Validation of a novel system to assess end-expiratory lung volume and alveolar recruitment in an ARDS model.

BACKGROUND: Personalizing mechanical ventilation requires the development of reliable bedside monitoring techniques. The multiple-breaths nitrogen washin-washout (MBNW) technique is currently available to measure end-expiratory lung volume (EELVMBNW), but the precision of the technique may be poor, with percentage errors ranging from 28 to 57%. The primary aim of the study was to evaluate the reliability of a novel MBNW bedside system using fast mainstream sensors to assess EELV in an experimental acute respiratory distress syndrome (ARDS) model, using computed tomography (CT) as the gold standard. The secondary aims of the study were: (1) to evaluate trending ability of the novel system to assess EELV; (2) to evaluate the reliability of estimated alveolar recruitment induced by positive end-expiratory pressure (PEEP) changes computed from EELVMBNW, using CT as the gold standard. RESULTS: Seven pigs were studied in 6 experimental conditions: at baseline, after experimental ARDS and during a decremental PEEP trial at PEEP 16, 12, 6 and 2 cmH2O. EELV was computed at each PEEP step by both the MBNW technique (EELVMBNW) and CT (EELVCT). Repeatability was assessed by performing replicate measurements. Alveolar recruitment between two consecutive PEEP levels after lung injury was measured with CT (VrecCT), and computed from EELV measurements (VrecMBNW) as ΔEELV minus the product of ΔPEEP by static compliance. EELVMBNW and EELVCT were significantly correlated (R2 = 0.97). An acceptable non-constant bias between methods was identified, slightly decreasing toward more negative values as EELV increased. The conversion equation between EELVMBNW and EELVCT was: EELVMBNW = 0.92 × EELVCT + 36. The 95% prediction interval of the bias amounted to ± 86 mL and the percentage error between both methods amounted to 13.7%. The median least significant change between repeated measurements amounted to 8% [CI95%: 4-10%]. EELVMBNW adequately tracked EELVCT changes over time (concordance rate amounting to 100% [CI95%: 87%-100%] and angular bias amounting to - 2° ± 10°). VrecMBNW and VrecCT were significantly correlated (R2 = 0.92). A non-constant bias between methods was identified, slightly increasing toward more positive values as Vrec increased. CONCLUSIONS: We report a new bedside MBNW technique that reliably assesses EELV in an experimental ARDS model with high precision and excellent trending ability.

Mechanical Ventilation Strategies Targeting Different Magnitudes of Collapse and Tidal Recruitment in Porcine Acid Aspiration-Induced Lung Injury.

Reducing ventilator-associated lung injury by individualized mechanical ventilation (MV) in patients with Acute Respiratory Distress Syndrome (ARDS) remains a matter of research. We randomly assigned 27 pigs with acid aspiration-induced ARDS to three different MV protocols for 24 h, targeting different magnitudes of collapse and tidal recruitment (collapse&TR): the ARDS-network (ARDSnet) group with low positive end-expiratory pressure (PEEP) protocol (permissive collapse&TR); the Open Lung Concept (OLC) group, PaO2/FiO2 >400 mmHg, indicating collapse&TR <10%; and the minimized collapse&TR monitored by Electrical Impedance Tomography (EIT) group, standard deviation of regional ventilation delay, SDRVD. We analyzed cardiorespiratory parameters, computed tomography (CT), EIT, and post-mortem histology. Mean PEEP over post-randomization measurements was significantly lower in the ARDSnet group at 6.8 ± 1.0 cmH2O compared to the EIT (21.1 ± 2.6 cmH2O) and OLC (18.7 ± 3.2 cmH2O) groups (general linear model (GLM) p < 0.001). Collapse&TR and SDRVD, averaged over all post-randomization measurements, were significantly lower in the EIT and OLC groups than in the ARDSnet group (collapse p < 0.001, TR p = 0.006, SDRVD p < 0.004). Global histological diffuse alveolar damage (DAD) scores in the ARDSnet group (10.1 ± 4.3) exceeded those in the EIT (8.4 ± 3.7) and OLC groups (6.3 ± 3.3) (p = 0.16). Sub-scores for edema and inflammation differed significantly (ANOVA p < 0.05). In a clinically realistic model of early ARDS with recruitable and nonrecruitable collapse, mechanical ventilation involving recruitment and high-PEEP reduced collapse&TR and resulted in improved hemodynamic and physiological conditions with a tendency to reduced histologic lung damage.

