Diaphragmatic Dysfunction Research Articles

Agreement between Diaphragm Ultrasound and Pulmonary Function Testing in the Evaluation of Diaphragm Function in Patients with ALS

Background: In ALS patients, diaphragmatic dysfunction is usually assessed by pulmonary function testing (PFTs) that requires patient cooperation. Evidence suggest that diaphragm ultrasound (DU) can be utilized, as an alternative to PFTs, to detect reduced diaphragmatic motility in ALS patients. This study aimed to verify the agreement between the results obtained by DU with those obtained by PFTs in both standing-up and supine positions.Methods: Twenty nine spinal ALS and thirteen healthy controls were studied in standing up and lying 30° supine position. All subjects performed PFTs and DU, to assess of diaphragmatic excursion, delta-thickness between end inspiration and end expiration (ΔT), and the thickening fraction (TF). Results: The standing position, ΔT correlates with VC (r=0.58p=0.001) and FVC (r=0.61 p<0.001); in lying 30° supine position, ΔT correlates with VC(r=0.59 p=0.001) and FVC (r=0.62 p<0.001). In standing up position, TF correlates with VC (r=0.55 p=0.003) and FVC (r=0.53 p=0.005); in lying 30° supine position, TF correlates with VC (r=0.55 p=0.003) and FVC (r=0.51 p=0.007). The following correlations were also observed: the standing position, diaphragmatic excursion correlated with VC(r=0.55 p=0.007) and FVC (r =0.65 p<0.001). In lying 30° supine position, diaphragmatic excursion correlated with VC(r=0.59 p=0.003); and FVC(r=0.63 p=0.001).Conclusion: DU adequately assesses the diaphragmatic impairment in ALS patients. Thickening and excursion appear as complementary indices in the evaluation of diaphragm motility.

Closed-loop parameter optimization for patient-specific phrenic nerve stimulation.

Ventilator-induced diaphragm dysfunction occurs rapidly following the onset of mechanical ventilation and has significant clinical consequences. Phrenic nerve stimulation has shown promise in maintaining diaphragm function by inducing diaphragm contractions. Non-invasive stimulation is an attractive option as it minimizes the procedural risks associated with invasive approaches. However, this method is limited by sensitivity to electrode position and inter-individual variability in stimulation thresholds. This makes clinical application challenging due to potentially time-consuming calibration processes to achieve reliable stimulation. We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. A closed-loop system recorded the respiratory flow produced by stimulation and automatically adjusted the electrode position and stimulation amplitude based on the respiratory response. By iterating over electrodes, the optimal electrode was selected. A binary search method over stimulation amplitudes was then employed to determine an individualized stimulation threshold. Pulse trains above this threshold were delivered to produce diaphragm contraction. Nine healthy volunteers were recruited. Mean threshold stimulation amplitude was 36.17 ± 14.34 mA (range 19.38-59.06 mA). The threshold amplitude for reliable nerve capture was moderately correlated with BMI (Pearson's r = 0.66, p = 0.049). Repeating threshold measurements within subjects demonstrated low intra-subject variability of 2.15 ± 1.61 mA between maximum and minimum thresholds on repeated trials. Bilateral stimulation with individually optimized parameters generated reliable diaphragm contraction, resulting in significant inhaled volumes following stimulation. We demonstrate the feasibility of a system for automatic optimization of electrode position and stimulation parameters using a closed-loop system. This opens the possibility of easily deployable individualized stimulation in the intensive care setting to reduce ventilator-induced diaphragm dysfunction.

Lung Ultrasound and Non-Invasive Ventilation Outcome in Acute Respiratory Failure

Objective: This study aimed to assess the diaphragmatic dysfunction in critically ill non-intubated patients admitted to respiratory critical care unit with acute respiratory failure.
 Methods: This was a prospective study conducted on 200 mechanically ventilated patients. The following data were collected: demographic characteristics, anthropometric measurements. Disease severity and hemodynamics. In addition, ICU length of stay, duration mechanical ventilation, outcome and duration of hospital stay. Besides, parameters of MV like (PaO2 / FiO2 Ratio), and respiratory rate were noticed. The laboratory workup included arterial blood gases, Na+, K+, Mg++, Ca++, PH, PCO2, HCO3-. The ultrasound was performed before and after weaning and included the diaphragmatic excursion and diaphragmatic thickness traction. The patients were split into two categories regarding their reaction to weaning attempts: Category A represented successful weaning. Category B represented unsuccessful weaning followed by reintubation and mechanically ventilated.
 Results: The weaning success was reported for 123 patients (61.5%) and mortality reported for 28 patients (14.0%). Weaning success was associated with male gender, younger age and slightly higher BMI. Obstructive airway disease showed significant increase in success than failure (25.2% vs 11.7% respectively). Weaning failure was significantly associated increased septic shock and pneumonia. The muscle thickness in inspiration was significantly increased in success than failure (25.56 vs 24.08 respectively). DE before weaning was the most sensitive indicator at cut-off value > 15 followed by DE after weaning at cutoff value >17; while DTF after weaning was more sensitive than DTF before weaning (93.55% and 80.65% respectively) at cutoff points > 20.4 and > 18.5, respectively.
 Conclusion: Assessment of DTF and DE by diaphragm ultrasound is an easy to obtain new weaning index that can be a bedside method in clinical practice with promising predictors of weaning success or failure before and after weaning.

