Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid-base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS. METHODS: ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included. Neuromuscular blockade recipients were excluded. Respiratory drive was measured as PES0.1, the change in esophageal pressure during the first 0.1 s of inspiratory effort. Plasma angiopoietin-2, interleukin-6, and interleukin-8 were measured concomitantly, and 60-day clinical outcomes evaluated. RESULTS: 54.8% of 124 included patients had detectable respiratory drive (PES0.1 range of 0-5.1 cm H2O). Angiopoietin-2 and interleukin-8, but not interleukin-6, were associated with respiratory drive independently of acid-base, oxygenation, respiratory mechanics, and sedation depth. Sedation depth was not significantly associated with PES0.1 in an unadjusted model, or after adjusting for mechanics and chemoreceptor input. However, upon adding angiopoietin-2, interleukin-6, or interleukin-8 to models, lighter sedation was significantly associated with higher PES0.1. Risk of death was less with moderate drive (PES0.1 of 0.5-2.9 cm H2O) compared to either lower drive (hazard ratio 1.58, 95% CI 0.82-3.05) or higher drive (2.63, 95% CI 1.21-5.70) (p = 0.049). CONCLUSIONS: Among patients with ARDS, systemic inflammatory and vascular permeability markers were independently associated with higher respiratory drive. The heterogeneous response of respiratory drive to varying sedation depth may be explained in part by differences in inflammation and vascular permeability.

Do Thresholds for Invasive Ventilation in Hypoxemic Respiratory Failure Exist? A Cohort Study.

Rationale: Invasive ventilation is a significant event for patients with respiratory failure. Physiologic thresholds standardize the use of invasive ventilation in clinical trials, but it is unknown whether thresholds prompt invasive ventilation in clinical practice. Objectives: To measure, in patients with hypoxemic respiratory failure, the probability of invasive ventilation within 3 hours after meeting physiologic thresholds. Methods: We studied patients admitted to intensive care receiving FiO2 of 0.4 or more via nonrebreather mask, noninvasive positive pressure ventilation, or high-flow nasal cannula, using data from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019) and the Amsterdam University Medical Centers Database (AmsterdamUMCdb) (2003-2016). We evaluated 17 thresholds, including the ratio of arterial to inspired oxygen, the ratio of saturation to inspired oxygen ratio, composite scores, and criteria from randomized trials. We report the probability of invasive ventilation within 3 hours of meeting each threshold and its association with covariates using odds ratios (ORs) and 95% credible intervals (CrIs). Measurements and Main Results: We studied 4,726 patients (3,365 from MIMIC, 1,361 from AmsterdamUMCdb). Invasive ventilation occurred in 28% (1,320). In MIMIC, the highest probability of invasive ventilation within 3 hours of meeting a threshold was 20%, after meeting prespecified neurologic or respiratory criteria while on vasopressors, and 19%, after a ratio of arterial to inspired oxygen of <80 mm Hg. In AmsterdamUMCdb, the highest probability was 34%, after vasopressor initiation, and 25%, after a ratio of saturation to inspired oxygen of <90. The probability after meeting the threshold from randomized trials was 9% (MIMIC) and 13% (AmsterdamUMCdb). In MIMIC, a race/ethnicity of Black (OR, 0.75; 95% CrI, 0.57-0.96) or Asian (OR, 0.6; 95% CrI, 0.35-0.95) compared with White was associated with decreased probability of invasive ventilation after meeting a threshold. Conclusions: The probability of invasive ventilation within 3 hours of meeting physiologic thresholds was low and associated with patient race/ethnicity.

[Differences in the elastic work of breathing of the pulmonary parenchyma in patients with bronchial asthma and COPD].

