Comparison of different degrees of variability in tidal volume to prevent deterioration of respiratory system elastance in experimental acute lung inflammation

Kiss, Thomas; Silva, Pedro L.; Huhle, Robert; Moraes, Lillian; Santos, Rodrigues dos; Felix, Nathane Santanna; Santos, Carlos Antônio Cabral; Morales, Marcelo M.; Capelozzi, Vera Luíza; Kasper, Michael; Pelosi, Paolo; Abreu, Marcelo Gama de; Rocco, Patricia R. M.

doi:10.1093/bja/aew093

Cited by 34 publications

(38 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, different aspects of the pneumonia model, including functional, structural, and ultrastructural features, the inflammatory response, and the potential for translocation of bacteria during mechanical ventilation, were characterized in detail (Additional file 1: Figure S1, Tables S1, S2, and S3). We chose a CV of 30% in V T because this level of variability has been shown to improve lung function [8, 23] and reduce lung damage in direct ARDS in rats [8], as well as other species [9, 24–27]. Additionally, controls with i.t.…”

Section: Discussionmentioning

confidence: 99%

Variable ventilation improves pulmonary function and reduces lung damage without increasing bacterial translocation in a rat model of experimental pneumonia

et al. 2016

View full text Add to dashboard Cite

BackgroundVariable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (VT) and airway pressures might worsen the impairment of alveolar barrier function usually seen in pneumonia and could increase bacterial translocation into the bloodstream. We investigated the impact of variable ventilation on lung function and histologic damage, as well as markers of lung inflammation, epithelial and endothelial cell damage, and alveolar stress, and bacterial translocation in experimental pneumonia.MethodsThirty-two Wistar rats were randomly assigned to receive intratracheal of Pseudomonas aeruginosa (PA) or saline (SAL) (n = 16/group). After 24-h, animals were anesthetized and ventilated for 2 h with either conventional volume-controlled (VCV) or variable volume-controlled ventilation (VV), with mean VT = 6 mL/kg, PEEP = 5cmH2O, and FiO2 = 0.4. During VV, tidal volume varied randomly with a coefficient of variation of 30% and a Gaussian distribution. Additional animals assigned to receive either PA or SAL (n = 8/group) were not ventilated (NV) to serve as controls.ResultsIn both SAL and PA, VV improved oxygenation and lung elastance compared to VCV. In SAL, VV decreased interleukin (IL)-6 expression compared to VCV (median [interquartile range]: 1.3 [0.3–2.3] vs. 5.3 [3.6–7.0]; p = 0.02) and increased surfactant protein-D expression compared to NV (2.5 [1.9–3.5] vs. 1.2 [0.8–1.2]; p = 0.0005). In PA, compared to VCV, VV reduced perivascular edema (2.5 [2.0–3.75] vs. 6.0 [4.5–6.0]; p < 0.0001), septum neutrophils (2.0 [1.0–4.0] vs. 5.0 [3.3–6.0]; p = 0.0008), necrotizing vasculitis (3.0 [2.0–5.5] vs. 6.0 [6.0–6.0]; p = 0.0003), and ultrastructural lung damage scores (16 [14–17] vs. 24 [14–27], p < 0.0001). Blood colony-forming-unit (CFU) counts were comparable (7 [0–28] vs. 6 [0–26], p = 0.77). Compared to NV, VCV, but not VV, increased expression amphiregulin, IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-1 (2.1 [1.6–2.5] vs. 0.9 [0.7–1.2], p = 0.025; 12.3 [7.9–22.0] vs. 0.8 [0.6–1.9], p = 0.006; and 4.4 [2.9–5.6] vs. 0.9 [0.8–1.4], p = 0.003, respectively). Angiopoietin-2 expression was lower in VV compared to NV animals (0.5 [0.3–0.8] vs. 1.3 [1.0–1.5], p = 0.01).ConclusionIn this rat model of pneumonia, VV improved pulmonary function and reduced lung damage as compared to VCV, without increasing bacterial translocation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0476-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Variable ventilation improves pulmonary function and reduces lung damage without increasing bacterial translocation in a rat model of experimental pneumonia

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Variable ventilation mimics the physiological fluctuation of tidal volume observed in resting subjects (Tobin et al, 1988; Frey et al, 1998), and compared to conventional protective, but non-variable mechanical ventilation, has been associated with better lung mechanics (Gama de Abreu et al, 2008; Spieth et al, 2009), reduced lung damage (Spieth et al, 2009; Kiss et al, 2016; Samary et al, 2016), and, ultimately, better mechanotransduction at the alveolar-capillary membrane level in experimental lung injury induced by surfactant depletion through saline lavage (Spieth et al, 2009), acid aspiration (Ma et al, 2011), and endotoxin (Samary et al, 2016). However, to date, no study has compared the biological impact of VV vs. conventional protective volume-controlled ventilation (VCV) mode in ARDS induced by lung ischemia-reperfusion.…”

