Individualized positive end-expiratory pressure reduces driving pressure in obese patients during laparoscopic surgery under pneumoperitoneum: a randomized clinical trial.

Introduction: During pneumoperitoneum (PNP), airway driving pressure (ΔPRS) increases due to the stiffness of the chest wall and cephalic shift of the diaphragm, which favors atelectasis. In addition, depending on the mechanical power (MP) formulas, they may lead to different interpretations. Methods: Patients >18 years of age with body mass index >35 kg/m2 were included in a single-center randomized controlled trial during their admission for bariatric surgery by abdominal laparoscopy. Intra-abdominal pressure was set at 15 mmHg at the pneumoperitoneum time point (PNP). After the recruitment maneuver, the lowest respiratory system elastance (ERS) was detected during the positive end-expiratory pressure (PEEP) step-wise decrement. Patients were randomized to the 1) CTRL group: ventilated with PEEP of 5 cmH2O and 2) PEEPIND group: ventilated with PEEP value associated with ERS that is 5% higher than its lowest level. Respiratory system mechanics and mean arterial pressure (MAP) were assessed at the PNP, 5 min after randomization (T1), and at the end of the ventilation protocol (T2); arterial blood gas was assessed at PNP and T2. ΔPRS was the primary outcome. Three MP formulas were used: MPA, which computes static PEEP × volume, elastic, and resistive components; MPB, which computes only the elastic component; and MPC, which computes static PEEP × volume, elastic, and resistive components without inspiratory holds. Results: Twenty-eight patients were assessed for eligibility: eight were not included and 20 patients were randomized and allocated to CTRL and PEEPIND groups (n = 10/group). The PEEPIND ventilator strategy reduced ΔPRS when compared with the CTRL group (PEEPIND, 13 ± 2 cmH2O; CTRL, 22 ± 4 cmH2O; p < 0.001). Oxygenation improved in the PEEPIND group when compared with the CTRL group (p = 0.029), whereas MAP was comparable between the PEEPIND and CTRL groups. At the end of surgery, MPA and MPB were correlated in both the CTRL (rho = 0.71, p = 0.019) and PEEPIND (rho = 0.84, p = 0.020) groups but showed different bias (CTRL, -1.9 J/min; PEEPIND, +10.0 J/min). At the end of the surgery, MPA and MPC were correlated in both the CTRL (rho = 0.71, p = 0.019) and PEEPIND (rho = 0.84, p = 0.020) groups but showed different bias (CTRL, -1.9 J/min; PEEPIND, +10.0 J/min). Conclusion: Individualized PEEP was associated with a reduction in ΔPRS and an improvement in oxygenation with comparable MAP. The MP, which solely computes the elastic component, better reflected the improvement in ΔPRS observed in the individualized PEEP group. Clinical Trial Registration: The protocol was registered at the Brazilian Registry of Clinical Trials (U1111-1220-7296).

Worsening of lung perfusion to tissue density distributions during early acute lung injury.

