Individualized versus Fixed Positive End-expiratory Pressure for Intraoperative Mechanical Ventilation in Obese Patients: A Secondary Analysis.

BACKGROUND: General anesthesia may cause atelectasis and deterioration in oxygenation in obese patients. The authors hypothesized that individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and ventilation distribution compared to fixed PEEP. METHODS: This secondary analysis included all obese patients recruited at University Hospital of Leipzig from the multicenter Protective Intraoperative Ventilation with Higher versus Lower Levels of Positive End-Expiratory Pressure in Obese Patients (PROBESE) trial (n = 42) and likewise all obese patients from a local single-center trial (n = 54). Inclusion criteria for both trials were elective laparoscopic abdominal surgery, body mass index greater than or equal to 35 kg/m2, and Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score greater than or equal to 26. Patients were randomized to PEEP of 4 cm H2O (n = 19) or a recruitment maneuver followed by PEEP of 12 cm H2O (n = 21) in the PROBESE study. In the single-center study, they were randomized to PEEP of 5 cm H2O (n = 25) or a recruitment maneuver followed by individualized PEEP (n = 25) determined by electrical impedance tomography. Primary endpoint was Pao2/inspiratory oxygen fraction before extubation and secondary endpoints included intraoperative tidal volume distribution to dependent lung and driving pressure. RESULTS: Ninety patients were evaluated in three groups after combining the two lower PEEP groups. Median individualized PEEP was 18 (interquartile range, 16 to 22; range, 10 to 26) cm H2O. Pao2/inspiratory oxygen fraction before extubation was 515 (individual PEEP), 370 (fixed PEEP of 12 cm H2O), and 305 (fixed PEEP of 4 to 5 cm H2O) mmHg (difference to individualized PEEP, 145; 95% CI, 91 to 200; P < 0.001 for fixed PEEP of 12 cm H2O and 210; 95% CI, 164 to 257; P < 0.001 for fixed PEEP of 4 to 5 cm H2O). Intraoperative tidal volume in the dependent lung areas was 43.9% (individualized PEEP), 25.9% (fixed PEEP of 12 cm H2O) and 26.8% (fixed PEEP of 4 to 5 cm H2O) (difference to individualized PEEP: 18.0%; 95% CI, 8.0 to 20.7; P < 0.001 for fixed PEEP of 12 cm H2O and 17.1%; 95% CI, 10.0 to 20.6; P < 0.001 for fixed PEEP of 4 to 5 cm H2O). Mean intraoperative driving pressure was 9.8 cm H2O (individualized PEEP), 14.4 cm H2O (fixed PEEP of 12 cm H2O), and 18.8 cm H2O (fixed PEEP of 4 to 5 cm H2O), P < 0.001. CONCLUSIONS: This secondary analysis of obese patients undergoing laparoscopic surgery found better oxygenation, lower driving pressures, and redistribution of ventilation toward dependent lung areas measured by electrical impedance tomography using individualized PEEP. The impact on patient outcome remains unclear.

Physiological mechanism and spatial distribution of increased alveolar dead-space in early ARDS: An experimental study.

BACKGROUND: We aimed to investigate the physiological mechanism and spatial distribution of increased physiological dead-space, an early marker of ARDS mortality, in the initial stages of ARDS. We hypothesized that: increased dead-space results from the spatial redistribution of pulmonary perfusion, not ventilation; such redistribution is not related to thromboembolism (ie, areas with perfusion = 0 and infinite ventilation-perfusion ratio, V ˙ / Q ˙ ), but rather to moderate shifts of perfusion increasing V ˙ / Q ˙ in non-dependent regions. METHODS: Five healthy anesthetized sheep received protective ventilation for 20 hours, while endotoxin was continuously infused. Maps of voxel-level lung ventilation, perfusion, V ˙ / Q ˙ , CO2 partial pressures, and alveolar dead-space fraction were estimated from positron emission tomography at baseline and 20 hours. RESULTS: Alveolar dead-space fraction increased during the 20 hours (+0.05, P = .031), mainly in non-dependent regions (+0.03, P = .031). This was mediated by perfusion redistribution away from non-dependent regions (-5.9%, P = .031), while the spatial distribution of ventilation did not change, resulting in increased V ˙ / Q ˙ in non-dependent regions. The increased alveolar dead-space derived mostly from areas with intermediate V ˙ / Q ˙ (0.5≤ V ˙ / Q ˙ ≤10), not areas of nearly "complete" dead-space ( V ˙ / Q ˙ >10). CONCLUSIONS: In this early ARDS model, increases in alveolar dead-space occur within 20 hours due to the regional redistribution of perfusion and not ventilation. This moderate redistribution suggests changes in the interplay between active and passive perfusion redistribution mechanisms (including hypoxic vasoconstriction and gravitational effects), not the appearance of thromboembolism. Hence, the association between mortality and increased dead-space possibly arises from the former, reflecting gas-exchange inefficiency due to perfusion heterogeneity. Such heterogeneity results from the injury and exhaustion of compensatory mechanisms for perfusion redistribution.

