Clinical validation of the Air-Test for the non-invasive detection of perioperative atelectasis in children.

BACKGROUND: The incidence of anesthesia-induced atelectasis in children is high and closely related to episodes of hypoxemia. The Air-Test is a simple maneuver to detect lung collapse. By a step-reduction in FiO2 to 0.21, a fall in pulse-oximetry hemoglobin saturation <97% unmasks the presence of collapse-related shunt in healthy lungs. The aim of this study was to validate the Air-Test as a diagnostic tool to detect perioperative atelectasis in children using lung ultrasound as a reference. METHODS: We first assessed the Air-Test in a retrospective cohort of 88 anesthetized children (Retrospective study) followed by a prospective study performed in 72 children (45 postconceptional weeks to 16 years old) using a similar protocol (Validation study). We analyzed the performance of the Air-Test to detect atelectasis by an operating characteristic curve (ROC) analysis, using lung ultrasound consolidation score as reference. RESULTS: Preoperative SpO2 was normal in both studies (retrospective 98.7±0.6%, validation 99.0±0.9%). The Air-Test, with a SpO2 cut point <97%, resulted positive in 67 patients in the retrospective study (SpO2 93.3±2.1%) and in 59 in the validation study (SpO2 94.9±1.8%); both P<0.0001. In the validation study, the Air-Test showed a sensitivity of 0.91 (95% CI 0.85-0.92), specificity of 1.00 (95% CI 0.84-1) and an area under the curve (AUC) of 0.98 (95% CI 0.97-1.00). AUC between both studies was similar (P=0.16). CONCLUSIONS: The Air-Test is a noninvasive and accurate method to detect atelectasis in healthy anesthetized children. It can be used as a screening tool to individualize patients that can benefit from lung recruitment maneuvers.

Finger photopletysmography detects early acute blood loss in compensated blood donors: a pilot study.

Objective.Diagnosis of incipient acute hypovolemia is challenging as vital signs are typically normal and patients remain asymptomatic at early stages. The early identification of this entity would affect patients' outcome if physicians were able to treat it precociously. Thus, the development of a noninvasive, continuous bedside monitoring tool to detect occult hypovolemia before patients become hemodynamically unstable is clinically relevant. We hypothesize that pulse oximeter's alternant (AC) and continuous (DC) components of the infrared light are sensitive to acute and small changes in patient's volemia. We aimed to test this hypothesis in a cohort of healthy blood donors as a model of slight hypovolemia.Approach.We planned to prospectively study blood donor volunteers removing 450 ml of blood in supine position. Noninvasive arterial blood pressure, heart rate, and finger pulse oximetry were recorded. Data was analyzed before donation, after donation and during blood auto-transfusion generated by the passive leg-rising (PLR) maneuver.Main results.Sixty-six volunteers (44% women) accomplished the protocol successfully. No clinical symptoms of hypovolemia, arterial hypotension (systolic pressure < 90 mmHg), brady-tachycardia (heart rate <60 and >100 beats-per-minute) or hypoxemia (SpO2< 90%) were observed during donation. The AC signal before donation (median 0.21 and interquartile range 0.17 a.u.) increased after donation [0.26(0.19) a.u;p< 0.001]. The DC signal before donation [94.05(3.63) a.u] increased after blood extraction [94.65(3.49) a.u;p< 0.001]. When the legs' blood was auto-transfused during the PLR, the AC [0.21(0.13) a.u.;p= 0.54] and the DC [94.25(3.94) a.u.;p= 0.19] returned to pre-donation levels.Significance.The AC and DC components of finger pulse oximetry changed during blood donation in asymptomatic volunteers. The continuous monitoring of these signals could be helpful in detecting occult acute hypovolemia. New pulse oximeters should be developed combining the AC/DC signals with a functional hemodynamic monitoring of fluid responsiveness to define which patient needs fluid administration.

Monitoring CO2 kinetics as a marker of cardiopulmonary efficiency.