Recurrence plots for the assessment of patient-ventilator interactions quality during invasive mechanical ventilation.

Inappropriate patient-ventilator interactions' (PVI) quality is associated with adverse clinical consequences, such as patient anxiety/fear and increased need of sedative and paralytic agents. Thus, technological devices/tools to support the recognition and monitoring of different PVI quality are of great interest. In the present study, we investigate two tools based on a recent landmark study which applied recurrence plots (RPs) and recurrence quantification analysis (RQA) techniques in non-invasive mechanical ventilation. Our interest is in how this approach could be a daily part of critical care professionals' routine (which are not familiar with dynamical systems theory methods and concepts). Two representative time series of three typical PVI "scenarios" were selected from 6 critically ill patients subjected to invasive mechanical ventilation. First, both the (i) main signatures in RPs and the (ii) respective signals that provide the most (visually) discriminant RPs were identified. This allows one to propose a visual identification protocol for PVIs' quality through the RPs' overall aspect. Support for the effectiveness of this visual based assessment tool is given by a RQA-based assessment tool. A statistical analysis shows that both the recurrence rate and the Shannon entropy are able to identify the selected PVI scenarios. It is then expected that the development of an objective method can reliably identify PVI quality, where the results corroborate the potential of RPs/RQA in the field of respiratory pattern analysis.

Periodic Fluctuation of Tidal Volumes Further Improves Variable Ventilation in Experimental Acute Respiratory Distress Syndrome.

In experimental acute respiratory distress syndrome (ARDS), random variation of tidal volumes (VT ) during volume controlled ventilation improves gas exchange and respiratory system mechanics (so-called stochastic resonance hypothesis). It is unknown whether those positive effects may be further enhanced by periodic VT fluctuation at distinct frequencies, also known as deterministic frequency resonance. We hypothesized that the positive effects of variable ventilation on lung function may be further amplified by periodic VT fluctuation at specific frequencies. In anesthetized and mechanically ventilated pigs, severe ARDS was induced by saline lung lavage and injurious VT (double-hit model). Animals were then randomly assigned to 6 h of protective ventilation with one of four VT patterns: (1) random variation of VT (WN); (2) P04, main VT frequency of 0.13 Hz; (3) P10, main VT frequency of 0.05 Hz; (4) VCV, conventional non-variable volume controlled ventilation. In groups with variable VT , the coefficient of variation was identical (30%). We assessed lung mechanics and gas exchange, and determined lung histology and inflammation. Compared to VCV, WN, P04, and P10 resulted in lower respiratory system elastance (63 ± 13 cm H2O/L vs. 50 ± 14 cm H2O/L, 48.4 ± 21 cm H2O/L, and 45.1 ± 5.9 cm H2O/L respectively, P < 0.05 all), but only P10 improved PaO2/FIO2 after 6 h of ventilation (318 ± 96 vs. 445 ± 110 mm Hg, P < 0.05). Cycle-by-cycle analysis of lung mechanics suggested intertidal recruitment/de-recruitment in P10. Lung histologic damage and inflammation did not differ among groups. In this experimental model of severe ARDS, periodic VT fluctuation at a frequency of 0.05 Hz improved oxygenation during variable ventilation, suggesting that deterministic resonance adds further benefit to variable ventilation.

Mapping Regional Differences of Local Pressure-Volume Curves With Electrical Impedance Tomography.

