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Abstract Background Lung regions excluded from mechanical insufflation are traditionally assumed to be spared from ventilation-associated lung injury. However, preliminary data showed activation of potential mechanisms of injury within these non-ventilated regions (e.g., hypoperfusion, inflammation). Methods In the present study, we hypothesized that non-ventilated lung injury (NVLI) may develop within 24 h of unilateral mechanical ventilation in previously healthy pigs, and we performed extended pathophysiological measures to profile NVLI. We included two experimental groups undergoing exclusion of the left lung from the ventilation with two different tidal volumes (15 vs 7.5 ml/kg) and a control group on bilateral ventilation. Pathophysiological alteration including lung collapse, changes in lung perfusion, lung stress and inflammation were measured. Lung injury was quantified by histological score. Results Histological injury score of the non-ventilated lung is significantly higher than normally expanded lung from control animals. The histological score showed lower intermediate values (but still higher than controls) when the tidal volume distending the ventilated lung was reduced by 50%. Main pathophysiological alterations associated with NVLI were: extensive lung collapse; very low pulmonary perfusion; high inspiratory airways pressure; and higher concentrations of acute-phase inflammatory cytokines IL-6, IL-1β and TNF-α and of Angiopoietin-2 (a marker of endothelial activation) in the broncho-alveolar lavage. Only the last two alterations were mitigated by reducing tidal volume, potentially explaining partial protection. Conclusions Non-ventilated lung injury develops within 24 h of controlled mechanical ventilation due to multiple pathophysiological alterations, which are only partially prevented by low tidal volume.

Abstract Background Optimal noninvasive respiratory support for patients with hypoxemic respiratory failure should minimize work of breathing without increasing the transpulmonary pressure. Recently, an asymmetrical high flow nasal cannula (HFNC) interface (Duet, Fisher & Paykel Healthcare Ltd), in which the caliber of each nasal prong is different, was approved for clinical use. This system might reduce work of breathing by lowering minute ventilation and improving respiratory mechanics. Methods We enrolled 10 patients ≥ 18 years of age who were admitted to the Ospedale Maggiore Policlinico ICU in Milan, Italy, and had a PaO2/FiO2

Abstract Background There is very limited evidence identifying factors that increase respiratory drive in hypoxemic intubated patients. Most physiological determinants of respiratory drive cannot be directly assessed at the bedside (e.g., neural inputs from chemo- or mechano-receptors), but clinical risk factors commonly measured in intubated patients could be correlated with increased drive. We aimed to identify clinical risk factors independently associated with increased respiratory drive in intubated hypoxemic patients. Methods We analyzed the physiological dataset from a multicenter trial on intubated hypoxemic patients on pressure support (PS). Patients with simultaneous assessment of the inspiratory drop in airway pressure at 0.1-s during an occlusion (P 0.1) and risk factors for increased respiratory drive on day 1 were included. We evaluated the independent correlation of the following clinical risk factors for increased drive with P 0.1: severity of lung injury (unilateral vs. bilateral pulmonary infiltrates, PaO2/FiO2, ventilatory ratio); arterial blood gases (PaO2, PaCO2 and pHa); sedation (RASS score and drug type); SOFA score; arterial lactate; ventilation settings (PEEP, level of PS, addition of sigh breaths). Results Two-hundred seventeen patients were included. Clinical risk factors independently correlated with higher P 0.1 were bilateral infiltrates (increase ratio [IR] 1.233, 95%CI 1.047–1.451, p = 0.012); lower PaO2/FiO2 (IR 0.998, 95%CI 0.997–0.999, p = 0.004); higher ventilatory ratio (IR 1.538, 95%CI 1.267–1.867, p

Abstract Monitoring with electrical impedance tomography (EIT) during a decremental PEEP trial has been used to identify the PEEP that yields the optimal balance of pulmonary overdistension and collapse. This method is based on pixel-level changes in respiratory system compliance and depends on fixed or measured airway driving pressure. We developed a novel approach to quantify overdistension and collapse during pressure support ventilation (PSV) by integrating transpulmonary pressure and EIT monitoring and performed pilot tests in three hypoxemic patients. We report that our experimental approach is feasible and capable of identifying a PEEP that balances overdistension and collapse in intubated hypoxemic patients undergoing PSV.

