Neural Respiratory Drive During Different Dyspnea Relief Positions and Breathing Exercises in Individuals With COPD.

BACKGROUND: When the work load of the respiratory muscles increases and/or their capacity decreases in individuals with COPD, respiratory muscle activation increases to maintain gas exchange and respiratory mechanics, and perception of dyspnea occurs. The present study aimed to compare diaphragm and accessory respiratory muscle activation during normal breathing, pursed-lip breathing, and breathing control in different dyspnea relief positions, supine and side lying. METHODS: A cross-sectional study design was used. Sixteen individuals with COPD age between 40-75 y were included. Pulmonary function was evaluated by spirometry, muscle activation by surface electromyography, and dyspnea by the modified Borg scale. Muscle activation was measured in the diaphragm, scalene, sternocleidomastoid, and parasternal muscles. The evaluation was made in the dyspnea relief positions (sitting leaning forward, sitting leaning forward at a table, leaning forward with back against a wall, standing leaning forward, and high lying), seated erect, supine, and side lying. RESULTS: There were significant differences between the 8 positions (P < .001). There was no significant difference in muscle activation between sitting leaning forward and sitting leaning forward at a table position with analyzing post hoc test results (P > .99 for each muscle). However, muscle activation was lower in these 2 positions than in the other positions (P < .001 for each muscle). Muscle activation was greater in the supine position than in the other positions (P < .001 for each muscle). No difference was observed in muscle activation between the seated erect, leaning forward with back against a wall, standing leaning forward, high-lying, or side-lying positions (P > .05 for each muscle with a minimum P value of .09). CONCLUSIONS: The use of sitting leaning forward and sitting leaning forward at a table positions together with breathing control may help people with COPD to achieve more effective dyspnea relief and greater energy efficiency.

The diaphragmatic electrical activity during spontaneous breathing trial in patients with mechanical ventilation: physiological description and potential clinical utility.

BACKGROUNDS: Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. METHODS: We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. RESULTS: Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p < 0.01). Early increases in EAdi were observed in SBT, which are more prominent in SBT failure group. One minute, changes in EAdi and neuro-discharge per min also predicted weaning outcome (AUROCs 0.944 and 0.918, respectively). CONCLUSIONS: EAdi-based parameters, especially neuro-excursion efficiency and changes in neuro-discharge per min, may detect impending weaning failure earlier than conventional indices. EAdi monitoring provides physiological insights and a more tailored approach to facilitate successful weaning. Further research should validate these findings and explore the utility of combined EAdi and diaphragm ultrasound assessment in weaning ICU patients from mechanical ventilation. TRIAL REGISTRATION: Registered at ClinicalTrials.gov on 20 September 2022 (Identifier: NCT05632822).

A novel method to quantify breathing effort from respiratory mechanics and esophageal pressure.

Breathing effort is important to quantify to understand mechanisms underlying central and obstructive sleep apnea, respiratory-related arousals, and the timing and effectiveness of invasive or noninvasive mechanically assisted ventilation. Current quantitative methods to evaluate breathing effort rely on inspiratory esophageal or epiglottic pressure swings or changes in diaphragm electromyographic (EMG) activity, where units are problematic to interpret and compare between individuals and to measured ventilation. This paper derives a novel method to quantify breathing effort in units directly comparable with measured ventilation by applying respiratory mechanics first principles to convert continuous transpulmonary pressure measurements into "attempted" airflow expected to have arisen without upper airway obstruction. The method was evaluated using data from 11 subjects undergoing overnight polysomnography, including six patients with obesity with severe obstructive sleep apnea (OSA), including one who also had frequent central events, and five healthy-weight controls. Classic respiratory mechanics showed excellent fits of airflow and volume to transpulmonary pressures during wake periods of stable unobstructed breathing (means ± SD, r2 = 0.94 ± 0.03), with significantly higher respiratory system resistance in patients compared with healthy controls (11.2 ± 3.3 vs. 7.1 ± 1.9 cmH2O·L-1·s, P = 0.032). Subsequent estimates of attempted airflow from transpulmonary pressure changes clearly highlighted periods of acute and prolonged upper airway obstruction, including within the first few breaths following sleep onset in patients with OSA. This novel technique provides unique quantitative insights into the complex and dynamically changing interrelationships between breathing effort and achieved airflow during periods of obstructed breathing in sleep.NEW & NOTEWORTHY Ineffective breathing efforts with snoring and obstructive sleep apnea (OSA) are challenging to quantify. Measurements of esophageal or epiglottic pressure swings and diaphragm electromyography are useful, but units are problematic to interpret and compare between individuals and to measured ventilation. This paper derives a novel method that uses esophageal pressure and respiratory mechanics first principles to quantify breathing effort as "attempted" flow and volume in units directly comparable with measured airflow, volume, and ventilation.

