Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome.

BACKGROUND: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. METHODS: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg-1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. RESULTS: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. CONCLUSIONS: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).

A novel method for assessment of airway opening pressure without the need for low-flow insufflation.

BACKGROUND: Airway opening pressure (AOP) detection and measurement are essential for assessing respiratory mechanics and adapting ventilation. We propose a novel approach for AOP assessment during volume assist control ventilation at a usual constant-flow rate of 60 L/min. OBJECTIVES: To validate the conductive pressure (Pcond) method, which compare the Pcond-defined on the airway pressure waveform as the difference between the airway pressure level at which an abrupt change in slope occurs at the beginning of insufflation and PEEP-to resistive pressure for AOP detection and measurement, and to compare its respiratory and hemodynamic tolerance to the standard low-flow insufflation method. METHODS: The proof-of-concept of the Pcond method was assessed on mechanical (lung simulator) and physiological (cadavers) bench models. Its diagnostic performance was evaluated in 213 patients, using the standard low-flow insufflation method as a reference. In 45 patients, the respiratory and hemodynamic tolerance of the Pcond method was compared with the standard low-flow method. MEASUREMENTS AND MAIN RESULTS: Bench assessments validated the Pcond method proof-of-concept. Sensitivity and specificity of the Pcond method for AOP detection were 93% and 91%, respectively. AOP obtained by Pcond and standard low-flow methods strongly correlated (r = 0.84, p < 0.001). Changes in SpO2 were significantly lower during Pcond than during standard method (p < 0.001). CONCLUSION: Determination of Pcond during constant-flow assist control ventilation may permit to easily and safely detect and measure AOP.

Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.

Type-I Interferon assessment in 45 minutes using the FilmArray® PCR platform in SARS-CoV-2 and other viral infections.

Low concentrations of type-I interferon (IFN) in blood seem to be associated with more severe forms of Coronavirus disease 2019 (COVID-19). However, following the type-I interferon response (IR) in early stage disease is a major challenge. We evaluated detection of a molecular interferon signature on a FilmArray® system, which includes PCR assays for four interferon stimulated genes. We analyzed three types of patient populations: (i) children admitted to a pediatric emergency unit for fever and suspected infection, (ii) ICU-admitted patients with severe COVID-19, and (iii) healthcare workers with mild COVID-19. The results were compared to the reference tools, that is, molecular signature assessed with Nanostring® and IFN-α2 quantification by SIMOA® (Single MOlecule Array). A strong correlation was observed between the IR measured by the FilmArray®, Nanostring®, and SIMOA® platforms (r-Spearman 0.996 and 0.838, respectively). The FilmArray® panel could be used in the COVID-19 pandemic to evaluate the IR in 45-min with 2 min hand-on-time at hospitalization and to monitor the IR in future clinical trials.

Voxel-wise assessment of lung aeration changes on CT images using image registration: application to acute respiratory distress syndrome (ARDS).

PURPOSE: (1) To improve the accuracy of global and regional alveolar-recruitment quantification in CT scan pairs by accounting for lung-tissue displacements and deformation, (2) To propose a method for local-recruitment calculation. METHODS: Recruitment was calculated by subtracting the quantity of non-aerated lung tissues between expiration and inspiration. To assess global recruitment, lung boundaries were first interactively delineated at inspiration, and then they were warped based on automatic image registration to define the boundaries at expiration. To calculate regional recruitment, the lung mask defined at inspiration was cut into pieces, and these were also warped to encompass the same tissues at expiration. Local-recruitment map was calculated as follows: For each voxel at expiration, the matching location at inspiration was determined by image registration, non-aerated voxels were counted in the neighborhood of the respective locations, and the voxel count difference was normalized by the neighborhood size. The methods were evaluated on 120 image pairs of 12 pigs with experimental acute respiratory distress syndrome. RESULTS: The dispersion of global- and regional-recruitment values decreased when using image registration, compared to the conventional approach neglecting tissue motion. Local-recruitment maps overlaid onto the original images were visually consistent, and the sum of these values over the whole lungs was very close to the global-recruitment estimate, except four outliers. CONCLUSIONS: Image registration can compensate lung-tissue displacements and deformation, thus improving the quantification of alveolar recruitment. Local-recruitment calculation can also benefit from image registration, and its values can be overlaid onto the original image to display a local-recruitment map. They also can be integrated over arbitrarily shaped regions to assess regional or global recruitment.

Noninvasive quantitative assessment of pulmonary blood flow with 18F-FDG PET.

UNLABELLED: Pulmonary blood flow (PBF) is a critical determinant of oxygenation during acute lung injury (ALI). PET/CT with (18)F-FDG allows the assessment of both lung aeration and neutrophil inflammation as well as an estimation of the regional fraction of blood (FB) if compartmental modeling is used to quantify (18)F-FDG pulmonary uptake. The aim of this study was to validate the use of FB to assess PBF, with PET and compartmental modeling of (15)O-H2O kinetics as a reference method, in both control animals and animals with ALI. For the purpose of studying a wide range of PBF values, supine and prone positions and various positive end-expiratory pressures (PEEPs) and tidal volumes (V(T)s) were selected. METHODS: Pigs were randomized into 3 groups in which ALI was induced by HCl inhalation: pigs studied in the supine position with a low PEEP (5 ± 3 [mean ± SD] cm of H2O; n = 9) or a high PEEP (12 ± 1 cm of H2O; n = 8) and pigs studied in the prone position with a low PEEP (6 ± 3 cm of H2O; n = 9). Also included were a control group that did not have ALI (n = 6) and 2 additional groups (n = 6 each) that had a high V(T) to maintain a transpulmonary pressure of greater than or equal to 35 cm of H2O and that either received HCl inhalation or did not receive HCl inhalation. PBF and FB were measured with PET and compartmental modeling of (15)O-H2O and (18)F-FDG kinetics in 10 lung regions along the anterior-to-posterior lung dimension, and both were expressed in each region as a fraction of their values in the whole lung. RESULTS: PBF and FB were strongly correlated (R(2) = 0.9), with a slope of the regression line close to unity and a negligible intercept. The mean difference between PBF and FB was 0, and the 95% limits of agreement were -0.035 to 0.035. This good agreement between methods was obtained in both normal and injured lungs and under a wide range of V(T), PEEP, and regional PBF values (7-71 mL/kg, 0-15 cm of H2O, and 24-603 mL·min(-1)·100 mL of lung(-1), respectively). CONCLUSION: FB assessed with (18)F-FDG is a good surrogate for PBF in both normal animals and animals with ALI. PET/CT has the potential to be used to study ventilation, perfusion, and lung inflammation with a single tracer.