Impact of pressure-targeted modes of ventilation on diaphragmatic function as assessed using ultrasonography in critically ill patients with cerebral insult: a randomized clinical trial

BackgroundMechanical ventilation causes diaphragmatic atrophy and reduces diaphragmatic efficiency. Patients with diaphragmatic dysfunction have longer mechanical ventilation durations and intensive care unit stay. There is currently a scarcity of data on the effect of different modes of mechanical ventilation on diaphragmatic function and ultrasound-guided assessment of diaphragmatic efficiency.ResultsSixty mechanically ventilated patients were randomly divided into four equal groups (15 each): patients were ventilated using either assist control pressure-controlled mode (group A), synchronized intermittent mandatory ventilation pressure-controlled mode (group S), bi-level-positive airway pressure mode (group B) or pressure support ventilation mode (group P). The primary outcome was to assess the diaphragmatic excursion, while the secondary outcomes were to assess the diaphragmatic thickness fraction and the duration of the ICU stay. Patients in the P group had the highest diaphragmatic excursion indicating better diaphragmatic function.ConclusionsWhen compared to other pressure-targeted ventilation modes, the pressure support ventilation mode may have the least risk of diaphragmatic dysfunction as preserves diaphragmatic structure and strength.Trial registrationThe clinical trial was retrospectively registered at http://www.pactr.org PACTR202112653971335.

Prevalence of diaphragm dysfunction in patients with interstitial lung disease (ILD): The role of diaphragmatic ultrasound

BackgroundDiaphragm ultrasound (DUS) has been extensively used in critically ill patients while data on outpatients with interstitial lung disease (ILD) are limited. We hypothesized that diaphragm function, assessed by ultrasound, could be impaired in patients with ILD, considering both Idiopathic Pulmonary Fibrosis (IPF) and Connective Tissue Disease (CTD-ILD), compared to healthy subjects. Moreover, this impairment could impact clinical and functional parameters. MethodsAll consecutive CTD-ILD and IPF patients followed in our center (March–October 2020) were screened. Diaphragm displacement (DD), inspiratory thickness (Ti), expiratory thickness (Te), thickening fraction (TF), and respiratory functional parameters were collected. The prevalence of diaphragmatic dysfunction (TF <30%) was then recorded. ResultsEighty-two consecutive patients (41 CTD-ILD, 41 IPF) and 15 age- and sex-matched controls were enrolled. In the overall population, 24 out of 82 (29%) presented diaphragmatic dysfunction. In CTD-ILD, DD and Ti were lower as compared to IPF (p = 0.021 and p = 0.036, respectively); while diaphragmatic dysfunction was more prevalent compared to controls (37% vs 7%, p = 0.043). TF positively correlated to patients’ functional parameters in the CTD-ILD group (FVC%pred: p = 0.003; r = 0.45), while not in the IPF group. Diaphragmatic dysfunction was associated with moderate/severe dyspnea in both CTD-ILD and IPF (p = 0.021). ConclusionThe prevalence of diaphragmatic dysfunction was 29% in patients with ILD and was associated with moderate/severe dyspnea. CTD-ILD presented lower DD compared with IPF and a higher prevalence of diaphragmatic dysfunction (TF<30%) compared with controls. TF was associated with lung function only in CTD-ILD patients, suggesting its potential role in the comprehensive patient assessment.