A High Respiratory Drive Is Associated with Weaning Failure in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome: The Role of the Electrical Activity of the Diaphragm.

BACKGROUND: Mechanical ventilation is the main supportive treatment of severe cases of COVID-19-associated ARDS (C-ARDS). Weaning failure is common and associated with worse outcomes. We investigated the role of respiratory drive, assessed by monitoring the electrical activity of the diaphragm (EAdi), as a predictor of weaning failure. METHODS: Consecutive, mechanically ventilated patients admitted to the ICU for C-ARDS with difficult weaning were enrolled. Blood gas, ventilator, and respiratory mechanic parameters, as well as EAdi, were recorded at the time of placement of EAdi catheter, and then after 1, 2, 3, 7, and 10 days, and compared between patients with weaning success and weaning failure. RESULTS: Twenty patients were enrolled: age 66 (60-69); 85% males; PaO2/FiO2 at admission 148 (126-177) mmHg. Thirteen subjects (65%) were classified as having a successful weaning. A younger age (OR(95%CI): 0.02 (0.01-0.11) per year), a higher PaO2/FiO2 ratio (OR(95%CI): 1.10 (1.01-1.21) per mmHg), and a lower EAdi (OR(95%CI): 0.16 (0.08-0.34) per µV) were associated with weaning success. CONCLUSION: In critically ill patients with moderate-severe C-ARDS and difficult weaning from mechanical ventilation, a successful weaning was associated with a lower age, a higher oxygenation, and a lower respiratory drive, as assessed at the bedside via EAdi monitoring.

Neurophysiological basis of respiratory discomfort improvement by mandibular advancement in awake OSA patients.

Patients with obstructive sleep apneas (OSA) do not complain from dyspnea during resting breathing. Placement of a mandibular advancement device (MAD) can lead to a sense of improved respiratory comfort ("pseudo-relief") ascribed to a habituation phenomenon. To substantiate this conjecture, we hypothesized that, in non-dyspneic awake OSA patients, respiratory-related electroencephalographic figures, abnormally present during awake resting breathing, would disappear or change in parallel with MAD-associated pseudo-relief. In 20 patients, we compared natural breathing and breathing with MAD on: breathing discomfort (transitional visual analog scale, VAS-2); upper airway mechanics, assessed in terms of pressure peak/time to peak (TTP) ratio respiratory-related electroencephalography (EEG) signatures, including slow event-related preinspiratory potentials; and a between-state discrimination based on continuous connectivity evaluation. MAD improved breathing and upper airway mechanics. The 8 patients in whom the EEG between-state discrimination was considered effective exhibited higher Peak/TTP improvement and transitional VAS ratings while wearing MAD than the 12 patients where it was not. These results support the notion of habituation to abnormal respiratory-related afferents in OSA patients and fuel the causative nature of the relationship between dyspnea, respiratory-related motor cortical activity and impaired upper airway mechanics in this setting.

Neural respiratory drive assessment and its correlation with inspiratory muscle strength in patients undergoing open-heart surgery: A cross-sectional study.

BACKGROUND AND PURPOSE: Pulmonary dysfunction and inspiratory muscle weakness are frequently observed after cardiac surgery. Understanding the load on and capacity of respiratory muscles can provide valuable insights into the overall respiratory mechanics and neural regulation of breathing. This study aimed to assess the extent of neural respiratory drive (NRD) and determine whether admission-to-discharge differences in NRD were associated with inspiratory muscle strength changes among patients undergoing open-heart surgery. METHODS: This cross-sectional study was conducted on 45 patients scheduled for coronary artery bypass graft or heart valve surgery. NRD was measured using a surface parasternal intercostal electromyogram during resting breathing (sEMGpara tidal) and maximal inspiratory effort (sEMGpara max). Maximal inspiratory pressure (MIP) was used to determine inspiratory muscle strength. Evaluations were performed on the day of admission and discharge. RESULTS: There was a significant increase in sEMGpara tidal (6.9 ± 3.6 µV, p < 0.001), sEMGpara %max (13.7 ± 11.2%, p = 0.008), and neural respiratory drive index (NRDI, the product of EMGpara %max and respiratory rate) (337.7 ± 286.8%.breaths/min, p < 0.001), while sEMGpara max (-43.6 ± 20.4 µV, p < 0.01) and MIP (-24.4 ± 10.7, p < 0.001) significantly decreased during the discharge period. Differences in sEMGpara tidal (r = -0.369, p = 0.045), sEMGpara %max (r = -0.646, p = 0.001), and NRDI (r = -0.639, p = 0.001) were significantly associated with a reduction in MIP. DISCUSSION: The findings indicate that NRD increases after open-heart surgery, which corresponds to a decrease in inspiratory muscle strength.

Findings of ventilator-measured P0.1 in assessing respiratory drive in patients with severe ARDS.

BACKGROUND: Providers should adjust the depth of sedation to promote lung-protective ventilation in patients with severe ARDS. This recommendation was based on the assumption that the depth of sedation could be used to assess respiratory drive. OBJECTIVE: To assess the association between respiratory drive and sedation in patients with severe ARDS by using ventilator-measured P0.1 and RASS score. METHODS: Loss of spontaneous breathing was observed within 48 h of mechanical ventilation in patients with severe ARDS, and spontaneous breathing returned after 48 hours. P0.1 was measured by ventilator every 12 ± 2 hours, and the RASS score was measured synchronously. RESULTS: The RASS score was moderately correlated with P0.1 (R𝑆𝑝𝑒𝑎𝑟𝑚𝑎𝑛, 0.570; 95% CI, 0.475 to 0.637; p= 0.00). However, only patients with a RASS score of -5 were considered to have no excessive respiratory drive, but there was a risk for loss of spontaneous breathing. A P0.1 exceeding 3.5 cm H2O in patients with other RASS scores indicated an increase in respiratory drive. CONCLUSION: RASS score has little clinical significance in evaluating respiratory drive in severe ARDS. P0.1 should be evaluated by ventilator when adjusting the depth of sedation to promote lung-protective ventilation.

Protracted respiratory failure in a case of global spinal syringomyelia and Chiari malformation following administration of diazepam: illustrative case.

BACKGROUND: Syringomyelia is defined as dilation of the spinal cord's central canal and is often precipitated by skull base herniation disorders. Although respiratory failure (RF) can be associated with skull base abnormalities due to brainstem compression, most cases occur in pediatric patients and quickly resolve. The authors report the case of an adult patient with global spinal syringomyelia and Chiari malformation who developed refractory RF after routine administration of diazepam. OBSERVATIONS: A 31-year-old female presented with malnutrition, a 1-month history of right-sided weakness, and normal respiratory dynamics. After administration of diazepam prior to magnetic resonance imaging (MRI), she suddenly developed hypercapnic RF followed MRI and required intubation. MRI disclosed a Chiari malformation type I and syrinx extending from C1 to the conus medullaris. After decompressive surgery, her respiratory function progressively returned to baseline status, although 22 months after initial benzodiazepine administration, the patient continues to require nocturnal ventilation. LESSONS: Administration of central nervous system depressants should be closely monitored in patients with extensive syrinx formation given the potential to exacerbate diminished central respiratory drive. Early identification of syrinx in the context of Chiari malformation and hemiplegia should prompt clinical suspicion of underlying respiratory compromise and early involvement of intensive care consultants.

