Peter M. Spieth

Variable Tidal Volumes Improve Lung Protective Ventilation Strategies in Experimental Lung Injury

RATIONALE Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. OBJECTIVES To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. METHODS In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). MEASUREMENTS AND MAIN RESULTS Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. CONCLUSIONS Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

Noisy pressure support ventilation: A pilot study on a new assisted ventilation mode in experimental lung injury*

Objective:To describe and evaluate the effects of the new noisy pressure support ventilation (noisy PSV) on lung physiologic variables. Design:Crossover design with four modes of mechanical ventilation. Setting:Experimental research facility of a university hospital. Subjects:A total of 12 pigs weighing 25.0–36.5 kg. Interventions:Animals were anesthetized, the trachea was intubated, and lungs were ventilated with a mechanical ventilator (volume-controlled mode). Acute lung injury was then induced by surfactant depletion. Biphasic intermittent airway pressure/airway pressure release ventilation (BIPAP/APRV) was initiated, and anesthesia depth was decreased to allow spontaneous breathing. After that, each animal was ventilated with four different modes of assisted mechanical ventilation (1 hr each, Latin squares sequence): 1) PSV, 2) PSV combined with intermittent sighs (PSV + Sighs), 3) BIPAP/APRV + spontaneous breathing, and 4) noisy PSV with random variation of pressure support (normal distribution). The mean level of pressure support was set identical in all PSV forms. Measurements and Main Results:We found that noisy PSV increased tidal volume variability compared with PSV and PSV + Sighs (19% vs. 5% and 7%, respectively, p < .05) independently from the inspiratory effort; improved oxygenation and reduced venous admixture but did not affect the amount of nonaerated lung tissue as compared with other assisted ventilation modes; reduced mean airway pressure at comparable minute ventilation; redistributed pulmonary blood flow toward nondependent lung regions similar to other PSV forms, whereas BIPAP/APRV + spontaneous breathing did not; and reduced the inspiratory effort and cardiac output in comparison with BIPAP/APRV + spontaneous breathing. Conclusions:In the surfactant depletion model of acute lung injury, the new noisy PSV increased the variability of the respiratory pattern and improved oxygenation by a redistribution of perfusion toward the ventilated nondependent lung regions with simultaneous lower mean airway pressure, comparable minute ventilation, and no increase in the inspiratory effort or cardiac output.

Intraoperative protective mechanical ventilation for prevention of postoperative pulmonary complications: a comprehensive review of the role of tidal volume, positive end-expiratory pressure, and lung recruitment maneuvers.

Postoperative pulmonary complications are associated with increased morbidity, length of hospital stay, and mortality after major surgery. Intraoperative lung-protective mechanical ventilation has the potential to reduce the incidence of postoperative pulmonary complications. This review discusses the relevant literature on definition and methods to predict the occurrence of postoperative pulmonary complication, the pathophysiology of ventilator-induced lung injury with emphasis on the noninjured lung, and protective ventilation strategies, including the respective roles of tidal volumes, positive end-expiratory pressure, and recruitment maneuvers. The authors propose an algorithm for protective intraoperative mechanical ventilation based on evidence from recent randomized controlled trials.

Effects of Different Levels of Pressure Support Variability in Experimental Lung Injury

Background:Noisy pressure support ventilation has been reported to improve respiratory function compared to conventional assisted mechanical ventilation. We aimed at determining the optimal level of pressure support variability during noisy pressure support ventilation. Methods:Twelve pigs were anesthetized and mechanically ventilated. Acute lung injury was induced by surfactant depletion. At four levels of pressure support variability (coefficients of variation of pressure support equal to 7.5, 15, 30, and 45%, 30 min each, crossover design, special Latin squares sequence), we measured respiratory variables, gas exchange, hemodynamics, inspiratory effort, and comfort of breathing. The mean level of tidal volume was constant among variability levels. Results:Compared to conventional pressure support ventilation, different levels of variability in pressure support improved the elastance of the respiratory system, peak airway pressure, oxygenation, and intrapulmonary shunt. Oxygenation and venous admixture benefited more from intermediate (30%) levels of variability, whereas elastance and peak airway pressure improved linearly with increasing variability. Heart rate as well as mean arterial and pulmonary arterial pressures decreased slightly at intermediate to high (30–45%) levels of variability in pressure support. Inspiratory effort and comfort of breathing were not importantly influenced by increased variability in pressure support. Conclusion:In a surfactant depletion model of acute lung injury, variability of pressure support improves lung function. The variability level of 30% seems to represent a reasonable compromise to improve lung functional variables during noisy pressure support ventilation.

Mechanical stress induces lung fibrosis by epithelial–mesenchymal transition*

Objectives: Many mechanically ventilated patients with acute respiratory distress syndrome develop pulmonary fibrosis. Stresses induced by mechanical ventilation may explain the development of fibrosis by a number of mechanisms (e.g., damage the alveolar epithelium, biotrauma). The objective of this study was t test the hypothesis that mechanical ventilation plays an important role in the pathogenesis of lung fibrosis. Methods: C57BL/6 mice were randomized into four groups: healthy controls; hydrochloric acid aspiration alone; vehicle control solution followed 24 hrs later by mechanical ventilation (peak inspiratory pressure 22 cm H2O and positive end-expiratory pressure 2 cm H2O for 2 hrs); and acid aspiration followed 24 hrs later by mechanical ventilation. The animals were monitored for up to 15 days after acid aspiration. To explore the direct effects of mechanical stress on lung fibrotic formation, human lung epithelial cells (BEAS-2B) were exposed to mechanical stretch for up to 48 hrs. Measurement and Main Results: Impaired lung mechanics after mechanical ventilation was associated with increased lung hydroxyproline content, and increased expression of transforming growth factor-&bgr;, &bgr;-catenin, and mesenchymal markers (&agr;-smooth muscle actin and vimentin) at both the gene and protein levels. Expression of epithelial markers including cytokeratin-8, E-cadherin, and prosurfactant protein B decreased. Lung histology demonstrated fibrosis formation and potential epithelia–mesenchymal transition. In vitro direct mechanical stretch of BEAS-2B cells resulted in similar fibrotic and epithelia–mesenchymal transition formation. Conclusions: Mechanical stress induces lung fibrosis, and epithelia–mesenchymal transition may play an important role in mediating the ventilator-induced lung fibrosis.