0995 Sleep-related Hypoventilation in a 62-Year-Old Female with a Rare Genetic Neuromuscular Disorder

Abstract Introduction Central Core Myopathy (CCM) is a rare genetic neuromuscular disorder involving a mutation in the ‘Ryanodine Receptor’ (RyR1) gene, also known as the gatekeeper of calcium within the muscle cells. CCM typically manifests as slowly progressive proximal muscle weakness Currently, there is limited data regarding the management of nocturnal hypoventilation in adults with neuromuscular disorders. Report of case(s) We present a 62-year-old woman with CCM, as identified via RyR1 mutation (c14818G&amp;gt;A) on genetic testing, as well as muscle biopsy. This genotype is associated with &amp;lt; 10% respiratory muscle involvement. She presented to the sleep clinic with complaints of morning headaches, non-restorative sleep, and daytime sleepiness. Her polysomnogram (PSG) showed an overall Apnea-Hypopnea-Index in the normal range. However, there was a progressive increase in transcutaneous carbon dioxide levels (PtcCO2), reaching a peak of 53 mmHg during rapid eye movement (REM) sleep from 38 mmHg during wakefulness, consistent with sleep-related neuromuscular hypoventilation. On further evaluation, this patient had no evidence of neuromuscular restrictive lung physiology or overt diaphragmatic dysfunction, as suggested by &amp;lt; 20% variation in the supine forced vital capacity. Moreover, her negative inspiratory force (NIF) value was not less than negative 40. However, in the setting of her sleep-related symptoms and evidence of nocturnal hypoventilation, our team decided to trial non-invasive positive pressure ventilation (NIPPV). Since we had concerns about respiratory alkalosis in NREM sleep in the setting of normal body mass index, normal pulmonary function tests, and hypoventilation limited to REM sleep, the patient was sent for in-lab titration of pressures with measurement of PtcCO2 to appropriately recommend NIPPV settings. The study demonstrated bi-level positive airway pressure settings of IPAP 7 cmH20, EPAP 5 cmH20, and a backup rate of 12/min resulting in sustained eucarbia and steady PtcCO2 levels during both REM and NREM sleep. Conclusion This case highlights the importance of evaluation for nocturnal hypoventilation in symptomatic patients with rare neuromuscular disorders and the potential for symptomatic improvement with treatment with NIPPV. Moreover, the case demonstrates the importance of in-lab titration of pressure settings for NIPPV when hypoventilation is limited to REM sleep, due to concern for iatrogenic hyperventilation and respiratory alkalosis. Support (if any)

Evaluating diaphragmatic dysfunction and predicting non-invasive ventilation failure in acute exacerbation of chronic obstructive pulmonary disease in India.

Baseline diaphragmatic dysfunction (DD) at the initiation of non-invasive ventilation (NIV) correlates positively with subsequent intubation. We investigated the utility of DD detected 2 hours after NIV initiation in estimating NIV failure in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. In a prospective-cohort design, we enrolled 60 consecutive patients with AECOPD initiated on NIV at intensive care unit admission, and NIV failure events were noted. The DD was assessed at baseline (T1 timepoint) and 2 hours after initiating NIV (T2 timepoint). We defined DD as ultrasound-assessed change in diaphragmatic thickness (ΔTDI) <20% (predefined criteria [PC]) or its cut-off that predicts NIV failure (calculated criteria [CC]) at both timepoints. A predictive-regression analysis was reported. In total, 32 patients developed NIV failure, nine within 2 hours of NIV and remaining in next 6 days. The ∆TDI cut-off that predicted NIV failure (DD-CC) at T1 was ≤19.04% (area under the curve [AUC], 0.73; sensitivity, 50%; specificity, 85.71%; accuracy; 66.67%), while that at T2 was ≤35.3% (AUC, 0.75; sensitivity, 95.65%; specificity, 57.14%; accuracy, 74.51%; hazard ratio, 19.55). The NIV failure rate was 35.1% in those with normal diaphragmatic function by PC (T2) versus 5.9% by CC (T2). The odds ratio for NIV failure with DD criteria ≤35.3 and <20 at T2 was 29.33 and 4.61, while that for ≤19.04 and <20 at T1 was 6, respectively. The DD criterion of ≤35.3 (T2) had a better diagnostic profile compared to baseline and PC in prediction of NIV failure.

Lack of Association between Diaphragm Thickening Fraction and Transdiaphragmatic Pressure Swing in COVID-19 Pneumonia during Helmet Continuous Positive Airway Pressure: Research Letter.