Respiratory Function Changes as Early Signs of Amyotrophic Lateral Sclerosis.

BACKGROUND: The current diagnostic criteria for amyotrophic lateral sclerosis (ALS) may remain unsatisfactory for months or years in the early disease. Pulmonary assessment has never been considered useful in the early diagnosis of ALS, and studies of pulmonary function in this patient category are lacking. OBJECTIVES: The objective of this study was to assess the pulmonary function in subjects with unspecific symptoms of ALS in whom an ALS diagnosis cannot be reached based on the current available guidelines. METHODS: We performed pulmonary function tests, arterial gas analysis, maximal inspiratory (MIP) and expiratory (MEP) pressure, and respiratory drive (P0.1) assessment in 35 patients with unspecific neurological symptoms at the time of the visit and those were subsequently diagnosed with ALS 2 years after the initial visit ("pre-ALS"); we compared these patients with 29 patients with established ALS and with 28 control subjects. RESULTS: Spirometric parameters were not different between the three groups. However, MIP was significantly lower and P0.1 was significantly increased (with the ratio P0.1/MIP significantly higher) in both established and pre-ALS patients compared to controls, while both MIP and P0.1 were similar between established ALS and pre-ALS. CONCLUSIONS: Changes in MIP, P0.1, and P0.1/MIP ratio are highly suggestive of preclinical ALS when the spirometry and neurodiagnostic tests are still inconclusive. MIP and P0.1 are noninvasive measurements that can be easily assessed in an ambulatory setting. Future studies on larger cohorts are needed to validate the use of these parameters in the preclinical diagnosis of ALS as well as in other neuromuscular diseases.

Effects of three spontaneous ventilation modes on respiratory drive and muscle effort in COVID-19 pneumonia patients.

BACKGROUND: High drive and high effort during spontaneous breathing can generate patient self-inflicted lung injury (P-SILI) due to uncontrolled high transpulmonary and transvascular pressures, with deterioration of respiratory failure. P-SILI has been demonstrated in experimental studies and supported in recent computational models. Different treatment strategies have been proposed according to the phenotype of elastance of the respiratory system (Ers) for patients with COVID-19. This study aimed to investigate the effect of three spontaneous ventilation modes on respiratory drive and muscle effort in clinical practice and their relationship with different phenotypes. This was achieved by obtaining the following respiratory signals: airway pressure (Paw), flow (V´) and volume (V) and calculating muscle pressure (Pmus). METHODS: A physiologic observational study of a series of cases in a university medical-surgical ICU involving 11 mechanically ventilated patients with COVID-19 pneumonia at the initiation of spontaneous breathing was conducted. Three spontaneous ventilation modes were evaluated in each of the patients: pressure support ventilation (PSV), airway pressure release ventilation (APRV), and BiLevel positive airway pressure ventilation (BIPAP). Pmus was calculated through the equation of motion. For this purpose, we acquired the signals of Paw, V´ and V directly from the data transmission protocol of the ventilator (Dräger). The main physiological measurements were calculation of the respiratory drive (P0.1), muscle effort through the ΔPmus, pressure‒time product (PTP/min) and work of breathing of the patient in joules multiplied by respiratory frequency (WOBp, J/min). RESULTS: Ten mechanically ventilated patients with COVID-19 pneumonia at the initiation of spontaneous breathing were evaluated. Our results showed similar high drive and muscle effort in each of the spontaneous ventilatory modes tested, without significant differences between them: median (IQR): P0.1 6.28 (4.92-7.44) cm H2O, ∆Pmus 13.48 (11.09-17.81) cm H2O, PTP 166.29 (124.02-253.33) cm H2O*sec/min, and WOBp 12.76 (7.46-18.04) J/min. High drive and effort were found in patients even with low Ers. There was a significant relationship between respiratory drive and WOBp and Ers, though the coefficient of variation widely varied. CONCLUSIONS: In our study, none of the spontaneous ventilatory methods tested succeeded in reducing high respiratory drive or muscle effort, regardless of the Ers, with subsequent risk of P-SILI.

