Kasper M, Schubert R, Carvalho NC, et al. Pressure support improves oxygenation and lung protection compared to pressure-controlled ventilation and is further improved by random variation of pressure support. Crit Care Med. 2011;39(4):746-55. 25 Ruth Graham M, Goertzen AL, Girling LG, Friedman T, Pauls RJ, Dickson T, et al. Quantitative computed tomography in porcine lung injury with variable versus conventional ventilation: Recruitment and surfactant replacement. Crit Care Med. 2011;39(7):1721-30.^-²⁶26 Graham MR, Gulati H, Kha L, Girling LG, Goertzen A, Mutch WA. Resolution of pulmonary edema with variable mechanical ventilation in a porcine model of acute lung injury. Can J Anesth. 2011;58(8):740-50.^,³⁰30 Thammanomai A, Hamakawa H, Bartolák-Suki E, Suki B. Combined effects of ventilation mode and positive end-expiratory pressure on mechanics, gas exchange and the epithelium in mice with acute lung injury. PLoS One. 2013;8(1):e53934.⁾ and clinical evidence⁽³²32 Boker A, Haberman CJ, Girling L, Guzman RP, Louridas G, Tanner JR, et al. Variable ventilation improves perioperative lung function in patients undergoing abdominal aortic aneurysmectomy. Anesthesiology. 2004;100(3):608-16.⁾)
Improved the ventilation-to-perfusion ratio (experimental evidence⁽¹³13 Mutch WA, Harms S, Lefevre GR, Graham MR, Girling LG, Kowalski SE. Biologically variable ventilation increases arterial oxygenation over that seen with positive end-expiratory pressure alone in a porcine model of acute respiratory distress syndrome. Crit Care Med. 2000;28(7):2457-64.^,¹⁵15 Boker A, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, et al. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002;165(4):456-62.^,¹⁸18 Funk DJ, Graham MR, Girling LG, Thliveris JA, McManus BM, Walker EK, et al. A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury. Respir Res. 2004;5:22.^,²²22 Spieth PM, Carvalho AR, Pelosi P, Hoehn C, Meissner C, Kasper M, et al. Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury. Am J Respir Crit Care Med. 2009;179(8):684-93.^,²⁵25 Ruth Graham M, Goertzen AL, Girling LG, Friedman T, Pauls RJ, Dickson T, et al. Quantitative computed tomography in porcine lung injury with variable versus conventional ventilation: Recruitment and surfactant replacement. Crit Care Med. 2011;39(7):1721-30.^,²⁸28 Carvalho AR, Spieth PM, Güldner A, Cuevas M, Carvalho NC, Beda A, et al. Distribution of regional lung aeration and perfusion during conventional and noisy pressure support ventilation in experimental lung injury. J Appl Physiol (1985). 2011;110(4):1083-92.^,²⁹29 Spieth PM, Güldner A, Beda A, Carvalho N, Nowack T, Krause A, et al. Comparative effects of proportional assist and variable pressure support ventilation on lung function and damage in experimental lung injury. Crit Care Med. 2012;40(9):2654-61.^,³⁵35 Mutch WA, Harms S, Ruth Graham M, Kowalski SE, Girling LG, Lefevre GR. Biologically variable or naturally noisy mechanical ventilation recruits atelectatic lung. Am J Respir Crit Care Med. 2000;162(1):319-23.⁾)
Released surfactant (experimental evidence⁽¹⁷17 Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003;285(2):L370-5.⁾)
Reduced the inflammatory response (experimental evidence⁽¹⁵15 Boker A, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, et al. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002;165(4):456-62.^,¹⁷17 Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003;285(2):L370-5.^,²⁴24 Spieth PM, Carvalho AR, Güldner A, Kasper M, Schubert R, Carvalho NC, et al. Pressure support improves oxygenation and lung protection compared to pressure-controlled ventilation and is further improved by random variation of pressure support. Crit Care Med. 2011;39(4):746-55.⁾ and clinical evidence⁽³⁴34 Wang R, Chen J, Wu G. Variable lung protective mechanical ventilation decreases incidence of postoperative delirium and cognitive dysfunction during open abdominal surgery. Int J Clin Exp Med. 2015;8(11):21208-14.⁾)
Reduced lung injury (experimental evidence⁽¹¹11 Bellardine CL, Hoffman AM, Tsai L, Ingenito EP, Arold SP, Lutchen KR, et al. Comparison of variable and conventional ventilation in a sheep saline lavage lung injury model. Crit Care Med. 2006;34(2):439-45.^,¹⁷17 Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003;285(2):L370-5.^,²²22 Spieth PM, Carvalho AR, Pelosi P, Hoehn C, Meissner C, Kasper M, et al. Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury. Am J Respir Crit Care Med. 2009;179(8):684-93.⁾)
Improved patient-ventilator synchrony (clinical evidence⁽³³33 Spieth PM, Güldner A, Huhle R, Beda A, Bluth T, Schreiter D, et al. Short-term effects of noisy pressure support ventilation in patients with acute hypoxemic respiratory failure. Crit Care. 2013;17(5):R261.⁾)
Knowledge gaps
Clinical studies that use randomized controlled clinical trials in different clinical settings, including patients with and without acute pulmonary impairment

[1] Corresponding author: Gilberto Friedman, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Pneumológicas da Universidade Federal do Rio Grande do Sul, Rua Fernandes Vieira, 181 - Bom Fim, Zip code: 90035-091 - Porto Alegre (RS), Brazil, E-mail: gfriedman@hcpa.edu.br

Brasil

Brasil

Variable mechanical ventilation

ABSTRACT

Objective:

Methods:

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Conclusion: