Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial.

Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain. Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP. Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018. Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight. Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute). Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001). Conclusions and Relevance: Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02148692.

Intraoperative ventilation settings and their associations with postoperative pulmonary complications in obese patients.

BACKGROUND: There is limited information concerning the current practice of intraoperative mechanical ventilation in obese patients, and the optimal ventilator settings for these patients are debated. We investigated intraoperative ventilation parameters and their associations with the development of postoperative pulmonary complications (PPCs) in obese patients. METHODS: We performed a secondary analysis of the international multicentre Local ASsessment of VEntilatory management during General Anesthesia for Surgery' (LAS VEGAS) study, restricted to obese patients, with a predefined composite outcome of PPCs as primary end-point. RESULTS: We analysed 2012 obese patients from 135 hospitals across 29 countries in Europe, North America, North Africa, and the Middle East. Tidal volume was 8.8 [25th-75th percentiles: 7.8-9.9] ml kg-1 predicted body weight, PEEP was 4 [1-5] cm H2O, and recruitment manoeuvres were performed in 7.7% of patients. PPCs occurred in 11.7% of patients and were independently associated with age (P<0.001), body mass index ≥40 kg m-2 (P=0.033), obstructive sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an increased length of hospital stay (P<0.001). CONCLUSIONS: Obese patients are frequently ventilated with high tidal volume and low PEEP, and seldom receive recruitment manoeuvres. PPCs increase hospital stay, and are associated with preoperative conditions, duration of anaesthesia and intraoperative ventilation settings. Randomised trials are warranted to clarify the role of different ventilatory parameters in obese patients. CLINICAL TRIAL REGISTRATION: NCT01601223.

High intraoperative inspiratory oxygen fraction and risk of major respiratory complications.

BACKGROUND: High inspiratory oxygen fraction ( FIO2 ) may improve tissue oxygenation but also impair pulmonary function. We aimed to assess whether the use of high intraoperative FIO2 increases the risk of major respiratory complications. METHODS: We studied patients undergoing non-cardiothoracic surgery involving mechanical ventilation in this hospital-based registry study. The cases were divided into five groups based on the median FIO2 between intubation and extubation. The primary outcome was a composite of major respiratory complications (re-intubation, respiratory failure, pulmonary oedema, and pneumonia) developed within 7 days after surgery. Secondary outcomes included 30-day mortality. Several predefined covariates were included in a multivariate logistic regression model. RESULTS: The primary analysis included 73 922 cases, of whom 3035 (4.1%) developed a major respiratory complication within 7 days of surgery. For patients in the high- and low-oxygen groups, the median FIO2 was 0.79 [range 0.64-1.00] and 0.31 [0.16-0.34], respectively. Multivariate logistic regression analysis revealed that the median FIO2 was associated in a dose-dependent manner with increased risk of respiratory complications (adjusted odds ratio for high vs low FIO2 1.99, 95% confidence interval [1.72-2.31], P -value for trend <0.001). This finding was robust in a series of sensitivity analyses including adjustment for intraoperative oxygenation. High median FIO2 was also associated with 30-day mortality (odds ratio for high vs low FIO2 1.97, 95% confidence interval [1.30-2.99], P -value for trend <0.001). CONCLUSIONS: In this analysis of administrative data on file, high intraoperative FIO2 was associated in a dose-dependent manner with major respiratory complications and with 30-day mortality. The effect remained stable in a sensitivity analysis controlled for oxygenation. CLINICAL TRIAL REGISTRATION: NCT02399878.

The association of postoperative pulmonary complications in 109,360 patients with pressure-controlled or volume-controlled ventilation.

We thought that the rate of postoperative pulmonary complications might be higher after pressure-controlled ventilation than after volume-controlled ventilation. We analysed peri-operative data recorded for 109,360 adults, whose lungs were mechanically ventilated during surgery at three hospitals in Massachusetts, USA. We used multivariable regression and propensity score matching. Postoperative pulmonary complications were more common after pressure-controlled ventilation, odds ratio (95%CI) 1.29 (1.21-1.37), p < 0.001. Tidal volumes and driving pressures were more varied with pressure-controlled ventilation compared with volume-controlled ventilation: mean (SD) variance from the median 1.61 (1.36) ml.kg-1 vs. 1.23 (1.11) ml.kg-1 , p < 0.001; and 3.91 (3.47) cmH2 O vs. 3.40 (2.69) cmH2 O, p < 0.001. The odds ratio (95%CI) of pulmonary complications after pressure-controlled ventilation compared with volume-controlled ventilation at positive end-expiratory pressures < 5 cmH2 O was 1.40 (1.26-1.55) and 1.20 (1.11-1.31) when ≥ 5 cmH2 O, both p < 0.001, a relative risk ratio of 1.17 (1.03-1.33), p = 0.023. The odds ratio (95%CI) of pulmonary complications after pressure-controlled ventilation compared with volume-controlled ventilation at driving pressures of < 19 cmH2 O was 1.37 (1.27-1.48), p < 0.001, and 1.16 (1.04-1.30) when ≥ 19 cmH2 O, p = 0.011, a relative risk ratio of 1.18 (1.07-1.30), p = 0.016. Our data support volume-controlled ventilation during surgery, particularly for patients more likely to suffer postoperative pulmonary complications.

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. METHODS/DESIGN: The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH2O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH2O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. DISCUSSION: To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016.

Relationship between airway narrowing, patchy ventilation and lung mechanics in asthmatics.

Bronchoconstriction in asthma results in patchy ventilation forming ventilation defects (VDefs). Patchy ventilation is clinically important because it affects obstructive symptoms and impairs both gas exchange and the distribution of inhaled medications. The current study combined functional imaging, oscillatory mechanics and theoretical modelling to test whether the degrees of constriction of airways feeding those units outside VDefs were related to the extent of VDefs in bronchoconstricted asthmatic subjects. Positron emission tomography was used to quantify the regional distribution of ventilation and oscillatory mechanics were measured in asthmatic subjects before and after bronchoconstriction. For each subject, ventilation data was mapped into an anatomically based lung model that was used to evaluate whether airway constriction patterns, consistent with the imaging data, were capable of matching the measured changes in airflow obstruction. The degree and heterogeneity of constriction of the airways feeding alveolar units outside VDefs was similar among the subjects studied despite large inter-subject variability in airflow obstruction and the extent of the ventilation defects. Analysis of the data amongst the subjects showed an inverse relationship between the reduction in mean airway conductance, measured in the breathing frequency range during bronchoconstriction, and the fraction of lung involved in ventilation defects. The current data supports the concept that patchy ventilation is an expression of the integrated system and not just the sum of independent responses of individual airways.

Estimate of pulmonary diffusing capacity for oxygen during exercise in humans from routine O(2) and CO(2) measurements.

A method to estimate pulmonary diffusing capacity for O(2) (D(LO2)) during exercise based on routine O(2) and CO(2) transport variables is presented. It is based on the fitting of a mathematical model to gas exchange data. The model includes heterogeneity (described as two exchanging compartments), diffusion limitation and right-to-left shunt. Mass conservation equations and Bohr integration were solved to calculate partial pressures in each compartment. Diffusion was distributed with perfusion. Two-compartment ventilation and perfusion distributions were estimated at rest during conditions of negligible diffusion limitation. These distributions were used during hypoxic and normoxic exercise to obtain the D(LO2) from the model computations (D(LO2)2C) compatible with experimental data. Three normals, four sarcoid patients and four patients after lung resection were studied. An independent technique for carbon monoxide was used to provide experimental estimates of DLo2 (D(LO2)EXP, rebreathing technique for sarcoid patients and single breath for lung resection). D(LO2)2C was highly correlated with D(LO2)EXP (r2 = 0.95, P<0.001) and the slope of the regression line was not statistically different from 1. The mean (D(LO2)EXP - D(LO2)2C) difference was -1.0 +/- 7.4 ml min-1 mmHg-1. The results suggest that use of a refined analytical procedure allows for assessment of D(LO2) from routine O(2) and CO(2) measurements comparable with those obtained from independent carbon monoxide techniques. The method may be an alternative for estimates of D(LO2) during exercise.

Effect of cardiac output on pulmonary gas exchange: role of diffusion limitation with VA/Q mismatch.

We studied the effect of the interaction between diffusion limitation and alveolar ventilation to perfusion ratio (VA/Q) mismatch in the relation between blood gas partial pressures and cardiac output (Q). The analysis was based on a mathematical model of gas exchange involving two exchanging compartments and a right to left shunt. A system of equations describing alveolar-arterial mass conservation for O2, CO2 and N2 and Bohr integration for O2 and CO2 was interactively solved to find sets of alveolar and blood gas partial pressures fitting input data. Simulations used values compatible with patients in respiratory failure and neonate piglets. Association of (VA/Q) mismatch and diffusion impairment limited the increase of PaO2 with Q. A maximum in the PaO2 vs. Q curve can be attained, further Q increases lead to reductions in PaO2. The effect was accentuated by increasing (VA/Q) and diffusion to perfusion heterogeneity. Combination of (VA/Q) mismatch and diffusion limitation was synergistic leading to greater reductions in PaO2 than expected from simple addition of their independent influences. The findings are compatible with experimental data.

