Positive End-expiratory Pressure and Mechanical Power.

BACKGROUND: Positive end-expiratory pressure is usually considered protective against ventilation-induced lung injury by reducing atelectrauma and improving lung homogeneity. However, positive end-expiratory pressure, together with tidal volume, gas flow, and respiratory rate, contributes to the mechanical power required to ventilate the lung. This study aimed at investigating the effects of increasing mechanical power by selectively modifying its positive end-expiratory pressure component. METHODS: Thirty-six healthy piglets (23.3 ± 2.3 kg) were ventilated prone for 50 h at 30 breaths/min and with a tidal volume equal to functional residual capacity. Positive end-expiratory pressure levels (0, 4, 7, 11, 14, and 18 cm H2O) were applied to six groups of six animals. Respiratory, gas exchange, and hemodynamic variables were recorded every 6 h. Lung weight and wet-to-dry ratio were measured, and histologic samples were collected. RESULTS: Lung mechanical power was similar at 0 (8.8 ± 3.8 J/min), 4 (8.9 ± 4.4 J/min), and 7 (9.6 ± 4.3 J/min) cm H2O positive end-expiratory pressure, and it linearly increased thereafter from 15.5 ± 3.6 J/min (positive end-expiratory pressure, 11 cm H2O) to 18.7 ± 6 J/min (positive end-expiratory pressure, 14 cm H2O) and 22 ± 6.1 J/min (positive end-expiratory pressure, 18 cm H2O). Lung elastances, vascular congestion, atelectasis, inflammation, and septal rupture decreased from zero end-expiratory pressure to 4 to 7 cm H2O (P < 0.0001) and increased progressively at higher positive end-expiratory pressure. At these higher positive end-expiratory pressure levels, striking hemodynamic impairment and death manifested (mortality 0% at positive end-expiratory pressure 0 to 11 cm H2O, 33% at 14 cm H2O, and 50% at 18 cm H2O positive end-expiratory pressure). From zero end-expiratory pressure to 18 cm H2O, mean pulmonary arterial pressure (from 19.7 ± 5.3 to 32.2 ± 9.2 mmHg), fluid administration (from 537 ± 403 to 2043 ± 930 ml), and noradrenaline infusion (0.04 ± 0.09 to 0.34 ± 0.31 µg · kg(-1) · min(-1)) progressively increased (P < 0.0001). Lung weight and lung wet-to-dry ratios were not significantly different across the groups. The lung mechanical power level that best discriminated between more versus less severe damage was 13 ± 1 J/min. CONCLUSIONS: Less than 7 cm H2O positive end-expiratory pressure reduced atelectrauma encountered at zero end-expiratory pressure. Above a defined power threshold, sustained positive end-expiratory pressure contributed to potentially lethal lung damage and hemodynamic impairment.

Extracorporeal CO2 Removal: The Minimally Invasive Approach, Theory, and Practice.

OBJECTIVES: Minimally invasive extracorporeal CO2 removal is an accepted supportive treatment in chronic obstructive pulmonary disease patients. Conversely, the potential of such technique in treating acute respiratory distress syndrome patients remains to be investigated. The aim of this study was: 1) to quantify membrane lung CO2 removal (VCO2ML) under different conditions and 2) to quantify the natural lung CO2 removal (VCO2NL) and to what extent mechanical ventilation can be reduced while maintaining total expired CO2 (VCO2tot = VCO2ML + VCO2NL) and arterial PCO2 constant. DESIGN: Experimental animal study. SETTING: Department of Experimental Animal Medicine, University of Göttingen, Germany. SUBJECTS: Eight healthy pigs (57.7 ± 5 kg). INTERVENTIONS: The animals were sedated, ventilated, and connected to the artificial lung system (surface 1.8 m, polymethylpentene membrane, filling volume 125 mL) through a 13F catheter. VCO2ML was measured under different combinations of inflow PCO2 (38.9 ± 3.3, 65 ± 5.7, and 89.9 ± 12.9 mm Hg), extracorporeal blood flow (100, 200, 300, and 400 mL/min), and gas flow (4, 6, and 12 L/min). At each setting, we measured VCO2ML, VCO2NL, lung mechanics, and blood gases. MEASUREMENTS AND MAIN RESULTS: VCO2ML increased linearly with extracorporeal blood flow and inflow PCO2 but was not affected by gas flow. The outflow PCO2 was similar regardless of inflow PCO2 and extracorporeal blood flow, suggesting that VCO2ML was maximally exploited in each experimental condition. Mechanical ventilation could be reduced by up to 80-90% while maintaining a constant PaCO2. CONCLUSIONS: Minimally invasive extracorporeal CO2 removal removes a relevant amount of CO2 thus allowing mechanical ventilation to be significantly reduced depending on extracorporeal blood flow and inflow PCO2. Extracorporeal CO2 removal may provide the physiologic prerequisites for controlling ventilator-induced lung injury.