Abstract Veno-venous Extracorporeal Membrane Oxygenation (ECMO) is used in the most severe cases of respiratory failure and further exacerbates the patients’ inflammatory status. Antithrombin is supplemented during ECMO for its anticoagulant effects, but it also deploys anti-inflammatory properties. In this pre-specified ancillary study of the GATRA trial [NCT03208270] we aimed to evaluate the relationship between antithrombin and inflammation during ECMO. Forty-six patients were included in the study, 23 were randomized to receive antithrombin to maintain a level of 80–120% (study group) and 23 were randomized not to be supplemented (control group). Anticoagulation was provided in both groups with heparin infusion. Six cytokines were measured at 5 timepoints from prior to ECMO start to 7 days after ECMO removal. Cytokines decreased during the study but overall were not very different in the two groups. Testing the interaction between the study group and timepoints suggests that the administration of antithrombin led to a more rapid decrease over time of IL-6, IL-1β, TNF-⍺ and Pro-ADM. Plasma levels of antithrombin (either endogenous or exogenous) were negatively associated with all cytokines. Inflammation decreases during ECMO but a causal effect of antithrombin administration on the reduction of inflammation (and its clinical relevance) must be confirmed by appropriately powered studies.

Esophageal pressure is the closest estimate of pleural pressure. Changes in esophageal pressure reflect changes in intrathoracic pressure and affect transpulmonary pressure, both of which have multiple effects on right and left ventricular performance. During passive breathing, increasing esophageal pressure is associated with lower venous return and higher right ventricular afterload and lower left ventricular afterload and oxygen consumption. In spontaneously breathing patients, negative pleural pressure swings increase venous return, while right heart afterload increases as in passive conditions; for the left ventricle, end-diastolic pressure is increased potentially favoring lung edema. Esophageal pressure monitoring represents a simple bedside method to estimate changes in pleural pressure and can advance our understanding of the cardiovascular performance of critically ill patients undergoing passive or assisted ventilation and guide physiologically personalized treatments.

There is a well-recognised importance for personalising mechanical ventilation settings to protect the lungs and the diaphragm for each individual patient. Measurement of oesophageal pressure (Poes) as an estimate of pleural pressure allows assessment of partitioned respiratory mechanics and quantification of lung stress, which helps our understanding of the patient's respiratory physiology and could guide individualisation of ventilator settings. Oesophageal manometry also allows breathing effort quantification, which could contribute to improving settings during assisted ventilation and mechanical ventilation weaning. In parallel with technological improvements, Poes monitoring is now available for daily clinical practice. This review provides a fundamental understanding of the relevant physiological concepts that can be assessed using Poes measurements, both during spontaneous breathing and mechanical ventilation. We also present a practical approach for implementing oesophageal manometry at the bedside. While more clinical data are awaited to confirm the benefits of Poes-guided mechanical ventilation and to determine optimal targets under different conditions, we discuss potential practical approaches, including positive end-expiratory pressure setting in controlled ventilation and assessment of inspiratory effort during assisted modes.

Abstract Purpose In the acute respiratory distress syndrome (ARDS), decreasing Ventilation-Perfusion $$\left( {{{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}} \right)$$ V ˙ / Q ˙ mismatch might enhance lung protection. We investigated the regional effects of higher Positive End Expiratory Pressure (PEEP) on $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ mismatch and their correlation with recruitability. We aimed to verify whether PEEP improves regional $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ mismatch, and to study the underlying mechanisms. Methods In fifteen patients with moderate and severe ARDS, two PEEP levels (5 and 15 cmH2O) were applied in random order. $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ mismatch was assessed by Electrical Impedance Tomography at each PEEP. Percentage of ventilation and perfusion reaching different ranges of $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ ratios were analyzed in 3 gravitational lung regions, leading to precise assessment of their distribution throughout different $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ mismatch compartments. Recruitability between the two PEEP levels was measured by the recruitment-to-inflation ratio method. Results In the non-dependent region, at higher PEEP, ventilation reaching the normal $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ compartment (p = 0.018) increased, while it decreased in the high $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ one (p = 0.023). In the middle region, at PEEP 15 cmH2O, ventilation and perfusion to the low $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ compartment decreased (p = 0.006 and p = 0.011) and perfusion to normal $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ increased (p = 0.003). In the dependent lung, the percentage of blood flowing through the non-ventilated compartment decreased (p = 0.041). Regional $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ mismatch improvement was correlated to lung recruitability and changes in regional tidal volume. Conclusions In patients with ARDS, higher PEEP optimizes the distribution of both ventilation (in the non-dependent areas) and perfusion (in the middle and dependent lung). Bedside measure of recruitability is associated with improved $${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$ V ˙ / Q ˙ mismatch.