OBJECTIVES: Lung-protective mechanical ventilation aims to prevent alveolar collapse and overdistension, but reliable bedside methods to quantify them are lacking. We propose a quantitative descriptor of the shape of local pressure-volume curves derived from electrical impedance tomography, for computing maps that highlight the presence and location of regions of presumed tidal recruitment (i.e., elastance decrease during inflation, pressure-volume curve with upward curvature) or overdistension (i.e., elastance increase during inflation, downward curvature). DESIGN: Secondary analysis of experimental cohort study. SETTING: University research facility. SUBJECTS: Twelve mechanically ventilated pigs. INTERVENTIONS: After induction of acute respiratory distress syndrome by hydrochloric acid instillation, animals underwent a decremental positive end-expiratory pressure titration (steps of 2 cm H2O starting from ≥ 26 cm H2O). MEASUREMENTS AND MAIN RESULTS: Electrical impedance tomography-derived maps were computed at each positive end-expiratory pressure-titration step, and whole-lung CT taken every second steps. Airway flow and pressure were recorded to compute driving pressure and elastance. Significant correlations between electrical impedance tomography-derived maps and positive end-expiratory pressure indicate that, expectedly, tidal recruitment increases in dependent regions with decreasing positive end-expiratory pressure (p < 0.001) and suggest that overdistension increases both at high and low positive end-expiratory pressures in nondependent regions (p < 0.027), supporting the idea of two different scenarios of overdistension occurrence. Significant correlations with CT measurements were observed: electrical impedance tomography-derived tidal recruitment with poorly aerated regions (r = 0.43; p < 0.001); electrical impedance tomography-derived overdistension with nonaerated regions at lower positive end-expiratory pressures and with hyperaerated regions at higher positive end-expiratory pressures (r ≥ 0.72; p < 0.003). Even for positive end-expiratory pressure levels minimizing global elastance and driving pressure, electrical impedance tomography-derived maps showed nonnegligible regions of presumed overdistension and tidal recruitment. CONCLUSIONS: Electrical impedance tomography-derived maps of pressure-volume curve shapes allow to detect regions in which elastance changes during inflation. This could promote individualized mechanical ventilation by minimizing the probability of local tidal recruitment and/or overdistension. Electrical impedance tomography-derived maps might become clinically feasible and relevant, being simpler than currently available alternative approaches.

Experimental blunt chest trauma--cardiorespiratory effects of different mechanical ventilation strategies with high positive end-expiratory pressure: a randomized controlled study.

BACKGROUND: Uncertainty persists regarding the optimal ventilatory strategy in trauma patients developing acute respiratory distress syndrome (ARDS). This work aims to assess the effects of two mechanical ventilation strategies with high positive end-expiratory pressure (PEEP) in experimental ARDS following blunt chest trauma. METHODS: Twenty-six juvenile pigs were anesthetized, tracheotomized and mechanically ventilated. A contusion was applied to the right chest using a bolt-shot device. Ninety minutes after contusion, animals were randomized to two different ventilation modes, applied for 24 h: Twelve pigs received conventional pressure-controlled ventilation with moderately low tidal volumes (VT, 8 ml/kg) and empirically chosen high external PEEP (16 cmH2O) and are referred to as the HP-CMV-group. The other group (n = 14) underwent high-frequency inverse-ratio pressure-controlled ventilation (HFPPV) involving respiratory rate of 65 breaths · min(-1), inspiratory-to-expiratory-ratio 2:1, development of intrinsic PEEP and recruitment maneuvers, compatible with the rationale of the Open Lung Concept. Hemodynamics, gas exchange and respiratory mechanics were monitored during 24 h. Computed tomography and histology were analyzed in subgroups. RESULTS: Comparing changes which occurred from randomization (90 min after chest trauma) over the 24-h treatment period, groups differed statistically significantly (all P values for group effect <0.001, General Linear Model analysis) for the following parameters (values are mean ± SD for randomization vs. 24-h): PaO2 (100% O2) (HFPPV 186 ± 82 vs. 450 ± 59 mmHg; HP-CMV 249 ± 73 vs. 243 ± 81 mmHg), venous admixture (HFPPV 34 ± 9.8 vs. 11.2 ± 3.7%; HP-CMV 33.9 ± 10.5 vs. 21.8 ± 7.2%), PaCO2 (HFPPV 46.9 ± 6.8 vs. 33.1 ± 2.4 mmHg; HP-CMV 46.3 ± 11.9 vs. 59.7 ± 18.3 mmHg) and normally aerated lung mass (HFPPV 42.8 ± 11.8 vs. 74.6 ± 10.0 %; HP-CMV 40.7 ± 8.6 vs. 53.4 ± 11.6%). Improvements occurring after recruitment in the HFPPV-group persisted throughout the study. Peak airway pressure and VT did not differ significantly. HFPPV animals had lower atelectasis and inflammation scores in gravity-dependent lung areas. CONCLUSIONS: In this model of ARDS following unilateral blunt chest trauma, HFPPV ventilation improved respiratory function and fulfilled relevant ventilation endpoints for trauma patients, i.e. restoration of oxygenation and lung aeration while avoiding hypercapnia and respiratory acidosis.