The role of dexmedetomidine in ARDS: an approach to non-intensive care sedation.

Introduction: Severe COVID-19 is a life-threatening condition characterized by complications such as interstitial pneumonia, hypoxic respiratory failure, and acute respiratory distress syndrome (ARDS). Non-pharmacological intervention with mechanical ventilation plays a key role in treating COVID-19-related ARDS but is influenced by a high risk of failure in more severe patients. Dexmedetomidine is a new generation highly selective α2-adrenergic receptor (α2-AR) agonist that provides sedative effects with preservation of respiratory function. The aim of this study is to assess how dexmedetomidine influences gas exchange during non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) in moderate to severe ARDS caused by COVID-19 in a non-intensive care setting. Methods: This is a single center retrospective cohort study. We included patients who showed moderate to severe respiratory distress. All included subjects had indication to NIV and were suitable for a non-intensive setting of care. A total of 170 patients were included, divided in a control group (n = 71) and a treatment group (DEX group, n = 99). Results: A total of 170 patients were hospitalized for moderate to severe ARDS and COVID-19. The median age was 71 years, 29% females. The median Charlson comorbidity index (CCI) was 2.5. Obesity affected 21% of the study population. The median pO2/FiO2 was 82 mmHg before treatment. After treatment, the increase of pO2/FiO2 ratio was clinically and statistically significant in the DEX group compared to the controls (125 mmHg [97-152] versus 94 mmHg [75-122]; ***p < 0.0001). A significative reduction of NIV duration was observed in DEX group (10 [7-16] days vs. 13 [10-17] days; *p < 0.02). Twenty four patients required IMV in control group (n = 71) and 16 patients in DEX group (n = 99) with a reduction of endotracheal intubation of 62% (OR 0.38; **p < 0.008). A higher incidence of sinus bradycardia was observed in the DEX group. Conclusion: Dexmedetomidine provides a "calm and arousal" status which allows spontaneous ventilation in awake patients treated with NIV and HFNC. The adjunctive therapy with dexmedetomidine is associated with a higher pO2/FiO2, lower duration of NIV, and a lower risk of NIV failure. A higher incidence of sinus bradycardia needs to be considered.

Chronic pulmonary fibrosis alters the functioning of the respiratory neural network.

Some patients with idiopathic pulmonary fibrosis present impaired ventilatory variables characterised by low forced vital capacity values associated with an increase in respiratory rate and a decrease in tidal volume which could be related to the increased pulmonary stiffness. The lung stiffness observed in pulmonary fibrosis may also have an effect on the functioning of the brainstem respiratory neural network, which could ultimately reinforce or accentuate ventilatory alterations. To this end, we sought to uncover the consequences of pulmonary fibrosis on ventilatory variables and how the modification of pulmonary rigidity could influence the functioning of the respiratory neuronal network. In a mouse model of pulmonary fibrosis obtained by 6 repeated intratracheal instillations of bleomycin (BLM), we first observed an increase in minute ventilation characterised by an increase in respiratory rate and tidal volume, a desaturation and a decrease in lung compliance. The changes in these ventilatory variables were correlated with the severity of the lung injury. The impact of lung fibrosis was also evaluated on the functioning of the medullary areas involved in the elaboration of the central respiratory drive. Thus, BLM-induced pulmonary fibrosis led to a change in the long-term activity of the medullary neuronal respiratory network, especially at the level of the nucleus of the solitary tract, the first central relay of the peripheral afferents, and the Pre-Bötzinger complex, the inspiratory rhythm generator. Our results showed that pulmonary fibrosis induced modifications not only of pulmonary architecture but also of central control of the respiratory neural network.