Abstract Mechanical ventilation is a life-saving technology, but it can also inadvertently induce lung injury and increase morbidity and mortality. Currently, there is no easy method of assessing the impact that ventilator settings have on the degree of lung inssflation. Computed tomography (CT), the gold standard for visually monitoring lung function, can provide detailed regional information of the lung. Unfortunately, it necessitates moving critically ill patients to a special diagnostic room and involves exposure to radiation. A technique introduced in the 1980s, electrical impedance tomography (EIT) can non-invasively provide similar monitoring of lung function. However, while CT provides information on the air content, EIT monitors ventilation-related changes of lung volume and changes of end expiratory lung volume (EELV). Over the past several decades, EIT has moved from the research lab to commercially available devices that are used at the bedside. Being complementary to well-established radiological techniques and conventional pulmonary monitoring, EIT can be used to continuously visualize the lung function at the bedside and to instantly assess the effects of therapeutic maneuvers on regional ventilation distribution. EIT provides a means of visualizing the regional distribution of ventilation and changes of lung volume. This ability is particularly useful when therapy changes are intended to achieve a more homogenous gas distribution in mechanically ventilated patients. Besides the unique information provided by EIT, its convenience and safety contribute to the increasing perception expressed by various authors that EIT has the potential to be used as a valuable tool for optimizing PEEP and other ventilator settings, either in the operative room and in the intensive care unit. The effects of various therapeutic interventions and applications on ventilation distribution have already been assessed with the help of EIT, and this document gives an overview of the literature that has been published in this context.

Abstract Background In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients’ individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient’s individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial). Methods IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28–30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment. Discussion The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS. Trial registration ClinicalTrials.gov NCT04012073 . Registered 9 July 2019.

Abstract Background In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions might reflect ARDS severity and affect the risk of ventilation-induced lung injury. Despite pathophysiological relevance, unmatched ventilation and perfusion are not routinely assessed at the bedside. The aims of this study were to quantify unmatched ventilation and perfusion at the bedside by electrical impedance tomography (EIT) investigating their association with mortality in patients with ARDS and to explore the effects of positive end-expiratory pressure (PEEP) on unmatched ventilation and perfusion in subgroups of patients with different ARDS severity based on PaO2/FiO2 and compliance. Methods Prospective observational study in 50 patients with mild (36%), moderate (46%), and severe (18%) ARDS under clinical ventilation settings. EIT was applied to measure the regional distribution of ventilation and perfusion using central venous bolus of saline 5% during end-inspiratory pause. We defined unmatched units as the percentage of only ventilated units plus the percentage of only perfused units. Results Percentage of unmatched units was significantly higher in non-survivors compared to survivors (32[27–47]% vs. 21[17–27]%, p