Short-term adaptations in sedentary individuals during indoor cycling clases / Adaptaciones a corto plazo en individuos sedentarios durante las clases de ciclismo indoor

Indoor cycling (IC) has recently been increasing in popularity and gaining recognition as an effective training activity. However, few studies have investigated the benefits of IC for sedentary participants, and the electrical activity of muscles during IC classes, in fitness clubs, has not been reported. The aim of this study was to compare muscle activity, heart rate (HR), and subjective effort between two groups (sedentary participants and trained teachers of the fitness club), over three IC classes. Thirty-eight volunteers were split into two groups according to their fitness status and weekly training load. Each participant completed three IC classes in a private gym over separate days. Variables were compared both between groups and within classes. Exercise intensity, assessed using the HR, was similar in both groups. The subjective perceived effort, assessed using the Borg Scale, was significantly higher in the sedentary group. However, the surface electromyographic (sEMG) data showed adaptive responses in this group after three classes. There was a trend for a gradual reduction in fatigue in sedentary participants, especially for the gluteus maximus and biceps femoris muscles, raising doubts regarding the inclusion of individuals with different training levels in the same class. The root mean square and median frequency of the sEMG data changed over the three IC classes, indicating adaptation to fatigue in the sedentary group, but not in trained participants. Thus, IC can be incorporated into protocols for sedentary individuals, but the short-term adaptation suggests that developing a specific class/ protocol for beginners might be appropriate. They could then be included in an advanced class after the third day of training (AU)

Ciclismo indoor (CI) está ganando reconocimiento y popularidad en los últimos años y pocos estudios han investigado los beneficios para los participantes sedentarios. No se han publicado estudios sobre la actividad eléctrica de los músculos que participan en las clases reales de CI. El objetivo de este estudio fue comparar el tiempo y el efecto del grupo en las variables de la actividad eléctrica muscular, frecuencia cardíaca (FC) y el esfuerzo subjetivo en ambos grupos (profesores sedentarios y entrenados en un gimnasio). Treinta y ocho voluntarios fueron divididos en dos grupos de acuerdo a su estado de entrenamiento semanal. Cada sujeto completó en días separados, tres clases CI en un gimnasio privado. Las variables se compararon entre los grupos y entre las clases. La intensidad del ejercicio que llegaron los sujetos, en términos de FC, fue similar en ambos grupos, aunque el esfuerzo subjetivo, medido por la escala de Borg, mostró diferencias signicativas en la percepción del esfuerzo entre los grupos, siendo mayor en el grupo sedentario. Sin embargo, los datos muestran respuestas sEMG adaptativas en este grupo después de tres clases. Hubo una tendencia de reducción gradual de la fatiga en sedentarios, especialmente para GM y BF, y hace cuestionable la inclusión de las personas con diferente nivel de entrenamiento en el mismo salón de clases. Los resultados mostraron que tres clases de CI llevaron a cambios de comportamiento en el RMS y en la FM, lo que indica la adaptación a la fatiga en el grupo sedentario, pero no en los entrenados. Por lo tanto, IC puede ser incorporado en los protocolos para sedentarios, pero esta adaptación a corto plazo a la fatiga sugiere la posibilidad de posibilidad de nuevos estudios, con clase / protocolo especí_co para los principiantes. Ellos podrían ser incluidos en la clase avanzada a partir del tercer día de entrenamiento (AU)

Effects of ultraprotective ventilation, extracorporeal carbon dioxide removal, and spontaneous breathing on lung morphofunction and inflammation in experimental severe acute respiratory distress syndrome.