AIM: To determine and compare the work of breathing to overcome elastic resistance (Ael) in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) with similar changes in the elastic properties of the parenchyma in the same settings of ventilation disorders (grade 1). MATERIALS AND METHODS: Differences in the manifestations of similar changes in the elastic properties of the lungs in patients with BA and COPD were evaluated. To identify differences, a comparative study was conducted on Аel overcome in BA patients with positive bronchodilator (with salbutamol) and bronchoconstrictor (with methacholine) tests, with reduced and preserved bronchial conductance (groups 1 and 2, respectively), and in COPD patients with negative bronchodilator and bronchoconstrictor tests (group 3). All study patients showed a grade 1 lung ventilation disorder (a decrease in the one-second forced expiratory volume by 15-35%). The results were compared with each other and with the control group (group 4, healthy non-smokers). All study patients were comparable by age and sex. The respiration mechanics was studied using simultaneous registration of spirogram and transpulmonary pressure, and the parameters of bronchial conductance and ventilation were determined using body plethysmopressography using the Jager software and hardware system. RESULTS AND CONCLUSION: In COPD patients, Ael was significantly increased (p>0.05), whereas in both BA groups, it was unchanged. Increased elastic work of breathing in patients with COPD may be associated with the involvement of certain types of contractile elements, which are preserved in patients with BA at the initial stages of the disease.

Attenuating intrathoracic pressure swings decreases cardiac output at different intensities of exercise.

Intrathoracic pressure (ITP) swings that permit spontaneous ventilation have physiological implications for the heart. We sought to determine the effect of respiration on cardiac output ( Q ̇ $\dot Q$ ) during semi-supine cycle exercise using a proportional assist ventilator to minimize ITP changes and lower the work of breathing (Wb ). Twenty-four participants (12 females) completed three exercise trials at 30%, 60% and 80% peak power (Wmax ) with unloaded (using a proportional assist ventilator, PAV) and spontaneous breathing. Intrathoracic and intraabdominal pressures were measured with balloon catheters placed in the oesophagus and stomach. Left ventricular (LV) volumes and Q ̇ $\dot Q$ were determined via echocardiography. Heart rate (HR) was measured with electrocardiogram and a customized metabolic cart measured oxygen uptake ( V ̇ O 2 ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}}}$ ). Oesophageal pressure swings decreased from spontaneous to PAV breathing by -2.8 ± 3.1, -4.9 ± 5.7 and -8.1 ± 7.7 cmH2 O at 30%, 60% and 80% Wmax , respectively (P = 0.01). However, the decreases in Wb were similar across exercise intensities (27 ± 42 vs. 35 ± 24 vs. 41 ± 22%, respectively, P = 0.156). During PAV breathing compared to spontaneous breathing, Q ̇ $\dot Q$ decreased by -1.0 ± 1.3 vs. -1.4 ± 1.4 vs. -1.5 ± 1.9 l min-1 (all P < 0.05) and stroke volume decreased during PAV breathing by -11 ± 12 vs. -9 ± 10 vs. -7 ± 11 ml from spontaneous breathing at 30%, 60% and 80% Wmax , respectively (all P < 0.05). HR was lower during PAV breathing by -5 ± 4 beats min-1 at 80% Wmax (P < 0.0001). Oxygen uptake decreased by 100 ml min-1 during PAV breathing compared to spontaneous breathing at 80% Wmax (P < 0.0001). Overall, attenuating ITPs mitigated LV preload and ejection, thereby suggesting that the ITPs associated with spontaneous respiration impact cardiac function during exercise. KEY POINTS: Pulmonary ventilation is accomplished by alterations in intrathoracic pressure (ITP), which have physiological implications on the heart and dynamically influence the loading parameters of the heart. Proportional assist ventilation was used to attenuate ITP changes and decrease the work of breathing during exercise to examine its effects on left ventricular (LV) function. Proportional assist ventilation with progressive exercise intensities (30%, 60% and 80% Wmax ) led to reductions in cardiac output at all intensities, primarily through reductions in stroke volume. Decreases in LV end-diastolic volume (30% and 60% Wmax ) and increases in LV end-systolic volume (80% Wmax ) were responsible for the reduction in stroke volume. The relationship between cardiac output and oxygen uptake is disrupted during respiratory muscle unloading.

The effect of proportional assist ventilation on the electrical activity of the human diaphragm during exercise.

