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Purpose Esophageal pressure (Pes) is a minimally invasive advanced respiratory monitoring method with the potential to guide management of ventilation support and enhance specific diagnoses in acute respiratory failure patients. To date, the use of Pes in the clinical setting is limited, and it is often seen as a research tool only. Methods This is a review of the relevant technical, physiological and clinical details that support the clinical utility of Pes. Results After appropriately positioning of the esophageal balloon, Pes monitoring allows titration of controlled and assisted mechanical ventilation to achieve personalized protective settings and the desired level of patient effort from the acute phase through to weaning. Moreover, Pes monitoring permits accurate measurement of transmural vascular pressure and intrinsic positive end-expiratory pressure and facilitates detection of patient–ventilator asynchrony, thereby supporting specific diagnoses and interventions. Finally, some Pes-derived measures may also be obtained by monitoring electrical activity of the diaphragm. Conclusions Pes monitoring provides unique bedside measures for a better understanding of the pathophysiology of acute respiratory failure patients. Including Pes monitoring in the intensivist’s clinical armamentarium may enhance treatment to improve clinical outcomes.

Background Whether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes. Methods Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmH 2 O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO 2 /FiO 2 , FiO 2 , PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study. Results Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th–75th percentiles] PaO 2 /FiO 2 in the two groups was 119 mmHg [101–142] and 116 mmHg [87–154]. Average compliance (41 ml/cmH 2 O [32–52] vs. 36 ml/cmH 2 O [27–42], p  = 0.045) and ventilatory ratio (2.1 [1.7–2.3] vs. 1.6 [1.4–2.1], p  = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO 2 /FiO 2 was linearly correlated with respiratory system compliance ( r  = 0.52 p  = 0.003). High PEEP improved PaO 2 /FiO 2 in both cohorts, but more remarkably in COVID-19 patients ( p  = 0.005). Recruitability was not different between cohorts ( p  = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP. Conclusions Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small.

Purpose We hypothesized that the ventilator-related causes of lung injury may be unified in a single variable: the mechanical power. We assessed whether the mechanical power measured by the pressure–volume loops can be computed from its components: tidal volume (TV)/driving pressure (∆ P aw ), flow, positive end-expiratory pressure (PEEP), and respiratory rate (RR). If so, the relative contributions of each variable to the mechanical power can be estimated. Methods We computed the mechanical power by multiplying each component of the equation of motion by the variation of volume and RR: Power rs = RR · Δ V 2 · 1 2 · EL rs + RR · 1 + I : E 60 · I : E · R aw + Δ V · PEEP , where ∆ V is the tidal volume, EL rs is the elastance of the respiratory system, I : E is the inspiratory-to-expiratory time ratio, and R aw is the airway resistance. In 30 patients with normal lungs and in 50 ARDS patients, mechanical power was computed via the power equation and measured from the dynamic pressure–volume curve at 5 and 15 cmH 2 O PEEP and 6, 8, 10, and 12 ml/kg TV. We then computed the effects of the individual component variables on the mechanical power. Results Computed and measured mechanical powers were similar at 5 and 15 cmH 2 O PEEP both in normal subjects and in ARDS patients (slopes = 0.96, 1.06, 1.01, 1.12 respectively, R 2  > 0.96 and p  < 0.0001 for all). The mechanical power increases exponentially with TV, ∆ P aw , and flow (exponent = 2) as well as with RR (exponent = 1.4) and linearly with PEEP. Conclusions The mechanical power equation may help estimate the contribution of the different ventilator-related causes of lung injury and of their variations. The equation can be easily implemented in every ventilator’s software.

PurposeIn acute respiratory distress syndrome (ARDS), physiological parameters associated with outcome may help defining targets for mechanical ventilation. This study aimed to address whether transpulmonary pressures (PL), including transpulmonary driving pressure (DPL), elastance-derived plateau PL, and directly-measured end-expiratory PL, are better associated with 60-day outcome than airway driving pressure (DPaw). We also tested the combination of oxygenation and stretch index [PaO2/(FiO2*DPaw)].MethodsProspective, observational, multicentre registry of ARDS patients. Respiratory mechanics were measured early after intubation at 6 kg/ml tidal volume. We compared the predictive power of the parameters for mortality at day-60 through receiver operating characteristic (ROC) and assessed their association with 60-day mortality through unadjusted and adjusted Cox regressions. Finally, each parameter was dichotomized, and Kaplan–Meier survival curves were compared.Results385 patients were enrolled 2 [1–4] days from intubation (esophageal pressure and arterial blood gases in 302 and 318 patients). As continuous variables, DPaw, DPL, and oxygenation stretch index were associated with 60-day mortality after adjustment for age and Sequential Organ Failure Assessment, whereas elastance-derived plateau PL was not. DPaw and DPL performed equally in ROC analysis (P = 0.0835). DPaw had the best-fit Cox regression model. When dichotomizing the variables, DPaw ≥ 15, DPL ≥ 12, plateau PL ≥ 24, and oxygenation stretch index < 10 exhibited lower 60-day survival probability. Directly measured end-expiratory PL ≥ 0 was associated with better outcome in obese patients.ConclusionDPL was equivalent predictor of outcome than DPaw. Our study supports the soundness of limiting lung and airway driving pressure and maintaining positive end-expiratory PL in obese patients.