BACKGROUND: To investigate the role of ultraprotective mechanical ventilation (UP-MV) and extracorporeal carbon dioxide removal with and without spontaneous breathing (SB) to improve respiratory function and lung protection in experimental severe acute respiratory distress syndrome. METHODS: Severe acute respiratory distress syndrome was induced by saline lung lavage and mechanical ventilation (MV) with higher tidal volume (VT) in 28 anesthetized pigs (32.8 to 52.5 kg). Animals (n = 7 per group) were randomly assigned to 6 h of MV (airway pressure release ventilation) with: (1) conventional P-MV with VT ≈6 ml/kg (P-MVcontr); (2) UP-MV with VT ≈3 ml/kg (UP-MVcontr); (3) UP-MV with VT ≈3 ml/kg and SB (UP-MVspont); and (4) UP-MV with VT ≈3 ml/kg and pressure supported SB (UP-MVPS). In UP-MV groups, extracorporeal carbon dioxide removal was used. RESULTS: The authors found that: (1) UP-MVcontr reduced diffuse alveolar damage score in dorsal lung zones (median[interquartile]) (12.0 [7.0 to 16.8] vs. 22.5 [13.8 to 40.8]), but worsened oxygenation and intrapulmonary shunt, compared to P-MVcontr; (2) UP-MVspont and UP-MVPS improved oxygenation and intrapulmonary shunt, and redistributed ventilation towards dorsal areas, as compared to UP-MVcontr; (3) compared to P-MVcontr, UP-MVcontr and UP-MVspont, UP-MVPS yielded higher levels of tumor necrosis factor-α (6.9 [6.5 to 10.1] vs. 2.8 [2.2 to 3.0], 3.6 [3.0 to 4.7] and 4.0 [2.8 to 4.4] pg/mg, respectively) and interleukin-8 (216.8 [113.5 to 343.5] vs. 59.8 [45.3 to 66.7], 37.6 [18.8 to 52.0], and 59.5 [36.1 to 79.7] pg/mg, respectively) in dorsal lung zones. CONCLUSIONS: In this model of severe acute respiratory distress syndrome, MV with VT ≈3 ml/kg and extracorporeal carbon dioxide removal without SB slightly reduced lung histologic damage, but not inflammation, as compared to MV with VT = 4 to 6 ml/kg. During UP-MV, pressure supported SB increased lung inflammation.

Liquid- and air-filled catheters without balloon as an alternative to the air-filled balloon catheter for measurement of esophageal pressure.

BACKGROUND: Measuring esophageal pressure (Pes) using an air-filled balloon catheter (BC) is the common approach to estimate pleural pressure and related parameters. However, Pes is not routinely measured in mechanically ventilated patients, partly due to technical and practical limitations and difficulties. This study aimed at comparing the conventional BC with two alternative methods for Pes measurement, liquid-filled and air-filled catheters without balloon (LFC and AFC), during mechanical ventilation with and without spontaneous breathing activity. Seven female juvenile pigs (32-42 kg) were anesthetized, orotracheally intubated, and a bundle of an AFC, LFC, and BC was inserted in the esophagus. Controlled and assisted mechanical ventilation were applied with positive end-expiratory pressures of 5 and 15 cmH2O, and driving pressures of 10 and 20 cmH2O, in supine and lateral decubitus. MAIN RESULTS: Cardiogenic noise in BC tracings was much larger (up to 25% of total power of Pes signal) than in AFC and LFC (<3%). Lung and chest wall elastance, pressure-time product, inspiratory work of breathing, inspiratory change and end-expiratory value of transpulmonary pressure were estimated. The three catheters allowed detecting similar changes in these parameters between different ventilation settings. However, a non-negligible and significant bias between estimates from BC and those from AFC and LFC was observed in several instances. CONCLUSIONS: In anesthetized and mechanically ventilated pigs, the three catheters are equivalent when the aim is to detect changes in Pes and related parameters between different conditions, but possibly not when the absolute value of the estimated parameters is of paramount importance. Due to a better signal-to-noise ratio, and considering its practical advantages in terms of easier calibration and simpler acquisition setup, LFC may prove interesting for clinical use.

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, > 0-30%; 3) biphasic positive airway pressure/airway pressure release ventilation, > 30-60%, and 4) biphasic positive airway pressure/airway pressure release ventilation, > 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 < 0.05), and decreased the level of tumor necrosis factor-α 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 < 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 ventilation.

Low-frequency heart rate variability is related to the breath-to-breath variability in the respiratory pattern.

Changes in heart rate variability (HRV) at "respiratory" frequencies (0.15-0.5 Hz) may result from changes in respiration rather than autonomic control. We now investigate if the differences in HRV power in the low-frequency (LF) band (0.05-0.15 Hz, HRV(LF)) can also be predicted by respiration variability, quantified by the fraction of tidal volume power in the LF (V(LF,n)). Three experimental protocols were considered: paced breathing, mental effort tasks, and a repeated attentional task. Significant intra- and interindividual correlations were found between changes in HRV(LF) and V(LF,n) despite all subjects having a respiratory frequency above the LF band. Respiratory parameters (respiratory period, tidal volume, and V(LF,n)) could predict up to 79% of HRV(LF) differences in some cases. This suggests that respiratory variability is another mechanism of HRV(LF) generation, which should be always monitored, assessed, and considered in the interpretation of HRV changes.

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 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 ± 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.

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.

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.

Effects of assisted and variable mechanical ventilation on cardiorespiratory interactions in anesthetized pigs.