PURPOSE OF REVIEW: To describe current and near future developments and applications of CO2 kinetics in clinical respiratory and cardiovascular monitoring. RECENT FINDINGS: In the last years, we have witnessed a renewed interest in CO2 kinetics in relation with a better understanding of volumetric capnography and its derived parameters. This together with technological advances and improved measurement systems have expanded the monitoring potential of CO2 kinetics including breath by breath continuous end-expiratory lung volume and continuous noninvasive cardiac output. Dead space has slowly been gaining relevance in clinical monitoring and prognostic evaluation. Easy to measure dead space surrogates such as the ventilatory ratio have demonstrated a strong prognostic value in patients with acute respiratory failure. SUMMARY: The kinetics of carbon dioxide describe many relevant physiological processes. The clinical introduction of new ways of assessing respiratory and circulatory efficiency based on advanced analysis of CO2 kinetics are paving the road to a long-desired goal in clinical monitoring of critically ill patients: the integration of respiratory and circulatory monitoring during mechanical ventilation.

Impact of respiratory cycle during mechanical ventilation on beat-to-beat right ventricle stroke volume estimation by pulmonary artery pulse wave analysis.

BACKGROUND: The same principle behind pulse wave analysis can be applied on the pulmonary artery (PA) pressure waveform to estimate right ventricle stroke volume (RVSV). However, the PA pressure waveform might be influenced by the direct transmission of the intrathoracic pressure changes throughout the respiratory cycle caused by mechanical ventilation (MV), potentially impacting the reliability of PA pulse wave analysis (PAPWA). We assessed a new method that minimizes the direct effect of the MV on continuous PA pressure measurements and enhances the reliability of PAPWA in tracking beat-to-beat RVSV. METHODS: Continuous PA pressure and flow were simultaneously measured for 2-3 min in 5 pigs using a high-fidelity micro-tip catheter and a transonic flow sensor around the PA trunk, both pre and post an experimental ARDS model. RVSV was estimated by PAPWA indexes such as pulse pressure (SVPP), systolic area (SVSystAUC) and standard deviation (SVSD) beat-to-beat from both corrected and non-corrected PA signals. The reference RVSV was derived from the PA flow signal (SVref). RESULTS: The reliability of PAPWA in tracking RVSV on a beat-to-beat basis was enhanced after accounting for the direct impact of intrathoracic pressure changes induced by MV throughout the respiratory cycle. This was evidenced by an increase in the correlation between SVref and RVSV estimated by PAPWA under healthy conditions: rho between SVref and non-corrected SVSD - 0.111 (0.342), corrected SVSD 0.876 (0.130), non-corrected SVSystAUC 0.543 (0.141) and corrected SVSystAUC 0.923 (0.050). Following ARDS, correlations were SVref and non-corrected SVSD - 0.033 (0.262), corrected SVSD 0.839 (0.077), non-corrected SVSystAUC 0.483 (0.114) and corrected SVSystAUC 0.928 (0.026). Correction also led to reduced limits of agreement between SVref and SVSD and SVSystAUC in the two evaluated conditions. CONCLUSIONS: In our experimental model, we confirmed that correcting for mechanical ventilation induced changes during the respiratory cycle improves the performance of PAPWA for beat-to-beat estimation of RVSV compared to uncorrected measurements. This was demonstrated by a better correlation and agreement between the actual SV and the obtained from PAPWA.

Respiratory gating improves correlation between pulse wave transit time and pulmonary artery pressure in experimental pulmonary hypertension.

Objective. Since pulse wave transit time (PWTT) shortens as pulmonary artery pressure (PAP) increases it was suggested as a potential non-invasive surrogate for PAP. The state of tidal lung filling is also known to affect PWTT independently of PAP. The aim of this retrospective analysis was to test whether respiratory gating improved the correlation coefficient between PWTT and PAP.Approach. In each one of five anesthetized and mechanically ventilated pigs two high-fidelity pressure catheters were placed, one directly behind the pulmonary valve, and the second one in a distal branch of the pulmonary artery. PAP was raised using the thromboxane A2 analogue U46619 and animals were ventilated in a pressure controlled mode (I:E ratio 1:2, respiratory rate 12/min, tidal volume of 6 ml kg-1). All signals were recorded using the multi-channel platform PowerLab®. The arrival of the pulse wave at each catheter tip was determined using a MATLAB-based modified hyperbolic tangent algorithm and PWTT calculated as the time interval between these arrivals.Main results. Correlation coefficient for PWTT and mean PAP wasr= 0.932 for thromboxane. This correlation coefficient increased considerably when heart beats either at end-inspiration (r= 0.978) or at end-expiration (r= 0.985) were selected (=respiratory gating).Significance. The estimation of mean PAP from PWTT improved significantly when taking the respiratory cycle into account. Respiratory gating is suggested to improve for the estimation of PAP by PWTT.