Recently, evaluation of the diaphragm by means of ultrasound has become popular.1 The increase in diaphragm thickness during inspiration (thickening fraction) has been proposed as a noninvasive bedside measure of diaphragm function,2,3 although previous studies have reported wide variability between thickening, inspiratory effort, and transdiaphragmatic pressure.4–6 We hypothesized that the force-length and force-generating relationship in the diaphragm is altered by different positive end-expiratory pressure (PEEP) levels in patients with SARS-CoV-2.7We investigated the relationship between diaphragm thickening fraction and transdiaphragmatic pressure swing during noninvasive helmet continuous positive airway pressure. From March to December 2021, a total of 26 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the intensive care unit of Santa Chiara Hospital (Trento, Italy) were prospectively enrolled. The study was approved by the ethics committee (Rep. Int. 282/2022), and written informed consent was obtained. At intensive care unit admission, according to the local protocol, noninvasive respiratory assistance with helmet continuous positive airway pressure was started, and a nasogastric tube provided with two balloons for registering the esophageal and gastric pressures was inserted.8 Intragastric positioning of the tube was checked with standard methods; both balloons were inflated with manufacturer- recommended volume. Intragastric position of the lower balloon was confirmed by positive pressure deflections during gentle abdominal compressions; the mid-lower third esophageal position of the proximal balloon was confirmed by inspiratory negative deflections and the presence of cardiac artifacts. In vivo calibration of the filling volume was performed. Patients underwent a trial with three increasing levels of PEEP, lasting 30 min each. The first level was set at 0 cm H2O. PEEP was then increased to 5 and 10 cm H2O; fractional expired oxygen tension was left unchanged. An average of three measurements was made, with careful attention to select the same breaths for the diaphragm ultrasound and for esophageal/gastric pressure measurements. During the last 5 min of each step, esophageal and transdiaphragmatic pressure swing and diaphragmatic ultrasound were recorded. The right hemidiaphragm was identified in the zone of apposition as a three-layered structure by B-mode ultrasonography, with the probe at the mid-axillary line at the 10th intercostal space.1 Thickness was measured from frozen M-mode images as the distance from the pleural to the peritoneal line. All the examinations were performed by the same expert physician and recorded for a subsequent offline analysis.The study population had a median age of 67.5 [62.3–72.5 interquartile range] yr, 16 (61.5%) were male, body mass index was 27 [24–33 interquartile range] kg/m2, and Pao2/fractional expired oxygen tension ratio and Paco2 at admission were 122 [103–139 interquartile range] and 39 [37–44 interquartile range] mmHg, respectively. No association was found between diaphragm thickening fraction and transdiaphragmatic pressure swings or esophageal pressure swings, at 0 cm H2O, 5 cm H2O, and 10 cm H2O (fig. 1).In a previous investigation, Steinberg et al.9 found that neither thickening fraction nor diaphragmatic excursion was able to estimate esophageal pressure swings in patients with SARS-CoV-2. We sought to extend these findings by investigating the relationship between diaphragm ultrasound and the transdiaphragmatic pressure swing, which should be more representative of the contribution of the diaphragm to the total inspiratory effort. Similar to other authors,4 we confirm the lack of association between diaphragm thickening and the transdiaphragmatic pressure. Despite that it may lie on the nonlinear pressure–volume relationship of the diaphragm, during a single breath, the diaphragm inspiratory thickening and the transdiaphragmatic pressure generated depend on the specific pattern of thoracoabdominal motion (i.e., a descent of the diaphragm rather than expansion of the rib cage). The application of PEEP also causes changes in the diaphragm geometry also modifying the force generated by the diaphragm that may not be uniform across the muscle.The different position of the diaphragm muscle over its force or length relationship is likely explained by changes in end-expiratory lung volume during the PEEP trial. Although not directly measured, diaphragm dysfunction can also be a contributing factor; COVID-19 is associated with a viral myositis,10 which might have affected diaphragm force-generating capacity.However, the impact of the small sample size on any statistical inference must be considered, and the lack of Gilbert index and pressure-time product of diaphragmatic pressure calculation reduces the interpretation of our results.In summary, despite being promising for its feasibility and noninvasive characteristics, the assessment of diaphragm thickening should not be used as a surrogate for inspiratory effort. In SARS-CoV-2 patients during helmet continuous positive airway pressure in the acute setting, an increase in inspiratory effort, as measured by transdiaphragmatic pressure swings, is not related to diaphragm thickening fraction. We suggest caution against using this tool to inform clinical choices about respiratory support, at least until more robust data will be available.Support was provided solely from institutional and/or departmental sources.The authors declare no competing interests.

A Trend towards Diaphragmatic Muscle Waste after Invasive Mechanical Ventilation in Multiple Trauma Patients-What to Expect?

Considering the prioritization of life-threatening injuries in trauma care, secondary dysfunctions such as ventilator-induced diaphragmatic dysfunction (VIDD) are often overlooked. VIDD is an entity induced by muscle inactivity during invasive mechanical ventilation, associated with a profound loss of diaphragm muscle mass. In order to assess the incidence of VIDD in polytrauma patients, we performed an observational, retrospective, longitudinal study that included 24 polytraumatized patients. All included patients were mechanically ventilated for at least 48 h and underwent two chest CT scans during their ICU stay. Diaphragmatic thickness was measured by two independent radiologists on coronal and axial images at the level of celiac plexus. The thickness of the diaphragm was significantly decreased on both the left and right sides (left side: -0.82 mm axial p = 0.034; -0.79 mm coronal p = 0.05; right side: -0.94 mm axial p = 0.016; -0.91 coronal p = 0.013). In addition, we obtained a positive correlation between the number of days of mechanical ventilation and the difference between the two measurements of the diaphragm thickness on both sides (r =0.5; p = 0.02). There was no statistically significant correlation between the body mass indexes on admission, the use of vitamin C or N-acetyl cysteine, and the differences in diaphragmatic thickness.

