Alveolar Tidal recruitment/derecruitment and Overdistension During Four Levels of End-Expiratory Pressure with Protective Tidal Volume During Anesthesia in a Murine Lung-Healthy Model.

PURPOSE: We compared respiratory mechanics between the positive end-expiratory pressure of minimal respiratory system elastance (PEEPminErs) and three levels of PEEP during low-tidal-volume (6 mL/kg) ventilation in rats. METHODS: Twenty-four rats were anesthetized, paralyzed, and mechanically ventilated. Airway pressure (Paw), flow (F), and volume (V) were fitted by a linear single compartment model (LSCM) Paw(t) = Ers × V(t) + Rrs × F(t) + PEEP or a volume- and flow-dependent SCM (VFDSCM) Paw(t) = (E1 + E2 × V(t)) × V(t) + (K1 + K2 × |F(t)|) × F(t) + PEEP, where Ers and Rrs are respiratory system elastance and resistance, respectively; E1 and E2× V are volume-independent and volume-dependent Ers, respectively; and K1 and K2 × F are flow-independent and flow-dependent Rrs, respectively. Animals were ventilated for 1 h at PEEP 0 cmH2O (ZEEP); PEEPminErs; 2 cmH2O above PEEPminErs (PEEPminErs+2); or 4 cmH2O above PEEPminErs (PEEPminErs+4). Alveolar tidal recruitment/derecruitment and overdistension were assessed by the index %E2 = 100 × [(E2 × VT)/(E1 + |E2| × VT)], and alveolar stability by the slope of Ers(t). RESULTS: %E2 varied between 0 and 30% at PEEPminErs in most respiratory cycles. Alveolar Tidal recruitment/derecruitment (%E2 < 0) and overdistension (%E2 > 30) were predominant in the absence of PEEP and in PEEP levels higher than PEEPminErs, respectively. The slope of Ers(t) was different from zero in all groups besides PEEPminErs+4. CONCLUSIONS: PEEPminErs presented the best compromise between alveolar tidal recruitment/derecruitment and overdistension, during 1 h of low-VT mechanical ventilation.

Generalized estimation of the ventilatory distribution from the multiple-breath washout: a bench evaluation study.

BACKGROUND: The multiple-breath washout (MBW) is able to provide information about the distribution of ventilation-to-volume (v/V) ratios in the lungs. However, the classical, all-parallel model may return skewed results due to the mixing effect of a common dead space. The aim of this work is to examine whether a novel mathematical model and algorithm is able to estimate v/V of a physical model, and to compare its results with those of the classical model. The novel model takes into account a dead space in series with the parallel ventilated compartments, allows for variable tidal volume (VT) and end-expiratory lung volume (EELV), and does not require a ideal step change of the inert gas concentration. METHODS: Two physical models with preset v/V units and a common series dead space (vd) were built and mechanically ventilated. The models underwent MBW with N2 as inert gas, throughout which flow and N2 concentration signals were acquired. Distribution of v/V was estimated-via nonnegative least squares, with Tikhonov regularization-with the classical, all-parallel model (with and without correction for non-ideal inspiratory N2 step) and with the new, generalized model including breath-by-breath vd estimates given by the Fowler method (with and without constrained VT and EELV). RESULTS: The v/V distributions estimated with constrained EELV and VT by the generalized model were practically coincident with the actual v/V distribution for both physical models. The v/V distributions calculated with the classical model were shifted leftwards and broader as compared to the reference. CONCLUSIONS: The proposed model and algorithm provided better estimates of v/V than the classical model, particularly with constrained VT and EELV.

Generalized estimation of the ventilatory distribution from the multiple-breath nitrogen washout.