NEW FINDINGS: What is the central question of this study? What is the effect of lowering the normally occurring work of breathing on the electrical activity and pressure generated by the diaphragm during submaximal exercise in healthy humans? What is the main finding and its importance? Ventilatory assist during exercise elicits a proportional lowering of both the work performed by the diaphragm and diaphragm electrical activity. These findings have implications for exercise training studies using proportional assist ventilation to reduce diaphragm work in patients with cardiopulmonary disease. ABSTRACT: We hypothesized that when a proportional assist ventilator (PAV) is applied in order to reduce the pressure generated by the diaphragm, there would be a corresponding reduction in electrical activity of the diaphragm. Healthy participants (five male and four female) completed an incremental cycle exercise test to exhaustion in order to calculate workloads for subsequent trials. On the experimental day, participants performed submaximal cycling, and three levels of assisted ventilation were applied (low, medium and high). Ventilatory parameters, pulmonary pressures and EMG of the diaphragm (EMGdi ) were obtained. To compare the PAV conditions with spontaneous breathing intervals, ANOVA procedures were used, and significant effects were evaluated with a Tukey-Kramer test. Significance was set at P < 0.05. The work of breathing was not different between the lowest level of unloading and spontaneous breathing (P = 0.151) but was significantly lower during medium (25%, P = 0.02) and high (36%, P < 0.001) levels of PAV. The pressure-time product of the diaphragm (PTPdi ) was lower across PAV unloading conditions (P < 0.05). The EMGdi was significantly lower in medium and high PAV conditions (P = 0.035 and P < 0.001, respectively). The mean reductions of EMGdi with PAV unloading were 14, 22 and 39%, respectively. The change in EMGdi for a given lowering of PTPdi with the PAV was significantly correlated (r = 0.61, P = 0.01). Ventilatory assist during exercise elicits a reduction in the electrical activity of the diaphragm, and there is a proportional lowering of the work of breathing. Our findings have implications for exercise training studies using assisted ventilation to reduce diaphragm work in patients with cardiopulmonary disease.

Estimation of inspiratory effort using airway occlusion maneuvers in ventilated children: a secondary analysis of an ongoing randomized trial testing a lung and diaphragm protective ventilation strategy.

BACKGROUND: Monitoring respiratory effort in ventilated patients is important to balance lung and diaphragm protection. Esophageal manometry remains the gold standard for monitoring respiratory effort but is invasive and requires expertise for its measurement and interpretation. Airway pressures during occlusion maneuvers may provide an alternative, although pediatric data are limited. We sought to determine the correlation between change in esophageal pressure during tidal breathing (∆Pes) and airway pressure measured during three airway occlusion maneuvers: (1) expiratory occlusion pressure (Pocc), (2) airway occlusion pressure (P0.1), and (3) respiratory muscle pressure index (PMI) in children. We also sought to explore pediatric threshold values for these pressures to detect excessive or insufficient respiratory effort. METHODS: Secondary analysis of physiologic data from children between 1 month and 18 years of age with acute respiratory distress syndrome enrolled in an ongoing randomized clinical trial testing a lung and diaphragm protective ventilation strategy (REDvent, R01HL124666). ∆Pes, Pocc, P0.1, and PMI were measured. Repeated measure correlations were used to investigate correlation coefficients between ∆Pes and the three measures, and linear regression equations were generated to identify potential therapeutic thresholds. RESULTS: There were 653 inspiratory and 713 expiratory holds from 97 patients. Pocc had the strongest correlation with ∆Pes (r = 0.68), followed by PMI (r = 0.60) and P0.1 (r = 0.42). ∆Pes could be reliably estimated using the regression equation ∆Pes = 0.66 [Formula: see text] Pocc (R2 = 0.82), with Pocc cut-points having high specificity and moderate sensitivity to detect respective ∆Pes thresholds for high and low respiratory effort. There were minimal differences in the relationship between Pocc and ∆Pes based on age (infant, child, adolescent) or mode of ventilation (SIMV versus Pressure Support), although these differences were more apparent with P0.1 and PMI. CONCLUSIONS: Airway occlusion maneuvers may be appropriate alternatives to esophageal pressure measurement to estimate the inspiratory effort in children, and Pocc represents the most promising target. TRIAL REGISTRATION: NCT03266016; August 23, 2017.

The respiratory system and associated disorders.