Reclassifying Acute Respiratory Distress Syndrome.

RATIONALE: The ratio of PaO2 to FiO2 (P/F) defines acute respiratory distress syndrome (ARDS) severity and suggests appropriate therapies. OBJECTIVES: We investigated 1) whether a 150-mm-Hg P/F threshold within the range of moderate ARDS (100-200 mm Hg) would define two subgroups that were more homogeneous; and 2) which criteria led the clinicians to apply extracorporeal membrane oxygenation (ECMO) in severe ARDS. METHODS: At the 150-mm-Hg P/F threshold, moderate patients were split into mild-moderate (n = 50) and moderate-severe (n = 55) groups. Patients with severe ARDS (FiO2 not available in three patients) were split into higher (n = 63) and lower (n = 18) FiO2 groups at an 80% FiO2 threshold. MEASUREMENTS AND MAIN RESULTS: Compared with mild-moderate ARDS, patients with moderate-severe ARDS had higher peak pressures, PaCO2, and pH. They also had heavier lungs, greater inhomogeneity, more noninflated tissue, and greater lung recruitability. Within 84 patients with severe ARDS (P/F < 100 mm Hg), 75% belonged to the higher FiO2 subgroup. They differed from the patients with severe ARDS with lower FiO2 only in PaCO2 and lung weight. Forty-one of 46 patients treated with ECMO belonged to the higher FiO2 group. Within this group, the patients receiving ECMO had higher PaCO2 than the 22 non-ECMO patients. The inhomogeneity ratio, total lung weight, and noninflated tissue were also significantly higher. CONCLUSIONS: Using the 150-mm-Hg P/F threshold gave a more homogeneous distribution of patients with ARDS across the severity subgroups and identified two populations that differed in their anatomical and physiological characteristics. The patients treated with ECMO belonged to the severe ARDS group, and almost 90% of them belonged to the higher FiO2 subgroup.

Effects of regional perfusion block in healthy and injured lungs.

BACKGROUND: Severe hypoperfusion can cause lung damage. We studied the effects of regional perfusion block in normal lungs and in the lungs that had been conditioned by lavage with 500 ml saline and high V T (20 ml kg-1) ventilation. METHODS: Nineteen pigs (61.2 ± 2.5 kg) were randomized to five groups: controls (n = 3), the right lower lobe block alone (n = 3), lavage and high V T (n = 4), lung lavage, and high V T plus perfusion block of the right (n = 5) or left (n = 4) lower lobe. Gas exchange, respiratory mechanics, and hemodynamics were measured hourly. After an 8-h observation period, CT scans were obtained at 0 and 15 cmH2O airway pressure. RESULTS: Perfusion block did not damage healthy lungs. In conditioned lungs, the left perfusion block caused more edema in the contralateral lung (777 ± 62 g right lung vs 484 ± 204 g left; p < 0.05) than the right perfusion block did (581 ± 103 g right lung vs 484 ± 204 g left; p n.s.). The gas/tissue ratio, however, was similar (0.5 ± 0.3 and 0.8 ± 0.5; p n.s.). The lobes with perfusion block were not affected (gas/tissue ratio right 1.6 ± 0.9; left 1.7 ± 0.5, respectively). Pulmonary artery pressure, PaO2/FiO2, dead space, and lung mechanics were more markedly affected in animals with left perfusion block, while the gas/tissue ratios were similar in the non-occluded lobes. CONCLUSIONS: The right and left perfusion blocks caused the same "intensity" of edema in conditioned lungs. The total amount of edema in the two lungs differed because of differences in lung size. If capillary permeability is altered, increased blood flow may induce or increase edema.

Driving pressure and mechanical power: new targets for VILI prevention.