The physiological importance of respiratory sinus arrhythmia (RSA) and cardioventilatory coupling (CVC) has not yet been fully elucidated, but these phenomena might contribute to improve ventilation/perfusion matching, with beneficial effects on gas exchange. Furthermore, decreased RSA amplitude has been suggested as an indicator of impaired autonomic control and poor clinical outcome, also during positive-pressure mechanical ventilation (MV). However, it is currently unknown how different modes of MV, including variable tidal volumes (V(T)), affect RSA and CVC during anesthesia. We compared the effects of pressure controlled (PCV) versus pressure assisted (PSV) ventilation, and of random variable versus constant V(T), on RSA and CVC in eight anesthetized pigs. At comparable depth of anesthesia, global hemodynamics, and ventilation, RSA amplitude increased from 20 ms in PCV to 50 ms in PSV (p < 0.05). CVC was detected (using proportional Shannon entropy of the interval between each inspiration onset and the previous R-peak in ECG) in two animals in PCV and seven animals in PSV. Variable V(T) did not significantly influence these phenomena. Furthermore, heart period and systolic arterial pressure oscillations were in phase during PCV but in counter-phase during PSV. At the same depth of anesthesia in pigs, PSV increases RSA amplitude and CVC compared to PCV. Our data suggest that the central respiratory drive, but not the baroreflex or the mechano-electric feedback in the heart, is the main mechanism behind the RSA increase. Hence, differences in RSA and CVC between mechanically ventilated patients might reflect the difference in ventilation mode rather than autonomic impairment. Also, since gas exchange did not increase from PCV to PSV, it is questionable whether RSA has any significance in improving ventilation/perfusion matching during MV.

Mechanical ventilation during anaesthesia: challenges and opportunities for investigating the respiration-related cardiovascular oscillations.

The vast majority of the available literature regarding cardiovascular oscillations refers to spontaneously breathing subjects. Only a few studies investigated cardiovascular oscillations, and especially respiration-related ones (RCVO), during intermittent positive pressure mechanical ventilation (IPPV) under anaesthesia. Only a handful considered assisted IPPV, in which spontaneous breathing activity is supported, rather than replaced as in controlled IPPV. In this paper, we review the current understanding of RCVO physiology during IPPV, from literature retrieved through PubMed website. In particular, we describe how during controlled IPPV under anaesthesia respiratory sinus arrhythmia appears to be generated by non-neural mechano-electric feedback in the heart (indirectly influenced by tonic sympathetic regulation of vascular tone and heart contractility) and not by phasic vagal modulation of central origin and/or baroreflex mechanisms. Furthermore, assisted IPPV differs from controlled IPPV in terms of RCVO, reintroducing significant central respiratory vagal modulation of respiratory sinus arrhythmia. This evidence indicates against applying to IPPV interpretative paradigms of RCVO derived from spontaneously breathing subjects, and against considering together IPPV and spontaneously breathing subjects for RCVO-based risk assessment. Finally, we highlight the opportunities that IPPV offers for future investigations of RCVO genesis and interactions, and we indicate several possibilities for clinical applications of RCVO during IPPV.

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.

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.

A novel adaptive control system for noisy pressure-controlled ventilation: a numerical simulation and bench test study.

PURPOSE: There is growing interest in the use of both variable and pressure-controlled ventilation (PCV). The combination of these approaches as "noisy PCV" requires adaptation of the mechanical ventilator to the respiratory system mechanics. Thus, we developed and evaluated a new control system based on the least-mean-squares adaptive approach, which automatically and continuously adjusts the driving pressure during PCV to achieve the desired variability pattern of tidal volume (V (T)). METHODS: The controller was tested during numerical simulations and with a physical model reproducing the mechanical properties of the respiratory system. We applied step changes in respiratory system mechanics and mechanical ventilation settings. The time needed to converge to the desired V (T) variability pattern after each change (t (c)) and the difference in minute ventilation between the measured and target pattern of V (T) (DeltaMV) were determined. RESULTS: During numerical simulations, the control system for noisy PCV achieved the desired variable V (T) pattern in less than 30 respiratory cycles, with limited influence of the dynamic elastance (E*) on t (c), except when E* was underestimated by >25%. We also found that, during tests in the physical model, the control system converged in <60 respiratory cycles and was not influenced by airways resistance. In all measurements, the absolute value of DeltaMV was <25%. CONCLUSION: The new control system for noisy PCV can prove useful for controlled mechanical ventilation in the intensive care unit.