Respiratory disease is ubiquitous in hospitals and community healthcare settings in the UK. Nurses, therefore, must be able to understand the physiology and pathophysiology that underpins the care they provide for people living with a respiratory disorder. This article summarises the fundamental anatomy and physiology of the respiratory system and respiration. It also explores the pathophysiological changes that occur in the four most common respiratory conditions, namely pneumonia, lung cancer, asthma and chronic obstructive pulmonary disease. Key elements of a comprehensive respiratory assessment and how nurses can determine acute deterioration are explored. The case study and reflective questions aim to enhance the reader's understanding of respiratory assessment and nursing care.

Effect of pediatric ventilation weaning technique on work of breathing.

BACKGROUND: Ventilator liberation is one of the most challenging aspects in patients with respiratory failure. Most patients are weaned through a transition from full to partial respiratory support, whereas some advocate using a continuous spontaneous ventilation (CSV). However, there is little scientific evidence supporting the practice of pediatric ventilator liberation, including the timing of onset of and the approach to weaning mode. We sought to explore differences in patient effort between a pressure controlled continuous mode of ventilation (PC-CMV) [in this cohort PC assist/control (PC-A/C)] with a reduced ventilator rate and CSV, and to study changes in patient effort with decreasing PS. METHODS: In this prospective physiology cross-over study, we randomized children < 5 years to first PC-A/C with a 25% reduction in ventilator rate, or CSV (continuous positive airway pressure [CPAP] + PS). Patients were then crossed over to the other arm. Patient effort was measured by calculating inspiratory work of breathing (WOB) using the Campbell diagram (WOBCampbell), and by pressure-rate-product (PRP) and pressure-time-product (PTP). Respiratory inductance plethysmography (RIP) was used to calculate the phase angle. Measurements were obtained at baseline, during PC-A/C and CPAP + PS, and during decreasing set PS (maximum -6 cmH2O). RESULTS: Thirty-six subjects with a median age of 4.4 (IQR 1.5-11.9) months and median ventilation time of 4.9 (IQR 3.4-7.0) days were included. Nearly all patients (94.4%) were admitted with primary respiratory failure. WOBCampbell during baseline [0.67 (IQR 0.38-1.07) Joules/L] did not differ between CSV [0.49 (IQR 0.17-0.83) Joules/L] or PC-A/C [0.47 (IQR 0.17-1.15) Joules/L]. Neither PRP, PTP, ∆Pes nor phase angle was different between the two ventilator modes. Reducing pressure support resulted in a statistically significant increase in patient effort, albeit that these differences were clinically negligible. CONCLUSIONS: Patient effort during pediatric ventilation liberation was not increased when patients were in a CSV mode of ventilation compared to a ventilator mode with a ventilator back-up rate. Reducing the level of PS did not lead to clinically relevant increases in patient effort. These data may aid in a better approach to pediatric ventilation liberation. Trial registration clinicaltrials.gov NCT05254691. Registered 24 February 2022.

Work of breathing at different tidal volume targets in newborn infants with congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) results in varying degrees of pulmonary hypoplasia. Volume targeted ventilation (VTV) is a lung protective strategy but the optimal target tidal volume in CDH infants has not previously been studied. The aim of this study was to test the hypothesis that low targeted volumes would be better in CDH infants as determined by measuring the work of breathing (WOB) in CDH infants, at three different targeted tidal volumes. A randomised cross-over study was undertaken. Infants were eligible for inclusion in the study after surgical repair of their diaphragmatic defect. Targeted tidal volumes of 4, 5, and 6 ml/kg were each delivered in random order for 20-min periods with 20-min periods of baseline ventilation between. WOB was assessed and measured by using the pressure-time product of the diaphragm (PTPdi). Nine infants with a median gestational age at birth of 38 + 4 (range 36 + 4-40 + 6) weeks and median birth weight 3202 (range 2855-3800) g were studied. The PTPdi was higher at 4 ml/kg than at both 5, p = 0.008, and 6 ml/kg, p = 0.012. CONCLUSION: VTV of 4 ml/kg demonstrated an increased PTPdi compared to other VTV levels studied and should be avoided in post-surgical CDH infants. WHAT IS KNOWN: • Lung injury secondary to mechanical ventilation increases the mortality and morbidity of infants with CDH. • Volume targeted ventilation (VTV) reduces 'volutrauma' and ventilator-induced lung injury in other neonatal intensive care populations. WHAT IS NEW: • A randomised cross-over trial was carried out investigating the response to different VTV levels in infants with CDH. • Despite pulmonary hypoplasia being a common finding in CDH, a VTV of 5ml/kg significantly reduced the work of breathing in infants with CDH compared to a lower VTV level.