Effect of an Individualized Lung Protective Ventilation on Lung Strain and Stress in Children Undergoing Laparoscopy: An Observational Cohort Study.

BACKGROUND: Exaggerated lung strain and stress could damage lungs in anesthetized children. The authors hypothesized that the association of capnoperitoneum and lung collapse in anesthetized children increases lung strain-stress. Their primary aim was to describe the impact of capnoperitoneum on lung strain-stress and the effects of an individualized protective ventilation during laparoscopic surgery in children. METHODS: The authors performed an observational cohort study in healthy children aged 3 to 7 yr scheduled for laparoscopic surgery in a community hospital. All received standard protective ventilation with 5 cm H2O of positive end-expiratory pressure (PEEP). Children were evaluated before capnoperitoneum, during capnoperitoneum before and after lung recruitment and optimized PEEP (PEEP adjusted to get end-expiratory transpulmonary pressure of 0), and after capnoperitoneum with optimized PEEP. The presence of lung collapse was evaluated by lung ultrasound, positive Air-Test (oxygen saturation measured by pulse oximetry 96% or less breathing 21% O2 for 5 min), and negative end-expiratory transpulmonary pressure. Lung strain was calculated as tidal volume/end-expiratory lung volume measured by capnodynamics, and lung stress as the end-inspiratory transpulmonary pressure. RESULTS: The authors studied 20 children. Before capnoperitoneum, mean lung strain was 0.20 ± 0.07 (95% CI, 0.17 to 0.23), and stress was 5.68 ± 2.83 (95% CI, 4.44 to 6.92) cm H2O. During capnoperitoneum, 18 patients presented lung collapse and strain (0.29 ± 0.13; 95% CI, 0.23 to 0.35; P < 0.001) and stress (5.92 ± 3.18; 95% CI, 4.53 to 7.31 cm H2O; P = 0.374) increased compared to before capnoperitoneum. During capnoperitoneum and optimized PEEP, children presenting lung collapse were recruited and optimized PEEP was 8.3 ± 2.2 (95% CI, 7.3 to 9.3) cm H2O. Strain returned to values before capnoperitoneum (0.20 ± 0.07; 95% CI, 0.17 to 0.22; P = 0.318), but lung stress increased (7.29 ± 2.67; 95% CI, 6.12 to 8.46 cm H2O; P = 0.020). After capnoperitoneum, strain decreased (0.18 ± 0.04; 95% CI, 0.16 to 0.20; P = 0.090), but stress remained higher (7.25 ± 3.01; 95% CI, 5.92 to 8.57 cm H2O; P = 0.024) compared to before capnoperitoneum. CONCLUSIONS: Capnoperitoneum increased lung strain in healthy children undergoing laparoscopy. Lung recruitment and optimized PEEP during capnoperitoneum decreased lung strain but slightly increased lung stress. This little rise in pulmonary stress was maintained within safe, lung-protective, and clinically acceptable limits.

Effects of apparatus dead space on volumetric capnograms in neonates with healthy lungs: a simulation study.

BACKGROUND: Volumetric capnography in healthy ventilated neonates showed deformed waveforms, which are supposedly due to technological limitations of flow and carbon dioxide sensors. AIMS: This bench study analyzed the role of apparatus dead space on the shape of capnograms in simulated neonates with healthy lungs. METHODS: We simulated mechanical breaths in neonates of 2, 2.5, and 3 kg of body weight using a neonatal volumetric capnography simulator. The simulator was fed by a fixed amount of carbon dioxide of 6 mL/kg/min. Such simulator was ventilated in a volume control mode using fixed ventilatory settings with a tidal volume of 8 mL/kg and respiratory rates of 40, 35, and 30 breaths per minute for the 2, 2.5 and 3 kg neonates, respectively. We tested the above baseline ventilation with and without an additional apparatus dead space of 4 mL. RESULTS: Simulations showed that adding the apparatus dead space to baseline ventilation increased the amount of re-inhaled carbon dioxide in all neonates: 0.16 ± 0.01 to 0.32 ± 0.03 mL (2 kg), 0.14 ± 0.02 to 0.39 ± 0.05 mL (2.5 kg), and 0.13 ± 0.01 to 0.36 ± 0.05 mL (3 kg); (p < .001). Apparatus dead space was computed as part of the airway dead space, and therefore, the ratio of airway dead space to tidal volume increased from 0.51 ± 0.04 to 0.68 ± 0.06, from 0.43 ± 0.04 to 0.62 ± 0.01 and from 0.38 ± 0.01 to 0.60 ± 0.02 in the 2, 2.5 and 3 kg simulated neonates, respectively (p < .001). Compared to baseline ventilation, adding apparatus dead space decreased the ratio of the volume of phase III to VT size from 31% to 11% (2 kg), from 40% to 16% (2.5 kg) and from 50% to 18% (3 kg); (p < .001). CONCLUSIONS: The addition of a small apparatus dead space artificially deformed the volumetric capnograms in simulated neonates with healthy lungs.