Individualised positive end-expiratory pressure guided by electrical impedance tomography for robot-assisted laparoscopic radical prostatectomy: a prospective, randomised controlled clinical trial.

BACKGROUND: Robot-assisted laparoscopic radical prostatectomy requires general anaesthesia, extreme Trendelenburg positioning and capnoperitoneum. Together these promote impaired pulmonary gas exchange caused by atelectasis and may contribute to postoperative pulmonary complications. In morbidly obese patients, a recruitment manoeuvre (RM) followed by individualised PEEP improves intraoperative oxygenation and end-expiratory lung volume (EELV). We hypothesised that individualised PEEP with initial RM similarly improves intraoperative oxygenation and EELV in non-obese individuals undergoing robot-assisted prostatectomy. METHODS: Forty males (age, 49-76 yr; BMI <30 kg m-2) undergoing prostatectomy received volume-controlled ventilation (tidal volume 8 ml kg-1 predicted body weight). Participants were randomised to either (1) RM followed by individualised PEEP (RM/PEEPIND) optimised using electrical impedance tomography or (2) no RM with 5 cm H2O PEEP. The primary outcome was the ratio of arterial oxygen partial pressure to fractional inspired oxygen (Pao2/Fio2) before the last RM before extubation. Secondary outcomes included regional ventilation distribution and EELV which were measured before, during, and after anaesthesia. The cardiovascular effects of RM/PEEPIND were also assessed. RESULTS: In 20 males randomised to RM/PEEPIND, the median PEEPIND was 14 cm H2O [inter-quartile range, 8-20]. The Pao2/Fio2 was 10.0 kPa higher with RM/PEEPIND before extubation (95% confidence interval [CI], 2.6-17.3 kPa; P=0.001). RM/PEEPIND increased end-expiratory lung volume by 1.49 L (95% CI, 1.09-1.89 L; P<0.001). RM/PEEPIND also improved the regional ventilation of dependent lung regions. Vasopressor and fluid therapy was similar between groups, although 13 patients randomised to RM/PEEPIND required pharmacological therapy for bradycardia. CONCLUSION: In non-obese males, an individualised ventilation strategy improved intraoperative oxygenation, which was associated with higher end-expiratory lung volumes during robot-assisted laparoscopic prostatectomy. CLINICAL TRIAL REGISTRATION: DRKS00004199 (German clinical trials registry).

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.

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.

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.

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.

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

INTRODUCTION: This study aims at comparing the very short-term effects of conventional and noisy (variable) pressure support ventilation (PSV) in mechanically ventilated patients with acute hypoxemic respiratory failure. METHODS: Thirteen mechanically ventilated patients with acute hypoxemic respiratory failure were enrolled in this monocentric, randomized crossover study. Patients were mechanically ventilated with conventional and noisy PSV, for one hour each, in random sequence. Pressure support was titrated to reach tidal volumes approximately 8 mL/kg in both modes. The level of positive end-expiratory pressure and fraction of inspired oxygen were kept unchanged in both modes. The coefficient of variation of pressure support during noisy PSV was set at 30%. Gas exchange, hemodynamics, lung functional parameters, distribution of ventilation by electrical impedance tomography, breathing patterns and patient-ventilator synchrony were analyzed. RESULTS: Noisy PSV was not associated with any adverse event, and was well tolerated by all patients. Gas exchange, hemodynamics, respiratory mechanics and spatial distribution of ventilation did not differ significantly between conventional and noisy PSV. Noisy PSV increased the variability of tidal volume (24.4 ± 7.8% vs. 13.7 ± 9.1%, P <0.05) and was associated with a reduced number of asynchrony events compared to conventional PSV (5 (0 to 15)/30 min vs. 10 (1 to 37)/30 min, P <0.05). CONCLUSIONS: In the very short term, noisy PSV proved safe and feasible in patients with acute hypoxemic respiratory failure. Compared to conventional PSV, noisy PSV increased the variability of tidal volumes, and was associated with improved patient-ventilator synchrony, at comparable levels of gas exchange. TRIAL REGISTRATION: ClinicialTrials.gov, NCT00786292.