Several factors have been recognized as possible triggers of ventilator-induced lung injury (VILI). The first is pressure (thus the 'barotrauma'), then the volume (hence the 'volutrauma'), finally the cyclic opening-closing of the lung units ('atelectrauma'). Less attention has been paid to the respiratory rate and the flow, although both theoretical considerations and experimental evidence attribute them a significant role in the generation of VILI. The initial injury to the lung parenchyma is necessarily mechanical and it could manifest as an unphysiological distortion of the extracellular matrix and/or as micro-fractures in the hyaluronan, likely the most fragile polymer embedded in the matrix. The order of magnitude of the energy required to break a molecular bond between the hyaluronan and the associated protein is 1.12×10-16 Joules (J), 70-90% higher than the average energy delivered by a single breath of 1L assuming a lung elastance of 10 cmH2O/L (0.5 J). With a normal statistical distribution of the bond strength some polymers will be exposed each cycle to an energy large enough to rupture. Both the extracellular matrix distortion and the polymer fractures lead to inflammatory increase of capillary permeability with edema if a pulmonary blood flow is sufficient. The mediation analysis of higher vs. lower tidal volume and PEEP studies suggests that the driving pressure, more than tidal volume, is the best predictor of VILI, as inferred by increased mortality. This is not surprising, as both tidal volume and respiratory system elastance (resulting in driving pressure) may independently contribute to the mortality. For the same elastance driving pressure is a predictor similar to plateau pressure or tidal volume. Driving pressure is one of the components of the mechanical power, which also includes respiratory rate, flow and PEEP. Finding the threshold for mechanical power would greatly simplify assessment and prevention of VILI.

Positive end-expiratory pressure: how to set it at the individual level.

The positive end-expiratory pressure (PEEP), since its introduction in the treatment of acute respiratory failure, up to the 1980s was uniquely aimed to provide a viable oxygenation. Since the first application, a large debate about the criteria for selecting the PEEP levels arose within the scientific community. Lung mechanics, oxygen transport, venous admixture thresholds were all proposed, leading to PEEP recommendations from 5 up to 25 cmH2O. Throughout this period, the main concern was the hemodynamics. This paradigm changed during the 1980s after the wide acceptance of atelectrauma as one of the leading causes of ventilator induced lung injury. Accordingly, the PEEP aim shifted from oxygenation to lung protection. In this framework, the prevention of lung opening and closing became an almost unquestioned dogma. Consequently, as PEEP keeps open the pulmonary units opened during the previous inspiratory phase, new methods were designed to identify the 'optimal' PEEP during the expiratory phase. The open lung approach requires that every collapsed unit potentially openable is opened and maintained open. The methods to assess the recruitment are based on imaging (computed tomography, electric impedance tomography, ultrasound) or mechanically-driven gas exchange modifications. All the latest assume that whatever change in respiratory system compliance is due to changes in lung compliance, which in turn is uniquely function of the recruitment. Comparative studies, however, showed that the only possible approach to measure the amount of collapsed tissue regaining inflation is the CT scan. In fact, all the other methods estimate as recruitment the gas entry in pulmonary units already open at lower PEEP, but increasing their compliance at higher PEEP. Since higher PEEP is usually more indicated (also for oxygenation) when the recruitability is higher, as occurs with increasing severity, a meaningful PEEP selection requires the assessment of recruitment. The Berlin definition may help in this assessment.

The future of mechanical ventilation: lessons from the present and the past.

The adverse effects of mechanical ventilation in acute respiratory distress syndrome (ARDS) arise from two main causes: unphysiological increases of transpulmonary pressure and unphysiological increases/decreases of pleural pressure during positive or negative pressure ventilation. The transpulmonary pressure-related side effects primarily account for ventilator-induced lung injury (VILI) while the pleural pressure-related side effects primarily account for hemodynamic alterations. The changes of transpulmonary pressure and pleural pressure resulting from a given applied driving pressure depend on the relative elastances of the lung and chest wall. The term 'volutrauma' should refer to excessive strain, while 'barotrauma' should refer to excessive stress. Strains exceeding 1.5, corresponding to a stress above ~20 cmH2O in humans, are severely damaging in experimental animals. Apart from high tidal volumes and high transpulmonary pressures, the respiratory rate and inspiratory flow may also play roles in the genesis of VILI. We do not know which fraction of mortality is attributable to VILI with ventilation comparable to that reported in recent clinical practice surveys (tidal volume ~7.5 ml/kg, positive end-expiratory pressure (PEEP) ~8 cmH2O, rate ~20 bpm, associated mortality ~35%). Therefore, a more complete and individually personalized understanding of ARDS lung mechanics and its interaction with the ventilator is needed to improve future care. Knowledge of functional lung size would allow the quantitative estimation of strain. The determination of lung inhomogeneity/stress raisers would help assess local stresses; the measurement of lung recruitability would guide PEEP selection to optimize lung size and homogeneity. Finding a safety threshold for mechanical power, normalized to functional lung volume and tissue heterogeneity, may help precisely define the safety limits of ventilating the individual in question. When a mechanical ventilation set cannot be found to avoid an excessive risk of VILI, alternative methods (such as the artificial lung) should be considered.