Development of a Novel Infant Volumetric Capnography Simulator: Making the Invisible Visible Improves Understanding and Safety.

METHODS: An infant lung simulator was fed with CO2 supplied by a mass flow controller (VCO2-IN) and ventilated using standard settings. A volumetric capnograph was placed between the endotracheal tube and the ventilatory circuit. We simulated ventilated babies of different body weights (2, 2.5, 3, and 5 kg) with a VCO2 ranging from 12 to 30 mL/min. The correlation coefficient (r2), bias, coefficient of variation (CV = SD/x × 100), and precision (2 × CV) between the VCO2-IN and the elimination of CO2 recorded by the capnograph (VCO2-OUT) were calculated. The quality of the capnogram's waveforms was compared with real ones belonging to anesthetized infants using an 8-point scoring system, where 6 points or greater meant that the simulated capnogram showed good, 5 to 3 points acceptable, and less than 3 points an unacceptable shape. RESULTS: The correlation between VCO2-IN and VCO2-OUT was r2 = 0.9953 (P < 0.001), with a bias of 0.16 (95% confidence intervals from 0.12 to 0.20) mL/min. The CV was 5% or less and the precision was 10% or less. All simulated capnograms showed similar shapes compared with real babies, scoring 6 points for 3 kg and 6.5 points for 2-, 2.5-, and 5-kg babies. CONCLUSIONS: The simulator of volumetric capnograms was reliable, accurate, and precise for simulating the CO2 kinetics of ventilated infants.

Ventilation Induces Changes in Pulse Wave Transit Time in the Pulmonary Artery.

Pulse wave transit time (PWTT) shortens as pulmonary artery pressure (PAP) increases and was therefore suggested as a surrogate parameter for PAP. The aim of this analysis was to reveal patterns and potential mechanisms of ventilation-induced periodic changes in PWTT under resting conditions. To measure both PWTT and PAP in five healthy pigs, two pulmonary artery Mikro-Tip™ catheters were inserted into the pulmonary vasculature: one with the tip placed in the pulmonary artery trunk, and a second one placed in a distal segment of the pulmonary artery. Animals received pressure-controlled mechanical ventilation. Ventilation-dependent changes were seen in both variables, PWTT and mean PAP; however, changes in PWTT were not synchronous with changes in PAP. Thus, plotting the value of PWTT for each heartbeat over the respective PAP revealed a characteristic hysteresis. At the beginning of inspiration, PAP rose while PWTT remained constant. During further inspiration, PWTT started to decrease rapidly as mPAP was about to reach its plateau. The same time course was observed during expiration: while mPAP approached its minimum, PWTT increased rapidly. During apnea this hysteresis disappeared. Thus, non-synchronous ventilation-induced changes in PWTT and PAP were found with inspiration causing a significant shortening of PWTT. Therefore, it is suggested that the respiratory cycle should be considered when using PWTT as a surrogate for PAP.

Short communication: ultrasound-guided percutaneous cryoanalgesia of intercostal nerves for uniportal video-assisted thoracic surgery.