Bias and Precision of Continuous P0.1 Measurement by Various Ventilators: A Simulation Study.

BACKGROUND: Most ventilators measure airway occlusion pressure (occlusion P0.1) by occluding the breathing circuit; however, some ventilators can predict P0.1 for each breath without occlusion. Nevertheless, few studies have verified the accuracy of continuous P0.1 measurement. The aim of this study was to evaluate the accuracy of continuous P0.1 measurement compared with that of occlusion methods for various ventilators using a lung simulator. METHODS: A total of 42 breathing patterns were validated using a lung simulator in combination with 7 different inspiratory muscular pressures and 3 different rise rates to simulate normal and obstructed lungs. PB980 and Dräger V500 ventilators were used to obtain occlusion P0.1 measurements. The occlusion maneuver was performed on the ventilator, and a corresponding reference P0.1 was recorded from the ASL5000 breathing simulator simultaneously. Hamilton-C6, Hamilton-G5, and Servo-U ventilators were used to obtain sustained P0.1 measurements (continuous P0.1). The reference P0.1 measured with the simulator was analyzed by using a Bland-Altman plot. RESULTS: The 2 lung mechanical models capable of measuring occlusion P0.1 yielded values equivalent to reference P0.1 (bias and precision values were 0.51 and 1.06, respectively, for the Dräger V500, and were 0.54 and 0.91, respectively, for the PB980). Continuous P0.1 for the Hamilton-C6 was underestimated in both the normal and obstructive models (bias and precision values were -2.13 and 1.91, respectively), whereas continuous P0.1 for the Servo-U was underestimated only in the obstructive model (bias and precision values were -0.86 and 1.76, respectively). Continuous P0.1 for the Hamilton-G5 was mostly similar to but less accurate than occlusion P0.1 (bias and precision values were 1.62 and 2.06, respectively). CONCLUSIONS: The accuracy of continuous P0.1 measurements varies based on the characteristics of the ventilator and should be interpreted by considering the characteristics of each system. Moreover, measurements obtained with an occluded circuit could be desirable for determining the true P0.1.

Clinical risk factors for increased respiratory drive in intubated hypoxemic patients.

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 (P0.1) 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 P0.1: 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 P0.1 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 < 0.001); lower pHa (IR 0.104, 95%CI 0.024-0.464, p = 0.003). Higher PEEP was correlated with lower P0.1 (IR 0.951, 95%CI 0.921-0.982, p = 0.002), while sedation depth and drugs were not associated with P0.1. CONCLUSIONS: Independent clinical risk factors for higher respiratory drive in intubated hypoxemic patients include the extent of lung edema and of ventilation-perfusion mismatch, lower pHa, and lower PEEP, while sedation strategy does not affect drive. These data underline the multifactorial nature of increased respiratory drive.

Respiratory muscle metabolic activity on PET/CT correlates with obstructive ventilatory defect severity and prognosis in patients undergoing lung cancer surgery.