BACKGROUND: This work presents a generalized technique to estimate pulmonary ventilation-to-volume (v/V) distributions using the multiple-breath nitrogen washout, in which both tidal volume (V T ) and the end-expiratory lung volume (EELV) are allowed to vary during the maneuver. In addition, the volume of the series dead space (v d ), unlike the classical model, is considered a common series unit connected to a set of parallel alveolar units. METHODS: The numerical solution for simulated data, either error-free or with the N2 measurement contaminated with the addition of Gaussian random noise of 3 or 5 % standard deviation was tested under several conditions in a computational model constituted by 50 alveolar units with unimodal and bimodal distributions of v/V. Non-negative least squares regression with Tikhonov regularization was employed for parameter retrieval. The solution was obtained with either unconstrained or constrained (V T , EELV and v d ) conditions. The Tikhonov gain was fixed or estimated and a weighting matrix (WM) was considered. The quality of estimation was evaluated by the sum of the squared errors (SSE) (between reference and recovered distributions) and by the deviations of the first three moments calculated for both distributions. Additionally, a shape classification method was tested to identify the solution as unimodal or bimodal, by counting the number of shape agreements after 1000 repetitions. RESULTS: The accuracy of the results showed a high dependence on the noise amplitude. The best algorithm for SSE and moments included the constrained and the WM solvers, whereas shape agreement improved without WM, resulting in 97.2 % for unimodal and 90.0 % for bimodal distributions in the highest noise condition. CONCLUSIONS: In conclusion this generalized method was able to identify v/V distributions from a lung model with a common series dead space even with variable V T . Although limitations remain in presence of experimental noise, appropriate combination of processing steps were also found to reduce estimation errors.

Does acute exposure to aldehydes impair pulmonary function and structure?

Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1ß, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group.

Positive end-expiratory pressure and variable ventilation in lung-healthy rats under general anesthesia.

OBJECTIVES: Variable ventilation (VV) seems to improve respiratory function in acute lung injury and may be combined with positive end-expiratory pressure (PEEP) in order to protect the lungs even in healthy subjects. We hypothesized that VV in combination with moderate levels of PEEP reduce the deterioration of pulmonary function related to general anesthesia. Hence, we aimed at evaluating the alveolar stability and lung protection of the combination of VV at different PEEP levels. DESIGN: Randomized experimental study. SETTING: Animal research facility. SUBJECTS: Forty-nine male Wistar rats (200-270 g). INTERVENTIONS: Animals were ventilated during 2 hours with protective low tidal volume (VT) in volume control ventilation (VCV) or VV and PEEP adjusted at the level of minimum respiratory system elastance (Ers), obtained during a decremental PEEP trial subsequent to a recruitment maneuver, and 2 cmH2O above or below of this level. MEASUREMENTS AND MAIN RESULTS: Ers, gas exchange and hemodynamic variables were measured. Cytokines were determined in lung homogenate and plasma samples and left lung was used for histologic analysis and diffuse alveolar damage scoring. A progressive time-dependent increase in Ers was observed independent on ventilatory mode or PEEP level. Despite of that, the rate of increase of Ers and lung tissue IL-1 beta concentration were significantly lower in VV than in VCV at the level of the PEEP of minimum Ers. A significant increase in lung tissue cytokines (IL-6, IL-1 beta, CINC-1 and TNF-alpha) as well as a ventral to dorsal and cranial to caudal reduction in aeration was observed in all ventilated rats with no significant differences among groups. CONCLUSIONS: VV combined with PEEP adjusted at the level of the PEEP of minimal Ers seemed to better prevent anesthesia-induced atelectasis and might improve lung protection throughout general anesthesia.

Continuous positive airway pressure setups evaluated at simulated exercise conditions

INTRODUCTION: Studies have shown increases in airway opening pressure (Pao) swings and work of breathing (WOB) by different continuous positive airway pressure (CPAP) devices at rest, but few address this issue during exercise. The aim of the present work was to analyze the imposed WOB (WOBi), the apparent resistance (Rapp) and swings of Pao (deltaP) of 3 CPAP assemblies at simulated exercise conditions. METHODS: The CPAP measures were obtained from: a commercial CPAP (Assembly 1), a high flow CPAP (Assembly 2) and the parallel association of these devices (Assembly 3). In each assembly the spring-loaded positive end-expiratory pressure (PEEP) valve was set to fully opened (mode A) or at the same CPAP pressure (mode B). The exercise protocol simulation, performed manually by a calibrated syringe and a metronome, employed a respiratory frequency of 30 bpm, tidal volume of 2.7 L and inspiratory-to-expiratory ratio of 1. The setups were evaluated at CPAP settings of 5, 10 and 15 cmH2O. RESULTS: The lowest deltaP as well as Rapp and WOBi were obtained with Assembly 3 in mode A with an adjusted CPAP of 10 cmH2O (deltaP=8.1 (0.5) cmH2O, WOBi=1.4 (0.14) cmH2O/L/s, Rapp= 1.3 (0.07) J/s) showed as median (interquartile range). CONCLUSION: For the conditions studied, the best CPAP setup was obtained with mode A.

