Andreas Güldner

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.

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.

Distribution of regional lung aeration and perfusion during conventional and noisy pressure support ventilation in experimental lung injury

In acute lung injury (ALI), pressure support ventilation (PSV) may improve oxygenation compared with pressure-controlled ventilation (PCV), and benefit from random variation of pressure support (noisy PSV). We investigated the effects of PCV, PSV, and noisy PSV on gas exchange as well as the distribution of lung aeration and perfusion in 12 pigs with ALI induced by saline lung lavage in supine position. After injury, animals were mechanically ventilated with PCV, PSV, and noisy PSV for 1 h/mode in random sequence. The driving pressure was set to a mean tidal volume of 6 ml/kg and positive end-expiratory pressure to 8 cmH₂O in all modes. Functional variables were measured, and the distribution of lung aeration was determined by static and dynamic computed tomography (CT), whereas the distribution of pulmonary blood flow (PBF) was determined by intravenously administered fluorescent microspheres. PSV and noisy PSV improved oxygenation and reduced venous admixture compared with PCV. Mechanical ventilation with PSV and noisy PSV did not decrease nonaerated areas but led to a redistribution of PBF from dorsal to ventral lung regions and reduced tidal reaeration and hyperinflation compared with PCV. Noisy PSV further improved oxygenation and redistributed PBF from caudal to cranial lung regions compared with conventional PSV. We conclude that assisted ventilation with PSV and noisy PSV improves oxygenation compared with PCV through redistribution of PBF from dependent to nondependent zones without lung recruitment. Random variation of pressure support further redistributes PBF and improves oxygenation compared with conventional PSV.

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.

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

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 h 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 h of mechanical ventilation in patients with severe ARDS (PaO2/FIO2 <120 mmHg), 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.

Purpose of reviewThis review summarizes the most recent clinical and experimental data on the impact of spontaneous breathing in acute respiratory distress syndrome (ARDS). Recent findingsSpontaneous 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 h 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. SummaryClinical 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.

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

Objective: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 ≈6 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.

Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in Experimental Acute Respiratory Distress Syndrome.

Objective: Volutrauma and atelectrauma promote ventilator-induced lung injury, but their relative contribution to inflammation in ventilator-induced lung injury is not well established. The aim of this study was to determine the impact of volutrauma and atelectrauma on the distribution of lung inflammation in experimental acute respiratory distress syndrome. Design: Laboratory investigation. Setting: University-hospital research facility. Subjects: Ten pigs (five per group; 34.7–49.9 kg) Interventions: Animals were anesthetized and intubated, and saline lung lavage was performed. Lungs were separated with a double-lumen tube. Following lung recruitment and decremental positive end-expiratory pressure trial, animals were randomly assigned to 4 hours of ventilation of the left (ventilator-induced lung injury) lung with tidal volume of approximately 3 mL/kg and 1) high positive end-expiratory pressure set above the level where dynamic compliance increased more than 5% during positive end-expiratory pressure trial (volutrauma); or 2) low positive end-expiratory pressure to achieve driving pressure comparable with volutrauma (atelectrauma). The right (control) lung was kept on continuous positive airway pressure of 20 cm H2O, and CO2 was partially removed extracorporeally. Measurements and Main Results: Regional lung aeration, specific [18F]fluorodeoxyglucose uptake rate, and perfusion were assessed using computed and positron emission tomography. Volutrauma yielded higher [18F]fluorodeoxyglucose uptake rate in the ventilated lung compared with atelectrauma (median [interquartile range], 0.017 [0.014–0.025] vs 0.013 min–1 [0.010–0.014 min–1]; p < 0.01), mainly in central lung regions. Volutrauma yielded higher [18F]fluorodeoxyglucose uptake rate in ventilator-induced lung injury versus control lung (0.017 [0.014–0.025] vs 0.011 min–1 [0.010–0.016 min–1]; p < 0.05), whereas atelectrauma did not. Volutrauma decreased blood fraction at similar perfusion and increased normally as well as hyperaerated lung compartments and tidal hyperaeration. Atelectrauma yielded higher poorly and nonaerated lung compartments, and tidal recruitment. Driving pressure increased in atelectrauma. Conclusions: In this model of acute respiratory distress syndrome, volutrauma promoted higher lung inflammation than atelectrauma at comparable low tidal volume and lower driving pressure, suggesting that static stress and strain are major determinants of ventilator-induced lung injury.

Effects of intravascular volume replacement on lung and kidney function and damage in nonseptic experimental lung injury.

Background:Intravascular volume replacement is often required in the presence of increased pulmonary capillary leakage, for example in patients with volutrauma with major hemorrhage. In the present study, the effects of Ringer’s acetate (RA), gelatin-polysuccinate (GEL), and a modern hydroxyethyl starch (HES, 6% 130/0.42) on lung and kidney function and damage were compared in a two-hit model of acute lung injury. The authors hypothesized that GEL and HES, compared to RA: (1) reduced lung histological damage, (2) impaired kidney morphology and function. Methods:Acute lung injury was induced in 30 anesthetized pigs by tidal volumes approximately 40 ml/kg, after saline lung lavage. Protective ventilation was initiated and approximately≈25% of estimated blood volume was drawn. Animals were randomly assigned to receive RA, GEL, or HES (n = 10/group) aimed at approximately 90% of intrathoracic blood volume before blood drainage. Results:Fluid volumes were higher with RA (2,250 ± 764 ml) than GEL (704 ± 159 ml) and HES (837 ± 82 ml) (P < 0.05). Compared to RA, HES reduced diffuse alveolar damage overall, and GEL in nondependent zones only. GEL and HES yielded lower wet-to-dry ratios compared to RA (6.5 ± 0.5 and 6.5 ± 0.6 vs. 7.9 ± 0.9, respectively, P < 0.05). HES and RA resulted in less kidney damage than GEL, but kidney function did not differ significantly among groups. Compared to GEL, HES yielded lower lung elastance (55 ± 12 vs. 45 ± 13 cm H2O/l, P < 0.05) and intra-abdominal pressure (15 ± 5 vs. 11 ± 4 cm 14;H2O, P < 0.05). Conclusions:In this model of acute lung injury, intravascular volume expansion after major hemorrhage with HES yielded less lung damage than RA and less kidney damage than GEL.