BACKGROUND AND OBJECTIVE: Respiratory muscle activity is increased in patients with chronic respiratory disease. 18 F-FDG-PET/CT can assess respiratory muscle activity. We hypothesized that respiratory muscles metabolism was correlated to lung function impairment and was associated to prognosis in patients undergoing lung cancer surgery based on the research question whether respiratory muscle metabolism quantitatively correlates with the severity of lung function impairment in patients? Does respiratory muscle hypermetabolism have prognostic value? METHODS: Patients undergoing 18 F-FDG-PET/CT and pulmonary function tests prior to lung cancer surgery were identified. Maximum Standardized Uptake Value (SUVm) were measured in each respiratory muscle group (sternocleidomastoid, scalene, intercostal, diaphragm), normalized against deltoid SUVm. Respiratory muscle hypermetabolism was defined as SUVm >90th centile in any respiratory muscle group. Clinical outcomes were collected from a prospective cohort. RESULTS: One hundred fifty-six patients were included, mostly male [110 (71%)], 53 (34%) with previous diagnosis of COPD. Respiratory muscle SUVm were: scalene: 1.84 [1.51-2.25], sternocleidomastoid 1.64 [1.34-1.95], intercostal 1.01 [0.84-1.16], diaphragm 1.79 [1.41-2.27]. Tracer uptake was inversely correlated to FEV1 for the scalene (r = -0.29, p < 0.001) and SCM (r = -0.17, p = 0.03) respiratory muscle groups and positively correlated to TLC for the scalene (r = 0.17, p = 0.04). Respiratory muscle hypermetabolism was found in 45 patients (28.8%), who had a lower VO2 max (15.4 [14.2-17.5] vs. 17.2 mL/kg/min [15.2-21.1], p = 0.07) and poorer overall survival when adjusting to FEV1% (p < 0.01). CONCLUSION: Our findings show respiratory muscle hypermetabolism is associated with lung function impairment and has prognostic significance. 18 F-FDG/PET-CT should be considered as a tool for assessing respiratory muscle activity and to identify high-risk patients.

Ineffective Effort in Patients With Acute Brain Injury Undergoing Invasive Mechanical Ventilation.

BACKGROUND: Ineffective effort (IE) is a frequent patient-ventilator asynchrony in invasive mechanical ventilation. This study aimed to investigate the incidence of IE and to explore its relationship with respiratory drive in subjects with acute brain injury undergoing invasive mechanical ventilation. METHODS: We retrospectively analyzed a clinical database that assessed patient-ventilator asynchrony in subjects with acute brain injury. IE was identified based on airway pressure, flow, and esophageal pressure waveforms collected at 15-min intervals 4 times daily. At the end of each data set recording, airway-occlusion pressure (P0.1) was determined by the airway occlusion test. IE index was calculated to indicate the severity of IE. The incidence of IE in different types of brain injuries as well as its relationship with P0.1 was determined. RESULTS: We analyzed 852 data sets of 71 subjects with P0.1 measured and undergoing mechanical ventilation for at least 3 d after enrollment. IE was detected in 688 (80.8%) data sets, with a median index of 2.2% (interquartile range 0.4-13.1). Severe IE (IE index ≥ 10%) was detected in 246 (28.9%) data sets. The post craniotomy for brain tumor and the stroke groups had higher median IE index and lower P0.1 compared with the traumatic brain injury group (2.6% [0.7-9.7] vs 2.7% [0.3-21] vs 1.2% [0.1-8.5], P = .002; 1.4 [1-2] cm H2O vs 1.5 [1-2.2] cm H2O vs 1.8 [1.1-2.8] cm H2O, P = .001). Low respiratory drive (P0.1 < 1.14 cm H2O) was independently associated with severe IE in the expiratory phase (IEE) even after adjusting for confounding factors by logistic regression analysis (odds ratio 5.18 [95% CI 2.69-10], P < .001). CONCLUSIONS: IE was very common in subjects with acute brain injury. Low respiratory drive was independently associated with severe IEE.

Surface electromyography to quantify neuro-respiratory drive and neuro-mechanical coupling in mechanically ventilated children.