Mindfulness practice is beneficial for emotion regulation; however, the neural mechanisms underlying this effect are poorly understood. The current study focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice on aversive emotions at behavioral and brain levels. A key finding across different emotion regulation strategies is the modulation of amygdala and prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal cortex integrate with amygdala activation during emotional stimulation. We proposed that, during emotional stimulation, ATB down-regulates activation in the amygdala and increases its integration with prefrontal regions. To address this hypothesis, 26 healthy controls were trained in mindfulness-based attention-to-breath meditation for two weeks and then stimulated with aversive pictures during both attention-to-breath and passive viewing while undergoing fMRI. Data were controlled for breathing frequency. Results indicate that (1) ATB was effective in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was associated with ATB in general. (3) A fronto-parietal network was additionally recruited during emotional stimulation. (4) ATB down regulated amygdala activation and increased amygdala–prefrontal integration, with such increased integration being associated with mindfulness ability. Results suggest amygdala–dorsal prefrontal cortex integration as a potential neural pathway of emotion regulation by mindfulness practice. •Attention to breath (ATB) reduces emotional responses in the amygdala.•Amygdala–prefrontal cortex functional connectivity increases during ATB.•Connectivity increase is linked with individual differences in mindful disposition.

Purpose The selection and intensity of respiratory support for ARDS are guided by PaO 2 /FiO 2 . However, ventilator-induced lung injury (VILI) is linked to respiratory mechanics and ventilator settings. We explored whether the VILI risk is related to ARDS severity based on oxygenation. Methods We analysed data on 228 ARDS subjects with PaO 2 /FiO 2  < 200 mmHg, categorized into three severity groups: one based on PaO 2 /FiO 2 ratio, and the others based on tertiles of predictors of VILI: mechanical power ratio (MPR) and driving pressure (DP). In each group of oxygenation-based ARDS severity and MPR and DP tertiles, we measured CT anatomy, gas exchange, respiratory mechanics, VILI prerequisites (lung elastance and lung gas volume), and VILI determinants (tidal volume, PEEP, airway pressures). Results Predictors of VILI, such as MPR and DP, were similar across ARDS severity groups based on PaO 2 /FiO 2 ratio, while oxygenation remained comparable across different levels of VILI risk defined by MPR and DP. Oxygenation impairment was associated with increased lung weight, recruitability, and reduced well-inflated tissue. In contrast, MPR and DP tertiles affected variables associated with the baby lung size, such as lung gas volume and well-inflated tissue. Mechanical ventilation intensity increased progressively across MPR and DP tertiles, but remained similar across PaO 2 /FiO 2 severity groups. Conclusions ARDS severity based on oxygenation impairment does not reflect the prerequisites and determinants of VILI. This should prompt a reconsideration of recommending respiratory support based on oxygenation impairment, rather than VILI determinants.

Purpose To investigate whether neuromuscular blocking agents (NMBA) exert beneficial effects in acute respiratory distress syndrome (ARDS) by reason of their action on respiratory mechanics, particularly transpulmonary pressures ( P L ). Methods A prospective randomised controlled study in patients with moderate to severe ARDS within 48 h of the onset of ARDS. All patients were monitored by means of an oesophageal catheter and followed up for 48 h. Moderate ARDS patients were randomised into two groups according to whether they were given a 48-h continuous infusion of cisatracurium besylate or not (control group). Severe ARDS patients did not undergo randomisation and all received cisatracurium besylate per protocol. The changes during the 48-h study period in oxygenation and in respiratory mechanics, including inspiratory and expiratory P L and driving pressure, were assessed and compared. Delta P L (∆ P L ) was defined as inspiratory P L minus expiratory P L . Results Thirty patients were included, 24 with moderate ARDS and 6 with severe ARDS. NMBA infusion was associated with an improvement in oxygenation in both moderate and severe ARDS, accompanied by a decrease in both plateau pressure and total positive end-expiratory pressure. The mean inspiratory and expiratory P L were higher in the moderate ARDS group receiving NMBA than in the control group. In contrast, there was no change in either driving pressure or ∆ P L related to NMBA administration. Conclusions NMBA could exert beneficial effects in patients with moderate ARDS, at least in part, by limiting expiratory efforts.