Airflow restriction mask induces greater central fatigue after a non-exhaustive high-intensity interval exercise.

The airflow restriction mask (ARM) is a practical and inexpensive device for respiratory muscle training. Wearing an ARM has recently been combined with high-intensity interval exercise (HIIE), but its effect on neuromuscular fatigue is unknown. The present study investigated the effects of ARM wearing on neuromuscular fatigue after an HIIE session. Fourteen healthy men performed two HIIE sessions (4 × 4 min at 90% HRmax , 3 min recovery at 70% HRmax ) with or without an ARM. Neuromuscular fatigue was quantified via pre- to post-HIIE changes in maximal voluntary contraction (MVC), voluntary activation (VA, central fatigue), and potentialized evoked twitch force at 100, 10, and 1 Hz (peripheral fatigue). Blood pH and lactate were measured before and after the HIIE session, while HR, SpO2 , dyspnea, physical sensation of effort (P-RPE), and Task Effort and Awareness (TEA) were recorded every bout. The exercise-induced decrease in MVC was higher (p < 0.05) in the ARM (-28 ± 12%) than in the Control condition (-20 ± 11%). The VA decreased (p < 0.05) in the ARM (-11 ± 11%) but not in the control condition (-4 ± 5%, p > 0.05). Pre- to post-HIIE declines in evoked twitch at 100, 10, and 1 Hz were similar (p > 0.05) between ARM and control conditions (ARM: -18 ± 10, -43 ± 11 and -38 ± 12%; Control: -18 ± 14, -43 ± 12 and -37 ± 17%). When compared with the control, the HIIE bout wearing ARM was marked by higher heart rate, plasma lactate concentration, dyspnea, P-RPE and TEA, as well as lower SpO2 and blood pH. In conclusion, ARM increases perceptual and physiological stress during a HIIE, which may lead to a greater post-exercise central fatigue.

Accuracy of calculating mechanical power of ventilation by one commonly used equation.

Gattinoni's equation, [Formula: see text], now commonly used to calculate the mechanical power (MP) of ventilation. However, it calculates only inspiratory MP. In addition, the inclusion of PEEP in Gattinoni's equation raises debate because PEEP does not produce net displacement or contribute to MP. Measuring the area within the pressure-volume loop accurately reflects the MP received in a whole ventilation cycle and the MP thus obtained is not influenced by PEEP. The MP of 25 invasively ventilated patients were calculated by Gattinoni's equation and measured by integration of the areas within the pressure-volume loops of the ventilation cycles. The MP obtained from both methods were compared. The effects of PEEPs on MP were also evaluated. We found that the MP obtained from both methods were correlated by R2 = 0.75 and 0.66 at PEEP 5 and 10 cmH2O, respectively. The biases of the two methods were 3.13 (2.03 to 4.23) J/min (P < 0.0001) and - 1.23 (- 2.22 to - 0.24) J/min (P = 0.02) at PEEP 5 and 10 cmH2O, respectively. These P values suggested that both methods were significantly incongruent. When the tidal volume used was 6 ml/Kg, the MP by Gattinoni's equation at PEEP 5 and 10 cmH2O were significantly different (4.51 vs 7.21 J/min, P < 0.001), but the MP by PV loop area was not influenced by PEEPs (6.46 vs 6.47 J/min, P = 0.331). Similar results were observed across all tidal volumes. We conclude that the Gattinoni's equation is not accurate in calculating the MP of a whole ventilatory cycle and is significantly influenced by PEEP, which theoretically does not contribute to MP.

The influence of the post-pulmonary septum and submersion on the pulmonary mechanics of Trachemys scripta (Cryptodira: Emydidae).