A novel algorithm to assess the quality of 12-lead ECG recordings: validation in a real telecardiology application.

Objective. Automatic detection of Electrocardiograms (ECG) quality is fundamental to minimize costs and risks related to delayed diagnosis due to low ECG quality. Most algorithms to assess ECG quality include non-intuitive parameters. Also, they were developed using data non-representative of a real-world scenario, in terms of pathological ECGs and overrepresentation of low-quality ECG. Therefore, we introduce an algorithm to assess 12-lead ECG quality, Noise Automatic Classification Algorithm (NACA) developed in Telehealth Network of Minas Gerais (TNMG).Approach. NACA estimates a signal-to-noise ratio (SNR) for each ECG lead, where 'signal' is an estimated heartbeat template, and 'noise' is the discrepancy between the template and the ECG heartbeat. Then, clinically-inspired rules based on SNR are used to classify the ECG as acceptable or unacceptable. NACA was compared with Quality Measurement Algorithm (QMA), the winner of Computing in Cardiology Challenge 2011 (ChallengeCinC) by using five metrics: sensitivity (Se), specificity (Sp), positive predictive value (PPV),F2, and cost reduction resulting from adoption of the algorithm. Two datasets were used for validation: TestTNMG, consisting of 34 310 ECGs received by TNMG (1% unacceptable and 50% pathological); ChallengeCinC, consisting of 1000 ECGs (23% unacceptable, higher than real-world scenario).Main results. Both algorithms reached a similar performance on ChallengeCinC, although NACA performed considerably better than QMA in TestTNMG (Se = 0.89 versus 0.21; Sp = 0.99 versus 0.98; PPV = 0.59 versus 0.08;F2= 0.76 versus 0.16 and cost reduction 2.3 ± 1.8% versus 0.3 ± 0.3%, respectively).Significance. Implementing of NACA in a telecardiology service results in evident health and financial benefits for the patients and the healthcare system.

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.

Methods for Determination of Individual PEEP for Intraoperative Mechanical Ventilation Using a Decremental PEEP Trial.

(1) Background: Individual PEEP settings (PEEPIND) may improve intraoperative oxygenation and optimize lung mechanics. However, there is uncertainty concerning the optimal procedure to determine PEEPIND. In this secondary analysis of a randomized controlled clinical trial, we compared different methods for PEEPIND determination. (2) Methods: Offline analysis of decremental PEEP trials was performed and PEEPIND was retrospectively determined according to five different methods (EIT-based: RVDI method, Global Inhomogeneity Index [GI], distribution of tidal ventilation [EIT VT]; global dynamic and quasi-static compliance). (3) Results: In the 45 obese and non-obese patients included, PEEPIND using the RVDI method (PEEPRVD) was 16.3 ± 4.5 cm H2O. Determination of PEEPIND using the GI and EIT VT resulted in a mean difference of −2.4 cm H2O (95%CI: −1.2;−3.6 cm H2O, p = 0.01) and −2.3 cm H2O (95% CI: −0.9;3.7 cm H2O, p = 0.01) to PEEPRVD, respectively. PEEPIND selection according to quasi-static compliance showed the highest agreement with PEEPRVD (p = 0.67), with deviations > 4 cm H2O in 3/42 patients. PEEPRVD and PEEPIND according to dynamic compliance also showed a high level of agreement, with deviations > 4 cm H2O in 5/42 patients (p = 0.57). (4) Conclusions: High agreement of PEEPIND determined by the RVDI method and compliance-based methods suggests that, for routine clinical practice, PEEP selection based on best quasi-static or dynamic compliance is favorable.

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.

Extrapolation in the analysis of lung aeration by computed tomography: a validation study.