Abstract Recent studies applying the principles of respiratory mechanics to respiratory disease have used inconsistent and mutually exclusive definitions of the term “transpulmonary pressure.” By the traditional definition, transpulmonary pressure is the pressure across the whole lung, including the intrapulmonary airways, (i.e., the pressure difference between the opening to the pulmonary airway and the pleural surface). However, more recently transpulmonary pressure has also been defined as the pressure across only the lung tissue (i.e., the pressure difference between the alveolar space and the pleural surface), traditionally known as the “elastic recoil pressure of the lung.” Multiple definitions of the same term, and failure to recognize their underlying assumptions, have led to different interpretations of lung physiology and conclusions about appropriate therapy for patients. It is our view that many current controversies in the physiological interpretation of disease are caused by the lack of consistency in the definitions of these common physiological terms. In this article, we discuss the historical uses of these terms and recent misconceptions that may have resulted when these terms were confused. These misconceptions include assertions that normal pleural pressure must be negative (subatmospheric) and that a pressure in the pleural space may not be substantially positive when a subject is relaxed with an open airway. We urge specificity and uniformity when using physiological terms to define the physical state of the lungs, the chest wall, and the integrated respiratory system.

Introduction The objective was to compare the impact of three assistance levels of different modes of mechanical ventilation; neurally adjusted ventilatory assist (NAVA), proportional assist ventilation (PAV), and pressure support ventilation (PSV) on major features of patient-ventilator interaction. Methods PSV, NAVA, and PAV were set to obtain a tidal volume (V T ) of 6 to 8 ml/kg (PSV 100 , NAVA 100 , and PAV 100 ) in 16 intubated patients. Assistance was further decreased by 50% (PSV 50 , NAVA 50 , and PAV 50 ) and then increased by 50% (PSV 150 , NAVA 150 , and PAV 150 ) with all modes. The three modes were randomly applied. Airway flow and pressure, electrical activity of the diaphragm (EAdi), and blood gases were measured. V T , peak EAdi, coefficient of variation of V T and EAdi, and the prevalence of the main patient-ventilator asynchronies were calculated. Results PAV and NAVA prevented the increase of V T with high levels of assistance (median 7.4 (interquartile range (IQR) 5.7 to 10.1) ml/kg and 7.4 (IQR, 5.9 to 10.5) ml/kg with PAV 150 and NAVA 150 versus 10.9 (IQR, 8.9 to 12.0) ml/kg with PSV 150 , P <0.05). EAdi was higher with PAV than with PSV at level 100 and level 150 . The coefficient of variation of V T was higher with NAVA and PAV (19 (IQR, 14 to 31)% and 21 (IQR 16 to 29)% with NAVA 100 and PAV 100 versus 13 (IQR 11 to 18)% with PSV 100 , P <0.05). The prevalence of ineffective triggering was lower with PAV and NAVA than with PSV ( P <0.05), but the prevalence of double triggering was higher with NAVA than with PAV and PSV ( P <0.05). Conclusions PAV and NAVA both prevent overdistention, improve neuromechanical coupling, restore the variability of the breathing pattern, and decrease patient-ventilator asynchrony in fairly similar ways compared with PSV. Further studies are needed to evaluate the possible clinical benefits of NAVA and PAV on clinical outcomes. Trial registration Clinicaltrials.gov NCT02056093 . Registered 18 December 2013.

Objective To compare the effect of heated, humidified, high-flow nasal cannula (HHHFNC) and nasal continuous positive airways pressure (NCPAP) on lung function and mechanics in preterm infants with respiratory distress syndrome (RDS) at the same level of retropharyngeal pressure (Prp). Design Randomised crossover trial. Setting Neonatal intensive care unit, Ospedale Maggiore Policlinico, Milan, Italy. Patients 20 preterm infants (gestational age: 31±1 wks) with mild-moderate RDS requiring non-invasive respiratory support within 96 h after birth. Interventions Infants were exposed to a randomised sequence of NCPAP and HHHFNC at different settings (2, 4 and 6 cmH2O for NCPAP and 2, 4, 6 L/min for HHHFNC) to enable comparison at the same level of Prp. Main outcome measures Tidal volume by respiratory inductance plethysmography, pleural pressure estimated by oesophageal pressure, and gas exchange were evaluated at each setting and used to compute breathing pattern parameters, lung mechanics and work of breathing (WOB). Results A poor linear regression between flow and Prp was found during HHHFNC (Prp=0.3+0.7*flow; r2=0.37). Only in 15 out of 20 infants it was possible to compare HHHFNC and NCPAP at a Prp of 2 and 4 cmH2O. No statistically significant differences were found in breathing pattern, gas exchange, lung mechanics and total WOB. Resistive WOB in the upper airways was slightly but significantly higher during HHHFNC (0.65 (0.49;1.09) vs 1.57 (0.85;2.09) cmH2O median (IQR)). Conclusions Despite differing mechanisms for generating positive airway pressure, when compared at the same Prp, NCPAP and HHHFNC provide similar effects on all the outcomes explored.