Volume-independent elastance: a useful parameter for open-lung positive end-expiratory pressure adjustment.

BACKGROUND: A decremental positive end-expiratory pressure (PEEP) trial after full lung recruitment allows for the adjustment of the lowest PEEP that prevents end-expiratory collapse (open-lung PEEP). For a tidal volume (Vt) approaching zero, the PEEP of minimum respiratory system elastance (PEEP(minErs)) is theoretically equal to the pressure at the mathematical inflection point (MIP) of the pressure-volume curve, and seems to correspond to the open-lung PEEP in a decremental PEEP trial. Nevertheless, the PEEP(minErs) is dependent on Vt and decreases as Vt increases. To circumvent this dependency, we proposed the use of a second-order model in which the volume-independent elastance (E1) is used to set open-lung PEEP. METHODS: Pressure-volume curves and a recruitment maneuver followed by decremental PEEP trials, with a Vt of 6 and 12 mL/kg, were performed in 24 Wistar rats with acute lung injury induced by intraperitoneally injected (n = 8) or intratracheally instilled (n = 8) Escherichia coli lipopolysaccharide. In 8 control animals, the anterior chest wall was surgically removed after PEEP trials, and the protocol was repeated. Airway pressure (Paw) and flow (F) were continuously acquired and fitted by the linear single-compartment model (Paw = Rrs·F + Ers·V + PEEP, where Rrs is the resistance of the respiratory system, and V is volume) and the volume-dependent elastance model (Paw = Rrs·F + E1 + E2·V·V + PEEP, where E2·V is the volume-dependent elastance). From each model, PEEPs of minimum Ers and E1 (PEEP(minE1)) were identified and compared with each respective MIP. The accuracy of PEEPminE1 and PEEPminErs in estimating MIP was assessed by bias and precision plots. Comparisons among groups were performed with the unpaired t test whereas a paired t test was used between the control group before and after chest wall removal and within groups at different Vts. All P values were then corrected for multiple comparisons by the Bonferroni procedure. RESULTS: In all experimental groups, PEEPminErs, but not PEEPminE1, tended to decrease as Vt increased. The difference between MIP and PEEPminE1 exhibited a lower bias compared with the difference between MIP and PEEPminErs (P < 0.001). The PEEPminE1 was always significantly higher than the PEEPminErs (7.7 vs 3.8, P < 0.001) and better approached MIP (7.7 vs 7.3 cm H2O with P = 0.04 at low Vt, and 7.8 vs 7.1 cm H2O with P < 0.001 at high Vt). CONCLUSIONS: PEEPminE1 better identifies the open-lung PEEP independently of the adjusted Vt, and may be a practical, more individualized approach for PEEP titration.

Detection of tidal recruitment/overdistension in lung-healthy mechanically ventilated patients under general anesthesia.