BackgroundUnilateral ligation of the pulmonary artery (UPAL) induces bilateral lung injury in pigs undergoing controlled mechanical ventilation. Possible mechanisms include redistribution of ventilation toward the non-ligated lung and hypoperfusion of the ligated lung. The addition of 5% CO2 to the inspiratory gas (FiCO2) prevents the injury, but it is not clear whether lung protection is a direct effect of CO2 inhalation or it is mediated by plasmatic hypercapnia. This study aims to compare the effects and mechanisms of FiCO2vs. hypercapnia induced by low tidal volume ventilation or instrumental dead space.MethodsHealthy pigs underwent left UPAL and were allocated for 48 h to the following: Volume-controlled ventilation (VCV) with VT 10 ml/kg (injury, n = 6); VCV plus 5% FiCO2 (FiCO2, n = 7); VCV with VT 6 ml/kg (low VT, n = 6); VCV plus additional circuit dead space (instrumental VD, n = 6). Histological score, regional compliance, wet-to-dry ratio, and inflammatory infiltrate were assessed to evaluate lung injury at the end of the study. To investigate the mechanisms of protection, we quantified the redistribution of ventilation to the non-ligated lung, as the ratio between the percentage of tidal volume to the right and to the left lung (VTRIGHT/LEFT), and the hypoperfusion of the ligated lung as the percentage of blood flow reaching the left lung (PerfusionLEFT).ResultsIn the left ligated lung, injury was prevented only in the FiCO2 group, as indicated by lower histological score, higher regional compliance, lower wet-to-dry ratio and lower density of inflammatory cells compared to other groups. For the right lung, the histological score was lower both in the FiCO2 and in the low VT groups, but the other measures of injury showed lower intensity only in the FiCO2 group. VTRIGHT/LEFT was lower and PerfusionLEFT was higher in the FiCO2 group compared to other groups.ConclusionIn a model of UPAL, inhaled CO2 but not hypercapnia grants bilateral lung protection. Mechanisms of protection include reduced overdistension of the non-ligated and increased perfusion of the ligated lung.

Abstract Background The physiological behavior of lungs affected by the acute respiratory distress syndrome (ARDS) differs between inspiration and expiration and presents heterogeneous gravity-dependent distribution. This phenomenon, highlighted by the different distribution of opening/closing pressure and by the hysteresis of the pressure–volume curve, can be studied by CT scan, but the technique expose the patient to radiations, cannot track changes during time and is not feasible at the bedside. Electrical impedance tomography (EIT) could help in assessing at the bedside regional inspiratory and expiratory mechanical properties. We evaluated regional opening/closing pressures, hysteresis and atelectrauma during inspiratory and expiratory low-flow pressure–volume curves in ARDS using electrical impedance tomography. Methods Pixel-level inspiratory and expiratory PV curves (PVpixel) between 5 and 40 cmH2O were constructed integrating EIT images and airway opening pressure signal from 8 ARDS patients. The lower inflection point in the inspiratory and expiratory PVpixel were used to find opening (OPpixel) and closing (CPpixel) pressures. A novel atelectrauma index (AtI) was calculated as the percentage of pixels opening during the inspiratory and closing during the expiratory PV curves. The maximal hysteresis (HysMax) was calculated as the maximal difference between normalized expiratory and inspiratory PV curves. Analyses were conducted in the global, dependent and non-dependent lung regions. Results Gaussian distribution was confirmed for both global OPpixel (r2 = 0.90) and global CPpixel (r2 = 0.94). The two distributions were significantly different with higher values for OPpixel (p

Abstract Background Several studies have found only a weak to moderate correlation between oxygenation and lung aeration in response to changes in PEEP. This study aimed to investigate the association between changes in shunt, low and high ventilation/perfusion (V/Q) mismatch, and computed tomography-measured lung aeration following an increase in PEEP in patients with ARDS. Methods In this preliminary study, 12 ARDS patients were subjected to recruitment maneuvers followed by setting PEEP at 5 and then either 15 or 20 cmH2O. Lung aeration was measured by computed tomography. Values of pulmonary shunt and low and high V/Q mismatch were calculated by a model-based method from measurements of oxygenation, ventilation, and metabolism taken at different inspired oxygen levels and an arterial blood gas sample. Results Increasing PEEP resulted in reduced values of pulmonary shunt and the percentage of non-aerated tissue, and an increased percentage of normally aerated tissue (p

