Spontaneous breathing activity in acute lung injury and acute respiratory distress syndrome

Abstract PURPOSE OF REVIEW: We aimed at providing the most recent and relevant evidence regarding spontaneous breathing activity during mechanical ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical and experimental data are depicted. RECENT FINDINGS: The use of unsupported spontaneous breathing has been associated with the most beneficial effects reported to date, but recent data favors also pressure-supported breathing activity in experimental ALI. In patients with ALI/ARDS, unsupported spontaneous breathing in combination with mandatory cycles has been shown to improve lung function, reduce the need for sedation and cardiocirculatory drug therapy, and speed weaning, with no effect on mortality. On the other hand, strong clinical evidence shows that the use of neuromuscular blocking agents in the first 48\u200ah of mechanical ventilation with the volume assist-control ventilation mode reduces morbidity and mortality in severe ARDS compared to placebo. SUMMARY: In our opinion, spontaneous breathing activity should be avoided in the first 48\u200ah of mechanical ventilation in patients with severe ARDS (PaO2/FIO2 <120\u200ammHg), but it may be useful in less severe ARDS and ALI. Clearly, further clinical and experimental investigations on the use of different ventilation modes of supported/unsupported spontaneous breathing in ALI/ARDS are needed

Spontaneous breathing in mild and moderate versus severe acute respiratory distress syndrome.

This review summarizes the most recent clinical and experimental data on the impact of spontaneous breathing in acute respiratory distress syndrome (ARDS). RECENT FINDINGS: Spontaneous breathing during assisted as well as nonassisted modes of mechanical ventilation improves lung function and reduces lung damage in mild and moderate ARDS. New modes of assisted mechanical ventilation with improved patient ventilator interaction and enhanced variability of the respiratory pattern offer additional benefit on lung function and damage. However, data supporting an outcome benefit of spontaneous breathing in ARDS, even in its mild and moderate forms, are missing. In contrast, controlled mechanical ventilation with muscle paralysis in the first 48\u200ah of severe ARDS has been shown to improve survival, as compared with placebo. Currently, it is unclear whether ventilator settings, rather than the severity of lung injury, determine the potential of spontaneous breathing for benefit or harm. SUMMARY: Clinical and experimental studies show that controlled mechanical ventilation with muscle paralysis in the early phase of severe ARDS reduces lung injury and even mortality. At present, spontaneous breathing should be avoided in the early phase of severe ARDS, but considered in mild-to-moderate ARDS

Higher Levels of Spontaneous Breathing Induce Lung Recruitment and Reduce Global Stress/Strain in Experimental Lung Injury.

Spontaneous breathing (SB) in the early phase of the acute respiratory distress syndrome is controversial. Biphasic positive airway pressure/airway pressure release ventilation (BIPAP/APRV) is commonly used, but the level of SB necessary to maximize potential beneficial effects is unknown. METHODS:: Experimental acute respiratory distress syndrome was induced by saline lung lavage in anesthetized and mechanically ventilated pigs (n = 12). By using a Latin square and crossover design, animals were ventilated with BIPAP/APRV at four different levels of SB in total minute ventilation (60\u2009min each): (1) 0% (BIPAP/APRV0%); (2) greater than 0 to 30% (BIPAP/APRV>0-30%); (3) greater than 30 to 60% (BIPAP/APRV>30-60%); and (4) greater than 60% (BIPAP/APRV>60%). Gas exchange, hemodynamics, and respiratory variables were measured. Lung aeration was assessed by high-resolution computed tomography. The distribution of perfusion was marked with Ga-labeled microspheres and evaluated by positron emission tomography. RESULTS:: The authors found that higher levels of SB during BIPAP/APRV (1) improved oxygenation; (2) decreased mean transpulmonary pressure (stress) despite increased inspiratory effort; (3) reduced nonaerated lung tissue, with minimal changes in the distribution of perfusion, resulting in decreased low aeration/perfusion zones; and (4) decreased global strain (mean \ub1 SD) (BIPAP/APRV0%: 1.39\u2009\ub1\u20090.08; BIPAP/APRV0-30%: 1.33\u2009\ub1\u20090.03; BIPAP/APRV30-60%: 1.27\u2009\ub1\u20090.06; BIPAP/APRV>60%: 1.25\u2009\ub1\u20090.04, P 60% vs. BIPAP/APRV0-30%). CONCLUSIONS:: In a saline lung lavage model of experimental acute respiratory distress syndrome in pigs, levels of SB during BIPAP/APRV higher than currently recommended for clinical practice, that is, 10 to 30%, improve oxygenation by increasing aeration in dependent lung zones without relevant redistribution of perfusion. In presence of lung recruitment, higher levels of SB reduce global stress and strain despite an increase in inspiratory effort