Respiratory muscle strength should be continuously monitored for patients on mechanical ventilation

Mechanical ventilation (MV) is an effective treatment for respiratory failure. In recent years, it has been found that MV can not only cause ventilation-associated lung injury (VALI), but also cause ventilation-induced diaphragmatic dysfunction (VIDD). Although the injury site and etiology are not the same, they are interrelated and mutually causal, and eventually lead to weaning failure. Studies have indicated that diaphragmatic function protection strategy should be implemented in patients on MV. That is, the entire process from assessing the ability of spontaneous breathing before MV, to the initiation of spontaneous breathing and to weaning during MV. For patients on MV, continuous monitoring of respiratory muscle strength should be conducted. Early prevention, early intervention and timely detection of VIDD may reduce the occurrence of difficult weaning, resulting in improved prognosis. This study mainly discussed the risk factors and pathogenesis of VIDD.

Intraoperative Hemi-Diaphragm Electrical Stimulation Demonstrates Attenuated Mitochondrial Function without Change in Oxidative Stress in Cardiothoracic Surgery Patients.

Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm force production to offset VIDD; we also investigated changes in mitochondrial function after stimulation. During cardiothoracic surgeries (n = 21), supramaximal, unilateral phrenic nerve stimulation was performed every 30 min for 1 min. Diaphragm biopsies were collected after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers and protein expression and enzymatic activity of biomarkers of oxidative stress and mitophagy. Patients received, on average, 6.2 ± 1.9 stimulation bouts. Stimulated hemidiaphragms showed lower leak respiration, maximum electron transport system (ETS) capacities, oxidative phosphorylation (OXPHOS), and spare capacity compared with unstimulated sides. There were no significant differences between mitochondrial enzyme activities and oxidative stress and mitophagy protein expression levels. Intraoperative phrenic nerve electrical stimulation led to an acute decrease of mitochondrial respiration in the stimulated hemidiaphragm, without differences in biomarkers of mitophagy or oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes.

First non-invasive magnetic phrenic nerve and diaphragm stimulation in anaesthetized patients: a proof-of-concept study

BackgroundMechanical ventilation has side effects such as ventilator-induced diaphragm dysfunction, resulting in prolonged intensive care unit length of stays. Artificially evoked diaphragmatic muscle contraction may potentially maintain diaphragmatic muscle function and thereby ameliorate or counteract ventilator-induced diaphragm dysfunction. We hypothesized that bilateral non-invasive electromagnetic phrenic nerve stimulation (NEPNS) results in adequate diaphragm contractions and consecutively in effective tidal volumes.ResultsThis single-centre proof-of-concept study was performed in five patients who were 30 [IQR 21–33] years old, 60% (n = 3) females and undergoing elective surgery with general anaesthesia. Following anaesthesia and reversal of muscle relaxation, patients received bilateral NEPNS with different magnetic field intensities (10%, 20%, 30%, 40%); the stimulation was performed bilaterally with dual coils (connected to one standard clinical magnetic stimulator), specifically designed for bilateral non-invasive electromagnetic nerve stimulation. The stimulator with a maximal output of 2400 Volt, 160 Joule, pulse length 160 µs at 100% intensity was limited to 50% intensity, i.e. each single coil had a maximal output of 0.55 Tesla and 1200 Volt. There was a linear relationship between dosage (magnetic field intensity) and effect (tidal volume, primary endpoint, p < 0.001). Mean tidal volume was 0.00, 1.81 ± 0.99, 4.55 ± 2.23 and 7.43 ± 3.06 ml/kg ideal body weight applying 10%, 20%, 30% and 40% stimulation intensity, respectively. Mean time to find an initial adequate stimulation point was 89 (range 15–441) seconds.ConclusionsBilateral non-invasive electromagnetic phrenic nerve stimulation generated a tidal volume of 3–6 ml/kg ideal body weight due to diaphragmatic contraction in lung-healthy anaesthetized patients. Further perspectives in critically ill patients should include assessment of clinical outcomes to confirm whether diaphragm contraction through non-invasive electromagnetic phrenic nerve stimulation potentially ameliorates or prevents diaphragm atrophy.