Abstract Background High inspiratory flow might damage the lungs by mechanisms not fully understood yet. We hypothesized that increasing inspiratory flow would increase lung stress, ventilation heterogeneity, and pendelluft in ARDS patients undergoing volume-controlled ventilation with constant tidal volume and that higher PEEP levels would reduce this phenomenon. Methods Ten ARDS patients were studied during protective volume-controlled ventilation. Three inspiratory flows (400, 800, and 1200 ml/s) and two PEEP levels (5 and 15 cmH2O) were applied in random order to each patient. Airway and esophageal pressures were recorded, end-inspiratory and end-expiratory holds were performed, and ventilation distribution was measured with electrical impedance tomography. Peak and plateau airway and transpulmonary pressures were recorded, together with the airway and transpulmonary pressure corresponding to the first point of zero end-inspiratory flow (P1). Ventilation heterogeneity was measured by the EIT-based global inhomogeneity (GI) index. Pendelluft was measured as the absolute difference between pixel-level inflation measured at plateau pressure minus P1. Results Plateau airway and transpulmonary pressure was not affected by inspiratory flow, while P1 increased at increasing inspiratory flow. The difference between P1 and plateau pressure was higher at higher flows at both PEEP levels (p

Acute respiratory distress syndrome (ARDS) remains an important clinical challenge with a mortality rate of 35–45%. It is being increasingly demonstrated that the improvement of outcomes requires a tailored, individualized approach to therapy, guided by a detailed understanding of each patient’s pathophysiology. In patients with ARDS, disturbances in the physiological matching of alveolar ventilation (V) and pulmonary perfusion (Q) (V/Q mismatch) are a hallmark derangement. The perfusion of collapsed or consolidated lung units gives rise to intrapulmonary shunting and arterial hypoxemia, whereas the ventilation of non-perfused lung zones increases physiological dead-space, which potentially necessitates increased ventilation to avoid hypercapnia. Beyond its impact on gas exchange, V/Q mismatch is a predictor of adverse outcomes in patients with ARDS; more recently, its role in ventilation-induced lung injury and worsening lung edema has been described. Innovations in bedside imaging technologies such as electrical impedance tomography readily allow clinicians to determine the regional distributions of V and Q, as well as the adequacy of their matching, providing new insights into the phenotyping, prognostication, and clinical management of patients with ARDS. The purpose of this review is to discuss the pathophysiology, identification, consequences, and treatment of V/Q mismatch in the setting of ARDS, employing experimental data from clinical and preclinical studies as support.

Transpulmonary driving pressure (DPL) corresponds to the cyclical stress imposed on the lung parenchyma during tidal breathing and, therefore, can be used to assess the risk of ventilator-induced lung injury (VILI). Its measurement at the bedside requires the use of esophageal pressure (Peso), which is sometimes technically challenging. Recently, it has been demonstrated how in an animal model of ARDS, the transpulmonary pressure (PL) measured with Peso calculated with the absolute values method (PL = Paw—Peso) is equivalent to the transpulmonary pressure directly measured using pleural sensors in the central-dependent part of the lung. We hypothesized that, since the PL derived from Peso reflects the regional behavior of the lung, it could exist a relationship between regional parameters measured by electrical impedance tomography (EIT) and driving PL (DPL). Moreover, we explored if, by integrating airways pressure data and EIT data, it could be possible to estimate non-invasively DPL and consequently lung elastance (EL) and elastance-derived inspiratory PL (PI). We analyzed 59 measurements from 20 patients with ARDS. There was a significant intra-patient correlation between EIT derived regional compliance in regions of interest (ROI1) (r = 0.5, p = 0.001), ROI2 (r = −0.68, p < 0.001), and ROI3 (r = −0.4, p = 0.002), and DPL. A multiple linear regression successfully predicted DPL based on respiratory system elastance (Ers), ideal body weight (IBW), roi1%, roi2%, and roi3% (R2 = 0.84, p < 0.001). The corresponding Bland-Altmann analysis showed a bias of −1.4e-007 cmH2O and limits of agreement (LoA) of −2.4–2.4 cmH2O. EL and PI calculated using EIT showed good agreement (R2 = 0.89, p < 0.001 and R2 = 0.75, p < 0.001) with the esophageal derived correspondent variables. In conclusion, DPL has a good correlation with EIT-derived parameters in the central lung. DPL, PI, and EL can be estimated with good accuracy non-invasively combining information coming from EIT and airway pressure.