Pressure support improves oxygenation and lung protection compared to pressure-controlled ventilation and is further improved by random variation of pressure support

To explore whether 1) conventional pressure support ventilation improves lung function and attenuates the pulmonary inflammatory response compared to pressure-controlled ventilation and 2) random variation of pressure support levels (noisy pressure support ventilation) adds further beneficial effects to pressure support ventilation. DESIGN: Three-arm, randomized, experimental study. SETTING: University hospital research facility. SUBJECTS: Twenty-four juvenile pigs. INTERVENTIONS: Acute lung injury was induced by surfactant depletion. Animals were randomly assigned to 6 hrs of mechanical ventilation (n = 8 per group) with either 1) pressure-controlled ventilation, 2) pressure support ventilation, or 3) noisy pressure support ventilation. During noisy pressure support ventilation, the pressure support varied randomly, with values following a normal distribution. In all groups, the driving pressures were set to achieve a mean tidal volume of 6 mL/kg. At the end of experiments, animals were killed and lungs extracted for histologic and biochemical analysis. MEASUREMENTS AND MAIN RESULTS: Respiratory, gas-exchange, and hemodynamics variables were assessed hourly. The diffuse alveolar damage and the inflammatory response of lungs were quantified. Pressure support ventilation and noisy pressure support ventilation improved gas exchange and were associated with reduced histologic damage and interleukin-6 concentrations in lung tissue compared to pressure-controlled ventilation. Noisy pressure support ventilation further improved gas exchange and decreased the inspiratory effort while reducing alveolar edema and inflammatory infiltration compared to pressure support ventilation. CONCLUSIONS: In this model of acute lung injury, pressure support ventilation and noisy pressure support ventilation attenuated pulmonary inflammatory response and improved gas exchange as compared to pressure-controlled ventilation. Noisy pressure support ventilation further improved gas exchange, reduced the inspiratory effort, and attenuated alveolar edema and inflammatory infiltration as compared to conventional pressure support ventilation

Comparative effects of proportional assist and variable pressure support ventilation on lung function and damage in experimental lung injury*

To investigate the effects of proportional assist ventilation, variable pressure support, and conventional pressure support ventilation on lung function and damage in experimental acute lung injury. DESIGN: : Randomized experimental study. SETTING: University hospital research facility. SUBJECTS: : Twenty-four juvenile pigs. INTERVENTIONS: Pigs were anesthetized, intubated, and mechanically ventilated. Acute lung injury was induced by saline lung lavage. After resuming of spontaneous breathing, animals were randomly assigned to 6 hrs of assisted ventilation with pressure support ventilation, proportional assist ventilation, or variable pressure support (n = 8 per group). Mean tidal volume was kept at 486 mL/kg in all modes. MEASUREMENTS AND MAIN RESULTS: Lung functional parameters, distribution of ventilation by electrical impedance tomography, and breathing patterns were analyzed. Histological lung damage and pulmonary inflammatory response were determined postmortem. Variable -pressure support and proportional assist ventilation improved oxygenation and venous admixture compared with pressure support ventilation. Proportional assist ventilation led to higher esophageal pressure time product than variable pressure support and pressure support ventilation, and redistributed ventilation from central to dorsal lung regions compared to pressure support ventilation. Variable pressure support and proportional assist ventilation yielded higher tidal volume variability than pressure support ventilation. Such pattern was deterministic (self-organized) during proportional assist ventilation and stochastic (random) during variable pressure support. Subject-ventilator synchrony as well as pulmonary inflammatory response and damage did not differ among groups. CONCLUSIONS: In a lung lavage model of acute lung injury, both variable pressure support and proportional assist ventilation increased the variability of tidal volume and improved oxygenation and venous admixture, without influencing subject-ventilator synchrony or affecting lung injury compared with pressure support ventilation. However, variable pressure support yielded less inspiratory effort than proportional assist ventilation at comparable mean tidal volumes of 6 mL/kg