Lung perfusion magnitude and distribution are essential for oxygenation and, potentially, lung inflammation and protection during acute respiratory distress syndrome (ARDS). Yet, perfusion patterns and their relationship to inflammation are unknown pre-ARDS. We aimed to assess perfusion/density ratios and spatial perfusion-density distributions and associate these to lung inflammation, during early lung injury in large animals at different physiological conditions caused by different systemic inflammation and positive end-expiratory pressure (PEEP) levels. Sheep were protectively ventilated (16-24 h) and imaged for lung density, pulmonary capillary perfusion (13Nitrogen-saline), and inflammation (18F-fluorodeoxyglucose) using positron emission and computed tomography. We studied four conditions: permissive atelectasis (PEEP = 0 cmH2O); and ARDSNet low-stretch PEEP-setting strategy with supine moderate or mild endotoxemia, and prone mild endotoxemia. Perfusion/density heterogeneity increased pre-ARDS in all groups. Perfusion redistribution to density depended on ventilation strategy and endotoxemia level, producing more atelectasis in mild than moderate endotoxemia (P = 0.010) with the oxygenation-based PEEP-setting strategy. The spatial distribution of 18F-fluorodeoxyglucose uptake was related to local Q/D (P < 0.001 for Q/D group interaction). Moderate endotoxemia yielded markedly low/zero perfusion in normal-low density lung, with 13Nitrogen-saline perfusion indicating nondependent capillary obliteration. Prone animals' perfusion was remarkably homogeneously distributed with density. Lung perfusion redistributes heterogeneously to density during pre-ARDS protective ventilation in animals. This is associated with increased inflammation, nondependent capillary obliteration, and lung derecruitment susceptibility depending on endotoxemia level and ventilation strategy.NEW & NOTEWORTHY Perfusion redistribution does not follow lung density redistribution in the first 16-24 h of systemic endotoxemia and protective tidal volume mechanical ventilation. The same oxygenation-based positive end-expiratory pressure (PEEP)-setting strategy can lead at different endotoxemia levels to different perfusion redistributions, PEEP values, and lung aerations, worsening lung biomechanical conditions. During early acute lung injury, regional perfusion-to-tissue density ratio is associated with increased neutrophilic inflammation, and susceptibility to nondependent capillary occlusion and lung derecruitment, potentially marking and/or driving lung injury.

Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients.

BACKGROUND: The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients. METHODS: Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT). RESULTS: 184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation. CONCLUSIONS: A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.

A simplified 4-parameter model of volumetric capnograms improves calculations of airway dead space and slope of Phase III.

To evaluate a compact and easily interpretable 4-parameter model describing the shape of the volumetric capnogram, and the resulting estimates of anatomical dead space (VDAW) and Phase III (alveolar plateau) slope (SIII). Data from of 8 mildly-endotoxemic pre-acute respiratory distress syndrome sheep were fitted to the proposed 4-parameter model (4p) and a previously established 7-parameter model (7p). Root mean square error (RMSE) and Akaike information criterion (AIC), as well as VDAW and SIII derived from each model were compared. Confidence intervals for model's parameters, VDAW and SIII were estimated with a jackknife approach. RMSE values were similar (4p: 1.13 ± 0.01 mmHg vs 7p: 1.14 ± 0.01 mmHg) in the 791 breath cycles tested. However, the 7p overfitted the curve and had worse AIC in more than 50% of the cycles (p < 0.001). The large number of degrees of freedom also resulted in larger between-animal range of confidence intervals for 7p (VDAW: from 6.1 10-12 to 34 ml, SIII: from 9.53 10-7 to 1.80 mmHg/ml) as compared to 4p (VDAW: from 0.019 to 0.15 ml, SIII: from 3.9 10-4 to 0.011 mmHg/ml). Mean differences between VDAW (2.1 ± 0.04 ml) and SIII (0.047 ± 0.004 mmHg/ml) from 7 and 4p were significant (p < 0.001), but within the observed cycle-by-cycle variability. The proposed 4-parameter model of the volumetric capnogram improves data fitting and estimation of VDAW and SIII as compared to the 7-parameter model of reference. These advantages support the use of the 4-parameter model in future research and clinical applications.

Regional Lung Recruitability During Pneumoperitoneum Depends on Chest Wall Elastance - A Mechanical and Computed Tomography Analysis in Rats.