The respiratory system of chelonians needs to function within a mostly solid carapace, with ventilation depending on movements of the flanks. When submerged, inspiration has to work against hydrostatic pressure. We examined breathing mechanics in Trachemys scripta while underwater. Additionally, as the respiratory system of T. scripta possesses a well-developed post-pulmonary septum (PPS), we investigated its role by analyzing the breathing mechanics of lungs with and without their PPS attached. Static compliance was significantly increased in submerged animals and in animals with and without their PPS, while removal of the PPS did not result in a significantly different static compliance. Dynamic compliance was significantly affected by changes in volume and frequency in every treatment, with submergence significantly decreasing dynamic compliance. The presence of the PPS significantly increased dynamic compliance. Submersion did not significantly alter work per ventilation, but caused minute work of breathing to be much greater at any frequency and ventilation level analyzed. Lungs with or without their PPS did not show significantly different work per ventilation when compared with the intact animal. Our results demonstrate that submersion results in significantly altered breathing mechanics, increasing minute work of breathing greatly. The PPS was shown to maintain a constant volume within the animal's body cavity, wherein the lungs can be ventilated more easily, highlighting the importance of this coelomic subdivision in the chelonian body cavity.

Additional work of breathing from trigger errors in mechanically ventilated children.

BACKGROUND: Patient-ventilator asynchrony is associated with increased morbidity and mortality. A direct causative relationship between Patient-ventilator asynchrony and adverse clinical outcome have yet to be demonstrated. It is hypothesized that during trigger errors excessive pleural pressure swings are generated, contributing to increased work-of-breathing and self-inflicted lung injury. The objective of this study was to determine the additional work-of-breathing and pleural pressure swings caused by trigger errors in mechanically ventilated children. METHODS: Prospective observational study in a tertiary paediatric intensive care unit in an university hospital. Patients ventilated > 24 h and < 18 years old were studied. Patients underwent a 5-min recording of the ventilator flow-time, pressure-time and oesophageal pressure-time scalar. Pressure-time-product calculations were made as a proxy for work-of-breathing. Oesophageal pressure swings, as a surrogate for pleural pressure swings, during trigger errors were determined. RESULTS: Nine-hundred-and-fifty-nine trigger errors in 28 patients were identified. The additional work-of-breathing caused by trigger errors showed great variability among patients. The more asynchronous breaths were present the higher the work-of-breathing of these breaths. A higher spontaneous breath rate led to a lower amount of trigger errors. Patient-ventilator asynchrony was not associated with prolonged duration of mechanical ventilation or paediatric intensive care stay. CONCLUSIONS: The additional work-of-breathing caused by trigger errors in ventilated children can take up to 30-40% of the total work-of-breathing. Trigger errors were less common in patients breathing spontaneously and those able to generate higher pressure-time-product and pressure swings. TRIAL REGISTRATION: Not applicable.

The hyperpnoea of exercise in health: Respiratory influences on neurovascular control.

NEW FINDINGS: What is the topic of this review? Elevated demand is placed on the respiratory muscles during whole-body exercise-induced hyperpnoea. What is the role of elevated demand in neural modulation of cardiovascular control in respiratory and locomotor skeletal muscle, and what are the mechanisms involved? What advances does it highlight? There is a sympathetic restraint of blood flow to locomotor muscles during near-maximal exercise, which might function to maintain blood pressure. During submaximal exercise, respiratory muscle blood flow might be also be reduced if ventilatory load is sufficiently high. Methodological advances (near-infrared spectroscopy with indocyanine green) confirm that blood flow is diverted away from respiratory muscles when the work of breathing is alleviated. ABSTRACT: It is known that the respiratory muscles have a significant increasing oxygen demand in line with hyperpnoea during whole-body endurance exercise and are susceptible to fatigue, in much the same way as locomotor muscles. The act of ventilation can itself be considered a form of exercise. The manipulation of respiratory load at near-maximal exercise alters leg blood flow significantly, demonstrating a competitive relationship between different skeletal muscle vascular beds to perfuse both sets of muscles adequately with a finite cardiac output. In recent years, the question has moved towards whether this effect exists during submaximal exercise, and the use of more direct measurements of respiratory muscle blood flow itself to confirm assumptions that uphold the concept. Evidence thus far has shown that there is a reciprocal effect on blood flow redistribution during ventilatory load manipulation observed at the respiratory muscles themselves and that the effect is observable during submaximal exercise, where active limb blood flow was reduced in conditions that simulated a high work of breathing. This has clinical applications for populations with respiratory disease and heart failure, where the work of breathing is remarkably high, even during submaximal efforts.