Assessment of airway closure from deflation lung volume-pressure curve: sigmoidal equation revisited.

OBJECTIVE: To assess a sigmoidal equation for describing airway closure. DESIGN: Experimental study. SETTING: University laboratory. PARTICIPANTS: Eight piglets mechanically ventilated on zero end-expiratory pressure (ZEEP). INTERVENTIONS: Control and lung saline lavage. MEASUREMENTS AND RESULTS: Lungs were inflated up to transpulmonary pressure of 30 cmH(2)O at constant flow (0.12l s(-1)) then deflated at the same flow rate up to the point at which oesophageal pressure was constant, which was assumed to represent complete airway closure. The deflation volume-transpulmonary pressure curve was fitted to: (1) a sigmoidal equation focusing on inflexion point and pressure at maximal compliance increase and (2) an exponential equation above an inflexion point determined by eyeballing. Data deviate from the exponential equation at the point of airway closure onset. The zero-volume intercept was determined. Complete airway closure was reached at -8.3+/-3.5cmH(2)O in control conditions and at -1.3+/-3.7 cmH(2)O after lavage (p < 0.05). Between control and lavage, onset of airway closure was 3.0+/-1.9 vs. 6.0+/-2.8 cmH(2)O (p <0.05), inflexion point 3.2+/-1.8 vs. 7.7+/-2.6 cmH(2)O (p <0.001), pressure at maximal compliance increase -1.9+/-0.7 vs. -0.03+/-2.1cmH(2)O (p <0.05) and zero-volume intercept -1.5+/-1.4 vs. 0.3+/-2.3cmH(2)O (p <0.05). CONCLUSIONS: During mechanical ventilation airways stay open and close around ZEEP in control but are closed above ZEEP after lavage. Inflexion point might reflect onset of airways closure in control. Pressure at maximal compliance increase was not a marker of complete airways closure. In control and lavage, pressure at maximal compliance increase and zero-volume intercept were reasonably equivalent.

Quantitative assessment of regional alveolar ventilation and gas volume using 13N-N2 washout and PET.

UNLABELLED: Measurement of alveolar volume (Va) and regional ventilation (a) is crucial to understanding the pathophysiology of acute lung injury and ventilator-induced lung injury. PET has previously been used as a noninvasive, quantitative method to assess a, but formal validation of this technique in experimental lung injury is lacking. This study aims to validate Va and a regional assessment with PET, using inhaled (13)N-N(2) in pigs. METHODS: Two normal and 2 oleic acid-injured pigs were tracheotomized, mechanically ventilated, and studied in 5 different levels of ventilation by changing respiratory rate. In each experimental condition, lungs were washed-in and then washed-out with (13)N-N(2) through an open circuit in the ventilator. Using this method, multiframe images were acquired with a dedicated PET camera. Regions of interest (ROIs) were drawn on each lung. Regional time-activity curves during washout were generated for each ROI and fitted to a mono- and a bicompartmental model. Validation of this method was performed in 2 ways. First, regional values of predicted Va (Va(emission)) were compared with regional volume obtained independently from density analysis on a transmission scan (Va(trans)). Second, regional values of predicted a were summed in each animal during each experimental condition and compared with minute-ventilation values set on the ventilator. RESULTS: The bicompartmental model best fitted the experimental values in normal (94.7% [62.2%-100.0%] (median [interquartile range]) of the ROIs) as well as in injured animals (90.7% [81.6%-97.4%] of the ROIs) (P = 0.49). Va(emission) significantly correlated with Va(trans) (R(2) = 0.89, P < 0.001) but exceeded Va(trans) by 10%. Finally, a strongly and positively correlated with minute-ventilation in both normal (R(2) = 0.96, P < 0.001) and injured (R(2) = 0.96, P < 0.001) animals. CONCLUSION: Measurement of (13)N-N(2) washout using PET is accurate to assess regional alveolar volume and ventilation during experimental acute lung injury.

Clinical review: bedside assessment of alveolar recruitment.

Recruitment is a dynamic physiological process that refers to the reopening of previously gasless lung units. Cumulating evidence has led to a better understanding of the rules that govern both recruitment and derecruitment during mechanical ventilation of patients with acute respiratory distress syndrome. Therefore not only the positive end-expiratory pressure, but also the tidal volume, the inspired oxygen fraction, repeated tracheal suctioning as well as sedation and paralysis may affect recruitment of acute respiratory distress syndrome lungs that are particularly prone to alveolar instability. In the present article, we review the recently reported data concerning the physiological significance of the pressure-volume curve and its use to assess alveolar recruitment. We also describe alternate techniques that have been proposed to assess recruitment at the bedside. Whether recruitment should be optimized remains an ongoing controversy that warrants further clinical investigation.