Enhanced endoplasmic reticulum RyR1 receptor phosphorylation leads to diaphragmatic dysfunction in septic rats

To explore the role of endoplasmic reticulum ryanodine receptor 1 (RyR1) expression and phosphorylation in sepsis- induced diaphragm dysfunction. Thirty SPF male SD rats were randomized equally into 5 groups, including a sham-operated group, 3 sepsis model groups observed at 6, 12, or 24 h following cecal ligation and perforation (CLP; CLP-6h, CLP-12h, and CLP-24h groups, respectively), and a CLP-24h group with a single intraperitoneal injection of KN- 93 immediately after the operation (CLP-24h+KN-93 group). At the indicated time points, diaphragm samples were collected for measurement of compound muscle action potential (CMAP), fatigue index of the isolated diaphragm and fitted frequencycontraction curves. The protein expression levels of CaMK Ⅱ, RyR1 and P-RyR1 in the diaphragm were detected using Western blotting. In the rat models of sepsis, the amplitude of diaphragm CMAP decreased and its duration increased with time following CLP, and the changes were the most obvious at 24 h and significantly attenuated by KN-93 treatment (P < 0.05). The diaphragm fatigue index increased progressively following CLP (P < 0.05) irrespective of KN- 93 treatment (P>0.05). The frequency-contraction curve of the diaphragm muscle decreased progressively following CLP, and was significantly lower in CLP-24 h group than in CLP-24 h+KN-93 group (P < 0.05). Compared with that in the sham-operated group, RyR1 expression level in the diaphragm was significantly lowered at 24 h (P < 0.05) but not at 6 or 12 following CLP, irrespective of KN-93 treatment; The expression level of P-RyR1 increased gradually with time after CLP, and was significantly lowered by KN-93 treatment at 24 h following CLP (P < 0.05). The expression level of CaMKⅡ increased significantly at 24 h following CLP, and was obviously lowered by KN-93 treatment (P < 0.05). Sepsis causes diaphragmatic dysfunction by enhancing CaMK Ⅱ expression and RyR1 receptor phosphorylation in the endoplasmic reticulum of the diaphragm.

Influence of ultrasound-guided erector spinae plane block on post-operative pain and diaphragmatic dysfunction in obese patients undergoing repair of Epigastric Hernia

ABSTRACT Background Repair of ventral hernia is associated with pain after operation. We wanted to study the influence of ultrasound-guided (US) erector spine plane (ESP) block on postoperative pain and diaphragmatic dysfunction in obese cases undergoing repair of epigastric hernia. Methods This prospective randomized-controlled double-blinded research was conducted on 50 obese cases with body mass index (30–40), aged (21–65) and scheduled for elective open repair of epigastric hernia. Cases were randomized into two equal groups to receive either general anesthesia alone (Controls) or general anesthesia combined with bilateral ultrasound-guided ESP block. Postoperative pain, 24 h postoperative analgesic dose, and postoperative diaphragmatic excursion were assessed. Results There was a statistically evident decrease in NRS score in the ESP versus controls (30 min, 2 hr, 6 hr, 12 hr)(p < 0.001). There was a statistically evident decrease in the total intraoperative fentanyl (p < 0.001) and total 24 h morphine dose (p < 0.001) in the ESP versus controls. There was a statistically evident decrease in the postoperative diaphragmatic excursion in controls versus the ESP (p = 0.001). Conclusions The ESP block in obese cases undergoing open repair of epigastric hernia provided efficient postoperative analgesia. It decreased postoperative pain, reduced intraoperative and postoperative analgesic dose, and maintained diaphragmatic excursion.

Treatment with levosimendan in an experimental model of early ventilator-induced diaphragmatic dysfunction.

Mechanical ventilation (MV) is a life-saving approach in critically ill patients. However, it may affect the diaphragmatic structure and function, beyond the lungs. Levosimendan is a calcium sensitizer widely used in clinics to improve cardiac contractility in acute heart failure patients. In vitro studies have demonstrated that levosimendan increased force-generating capacity of the diaphragm in chronic obstructive pulmonary disease patients. Thus the aim of this study was to evaluate the effects of levosimendan administration in an animal model of ventilator-induced diaphragmatic dysfunction (VIDD) on muscle contraction and diaphragm muscle cell viability. Sprague-Dawley rats underwent prolonged MV (5 hours). VIDD+Levo group received a starting bolus of levosimendan immediately after intratracheal intubation and then an intravenous infusion of levosimendan throughout the study. Diaphragms were collected for ex vivo contractility measurement (with electric stimulation), histological analysis and Western blot analysis. Healthy rats were used as the control. Levosimendan treatment maintained an adequate mean arterial pressure during the entire experimental protocol, preserved levels of autophagy-related proteins (LC3BI and LC3BII) and the muscular cell diameter demonstrated by histological analysis. Levosimendan did not affect the diaphragmatic contraction or the levels of proteins involved in the protein degradation (atrogin). Our data suggest that levosimendan preserves muscular cell structure (cross-sectional area) and muscle autophagy after 5 hours of MV in a rat model of VIDD. However, levosimendan did not improve diaphragm contractile efficiency.