A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection.

Deterioration of lung function during the first week of COVID-19 has been observed when patients remain with insufficient respiratory support. Patient self-inflicted lung injury (P-SILI) is theorized as the responsible, but there is not robust experimental and clinical data to support it. Given the limited understanding of P-SILI, we describe the physiological basis of P-SILI and we show experimental data to comprehend the role of regional strain and heterogeneity in lung injury due to increased work of breathing.In addition, we discuss the current approach to respiratory support for COVID-19 under this point of view.

Oesophageal pressure and respiratory muscle ultrasonographic measurements indicate inspiratory effort during pressure support ventilation.

BACKGROUND: Bedside measures of patient effort are essential to properly titrate the level of pressure support ventilation. We investigated whether the tidal swing in oesophageal (ΔPes) and transdiaphragmatic pressure (ΔPdi), and ultrasonographic changes in diaphragm (TFdi) and parasternal intercostal (TFic) thickening are reliable estimates of respiratory effort. The effect of diaphragm dysfunction was also considered. METHODS: Twenty-one critically ill patients were enrolled: age 73 (14) yr, BMI 27 (7) kg m-2, and Pao2/Fio2 33.3 (9.2) kPa. A three-level pressure support trial was performed: baseline, 25% (PS-medium), and 50% reduction (PS-low). We recorded the oesophageal and transdiaphragmatic pressure-time products (PTPs), work of breathing (WOB), and diaphragm and intercostal ultrasonography. Diaphragm dysfunction was defined by the Gilbert index. RESULTS: Pressure support was 9.0 (1.6) cm H2O at baseline, 6.7 (1.3) (PS-medium), and 4.4 (1.0) (PS-low). ΔPes was significantly associated with the oesophageal PTP (R2=0.868; P<0.001) and the WOB (R2=0.683; P<0.001). ΔPdi was significantly associated with the transdiaphragmatic PTP (R2=0.820; P<0.001). TFdi was only weakly correlated with the oesophageal PTP (R2=0.326; P<0.001), and the correlation improved after excluding patients with diaphragm dysfunction (R2=0.887; P<0.001). TFdi was higher and TFic lower in patients without diaphragm dysfunction: 33.6 (18.2)% vs 13.2 (9.2)% and 2.1 (1.7)% vs 12.7 (9.1)%; P<0.0001. CONCLUSIONS: ΔPes and ΔPdi are adequate estimates of inspiratory effort. Diaphragm ultrasonography is a reliable indicator of inspiratory effort in the absence of diaphragm dysfunction. Additional measurement of parasternal intercostal thickening may discriminate a low inspiratory effort or a high effort in the presence of a dysfunctional diaphragm.

The effects of pressure- versus volume-controlled ventilation on ventilator work of breathing.

BACKGROUND: Measurement of work of breathing (WOB) during mechanical ventilation is essential to assess the status and progress of intensive care patients. Increasing ventilator WOB is known as a risk factor for ventilator-induced lung injury (VILI). In addition, the minimization of WOB is crucial to facilitate the weaning process. Several studies have assessed the effects of varying inspiratory flow waveforms on the patient's WOB during assisted ventilation, but there are few studies on the different effect of inspiratory flow waveforms on ventilator WOB during controlled ventilation. METHODS: In this paper, we analyze the ventilator WOB, termed mechanical work (MW) for three common inspiratory flow waveforms both in normal subjects and COPD patients. We use Rohrer's equation for the resistance of the endotracheal tube (ETT) and lung airways. The resistance of pulmonary and chest wall tissue are also considered. Then, the resistive MW required to overcome each component of the respiratory resistance is computed for square and sinusoidal waveforms in volume-controlled ventilation (VCV), and decelerating waveform of flow in pressure-controlled ventilation (PCV). RESULTS: The results indicate that under the constant I:E ratio, a square flow profile best minimizes the MW both in normal subjects and COPD patients. Furthermore, the large I:E ratio may be used to lower MW. The comparison of results shows that ETT and lung airways have the main contribution to resistive MW in normals and COPDs, respectively. CONCLUSION: These findings support that for lowering the MW especially in patients with obstructive lung diseases, flow with square waveforms in VCV, are more favorable than decelerating waveform of flow in PCV. Our analysis suggests the square profile is the best choice from the viewpoint of less MW.