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

Objectives: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.

Pressure support ventilation and biphasic positive airway pressure improve oxygenation by redistribution of pulmonary blood flow.

BACKGROUND:Spontaneous breathing (SB) activity may improve gas exchange during mechanical ventilation mainly by the recruitment of previously collapsed regions. Pressure support ventilation (PSV) and biphasic positive airway pressure (BIPAP) are frequently used modes of SB, but little is known about the mechanisms of improvement of lung function during these modes of assisted mechanical ventilation. We evaluated the mechanisms behind the improvement of gas exchange with PSV and BIPAP. METHODS:Five pigs (25–29.3 kg) were mechanically ventilated in supine position, and acute lung injury (ALI) was induced by surfactant depletion. After stabilization, BIPAP was initiated with lower continuous positive airway pressure equal to 5 cm H2O and the higher continuous positive airway pressure titrated to achieve a tidal volume between 6 and 8 mL/kg. The depth of anesthesia was reduced, and when SB represented ≥20% of total minute ventilation, PSV and BIPAP + SB were each performed for 1 h (random sequence). Whole chest helical computed tomography was performed during end-expiratory pauses and functional variables were obtained. Pulmonary blood flow (PBF) was marked with IV administered fluorescent microspheres, and spatial cluster analysis was used to determine the effects of each ventilatory mode on the distribution of PBF. RESULTS:ALI led to impairment of lung function and increase of poorly and nonaerated areas in dependent lung regions (P < 0.05). PSV and BIPAP + SB similarly improved oxygenation and reduced venous admixture compared with controlled mechanical ventilation (P < 0.05). Despite that, a significant increase of nonaerated areas in dependent regions with a concomitant decrease of normally aerated areas was observed during SB. In five of six lung clusters, redistribution of PBF from dependent to nondependent, better aerated lung regions were observed during PSV and BIPAP + SB. CONCLUSIONS:In this model of ALI, the improvements of oxygenation and venous admixture obtained during assisted mechanical ventilation with PSV and BIPAP + SB were explained by the redistribution of PBF toward nondependent lung regions rather than recruitment of dependent zones.

Mechanical ventilation-associated lung fibrosis in acute respiratory distress syndrome: a significant contributor to poor outcome.

One of the most challenging problems in critical care medicine is the management of patients with the acute respiratory distress syndrome. Increasing evidence from experimental and clinical studies suggests that mechanical ventilation, which is necessary for life support in patients with acute respiratory distress syndrome, can cause lung fibrosis, which may significantly contribute to morbidity and mortality. The role of mechanical stress as an inciting factor for lung fibrosis versus its role in lung homeostasis and the restoration of normal pulmonary parenchymal architecture is poorly understood. In this review, the authors explore recent advances in the field of pulmonary fibrosis in the context of acute respiratory distress syndrome, concentrating on its relevance to the practice of mechanical ventilation, as commonly applied by anesthetists and intensivists. The authors focus the discussion on the thesis that mechanical ventilation—or more specifically, that ventilator-induced lung injury—may be a major contributor to lung fibrosis. The authors critically appraise possible mechanisms underlying the mechanical stress–induced lung fibrosis and highlight potential therapeutic strategies to mitigate this fibrosis.

Higher levels of spontaneous breathing induce lung recruitment and reduce global stress/strain in experimental lung injury.

Background: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 min 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 68Ga-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 ± SD) (BIPAP/APRV0%: 1.39 ± 0.08; BIPAP/APRV0–30%: 1.33 ± 0.03; BIPAP/APRV30–60%: 1.27 ± 0.06; BIPAP/APRV>60%: 1.25 ± 0.04, P < 0.05 all vs. BIPAP/APRV0%, and BIPAP/APRV>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.

Circadian rhythms: From basic mechanisms to the intensive care unit

Objective:Circadian rhythms are intrinsic timekeeping mechanisms that allow for adaptation to cyclic environmental changes. Increasing evidence suggests that circadian rhythms may influence progression of a variety of diseases as well as effectiveness and toxicity of drugs commonly used in the intensive care unit. In this perspective, we provide a brief review of the molecular mechanisms of circadian rhythms and its relevance to critical care. Data Sources, Study Selection, Data Extraction, and Data Synthesis:Articles related to circadian rhythms and organ systems in normal and disease conditions were searched through the PubMed library with the goal of providing a concise review. Conclusions:Critically ill patients may be highly vulnerable to disruption of circadian rhythms as a result of the severity of their underlying diseases as well as the intensive care unit environment where noise and frequent therapeutic/diagnostic interventions take place. Further basic and clinical research addressing the importance of circadian rhythms in the context of critical care is warranted to develop a better understanding of the complex pathophysiology of critically ill patients as well as to identify novel therapeutic approaches for these patients.