Abstract Background Electrical impedance tomography (EIT) is a non-invasive radiation-free monitoring technique that provides images based on tissue electrical conductivity of the chest. Several investigations applied EIT in the context of perioperative medicine, which is not confined to the intraoperative period but begins with the preoperative assessment and extends to postoperative follow-up. Main body EIT could provide careful respiratory monitoring in the preoperative assessment to improve preparation for surgery, during anaesthesia to guide optimal ventilation strategies and to monitor the hemodynamic status and in the postoperative period for early detection of respiratory complications. Moreover, EIT could further enhance care of patients undergoing perioperative diagnostic procedures. This narrative review summarizes the latest evidence on the application of this technique to the surgical patient, focusing also on possible future perspectives. Conclusions EIT is a promising technique for the perioperative assessment of surgical patients, providing tailored adaptive respiratory and haemodynamic monitoring. Further studies are needed to address the current technological limitations, confirm the findings and evaluate which patients can benefit more from this technology.

Abstract Background Noninvasive monitoring of maximal inspiratory and expiratory flows (MIF and MEF, respectively) by electrical impedance tomography (EIT) might enable early recognition of changes in the mechanical properties of the respiratory system due to new conditions or in response to treatments. We aimed to validate EIT-based measures of MIF and MEF against spirometry in intubated hypoxemic patients during controlled ventilation and spontaneous breathing. Moreover, regional distribution of maximal airflows might interact with lung pathology and increase the risk of additional ventilation injury. Thus, we also aimed to describe the effects of mechanical ventilation settings on regional MIF and MEF. Methods We performed a new analysis of data from two prospective, randomized, crossover studies. We included intubated patients admitted to the intensive care unit with acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) undergoing pressure support ventilation (PSV, n = 10) and volume-controlled ventilation (VCV, n = 20). We measured MIF and MEF by spirometry and EIT during six different combinations of ventilation settings: higher vs. lower support during PSV and higher vs. lower positive end-expiratory pressure (PEEP) during both PSV and VCV. Regional airflows were assessed by EIT in dependent and non-dependent lung regions, too. Results MIF and MEF measured by EIT were tightly correlated with those measured by spirometry during all conditions (range of R 2 0.629–0.776 and R 2 0.606–0.772, respectively, p

Abstract Background Normal levels of plasma antithrombin (AT) activity might decrease heparin requirements to achieve an adequate level of anticoagulation during treatment with extracorporeal membrane oxygenation (ECMO). Acquired AT deficiency during ECMO is common, but formal recommendations on target, timing, and rate of AT supplementation are lacking. Thus, we conceived a pilot trial to evaluate the feasibility and safety of prolonged AT supplementation in patients requiring veno-venous ECMO for respiratory failure. Methods Grifols Antithrombin Research Awards (GATRA) is a prospective, randomized, single blinded, multicenter, controlled two-arm trial. Patients undergoing veno-venous ECMO will be randomized to either receive AT supplementation to maintain a functional AT level between 80 and 120% (AT supplementation group) or not (control group) for the entire ECMO course. In both study groups, anticoagulation will be provided with unfractionated heparin following a standardized protocol. The primary endpoint will be the dose of heparin required to maintain the ratio of activated partial thromboplastin time between 1.5 and 2. Secondary endpoints will be the adequacy of anticoagulation and the incidence of hemorrhagic and thrombotic complications. Discussion GATRA is a pilot trial that will test the efficacy of a protocol of AT supplementation in decreasing the heparin dose and improving anticoagulation adequacy during ECMO. If positive, it might provide the basis for a future larger trial aimed at verifying the impact of AT supplementation on a composite outcome endpoint including hemorrhagic events, transfusion requirements, and mortality. Trial registration ClinicalTrials.gov, NCT03208270. Registered on 5 July 2017.