BACKGROUND: Pain after thoracic surgery impairs lung function and increases the rate of postoperative pulmonary complications. Ultrasound-guided percutaneous cryoanalgesia of intercostal nerves constitutes a valid option for adequate postoperative analgesia. A key issue for a successful cryoanalgesia is placing the cryoprobe tip close to the intercostal nerve. This report describes an ultrasound technique using a high-resolution ultrasound probe to accomplish this goal. FINDINGS: Images of five anesthetized patients undergoing uniportal video-thoracoscopic surgeries are used as clinical examples. In the lateral position, a high-frequency 12 MHz probe is placed longitudinally at 5-7 cm parallel to the spine at the 4th, 5th, and 6th ipsilateral intercostal spaces. Ultrasound images detect the intercostal neurovascular bundle and a 14G angiocath is placed beside the nerve. The cryoprobe is inserted throughout the 14G catheter and the cryoanalgesia cycle is performed for 3 min. Two ultrasound signs confirm the right cryoprobe position close to the nerve: one is a color Doppler twinkling artifact that is seen as the quick shift of colors that delineates the cryoprobe contour. The other is a spherical hypoechoic image caused by the ice ball formed at the cryoprobe tip. CONCLUSIONS: Ultrasound images obtained with a high-frequency probe allow precise location of the cryoprobe tip close to the intercostal nerve for cold axonotmesis.

Dynamic Relative Regional Lung Strain Estimated by Electrical Impedance Tomography in an Experimental Model of ARDS.

BACKGROUND: To analyze the role of PEEP on dynamic relative regional strain (DRRS) in a model of ARDS, respective maps were generated by electrical impedance tomography (EIT). METHODS: Eight ARDS pigs submitted to PEEP steps of 0, 5, 10, and 15 cm H2O at fixed ventilation were evaluated by EIT images. DRRS was calculated as (VT-EIT/EELI)/(VT-EIT[15PEEP]/EELI[15PEEP]), where the tidal volume (VT)-EIT and end-expiratory lung impedance (EELI) are the tidal and end-expiratory change in lung impedance, respectively. The measurement at 15 PEEP was taken as reference (end-expiratory transpulmonary pressure > 0 cm H2O). The relationship between EIT variables (center of ventilation, EELI, and DRRS) and airway pressures was assessed with mixed-effects models using EIT measurements as dependent variables and PEEP as fixed-effect variable. RESULTS: At constant ventilation, respiratory compliance increased progressively with PEEP (lowest value at zero PEEP 10 ± 3 mL/cm H2O and highest value at 15 PEEP 16 ± 6 mL/cm H2O; P < .001), whereas driving pressure decreased with PEEP (highest value at zero PEEP 34 ± 6 cm H2O and lowest value at 15 PEEP 21 ± 4 cm H2O; P < .001). The mixed-effect regression models showed that the center of ventilation moved to dorsal lung areas with a slope of 1.81 (1.44-2.18) % points by each cm H2O of PEEP; P < .001. EELI increased with a slope of 0.05 (0.02-0.07) (arbitrary units) for each cm H2O of PEEP; P < .001. DRRS maps showed that local strain in ventral lung areas decreased with a slope of -0.02 (-0.24 to 0.15) with each cm H2O increase of PEEP; P < .001. CONCLUSIONS: EIT-derived DRRS maps showed high strain in ventral lung zones at low levels of PEEP. The findings suggest overdistention of the baby lung.

Perioperative Continuous Noninvasive Cardiac Output Monitoring in Cardiac Surgery Patients by a Novel Capnodynamic Method.

OBJECTIVES: To test the clinical performance of a novel continuous noninvasive cardiac output (CO) monitoring based on expired carbon dioxide kinetics in cardiac surgery patients. DESIGN: A prospective feasibility pragmatic clinical study. SETTING: A single-center, large community hospital. PARTICIPANTS: Thirty-two patients undergoing cardiac surgery were studied during the intraoperative (before cardiopulmonary bypass) and postoperative (in the intensive care unit before extubation) periods. INTERVENTIONS: CO was measured simultaneously by the continuous capnodynamic method and by transpulmonary thermodilution during changes in the patient's hemodynamic and/or respiratory conditions. MEASUREMENTS AND MAIN RESULTS: The current recommended comparative statistics for CO measurement methods were analyzed, including bias, precision, and percentage error obtained from Bland-Altman analysis, and concordance between methods obtained from the four-quadrant plot analysis to evaluate the trending ability. Bias ± limits of agreement and percentage error were -0.6 (-1.9 to +0.8; 95% CI of 3.73-5.25) L/min and 31% (n = 147 measurements) for the intraoperative period, -0.8 (-2.4 to +0.9; 95% CI of 3.03-5.21) L/min and 41% (n = 66) for the postoperative period, and -0.6 (-2.1 to +0.8; 95% CI of 3.74-5.00) L/min and 34% (n = 213) for the pooled data. The trending analysis obtained a concordance of 82% (n = 65) for the intraoperative and 71% (n = 24) for the early postoperative periods. Aggregation of both data sets gave a concordance of 79% (n = 89). CONCLUSIONS: The continuous capnodynamic method was reliable and in good agreement with the reference method, and had an accuracy and trending ability good enough to make it a possible future alternative for hemodynamic monitoring in the studied population of elective adult cardiac surgery patients.