Comparison of Changes in Chest Wall Mechanics and Respiratory Timing Between Patient-Controlled Epidural Analgesia and Intravenous Patient-Controlled Analgesia After Laparoscopic Gastrectomy: A Randomized Controlled Trial.

Upper abdominal surgery is associated with postoperative diaphragmatic dysfunction. Whether patient-controlled epidural analgesia (PCEA) is superior to intravenous patient-controlled analgesia (IV-PCA) in preventing postoperative diaphragmatic dysfunction is still unclear in laparoscopic gastric surgery. Sixteen patients undergoing laparoscopic gastrectomy randomly received either PCEA or IV-PCA. The primary outcomes were the change in chest wall mechanics and respiratory timing, measured by respiratory inductive plethysmography(Respitrace; Ambulatory Monitoring Inc., Ardsley, New York, United States) before and after surgery, and analyzed by a data acquisition system (PowerLab; ADInstruments, Dunedin, New Zealand). Inspiratory time (Ti), expiratory time (Te), total respiratory cycle time (Ttot), proportion of inspiratory time over total respiratory cycle time (Ti/Ttot), respiratory rate (RR), and abdominal contribution to tidal volume (AB/VT [%]) were calculated from the stored data. AB/VT, relative volume contribution of diaphragm to tidal breathing, represents an index of diaphragmatic function.Because the diaphragm is the main contributor to tidal volume, decreases in AB/VT indicate diaphragm dysfunction. Changes in outcomes over time between the two groups were analyzed using a linear mixed model, and two-sided p values < 0.05 were considered statistically significant. The secondary outcomes were postoperative pain score(visual analog scale (VAS)), bowel function recovery, and hospital stay duration. Postoperative AB/VT in the IV-PCA group was significantly decreased compared to preoperative levels. AB/VT in the PCEA group was significantly higher than the IV-PCA group on postoperative day (POD) 1. Change in AB/VT over time between the PCEA group and the IV-PCA group differed significantly (p = 0.01). A decrease of AB/VT during POD 1 to 3 was observed in the IV-PCA group but not in the PCEA group. As for respiratory timing, there were significant increases in RR with a reduction of Te and Ttot compared to preoperative levels on POD 1 in the PCEA group. There were significant decreases in RR and Ti/Ttot with an increase of Te and Ttot compared to preoperative levels on POD 1 in the IV-PCA group. There was a significant difference in the change of the Ttot over time between the two groups (p = 0.046). There were no significant differences in the changes of Te, Ti/Ttot, Ti, and RR over time between the two groups. There was no significant difference in VAS over time at rest and mobilization, recovery of bowel function, and hospital stay between the two groups. Continuous ropivacaine infusion with PCEA partially attenuated diaphragmatic dysfunction after laparoscopic gastrectomy, while pain relief by continuous intravenous administration of fentanyl could not attenuate diaphragmatic dysfunction. This suggests that PCEA might ameliorate postoperative diaphragmatic dysfunction after laparoscopic gastrectomy.

Managing respiratory muscle weakness during weaning from invasive ventilation.

Weaning is a critical stage of an intensive care unit (ICU) stay, in which the respiratory muscles play a major role. Weakness of the respiratory muscles, which is associated with significant morbidity in the ICU, is not limited to atrophy and subsequent dysfunction of the diaphragm; the extradiaphragmatic inspiratory and expiratory muscles also play important parts. In addition to the well-established deleterious effect of mechanical ventilation on the respiratory muscles, other risk factors such as sepsis may be involved. Weakness of the respiratory muscles can be suspected visually in a patient with paradoxical movement of the abdominal compartment. Measurement of maximal inspiratory pressure is the simplest way to assess respiratory muscle function, but it does not specifically take the diaphragm into account. A cut-off value of -30 cmH2O could identify patients at risk for prolonged ventilatory weaning; however, ultrasound may be better for assessing respiratory muscle function in the ICU. Although diaphragm dysfunction has been associated with weaning failure, this diagnosis should not discourage clinicians from performing spontaneous breathing trials and considering extubation. Recent therapeutic developments aimed at preserving or restoring respiratory muscle function are promising.

Short-term outcomes of robotic-assisted transthoracic diaphragmatic plication.