BACKGROUND: The volume-dependent single compartment model (VDSCM) has been applied for identification of overdistension in mechanically ventilated patients with acute lung injury. In this observational study we evaluated the use of the VDSCM to identify tidal recruitment/overdistension induced by tidal volume (Vt) and positive end-expiratory pressure (PEEP) in lung-healthy anesthetized subjects. METHODS: Fifteen patients (ASA physical status I-II) undergoing general anesthesia for elective plastic breast reconstruction surgery were mechanically ventilated in volume-controlled ventilation (VCV), with Vt of 8 mL•kg(-1) and PEEP of 0 cm H(2)O. With these settings, ventilatory mode was randomly adjusted in VCV or pressure-controlled ventilation (PCV) and PEEP was sequentially increased from 0 to 5 and 10 cm H(2)O, 5 min per step. Thereafter, PEEP was decreased to 0 cm H(2)O, Vt increased to 10 mL•kg(-1) and, keeping minute ventilation constant, PEEP was similarly increased to 5 and 10 cm H(2)O. Airway pressure and flow were continuously recorded and fitted to the VDSCM with or without considering flow-dependencies. A "distension index" (%E(2)) derived from the VDSCM was used to assess Vt and PEEP-induced recruitment/overdistension. Positive and negative values of %E(2) suggest tidal overdistension or tidal recruitment, respectively. In addition, the linear respiratory system elastance was calculated. Comparisons among variables at each PEEP value, Vt setting, ventilatory mode, and regression model considering or not considering flow-dependencies were performed with the Wilcoxon-sign rank test for paired samples (P < 0.05). Multiple comparisons were corrected with the Bonferroni method. The relative change in the estimated noisy variance was used as an index of the goodness of fit of the models. RESULTS: VDSCM including the flow-dependent parameter significantly improved estimated noisy variance in almost all experimental conditions (11.2 to 71.4, smallest of the lower and highest of the upper 95% confidence intervals). No differences in %E(2) were observed between VCV and PCV, at comparable Vt and PEEP levels, when flow-dependencies were included in the regression model. The negligence of the flow-dependent parameter systematically led to an underestimation of %E(2) in PCV compared to VCV mode (all P < 0.02). At a given Vt, %E(2) was negative at a PEEP of 0 cm H(2)O and significantly increased with PEEP, being almost 0 at a PEEP of 5 cm H(2)O. At a given level of PEEP, %E(2) significantly increased with Vt. CONCLUSIONS: The distension index %E(2), derived from the VDSCM considering flow-dependencies, seems able to identify tidal recruitment/overdistension induced by Vt and PEEP independent of flow waveform in healthy lung-anesthetized patients.

Tidal lung recruitment and exhaled nitric oxide during coronary artery bypass grafting in patients with and without chronic obstructive pulmonary disease.

BACKGROUND: We studied the occurrence of intraoperative tidal alveolar recruitment/derecruitment, exhaled nitric oxide (eNO), and lung dysfunction in patients with and without chronic obstructive pulmonary disease (COPD) undergoing coronary artery bypass grafting (CABG). METHODS: We performed a prospective observational physiological study at a university hospital. Respiratory mechanics, shunt, and eNO were assessed in moderate COPD patients undergoing on-pump (n = 12) and off-pump (n = 8) CABG and on-pump controls (n = 8) before sternotomy (baseline), after sternotomy and before cardiopulmonary bypass (CPB), and following CPB before and after chest closure. Respiratory system resistance (R (rs)), elastance (E (rs)), and stress index (to quantify tidal recruitment) were estimated using regression analysis. eNO was measured with chemiluminescence. RESULTS: Mechanical evidence of tidal recruitment/derecruitment (stress index <1.0) was observed in all patients, with stress index <0.8 in 29% of measurements. Rrs in on-pump COPD was larger than in controls (p < 0.05). Ers increased in controls from baseline to end of surgery (19.4 ± 5.5 to 27.0 ± 8.5 ml cm H(2)O(-1), p < 0.01), associated with increased shunt (p < 0.05). Neither Ers nor shunt increased significantly in the COPD on-pump group. eNO was comparable in the control (11.7 ± 7.0 ppb) and COPD on-pump (9.9 ± 6.8 ppb) groups at baseline, and decreased similarly by 29% at end of surgery(p < 0.05). Changes in eNO were not correlated to changes in lung function. CONCLUSIONS: Tidal recruitment/derecruitment occurs frequently during CABG and represents a risk for ventilator-associated lung injury. eNO changes are consistent with small airway injury, including that from tidal recruitment injury. However, those changes are not correlated with respiratory dysfunction. Controls have higher susceptibility to develop complete lung derecruitment.

Control of positive end-expiratory pressure (PEEP) for small animal ventilators.