Sequential lateral positioning as a new lung recruitment maneuver: an exploratory study in early mechanically ventilated Covid-19 ARDS patients.

BACKGROUND: A sequential change in body position from supine-to-both lateral positions under constant ventilatory settings could be used as a postural recruitment maneuver in case of acute respiratory distress syndrome (ARDS), provided that sufficient positive end-expiratory pressure (PEEP) prevents derecruitment. This study aims to evaluate the feasibility and physiological effects of a sequential postural recruitment maneuver in early mechanically ventilated COVID-19 ARDS patients. METHODS: A cohort of 15 patients receiving lung-protective mechanical ventilation in volume-controlled with PEEP based on recruitability were prospectively enrolled and evaluated in five sequentially applied positions for 30 min each: Supine-baseline; Lateral-1st side; 2nd Supine; Lateral-2nd side; Supine-final. PEEP level was selected using the recruitment-to-inflation ratio (R/I ratio) based on which patients received PEEP 12 cmH2O for R/I ratio ≤ 0.5 or PEEP 15 cmH2O for R/I ratio > 0.5. At the end of each period, we measured respiratory mechanics, arterial blood gases, lung ultrasound aeration, end-expiratory lung impedance (EELI), and regional distribution of ventilation and perfusion using electric impedance tomography (EIT). RESULTS: Comparing supine baseline and final, respiratory compliance (29 ± 9 vs 32 ± 8 mL/cmH2O; p < 0.01) and PaO2/FIO2 ratio (138 ± 36 vs 164 ± 46 mmHg; p < 0.01) increased, while driving pressure (13 ± 2 vs 11 ± 2 cmH2O; p < 0.01) and lung ultrasound consolidation score decreased [5 (4-5) vs 2 (1-4); p < 0.01]. EELI decreased ventrally (218 ± 205 mL; p < 0.01) and increased dorsally (192 ± 475 mL; p = 0.02), while regional compliance increased in both ventral (11.5 ± 0.7 vs 12.9 ± 0.8 mL/cmH2O; p < 0.01) and dorsal regions (17.1 ± 1.8 vs 18.8 ± 1.8 mL/cmH2O; p < 0.01). Dorsal distribution of perfusion increased (64.8 ± 7.3% vs 66.3 ± 7.2%; p = 0.01). CONCLUSIONS: Without increasing airway pressure, a sequential postural recruitment maneuver improves global and regional respiratory mechanics and gas exchange along with a redistribution of EELI from ventral to dorsal lung areas and less consolidation. Trial registration ClinicalTrials.gov, NCT04475068. Registered 17 July 2020, https://clinicaltrials.gov/ct2/show/NCT04475068.

Positive end-expiratory pressure individualization guided by continuous end-expiratory lung volume monitoring during laparoscopic surgery.

To determine whether end-expiratory lung volume measured with volumetric capnography (EELVCO2) can individualize positive end-expiratory pressure (PEEP) setting during laparoscopic surgery. We studied patients undergoing laparoscopic surgery subjected to Fowler (F-group; n = 20) or Trendelenburg (T-group; n = 20) positions. EELVCO2 was measured at 0° supine (baseline), during capnoperitoneum (CP) at 0° supine, during CP with Fowler (head up + 20°) or Trendelenburg (head down - 30°) positions and after CP back to 0° supine. PEEP was adjusted to preserve baseline EELVCO2 during and after CP. Baseline EELVCO2 was statistically similar to predicted FRC in both groups. At supine and CP, EELVCO2 decreased from baseline values in F-group [median and IQR 2079 (768) to 1545 (725) mL; p = 0.0001] and in T-group [2164 (789) to 1870 (940) mL; p = 0.0001]. Change in body position maintained EELVCO2 unchanged in both groups. PEEP adjustments from 5.6 (1.1) to 10.0 (2.5) cmH2O in the F-group (p = 0.0001) and from 5.6 (0.9) to 10.0 (2.6) cmH2O in T-group (p = 0.0001) were necessary to reach baseline EELVCO2 values. EELVCO2 increased close to baseline with PEEP in the F-group [1984 (600) mL; p = 0.073] and in the T-group [2175 (703) mL; p = 0.167]. After capnoperitoneum and back to 0° supine, PEEP needed to maintain EELVCO2 was similar to baseline PEEP in F-group [5.9 (1.8) cmH2O; p = 0.179] but slightly higher in the T-group [6.5 (2.2) cmH2O; p = 0.006]. Those new PEEP values gave EELVCO2 similar to baseline in the F-group [2039 (980) mL; p = 0.370] and in the T-group [2150 (715) mL; p = 0.881]. Breath-by-breath noninvasive EELVCO2 detected changes in lung volume induced by capnoperitoneum and body position and was useful to individualize the level of PEEP during laparoscopy.Trial registry: Clinicaltrials.gov NCT03693352. Protocol started 1st October 2018.