Breathing variability predicts the suggested need for corrective intervention due to the perceived severity of patient-ventilator asynchrony during NIV.

Patient-ventilator asynchrony is associated with intolerance to noninvasive ventilation (NIV) and worsened outcomes. Our goal was to develop a tool to determine a patient needs for  intervention by a practitioner due to the presence of patient-ventilator asynchrony. We postulated that a clinician can determine when a patient needs corrective intervention due to the perceived severity of patient-ventilator asynchrony. We hypothesized a new measure, patient breathing variability, would indicate when corrective intervention is suggested by a bedside practitioner due to the perceived severity of patient-ventilator asynchrony. With IRB approval data was collected on 78 NIV patients. A panel of experts reviewed retrospective data from a development set of 10 NIV patients to categorize them into one of the three categories. The three categories were; "No to mild asynchrony-no intervention needed", "moderate asynchrony-non-emergent corrective intervention required", and "severe asynchrony-immediate intervention required". A stepwise regression with a F-test forward selection criterion was used to develop a positive linear logic model predicting the expert panel's categorizations of the need for corrective intervention. The model was incorporated into a software tool for clinical implementation. The tool was implemented prospectively on 68 NIV patients simultaneous to a bedside practitioner scoring the need for corrective intervention due to the perceived severity of patient-ventilator asynchrony. The categories from the tool and the practitioner were compared with the rate of agreement, sensitivity, specificity, and receiver operator characteristic analyses. The rate of agreement in categorizing the suggested need for clinical intervention due to the perceived presence of patient-ventilator asynchrony between the tool and experienced bedside practitioners was 95% with a Kappa score of 0.85 (p < 0.001). Further analysis found a specificity of 84% and sensitivity of 99%. The tool appears to accurately match the suggested need for corrective intervention by a bedside practitioner. Application of the tool allows for continuous, real time, and non-invasive monitoring of patients receiving NIV, and may enable early corrective interventions to ameliorate potential patient-ventilator asynchrony.

Work of breathing during arm bracing in normal male subjects.

OBJECTIVE: Although chronic obstructive pulmonary disease patients get relief from their dyspnea by arm bracing, the mechanics of this effect are unknown. This study aimed to investigate the mechanisms by which arm bracing affects dyspnea by measuring the work of breathing (WOB) in the arm bracing posture. METHODS: Six normal male subjects were studied in two standing postures: erect and with their arms braced. For the arm bracing posture, the subjects leaned forward with their arms stretched and rested their hands on a platform. Respiratory frequency was set at 20 tidal breaths/min with the use of a metronome, and tidal volume was set at 1 L by observing the lung volume on a monitor. All the subjects randomly adopted the two postures, and a preset respiratory pattern was measured for 30 s in each posture. Lung volume and flow rate were measured using a hot-wire flowmeter. Esophageal pressure was measured using a 12-cm balloon catheter. The WOB was estimated using modified Campbell diagrams. RESULTS: Lung volume increased and inspiratory resistive WOB decreased, while inspiratory elastic WOB increased significantly with arm bracing compared with that of the erect posture (P < 0.05). CONCLUSION: Arm bracing posture increases the chest wall expansion thereby increasing the end-expiratory lung volume and decreasing the inspiratory resistive WOB among healthy individuals.

Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women.

KEY POINTS: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex-differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. ABSTRACT: We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60-80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: (i) normoxic helium-oxygen (HEL) to reduce the work of breathing (Wb ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2 O L-1  s-1 to increase Wb ; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category-ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.