Background: Laparoscopic surgery with pneumoperitoneum increases respiratory system elastance due to the augmented intra-abdominal pressure. We aim to evaluate to which extent positive end-expiratory pressure (PEEP) is able to counteract abdominal hypertension preventing progressive lung collapse and how rib cage elastance influences PEEP effect. Methods: Forty-four Wistar rats were mechanically ventilated and randomly assigned into three groups: control (CTRL), pneumoperitoneum (PPT) and pneumoperitoneum with restricted rib cage (PPT-RC). A pressure-volume (PV) curve followed by a recruitment maneuver and a decremental PEEP trial were performed in all groups. Thereafter, animals were ventilated using PEEP of 3 and 8 cmH2O divided into two subgroups used to evaluate respiratory mechanics or computed tomography (CT) images. In 26 rats, we compared respiratory system elastance (Ers) at the two PEEP levels. In 18 animals, CT images were acquired to calculate total lung volume (TLV), total volume and air volume in six anatomically delimited regions of interest (three along the cephalo-caudal and three along the ventro-dorsal axes). Results: PEEP of minimal Ers was similar in CTRL and PPT groups (3.8 ± 0.45 and 3.5 ± 3.89 cmH2O, respectively) and differed from PPT-RC group (9.8 ± 0.63 cmH2O). Chest restriction determined a right- and downward shift of the PV curve, increased Ers and diminished TLV and lung aeration. Increasing PEEP augmented TLV in CTRL group (11.8 ± 1.3 to 13.6 ± 2 ml, p < 0.05), and relative air content in the apex of PPT group (3.5 ± 1.4 to 4.6 ± 1.4% TLV, p < 0.03) and in the middle zones in PPT-RC group (21.4 ± 1.9 to 25.3 ± 2.1% TLV cephalo-caudally and 18.1 ± 4.3 to 22.0 ± 3.3% TLV ventro-dorsally, p < 0.005). Conclusion: Regional lung recruitment potential during pneumoperitoneum depends on rib cage elastance, reinforcing the concept of PEEP individualization according to the patient's condition.

Variable Ventilation Associated With Recruitment Maneuver Minimizes Tissue Damage and Pulmonary Inflammation in Anesthetized Lung-Healthy Rats.

BACKGROUND: Recruitment maneuver and positive end-expiratory pressure (PEEP) can be used to counteract intraoperative anesthesia-induced atelectasis. Variable ventilation can stabilize lung mechanics by avoiding the monotonic tidal volume and protect lung parenchyma as tidal recruitment is encompassed within the tidal volume variability. METHODS: Forty-nine (7 per group) male Wistar rats were anesthetized, paralyzed, and mechanically ventilated. A recruitment maneuver followed by stepwise decremental PEEP titration was performed while continuously estimating respiratory system mechanics using recursive least squares. After a new recruitment, animals were ventilated for 2 hours in volume-control with monotonic (VCV) or variable (VV) tidal volumes. PEEP was adjusted at a level corresponding to the minimum elastance or 2 cm H2O above or below this level. Lungs were harvested for histologic analysis (left lung) and cytokines measurement (right lung). Seven animals were euthanized before the first recruitment as controls. RESULTS: A time-dependent increase in respiratory system elastance was observed and significantly minimized by PEEP (P < .001). Variable ventilation attenuated the amount of concentrations of proinflammatory mediators in lung homogenate: neutrophil cytokine-induced neutrophil chemoattractant 1 (VV = 40 ± 5 and VCV = 57 ± 8 pg/mg; P < .0001) and interleukin-1ß (VV = 59 ± 25 and VCV = 261 ± 113 pg/mg; P < .0001). Variable ventilation was also associated with lower structural lung parenchyma damage. Significant reductions in air fraction at dorsal and caudal lung regions were observed in all ventilated animals (P < .001). CONCLUSIONS: Variable ventilation was more protective than conventional ventilation within the applied PEEP levels.

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.

An unpleasant emotional state reduces working memory capacity: electrophysiological evidence.

Emotional states can guide the actions and decisions we make in our everyday life through their influence on cognitive processes such as working memory (WM). We investigated the long-lasting interference that an unpleasant emotional state had on goal-relevant WM representations from an electrophysiological perspective. Participants performed a change detection task that was preceded by the presentation of unpleasant or neutral task-irrelevant pictures in a blocked fashion. We focused on the contralateral delay activity (CDA), an event-related potential that is sensitive to the number of task-relevant items stored in WM. We found that the asymptotic limit for the CDA amplitude was lower during the unpleasant emotional state than during the neutral one; that is, an emotional state was capable of reducing how many task-relevant items the participants could hold in WM. Furthermore, both the individuals who experienced more intrusive thoughts and those who were dispositionally anxious were more susceptible to the influence of the emotional state. We provide evidence that an unpleasant emotional state diminished visual WM for task-relevant items, particularly in susceptible individuals. These results open new avenues to uncover the emotional-cognitive processing that underlies maladaptive WM representations and the role of such processing in the development of mental illness.

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.

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.