Intraoperative open lung condition and postoperative pulmonary complications. A secondary analysis of iPROVE and iPROVE-O2 trials.

BACKGROUND: The preventive role of an intraoperative recruitment maneuver plus open lung approach (RM + OLA) ventilation on postoperative pulmonary complications (PPC) remains unclear. We aimed at investigating whether an intraoperative open lung condition reduces the risk of developing a composite of PPCs. METHODS: Post hoc analysis of two randomized controlled trials including patients undergoing abdominal surgery. Patients were classified according to the intraoperative lung condition as "open" (OL) or "non-open" (NOL) if PaO2 /FIO2 ratio was ≥ or <400 mmHg, respectively. We used a multivariable logistic regression model that included potential confounders selected with directed acyclic graphs (DAG) using Dagitty software built with variables that were considered clinically relevant based on biological mechanism or evidence from previously published data. PPCs included severe acute respiratory failure, acute respiratory distress syndrome, and pneumonia. RESULTS: A total of 1480 patients were included in the final analysis, with 718 (49%) classified as OL. The rate of severe PPCs during the first seven postoperative days was 6.0% (7.9% in the NOL and 4.4% in the OL group, p = .007). OL was independently associated with a lower risk for severe PPCs during the first 7 and 30 postoperative days [odds ratio of 0.58 (95% CI 0.34-0.99, p = .04) and 0.56 (95% CI 0.34-0.94, p = .03), respectively]. CONCLUSIONS: An intraoperative open lung condition was associated with a reduced risk of developing severe PPCs in intermediate-to-high risk patients undergoing abdominal surgery. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT02158923 (iPROVE), NCT02776046 (iPROVE-O2).

Unsuccessful and Successful Clinical Trials in Acute Respiratory Distress Syndrome: Addressing Physiology-Based Gaps.

The acute respiratory distress syndrome (ARDS) is a severe form of acute hypoxemic respiratory failure caused by an insult to the alveolar-capillary membrane, resulting in a marked reduction of aerated alveoli, increased vascular permeability and subsequent interstitial and alveolar pulmonary edema, reduced lung compliance, increase of physiological dead space, and hypoxemia. Most ARDS patients improve their systemic oxygenation, as assessed by the ratio between arterial partial pressure of oxygen and inspired oxygen fraction, with conventional intensive care and the application of moderate-to-high levels of positive end-expiratory pressure. However, in some patients hypoxemia persisted because the lungs are markedly injured, remaining unresponsive to increasing the inspiratory fraction of oxygen and positive end-expiratory pressure. For decades, mechanical ventilation was the only standard support technique to provide acceptable oxygenation and carbon dioxide removal. Mechanical ventilation provides time for the specific therapy to reverse the disease-causing lung injury and for the recovery of the respiratory function. The adverse effects of mechanical ventilation are direct consequences of the changes in pulmonary airway pressures and intrathoracic volume changes induced by the repetitive mechanical cycles in a diseased lung. In this article, we review 14 major successful and unsuccessful randomized controlled trials conducted in patients with ARDS on a series of techniques to improve oxygenation and ventilation published since 2010. Those trials tested the effects of adjunctive therapies (neuromuscular blocking agents, prone positioning), methods for selecting the optimum positive end-expiratory pressure (after recruitment maneuvers, or guided by esophageal pressure), high-frequency oscillatory ventilation, extracorporeal oxygenation, and pharmacologic immune modulators of the pulmonary and systemic inflammatory responses in patients affected by ARDS. We will briefly comment physiology-based gaps of negative trials and highlight the possible needs to address in future clinical trials in ARDS.