Patients who are symptomatic from diaphragmatic dysfunction may benefit from diaphragmatic plication. We recently modified our plication approach from open thoracotomy to robotic transthoracic. We report our short-term outcomes. We conducted a single-institution retrospective review of all patients who underwent transthoracic plications from 2018, when we began using the robotic approach, to 2022. The primary outcome was short-term recurrence of diaphragm elevation with symptoms noted before or during the first planned postoperative visit. We also compared proportions of short-term recurrences in patients that underwent plication with extracorporeal knot-tying device alone versus those that used intracorporeal instrument tying (alone or supplemental). Secondary outcomes included subjective postoperative improvement of dyspnea at follow-up visit and by postoperative patient questionnaire, chest tube duration, length of stay (LOS), 30-day readmission, operative time, estimated blood loss (EBL), intraoperative complications, and perioperative complications. Forty-one patients underwent robotic-assisted transthoracic plication. Four patients experienced recurrent diaphragm elevation with symptoms before or during their first routine postoperative visit, occurring on POD 6, 10, 37, and 38. All four recurrences occurred in patients whose plications were performed with the extracorporeal knot-tying device without supplemental intracorporeal instrument tying. Proportion of recurrences in the group that used extracorporeal knot-tying device alone was significantly greater than the recurrences in the group that used intracorporeal instrument tying (alone or supplemental) (P=0.016). The majority (36/41) reported clinical improvement postoperatively and 85% of questionnaire respondents also agreed they would recommend the surgery to others with similar condition. The median LOS and of chest tube duration were 3 days and 2 days, respectively. There were two patients with 30-day readmissions. Three patients developed postoperative pleural effusion necessitating thoracenteses and 8 patients (20%) had postoperative complications. No mortalities were observed. While our study shows the overall acceptable safety and favorable outcomes in patients undergoing robotic-assisted transthoracic diaphragmatic plications, the incidence of short-term recurrences and its association with the use of extracorporeally knot-tying device alone in diaphragm plication warrant further investigation.

Ultrasound assessment of diaphragmatic dysfunction and its improvement with levosimendan in patients with chronic obstructive pulmonary disease

Diaphragmatic Dysfunction (DD) is a clinical condition in which the diaphragm becomes weak or paralyzed, because of muscle strength reduction. It can be due to muscular issues or loss of proper innervation, but, also, to pulmonary hyperinflation or air trapping, such as in Chronic Obstructive Pulmonary Disease (COPD). DD impacts on COPD induced dyspnea, determining its progressive worsening, but levosimendan, an inodilator better known as Ca2+ sensitizer, may limit this phenomenon and diaphragmatic ultrasound assessment can be useful in monitoring its effect. Here, we show the case of a 77-year-old woman admitted to the Emergency department for acute exacerbation of chronic dyspnea in COPD, related to right ventricular failure and DD, which did not respond to medical therapy and non-invasive mechanical ventilation but did experience a favorable outcome after intravenous administration of levosimendan.

LncRNA H19 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-181/PDCD4 Axis

Chronic obstructive pulmonary disease (COPD) kills more than 3 million people worldwide every year. Despite progress in the treatment of symptoms and prevention of acute exacerbations, few advances have been made to ameliorate disease progression or affect mortality. Exercise plays a positive role in the prevention and treatment of diaphragm dysfunction in COPD, and the changes in diaphragm structure and function induced by exercise are closely related to the regulation of oxidative stress. But the mechanism remains unclear. So the aim of this study was to reveal the therapeutic mechanism of exercise to COPD using both in vivo and in vitro experiments. In this study, cigarette smoke (CS) induced COPD mice model, treadmill aerobic training for COPD mice were constructed and cigarette smoke extract (CSE) induced bronchial epithelial cells (BECs) model were used for COPD study. Bioinformatics analysis, luciferase reporting analysis, and RT-qPCR detection were used to clarify the interacted relationship among lncRNA, miRNA, and mRNA. ROS, inflammatory cytokines expression, and EMT relative protein α-SMA were detected using immunofluorescence and ELISA detection. The result shows that exercise ameliorates COPD induced lung injury by inhibit ROS, inflammation, and epithelial-mesenchymal transition (EMT) relative protein α-SMA expression. RT-qPCR detection shows that lnc-H19 expression was increased in lung tissues of COPD mice. Exercise decreased COPD induced lnc-H19 expression. Downregulation lnc-H19 inhibits COPD mediated lung injury. Bioinformatics analysis and luciferase reporting analysis confirmed that miR-181 and PDCD4 were downstream targets of lnc-H19. Upregulation of PDCD4 or downregulation of miR-181 reversed the protective effect of si-lnc-H19 to BECs after exposure to CSE. In conclusion, lncRNA H19 contributes to smoke-related chronic obstructive pulmonary disease by targeting miR-181/PDCD4 Axis.