Higher Levels of Spontaneous Breathing Reduce Lung Injury in Experimental Moderate Acute Respiratory Distress Syndrome

OBJECTIVES:: To assess the effects of different levels of spontaneous breathing during biphasic positive airway pressure/airway pressure release ventilation on lung function and injury in an experimental model of moderate acute respiratory distress syndrome. DESIGN:: Multiple-arm randomized experimental study. SETTING:: University hospital research facility. SUBJECTS:: Thirty-six juvenile pigs. INTERVENTIONS:: Pigs were anesthetized, intubated, and mechanically ventilated. Moderate acute respiratory distress syndrome was induced by repetitive saline lung lavage. Biphasic positive airway pressure/airway pressure release ventilation was conducted using the airway pressure release ventilation mode with an inspiratory/expiratory ratio of 1:1. Animals were randomly assigned to one of four levels of spontaneous breath in total minute ventilation (n = 9 per group, 6 hr each): 1) biphasic positive airway pressure/airway pressure release ventilation, 0%; 2) biphasic positive airway pressure/airway pressure release ventilation, &gt; 0-30%; 3) biphasic positive airway pressure/airway pressure release ventilation, &gt; 30-60%, and 4) biphasic positive airway pressure/airway pressure release ventilation, &gt; 60%. MEASUREMENTS AND MAIN RESULTS:: The inspiratory effort measured by the esophageal pressure time product increased proportionally to the amount of spontaneous breath and was accompanied by improvements in oxygenation and respiratory system elastance. Compared with biphasic positive airway pressure/airway pressure release ventilation of 0%, biphasic positive airway pressure/airway pressure release ventilation more than 60% resulted in lowest venous admixture, as well as peak and mean airway and transpulmonary pressures, redistributed ventilation to dependent lung regions, reduced the cumulative diffuse alveolar damage score across lungs (median [interquartile range], 11 [3-40] vs 18 [2-69]; p &lt; 0.05), and decreased the level of tumor necrosis factor-\u3b1 in ventral lung tissue (median [interquartile range], 17.7 pg/mg [8.4-19.8] vs 34.5 pg/mg [29.9-42.7]; p &lt; 0.05). Biphasic positive airway pressure/airway pressure release ventilation more than 0-30% and more than 30-60% showed a less consistent pattern of improvement in lung function, inflammation, and damage compared with biphasic positive airway pressure/airway pressure release ventilation more than 60%. CONCLUSIONS:: In this model of moderate acute respiratory distress syndrome in pigs, biphasic positive airway pressure/airway pressure release ventilation with levels of spontaneous breath higher than usually seen in clinical practice, that is, more than 30% of total minute ventilation, reduced lung injury with improved respiratory function, as compared with protective controlled mechanical ventilatio

Short-term effects of noisy pressure support ventilation in patients with acute hypoxemic respiratory failure

ABSTRACT: Introduction: This study aims at comparing the very short-term effects of conventional and noisy (variable) pressure support ventilation (PSV) in mechanically ventilated patients with acute hypoxemic respiratory failure. Methods: 13 mechanically ventilated patients with acute hypoxemic respiratory failure were enrolled in this monocentric, randomized crossover study. Patients were mechanically ventilated with conventional and noisy PSV, for one hour each, in random sequence. Pressure support was titrated to reach tidal volumes [almost equal to]8 mL/kg in both modes. The level of positive end-expiratory pressure and fraction of inspired oxygen were kept unchanged in both modes. The coefficient of variation of pressure support during noisy PSV was set at 30%. Gas exchange, hemodynamics, lung functional parameters, distribution of ventilation by electrical impedance tomography, breathing patterns and patient-ventilator synchrony were analyzed. Results: Noisy PSV was not associated with any adverse event, and was well tolerated by all patients. Gas exchange, hemodynamics, respiratory mechanics and spatial distribution of ventilation did not differ significantly between conventional and noisy PSV. Noisy PSV increased the variability of tidal volume (24.4 +/- 7.8% vs. 13.7 +/- 9.1%, P < 0.05) and was associated with a reduced number of asynchrony events compared to conventional PSV (5 [0--15]/30 min vs. 10 [1--37]/30 min, P < 0.05). Conclusions: In the very short term, noisy PSV proved safe and feasible in patients with acute hypoxemic respiratory failure. Compared to conventional PSV, noisy PSV increased the variability of tidal volumes, and was associated with improved patient-ventilator synchrony, at comparable levels of gas exchang