BACKGROUND: The patient's neuro-respiratory drive, measured as electrical activity of the diaphragm (EAdi), quantifies the mechanical load on the respiratory muscles. It correlates with respiratory effort but requires a dedicated esophageal catheter. Transcutaneous (surface) monitoring of respiratory muscle electromyographic (sEMG) signals may be considered a suitable alternative to EAdi because of its non-invasive character, with the additional benefit that it allows for simultaneously monitoring of other respiratory muscles. We therefore sought to study the neuro-respiratory drive and timing of inspiratory muscles using sEMG in a cohort of children enrolled in a pediatric ventilation liberation trial. The neuro-mechanical coupling, relating the pressure generated by the inspiratory muscles to the sEMG signals of these muscles, was also calculated. METHODS: This is a secondary analysis of data from a randomized cross-over trial in ventilated patients aged < 5 years. sEMG recordings of the diaphragm and parasternal intercostal muscles (ICM), esophageal pressure tracings and ventilator scalars were simultaneously recorded during continuous spontaneous ventilation and pressure controlled-intermittent mandatory ventilation, and at three levels of pressure support. Neuro-respiratory drive, timing of diaphragm and ICM relative to the mechanical ventilator's inspiration and neuro-mechanical coupling were quantified. RESULTS: Twenty-nine patients were included (median age: 5.9 months). In response to decreasing pressure support, both amplitude of sEMG (diaphragm: p = 0.001 and ICM: p = 0.002) and neuro-mechanical efficiency indices increased (diaphragm: p = 0.05 and ICM: p < 0.001). Poor correlations between neuro-respiratory drive and respiratory effort were found, with R2: 0.088 [0.021-0.152]. CONCLUSIONS: sEMG allows for the quantification of the electrical activity of the diaphragm and ICM in mechanically ventilated children. Both neuro-respiratory drive and neuro-mechanical efficiency increased in response to lower inspiratory assistance. There was poor correlation between neuro-respiratory drive and respiratory effort. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05254691. Registered 24 February 2022, registered retrospectively.

Orchiectomy exacerbates sleep-disordered breathing induced by intermittent hypoxia in mice.

We tested the hypothesis that low testosterone levels alter the regulation of breathing in mice exposed to intermittent hypoxia (IH). We used orchiectomized (ORX) or control (Sham-operated) mice exposed to normoxia or IH (12 h/day, 10 cycles/h, 6% O2) for 14 days. Breathing was measured by whole-body plethysmography to asses the stability of the breathing pattern (frequency distribution of total cycle time - Ttot) and the frequency and duration of spontaneous and post-sigh apneas (PSA). We characterized sighs as inducing one (S1) or more (S2) apnea and determined the sigh parameters (volume, peak inspiratory and expiratory flows, cycle times) associated with PSA. IH increased the frequency and duration of PSA and the proportion of S1 and S2 sighs. The PSA frequency was mostly related to the sigh expiratory time. The effects of IH on PSA frequency were amplified in ORX-IH mice. Our experiments using ORX support the hypothesis that testosterone is involved in the regulation of breathing in mice following IH.

Physiological adaptations during weaning from veno-venous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) has an established evidence base in acute respiratory distress syndrome (ARDS) and has seen exponential growth in its use over the past decades. However, there is a paucity of evidence regarding the approach to weaning, with variation of practice and outcomes between centres. Preconditions for weaning, management of patients' sedation and mechanical ventilation during this phase, criteria defining success or failure, and the optimal duration of a trial prior to decannulation are all debated subjects. Moreover, there is no prospective evidence demonstrating the superiority of weaning the sweep gas flow (SGF), the extracorporeal blood flow (ECBF) or the fraction of oxygen of the SGF (FdO2), thereby a broad inter-centre variability exists in this regard. Accordingly, the aim of this review is to discuss the required physiological basis to interpret different weaning approaches: first, we will outline the physiological changes in blood gases which should be expected from manipulations of ECBF, SGF and FdO2. Subsequently, we will describe the resulting adaptation of patients' control of breathing, with special reference to the effects of weaning on respiratory effort. Finally, we will discuss pertinent elements of the monitoring and mechanical ventilation of passive and spontaneously breathing patients during a weaning trial. Indeed, to avoid lung injury, invasive monitoring is often required in patients making spontaneous effort, as pressures measured at the airway may not reflect the degree of lung strain. In the absence of evidence, our approach to weaning is driven largely by an understanding of physiology.