Sistema computadorizado para monitorizaçäo cardio-respiratória / Computerized system for cardiorespiratory monitoring

Um sistema baseado em computador pessoal é usado para a monitorização cardio-respiratória de pacientes, em tempo-real, integrando sinais obtidos de diferentes equipamentos: monitor fisiológico (ECG), espectrômetro de massa respiratória (EMR: frações gasosas) e pneumotacógrafo (fluxo ventilatório). O sistema detecta complexos QRS e ciclos respiratórios, e calcula freqüência cardíaca e vários parâmetros respiratórios. O desempenho dos algoritmos é avaliado com sinais simulados, o MIT-BIH Arrhytmia Database e experimentos in-vivo. O sistema é empregado em pesquisa da fisiologia do exercício

Abstract- A modular system based on a personal computer is used to perform real-time cardio-respiratory monitoring of patients. integrating data from different equipments: a bed side monitor (ECG ), a respiratory mass spectrometer (RMS: gas fractions) and a pneumothacograph (respiratory tlow). The system includes an automatic detection of the QRS complexes and the respiratory cycles and it calculates heart rate and severa! respiratory parameters. The performance of the algorithms is estimated with simulated data. the MIT-BIH Arrhythrnia Database and in rivo experirnents. This system is being used for research in exercise physiology

Alveolar ventilation to perfusion heterogeneity and diffusion impairment in a mathematical model of gas exchange.

This study describes a two-compartment model of pulmonary gas exchange in which alveolar ventilation to perfusion (VA/Q) heterogeneity and impairment of pulmonary diffusing capacity (D) are simultaneously taken into account. The mathematical model uses as input data measurements usually obtained in the lung function laboratory. It consists of two compartments and an anatomical shunt. Each compartment receives fractions of alveolar ventilation and blood flow. Mass balance equations and integration of Fick's law of diffusion are used to compute alveolar and blood O2 and CO2 values compatible with input O2 uptake and CO2 elimination. Two applications are presented. The first is a method to partition O2 and CO2 alveolar-arterial gradients into VA/Q and D components. The technique is evaluated in data of patients with chronic obstructive pulmonary disease (COPD). The second is a theoretical analysis of the effects of blood flow variation in alveolar and blood O2 partial pressures. The results show the importance of simultaneous consideration of D to estimate VA/Q heterogeneity in patients with diffusion impairment. This factor plays an increasing role in gas alveolar-arterial gradients as severity of COPD increases. Association of VA/Q heterogeneity and D may produce an increase of O2 arterial pressure with decreasing QT which would not be observed if only D were considered. We conclude that the presented computer model is a useful tool for description and interpretation of data from COPD patients and for performing theoretical analysis of variables involved in the gas exchange process.

Heterogeneity of left ventricular perfusion during pulmonary edema and microembolism treated with positive end-expiratory pressure and norepinephrine.

Regional left ventricular myocardial blood flow was studied in an experimental model of pulmonary edema and microembolization (PEM) ventilated with positive end-expiratory pressure (PEEP). The analysis was based on a 3-dimensional extension of the autocorrelation function used to assess the spatial correlation (rspat) of myocardial perfusion. Experiments were performed on 8 premedicated, anesthetized and mechanically ventilated dogs. PEM was induced with oleic acid (0.01 mg/kg) and glass beads. Successive PEEP values of 10, 15 and 20 cm H2O (P20) were applied and norepinephrine (NE, 0.2-1.0 microgram min-1 kg-1) was administered after P20. Regional perfusion was measured with radioactive microspheres. The left ventricle (LV) was dissected into 256 samples. rspat was computed as the correlation of regional perfusions of samples p units apart in the apex-to-base, endo-epicardial and angular directions. Analysis was performed after anesthesia and instrumentation (control, C), P20 and NE. Control values of rspat were around 50% in the apex-to-base and angular directions and the sign was inverted in the endo-epicardial direction. A reduction of rspat to values close to zero was observed in all directions for P20 and NE. This is the typical pattern of independent distribution. Thus, the results indicate that, under the experimental conditions used, there is some degree of neighborhood dependence of regional LV myocardial blood flow. This dependence is not observed under PEM, mechanical ventilation with PEEP and NE.

Heterogeneity of left ventricular perfusion during pulmonary edema and microembolism treated with positive end-expiratory pressure and norepinephrine

Regional left ventricular myocardial blood flow was studied in an experimental model of pulmonary edema and microembolization (PEM) ventilated with positive end-expiratory pressure (PEEP). The analysis was based on a 3-dimensional extension of the autocorrelation function used to assess the spatial correlation (rspat) of myocardial perfusion. Experiments were performed on 8 premedicated, anesthetized and mechanically ventilated dogs. PEM was induced with oleic acid (0.01 mg/kg) and glass beads. Successive PEEP values of 10, 15 and 20 cm H2O (P20) were applied and norepinephrine (NE, 0.2-1.0 microgram min-1 kg-1) was administered after P20. Regional perfusion was measured with radioactive microspheres. The left ventricle (LV) was dissected into 256 samples. rspat was computed as the correlation of regional perfusions of samples p units apart in the apex-to-base, endo-epicardial and angular directions. Analysis was performed after anesthesia and instrumentation (control, C), P20 and NE. Control values of rspat were around 50 per cent in the apex-to-base and angular directions and the sign was inverted in the endo-epicardial direction. A reduction of rspat to values close to zero was observed in all directions for P20 and NE. This is the typical pattern of independent distribution. Thus, the results indicate that, under the experimental conditions used, there is some degree of neighborhood dependence of regional LV myocardial blood flow. This dependence is not observed under PEM, mechanical ventilation with PEEP and NE