BACKGROUND: The positive end-expiratory pressure (PEEP) for the mechanical ventilation of small animals is frequently obtained with water seals or by using ventilators developed for human use. An alternative mechanism is the use of an on-off expiratory valve closing at the moment when the alveolar pressure is equal to the target PEEP. In this paper, a novel PEEP controller (PEEP-new) and the PEEP system of a commercial small-animal ventilator, both based on switching an on-off valve, are evaluated. METHODS: The proposed PEEP controller is a discrete integrator monitoring the error between the target PEEP and the airways opening pressure prior to the onset of an inspiratory cycle. In vitro as well as in vivo experiments with rats were carried out and the PEEP accuracy, settling time and under/overshoot were considered as a measure of performance. RESULTS: The commercial PEEP controller did not pass the tests since it ignores the airways resistive pressure drop, resulting in a PEEP 5 cmH2O greater than the target in most conditions. The PEEP-new presented steady-state errors smaller than 0.5 cmH2O, with settling times below 10 s and under/overshoot smaller than 2 cmH2O. CONCLUSION: The PEEP-new presented acceptable performance, considering accuracy and temporal response. This novel PEEP generator may prove useful in many applications for small animal ventilators.

A numerical model of the respiratory modulation of pulmonary shunt and PaO2 oscillations for acute lung injury.

It is an accepted hypothesis that the amplitude of the respiratory-related oscillations of arterial partial pressure of oxygen (DeltaPaO2) is primarily modulated by fluctuations of pulmonary shunt (Deltas), the latter generated mainly by cyclic alveolar collapse/reopening, when present. A better understanding of the relationship between DeltaPaO2, Deltas, and cyclic alveolar collapse/reopening can have clinical relevance for minimizing the severe lung damage that the latter can cause, for example during mechanical ventilation (MV) of patients with acute lung injury (ALI). To this aim, we numerically simulated the effect of such a relationship on an animal model of ALI under MV, using a combination of a model of lung gas exchange during tidal ventilation with a model of time dependence of shunt on alveolar collapse/opening. The results showed that: (a) the model could adequately replicate published experimental results regarding the complex dependence of DeltaPaO2 on respiratory frequency, driving pressure (DeltaP), and positive end-expiratory pressure (PEEP), while simpler models could not; (b) such a replication strongly depends on the value of the model parameters, especially of the speed of alveolar collapse/reopening; (c) the relationship between DeltaPaO2 and Deltas was overall markedly nonlinear, but approximately linear for PEEP>or=6 cmH2O, with very large DeltaPaO2 associated with relatively small Deltas.

The endotracheal tube biases the estimates of pulmonary recruitment and overdistension.

To assess the impact of the endotracheal tube (ETT) and of different flow waveforms on estimates of alveolar cyclic recruitment (CR) and overdistension (AO). Numerical simulation of the respiratory system plus ETT (inertance L plus a flow-dependent resistance, K (1) and K (2)), with the following non-linear equation of motion PAW(t)= ((K1 + K2 x/V(t)/) x V(t) + L x V(t)) + Rrs x V(t) + (E1 + E2 x V(t) x V(t) + P0 (PAW pressure at the airways opening, V volume), under volume-controlled mechanical ventilation. An index %E2 = 100 x (E2 x V(T))/(E1 + E2)x V(T)) can be calculated where %E(2) > 30% represents AO and %E(2) < 0% represents CR. Parameters were estimated by the least-squares method, either with the complete equation or suppressing L, K(2) or both. %E(2) is always underestimated (down to -152 percent points) with incomplete equations of motion. The estimation of %E (2) may be strongly biased in the presence of an ETT excluded from the estimation model.

Positive end-expiratory pressure at minimal respiratory elastance represents the best compromise between mechanical stress and lung aeration in oleic acid induced lung injury.