Section: Introductionmentioning

confidence: 99%

Variable Ventilation Improved Respiratory System Mechanics and Ameliorated Pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion

et al. 2017

View full text Add to dashboard Cite

Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV (n = 6/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmH2O, fraction of inspired oxygen (FiO2) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated VT values (n = 1200; mean VT = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH20/ml and 2.0 ± 0.8 cmH20/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9–33.1] and VV 5.4% [3.1–8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.

show abstract

“…Current clinical ventilators, however, only utilize conventional ventilation (CV) in which both the delivered tidal volume and respiratory rate are fixed. On the other hand, VV provides physiological variation in tidal volumes and breathing frequencies on a breath-by-breath basis, which, in a mathematical model predicted to improve recruitment of atelectatic lung regions 23 , confirmed later by many animal studies [24][25][26][27][28][29][30][31][32][33][34][35][36][37] . Hence, with a distinct amplitude and frequency at each breath, the lung is exposed to multiple frequencies and tidal volumes surrounding those of natural breathing without the requirement of additional equipment.…”

mentioning

confidence: 79%

“…First, the study was administered when patients were in a stable condition and VV was always preceded by CV. Therefore, while statistically speaking improvement and deterioration would be equally likely, all 5 patients showed a decrease in both R and E. Second, previous studies provided evidence of improvement in lung mechanics, gas exchange, as well as reduction in ventilator-induced lung injury following VV compared to CV in both healthy and injured lungs of many animal models including pigs, mice, rats, and sheep [24][25][26][27][28][29][30][31][32][33][34][35][36][37] . Clinically, VV was also shown to improve gas exchange and respiratory mechanics 53 , improve patient-ventilator synchrony 54 , and reduce inflammatory response 55 .…”

Section: Human Clinical Trial Frommentioning

confidence: 92%

Tracking respiratory mechanics around natural breathing rates via variable ventilation

Jawde

Walkey

Majumdar

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Measuring respiratory resistance and elastance as a function of time, tidal volume, respiratory rate, and positive end-expiratory pressure can guide mechanical ventilation. However, current measurement techniques are limited since they are assessed intermittently at non-physiological frequencies or involve specialized equipment. to this end, we introduce ZVV, a practical approach to continuously track resistance and elastance during Variable Ventilation (VV), in which frequency and tidal volume vary from breath-to-breath. ZVV segments airway pressure and flow recordings into individual breaths, calculates resistance and elastance for each breath, bins them according to frequency or tidal volume and plots the results against bin means. ZVV's feasibility was assessed clinically in five human patients with acute lung injury, experimentally in five mice ventilated before and after lavage injury, and computationally using a viscoelastic respiratory model. ZVV provided continuous measurements in both settings, while the computational study revealed <2% estimation errors. Our findings support ZVV as a feasible technique to assess respiratory mechanics under physiological conditions. Additionally, in humans, ZVV detected a decrease in resistance and elastance with time by 12.8% and 6.2%, respectively, suggesting that VV can improve lung recruitment in some patients and can therefore potentially serve both as a dual diagnostic and therapeutic tool.Respiratory resistance (R) and elastance (E) in mechanically ventilated patients relate to disease severity and progression, and patient response to treatment or changes in ventilator settings 1-3 . The manner in which R and E vary with frequency can reflect lung heterogeneity, a sensitive indicator of pathology 4 . Thus, a technique that can continuously and reliably assess R and E at physiological frequencies and tidal volumes (V T 's) could advance the treatment of mechanically ventilated patients. For example, increases in R can reveal bronchospasm 5 or a blocked endotracheal tube 6,7 , while increases in E can reflect pulmonary edema and alveolar derecruitment 8,9 . Tracking continuously R and E including their frequency dependencies could improve patient management via detection of airway obstruction in asthma, or optimization of mechanical ventilator settings for preventing ventilation-induced lung injury 10-15 .Nevertheless, estimates of R and E are rarely performed in clinical practice 16 , likely due to current strategies of intermittent end inspiratory occlusion measurements that require deep patient sedation or paralysis or the need for specialized equipment 10,17 . In order to adjust ventilation settings, clinicians are currently guided by gas exchange parameters, breath-to-breath peak pressures, and plateau pressures 16,[18][19][20] . However, these measures lack the ability to reveal whether abnormalities in mechanics are related to altered R or E and often require a heavily sedated or paralyzed patient 9,21 . The limitations in measuring R and E are not only pres...

show abstract

Comparison of different degrees of variability in tidal volume to prevent deterioration of respiratory system elastance in experimental acute lung inflammation

Abstract: In this model of acute lung inflammation, a VT variability of 30%, compared with 15 and 7.5%, was necessary to avoid deterioration of respiratory system elastance and was not associated with lung histological damage.

Cited by 34 publications

References 30 publications

Variable ventilation improves pulmonary function and reduces lung damage without increasing bacterial translocation in a rat model of experimental pneumonia

Variable ventilation improves pulmonary function and reduces lung damage without increasing bacterial translocation in a rat model of experimental pneumonia

Variable Ventilation Improved Respiratory System Mechanics and Ameliorated Pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion

Tracking respiratory mechanics around natural breathing rates via variable ventilation

Contact Info

Product

Resources

About