Abstract Background The pressure-volume (P-V) curve has been suggested as a bedside tool to set mechanical ventilation; however, it reflects a global behavior of the lung without giving information on the regional mechanical properties. Regional P-V (PVr) curves derived from electrical impedance tomography (EIT) could provide valuable clinical information at bedside, being able to explore the regional mechanics of the lung. In the present study, we hypothesized that regional P-V curves would provide different information from those obtained from global P-V curves, both in terms of upper and lower inflection points. Therefore, we constructed pressure-volume curves for each pixel row from non-dependent to dependent lung regions of patients affected by acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS). Methods We analyzed slow-inflation P-V maneuvers data from 12 mechanically ventilated patients. During the inflation, the pneumotachograph was used to record flow and airway pressure while the EIT signals were recorded digitally. From each maneuver, global respiratory system P-V curve (PVg) and PVr curves were obtained, each one corresponding to a pixel row within the EIT image. PVg and PVr curves were fitted using a sigmoidal equation, and the upper (UIP) and lower (LIP) inflection points for each curve were mathematically identified; LIP and UIP from PVg were respectively called LIPg and UIPg. From each measurement, the highest regional LIP (LIPrMAX) and the lowest regional UIP (UIPrMIN) were identified and the pressure difference between those two points was defined as linear driving pressure (ΔP LIN). Results A significant difference (p

Rationale: Reducing the respiratory rate during extracorporeal membrane oxygenation (ECMO) decreases the mechanical power, but it might induce alveolar de-recruitment. Dissecting de-recruitment due to lung edema vs. the fraction due to hypoventilation may be challenging in injured lungs.Objectives: We characterized changes in lung physiology (primary endpoint: development of atelectasis) associated with progressive reduction of the respiratory rate in healthy animals on ECMO.Methods: Six female pigs underwent general anesthesia and volume control ventilation (Baseline: PEEP 5 cmH2O, Vt 10 ml/kg, I:E = 1:2, FiO2 0.5, rate 24 bpm). Veno-venous ECMO was started and respiratory rate was progressively reduced to 18, 12, and 6 breaths per minute (6-h steps), while all other settings remained unchanged. ECMO blood flow was kept constant while gas flow was increased to maintain stable PaCO2.Measurements and Main Results: At Baseline (without ECMO) and toward the end of each step, data from quantitative CT scan, electrical impedance tomography, and gas exchange were collected. Increasing ECMO gas flow while lowering the respiratory rate was associated with an increase in the fraction of non-aerated tissue (i.e., atelectasis) and with a decrease of tidal ventilation reaching the gravitationally dependent lung regions (p = 0.009 and p = 0.018). Intrapulmonary shunt increased (p < 0.001) and arterial PaO2 decreased (p < 0.001) at lower rates. The fraction of non-aerated lung was correlated with longer expiratory time spent at zero flow (r = 0.555, p = 0.011).Conclusions: Progressive decrease of respiratory rate coupled with increasing CO2 removal in mechanically ventilated healthy pigs is associated with development of lung atelectasis, higher shunt, and poorer oxygenation.

Abstract Background The high-flow nasal cannula (HFNC) delivers up to 60 l/min of humidified air/oxygen blend at a temperature close to that of the human body. In this study, we tested whether higher temperature and flow decrease patient comfort. In more severe patients, instead, we hypothesized that higher flow might be associated with improved comfort. Methods A prospective, randomized, cross-over study was performed on 40 acute hypoxemic respiratory failure (AHRF) patients (PaO2/FiO2 ≤ 300 + pulmonary infiltrates + exclusion of cardiogenic edema) supported by HFNC. The primary outcome was the assessment of patient comfort during HFNC delivery at increasing flow and temperature. Two flows (30 and 60 l/min), each combined with two temperatures (31 and 37 °C), were randomly applied for 20 min (four steps per patient), leaving clinical FiO2 unchanged. Toward the end of each step, the following were recorded: comfort by Visual Numerical Scale ranging between 1 (extreme discomfort) and 5 (very comfortable), together with respiratory parameters. A subgroup of more severe patients was defined by clinical FiO2 ≥ 45%. Results Patient comfort was reported as significantly higher during steps at the lower temperature (31 °C) in comparison to 37 °C, with the HFNC set at both 30 and 60 l/min (p

Following publication of the original article [1], the authors reported that one of the co-authors has a mistake in the author name; the middle name and surname are switched. This is the correct information.