INTRODUCTION: Computed tomography (CT) is considered the gold standard for quantification of global or regional lung aeration and lung mass. Quantitative CT, however, involves the exposure to ionizing radiation and requires manual image processing. We recently evaluated an extrapolation method which calculates quantitative CT parameters characterizing the entire lung from only 10 reference CT-slices thereby reducing radiation exposure and analysis time. We hypothesized that this extrapolation method could be further validated using CT-data from pigs and sheep, which have a different thoracic anatomy. METHODS: We quantified volume and mass of the total lung and differently aerated lung compartments in 168 ovine and 55 porcine whole-lung CTs covering lung conditions from normal to gross deaeration. Extrapolated volume and mass parameters were compared to the respective values obtained by whole-lung analysis. We also tested the accuracy of extrapolation for all possible numbers of CT slices between 15 and 5. Bias and limits of agreement (LOA) were analyzed by the Bland-Altman method. RESULTS: For extrapolation from 10 reference slices, bias (LOA) for the total lung volume and mass of sheep were 18.4 (-57.2 to 94.0) ml and 4.2 (-21.8 to 30.2) grams, respectively. The corresponding bias (LOA) values for pigs were 5.1 (-55.2 to 65.3) ml and 1.6 (-32.9 to 36.2) grams, respectively. All bias values for differently aerated lung compartments were below 1% of the total lung volume or mass and the LOA never exceeded ± 2.5%. Bias values diverged from zero and the LOA became considerably wider when less than 10 reference slices were used. CONCLUSIONS: The extrapolation method appears robust against variations in thoracic anatomy, which further supports its accuracy and potential usefulness for clinical and experimental application of quantitative CT.

Development of a method to measure regional perfusion of the lung in anesthetized ponies using computed tomography angiography and the maximum slope model.

OBJECTIVE: To develop a method based on CT angiography and the maximum slope model (MSM) to measure regional lung perfusion in anesthetized ponies. ANIMALS: 6 ponies. PROCEDURES: Anesthetized ponies were positioned in dorsal recumbency in the CT gantry. Contrast was injected, and the lungs were imaged while ponies were breathing spontaneously and while they were mechanically ventilated. Two observers delineated regions of interest in aerated and atelectatic lung, and perfusion in those regions was calculated with the MSM. Measurements obtained with a computerized method were compared with manual measurements, and computerized measurements were compared with previously reported measurements obtained with microspheres. RESULTS: Perfusion measurements obtained with the MSM were similar to previously reported values obtained with the microsphere method. While ponies were spontaneously breathing, mean ± SD perfusion for aerated and atelectatic lung regions were 4.0 ± 1.9 and 5.0 ± 1.2 mL/min/g of lung tissue, respectively. During mechanical ventilation, values were 4.6 ± 1.2 and 2.7 ± 0.7 mL/min/g of lung tissue at end expiration and 4.1 ± 0.5 and 2.7 ± 0.6 mL/min/g of lung tissue at peak inspiration. Intraobserver agreement was acceptable, but interobserver agreement was lower. Computerized measurements compared well with manual measurements. CLINICAL RELEVANCE: Findings showed that CT angiography and the MSM could be used to measure regional lung perfusion in dorsally recumbent anesthetized ponies. Measurements are repeatable, suggesting that the method could be used to determine efficacy of therapeutic interventions to improve ventilation-perfusion matching and for other studies for which measurement of regional lung perfusion is necessary.

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 > or = 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.

Sex-specific programming of cardiovascular physiology in children.

AIMS: Increasing evidence suggests that adverse prenatal environments, as indicated by low birth weight, cause long-term changes in cardiovascular physiology that predispose to circulatory disease. The mechanisms are poorly understood, most human studies have been carried out in adults and little is known about early pathophysiological changes. Therefore, we have assessed the relationship between birth weight and cardiovascular physiology in children. METHODS AND RESULTS: In 140 healthy boys and girls (aged 7-9 years), born at term and followed prospectively, we continuously recorded blood pressure, electrocardiograms and cardiac impedance before, during, and after 10 min of psychosocial stress (Trier Social Stress Test for Children). In boys, an association of lower birth weight with higher resting systemic arterial pressure (ß = -6.8 mmHg/kg, P= 0.03) and a trend towards higher vascular resistance (ß = -87 dyne s/cm(5)/kg, ns) were substantially strengthened following stress (ß = -9.5 mmHg/kg, P= 0.003 and ß = -139 dyne s/cm(5)/kg, P = 0.02, respectively). In girls, lower birth weight was associated with a shorter pre-ejection period (ß = 8.0 ms/kg, P = 0.005) and corrected QT interval (ß = 11.9 ms/kg, P = 0.003) at rest and little changed by stress. CONCLUSION: Smaller size at birth is associated with sex-specific alterations in cardiac physiology; boys had higher systemic vascular resistance and girls had increased cardiac sympathetic activation.

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.

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.