INTRODUCTION: Protective ventilatory strategies have been applied to prevent ventilator-induced lung injury in patients with acute lung injury (ALI). However, adjustment of positive end-expiratory pressure (PEEP) to avoid alveolar de-recruitment and hyperinflation remains difficult. An alternative is to set the PEEP based on minimizing respiratory system elastance (Ers) by titrating PEEP. In the present study we evaluate the distribution of lung aeration (assessed using computed tomography scanning) and the behaviour of Ers in a porcine model of ALI, during a descending PEEP titration manoeuvre with a protective low tidal volume. METHODS: PEEP titration (from 26 to 0 cmH2O, with a tidal volume of 6 to 7 ml/kg) was performed, following a recruitment manoeuvre. At each PEEP, helical computed tomography scans of juxta-diaphragmatic parts of the lower lobes were obtained during end-expiratory and end-inspiratory pauses in six piglets with ALI induced by oleic acid. The distribution of the lung compartments (hyperinflated, normally aerated, poorly aerated and non-aerated areas) was determined and the Ers was estimated on a breath-by-breath basis from the equation of motion of the respiratory system using the least-squares method. RESULTS: Progressive reduction in PEEP from 26 cmH2O to the PEEP at which the minimum Ers was observed improved poorly aerated areas, with a proportional reduction in hyperinflated areas. Also, the distribution of normally aerated areas remained steady over this interval, with no changes in non-aerated areas. The PEEP at which minimal Ers occurred corresponded to the greatest amount of normally aerated areas, with lesser hyperinflated, and poorly and non-aerated areas. Levels of PEEP below that at which minimal Ers was observed increased poorly and non-aerated areas, with concomitant reductions in normally inflated and hyperinflated areas. CONCLUSION: The PEEP at which minimal Ers occurred, obtained by descending PEEP titration with a protective low tidal volume, corresponded to the greatest amount of normally aerated areas, with lesser collapsed and hyperinflated areas. The institution of high levels of PEEP reduced poorly aerated areas but enlarged hyperinflated ones. Reduction in PEEP consistently enhanced poorly or non-aerated areas as well as tidal re-aeration. Hence, monitoring respiratory mechanics during a PEEP titration procedure may be a useful adjunct to optimize lung aeration.

Lung production of platelet-activating factor acetylhydrolase in oleic acid-induced acute lung injury.

Platelet-activating factor (PAF) is a proinflammatory mediator that plays a central role in acute lung injury (ALI). PAF- acetylhydrolases (PAF-AHs) terminate PAF's signals and regulate inflammation. In this study, we describe the kinetics of plasma and bronchoalveolar lavage (BAL) PAF-AH in the early phase of ALI. Six pigs with oleic acid induced ALI and two healthy controls were studied. Plasma and BAL samples were collected every 2h and immunohistochemical analysis of PAF-AH was performed in lung tissues. PAF-AH activity in BAL was increased at the end of the experiment (BAL PAF-AH Time 0=0.001+/-0.001 nmol/ml/min/g vs Time 6=0.031+/-0.018 nmol/ml/min/g, p=0.04) while plasma activity was not altered. We observed increased PAF-AH staining of macrophages and epithelial cells in the lungs of animals with ALI but not in healthy controls. Our data suggest that increases in PAF-AH levels are, in part, a result of alveolar production. PAF-AH may represent a modulatory strategy to counteract the excessive pro-inflammatory effects of PAF and PAF-like lipids in lung inflammation.

Heart-rate and blood-pressure variability during psychophysiological tasks involving speech: influence of respiration.

Changes in heart-rate and systolic arterial pressure variability (HRV and SAPV) indexes have been used in psychophysiology to assess autonomic activation, including during tasks involving speech. The current article clearly demonstrates in a sample of 25 adult subjects that the erratic and broadband respiratory patterns during such tasks violate the usual assumption that respiration is limited to the high-frequency band (0.15-0.4 Hz). For these tasks, interindividual differences and rest-task changes in HRV and SAPV in the low-frequency band (0.04-0.15 Hz) can be explained, to a large extent, by variations in the respiratory volume signal. This makes the use of HRV and SAPV as markers of autonomic function during these tasks highly questionable. Furthermore, a number of subjects with long respiratory period at rest were identified, whose presence in the sample can bias the estimation of baseline rest values.

Effects of descending positive end-expiratory pressure on lung mechanics and aeration in healthy anaesthetized piglets.