Variable versus conventional lung protective mechanical ventilation during open abdominal surgery (PROVAR): a randomised controlled trial

Background: Experimental studies showed that controlled variable ventilation (CVV) yielded better pulmonary function compared to non-variable ventilation (CNV) in injured lungs. We hypothesized that CVV improves intraoperative and postoperative respiratory function in patients undergoing open abdominal surgery. Methods: Fifty patients planned for open abdominal surgery lasting &gt;3 h were randomly assigned to receive either CVV or CNV. Mean tidal volumes and PEEP were set at 8 ml kg 121 (predicted body weight) and 5 cm H2O, respectively. In CVV, tidal volumes varied randomly, following a normal distribution, on a breath-by-breath basis. The primary endpoint was the forced vital capacity (FVC) on postoperative Day 1. Secondary endpoints were oxygenation, non-aerated lung volume, distribution of ventilation, and pulmonary and extrapulmonary complications until postoperative Day 5. Results: FVC did not differ significantly between CVV and CNV on postoperative Day 1, 61.5 (standard deviation 22.1) % vs 61.9 (23.6) %, respectively; mean [95% confidence interval (CI)] difference, 120.4 ( 1213.2\u201314.0), P=0.95. Intraoperatively, CVV did not result in improved respiratory function, haemodynamics, or redistribution of ventilation compared to CNV. Postoperatively, FVC, forced expiratory volume at the first second (FEV1), and FEV1/FVC deteriorated, while atelectasis volume and plasma levels of interleukin-6 and interleukin-8 increased, but values did not differ between groups. The incidence of postoperative pulmonary and extrapulmonary complications was comparable in CVV and CNV. Conclusions: In patients undergoing open abdominal surgery, CVV did not improve intraoperative and postoperative respiratory function compared with CNV

Modulation of Stress versus Time Product during Mechanical Ventilation Influences Inflammation as Well as Alveolar Epithelial and Endothelial Response in Rats

BACKGROUND:: Mechanical ventilation can lead to lung biotrauma when mechanical stress exceeds safety thresholds. The authors investigated whether the duration of mechanical stress, that is, the impact of a stress versus time product (STP), influences biotrauma. The authors hypothesized that higher STP levels are associated with increased inflammation and with alveolar epithelial and endothelial cell injury. METHODS:: In 46 rats, Escherichia coli lipopolysaccharide (acute lung inflammation) or saline (control) was administered intratracheally. Both groups were protectively ventilated with inspiratory-to-expiratory ratios 1:2, 1:1, or 2:1 (n = 12 each), corresponding to low, middle, and high STP levels (STPlow, STPmid, and STPhigh, respectively). The remaining 10 animals were not mechanically ventilated. RESULTS:: In animals with mild acute lung inflammation, but not in controls: (1) messenger RNA expression of interleukin-6 was higher in STPhigh (28.1\u2009\ub1\u200913.6; mean \ub1 SD) and STPlow (28.9\u2009\ub1\u200916.0) versus STPmid (7.4\u2009\ub1\u20097.5) (P < 0.05); (2) expression of the receptor for advanced glycation end-products was increased in STPhigh (3.6\u2009\ub1\u20091.6) versus STPlow (2.3\u2009\ub1\u20091.1) (P < 0.05); (3) alveolar edema was decreased in STPmid (0 [0 to 0]; median, Q1 to Q3) compared with STPhigh (0.8 [0.6 to 1]) (P < 0.05); and (4) expressions of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 were higher in STPlow (3.0\u2009\ub1\u20091.8) versus STPhigh (1.2\u2009\ub1\u20090.5) and STPmid (1.4\u2009\ub1\u20090.7) (P < 0.05), respectively. CONCLUSIONS:: In the mild acute lung inflammation model used herein, mechanical ventilation with inspiratory-to-expiratory of 1:1 (STPmid) minimized lung damage, whereas STPhigh increased the gene expression of biological markers associated with inflammation and alveolar epithelial cell injury and STPlow increased markers of endothelial cell damag