INTRODUCTION: Atelectasis and distal airway closure are common clinical entities of general anaesthesia. These two phenomena are expected to reduce the ventilation of dependent lung regions and represent major causes of arterial oxygenation impairment in anaesthetic conditions. In the present study, the behavior of the elastance of the respiratory system (Ers), as well as the lung aeration assessed by CT-scan, was evaluated during a descendent positive end-expiratory pressure (PEEP) titration. This work sought to evaluate the potential usefulness of the Ers monitoring to set the PEEP in order to prevent tidal recruitment and hyperinflation of healthy lungs under general anaesthesia. METHODS: PEEP titration (from 16 to 0 cmH2O, with a tidal volume of 8 ml/kg) was performed, and at each PEEP, helical CT-scans were obtained during end-expiratory and end-inspiratory pauses in six healthy, anaesthetized and paralyzed piglets. The distribution of lung compartments (hyperinflated (HA), normally- (NA), poorly- (PA), and non-aerated areas (N)) was determined and the tidal re-aeration was calculated as the difference between end-expiratory and end-inspiratory PA and NA areas. Similarly, the tidal hyperinflation was obtained as the difference between end-inspiratory and end-expiratory HA. The Ers was estimated on a breath-by-breath basis from the equation of motion of the respiratory system during all PEEP titration with the least squares method. RESULTS: HA decreased throughout PEEP descent from PEEP 16 cmH2O to ZEEP (ranges from 24-62% to 1-7% at end-expiratory and from 44-73% to 4-17% at end-inspiratory pauses) whereas NA areas increased (30-66% to 72-83% at end-expiratory and from 19-48% to 73-77% at end-inspiratory pauses). From 16 to 8 cmH2O, Ers decreased with a correspondent reduction in tidal hyperinflation. A flat minimum of Ers was observed from 8 to 4 cmH2O. For PEEP below 4 cmH2O, Ers increased associated with a rise in tidal re-aeration and a flat maximum of the NA areas. CONCLUSION: In healthy piglets under a descending PEEP protocol, the PEEP at minimum Ers presented a compromise between maximizing NA areas and minimizing tidal re-aeration and hyperinflation. High levels of PEEP, greater than 8 cmH2O, reduced tidal re-aeration but enlarged hyperinflation with a concomitant decrease in normally aerated areas.

Estimation of the VO2 peak, ventilatory threshold and the respiratory compensation point based on the gas exchange kinetics during the transition to constant-load exercise / Estimação do VO2 peak, do limiar ventilatório e do ponto de compensação respiratória baseada na cinética das trocas gasosas durante a transição para exercício com carga constante

The main goal of this work was to estimate the peak O2 uptake (VO2 peak), the ventilatory threshold (VT) and the respiratory compensation point (RC) based on the kinetics of the VO2, the CO2 output (VCO2) and the pulmonary ventilation (VE) for a given steady state workload. Thirty-two physically active healthy male subjects were submitted to an exercise equivalent to 50% of the maximal estimated workload, followed by a progressive workload (12.5 W/min) until exhaustion. During exercise, respiratory gas exchanges were measured breath-by-breath. VO2,VCO2 and VE time responses to constant workload were modeled through a triple exponential function using non-linear regression. VT and RC were detected automatically during progressive exercise, resulting in 73.7 ± 9.1% and 86.4 ± 7.2% of the VO2peak, respectively. Models of VO2peak, VT and RC were obtained through multiple linear regressions, and validated by the leave-one-out method. All models presented high significance (VO2peak: r2 = 0.84,SE = 230.2 ml/min; VT: r2 = 0.79, SE = 208.1 ml/min; and RC: r2 = 0.78, SE = 232.5 ml/min; p < 0.001) and were adequately validated, resulting in mean error of 238 ml/min. In conclusion, VT, RC as well as the VO2 peak were satisfactorily estimated through gas exchange kinetics. Therefore, this approach could be used as a potential tool for estimating maximal and sub-maximal responses to progressive exercise.

O objetivo central deste trabalho foi estimar o pico de captação de oxigênio (VO2peak), o limiar ventilatório (VT) e o ponto de compensação respiratória (RC) com base na cinética do VO2, da eliminação de CO2 (VCO2 ) e da ventilação pulmonar (VE) para uma determinada carga em regime permanente. Trinta e dois homens saudáveis e fisicamente ativos foram submetidos a um exercício equivalente a 50% da carga máxima estimada, seguido de cargas progressivas (12,5 W/min) até a exaustão. As trocas gasosas foram medidas ciclo-a-ciclo respiratório. As respostas temporais de VO2, VCO2 e VE à carga constante foram modeladas por uma função exponencial tripla empregando regressão não linear. Os valores de VT e RC foram detectados automaticamente durante o exercício progressivo, resultando em 73,7 ± 9,1% e 86,4 ± 7,2% de VO2peak, respectivamente. Modelos de VO2peak, VT e RC foram obtidos através de regressão linear múltipla e validados pelo método leave-one-out. Todos os modelos apresentaram alta significância (VO2 peak: r2 = 0,84, SE = 230,2 ml/min; VT: r2 = 0,79, SE = 208,1 ml/min; e RC: r2 = 0,78, SE = 232,5 ml/min; p < 0,001) e foram validados adequadamente, resultando num erro médio de 238 ml/min. Em conclusão, VT, RC e VO2peak foram satisfatoriamente estimados através da cinética das trocas gasosas, sendo este método uma ferramenta potencial para a estimativa das respostas máximas e sub-máximas a exercício progressivo.

Effects of filtering and delays on the estimates of a nonlinear respiratory mechanics model.

Estimation of mechanical properties of the respiratory system may be disturbed by instrumentation and physical set-up. The effects of lowpass filtering, filter mismatch and inter-channel delay in the digital converter are assessed on numerically simulated signals from a nonlinear model of the respiratory system. Large biases in model parameter estimates (up to about -300% for some parameters) were caused by these instrumental interferences and were reduced by including an inertance in the retrieved model. The results reinforce the importance of a careful evaluation of the instrumental set-up used in physiological measurements.

Comparison of computerized methods for detecting the ventilatory thresholds.

The aim of this study was to compare computerized automatic methods to detect the ventilatory threshold (VT). Thirty apparently healthy and physically active volunteers [22.5 (6.5) years; 1.72 (0.08) m; 71.9 (8.5) kg] were submitted to a progressive and maximal cycle exercise. The gas exchange was monitored breath-by-breath with a fast gas analyser. The VT and respiratory compensation (RC) were automatically detected based on the respiratory exchange ratio, the ventilatory equivalent for O2 and the ventilatory equivalent for CO2, pulmonary ventilation, end-tidal PO2 and PCO2, and v-slope. In addition, VT and RC were also determined independently by visual inspection by two experienced investigators, and the results were compared with those of the automatic procedures. The automatic VT averaged 77% of the maximal VO2 and the RC 88%. The agreement between the experienced observers was very close [mean difference: 44.4 (16.1) ml, r = 0.94, not significant]. Data were expressed as the mean value together with the standard deviation in each case. The automatic and visual inspection procedures did not present significant differences, resulting in 29.6 (29.6) ml with a reliability of r = 0.86. All methods were significantly correlated for VT and RC (r = 0.93 on average, P < 0.01). ANOVA did not show differences between either the VT methods (P = 0.131) or the RC methods (P = 0.41). In conclusion, the present study has compared several simultaneous breath-by-breath ergospirometric methods that are used to describe the anaerobic threshold, showing high confidence when compared to visual inspection. No statistical differences were found between the VT and RC techniques for physically active subjects indicating that these methods may be equally effectively employed.

A closed-loop mechanical ventilation controller with explicit objective functions.

A closed-loop lung ventilation controller was designed, aiming to: 1) track a desired end-tidal CO2 pressure (Pet CO2), 2) find the positive end-expiratory pressure (PEEP) of minimum estimated respiratory system elastance (Ers,e), and 3) follow objective functions conjectured to reduce lung injury. After numerical simulations, tests were performed in six paralyzed piglets. Respiratory mechanics parameters were estimated by the recursive least squares (RLS) method. The controller incorporated a modified PI controller for Pet CO2 and a gradient descent method for PEEP. In each animal, three automated PEEP control runs were performed, as well as a manual PEEP titration of Ers,e and a multiple PetCO2 step change trial. Overall performance indexes were obtained from PEEP control, such as minimum Ers,e (37.0 +/- 4.5 cmH2O x L(-1)), time to reach the minimum Ers,e (235 +/- 182 s) and associated PEEP (6.5 +/- 1.0 cmH2O), and from Pet CO2 control, such as rise time (53 +/- 22 s), absolute overshoot/undershoot of PetCO2 (3 +/- 1 mmHg), and settling time (145 +/- 72 s). The resulting CO2 controller dynamics approximate physiological responses, and results from PEEP control were similar to those obtained by manual titration. Multiple dependencies linking the involved variables are discussed. The present controller can help to implement and evaluate objective functions that meet clinical goals.