Diaphragmatic Dysfunction Research Articles

Ultrasound-assessed diaphragm dysfunction predicts clinical outcomes in hemodialysis patients

Skeletal muscle atrophy is prevalent and remarkably increases the risk of cardiovascular (CV) events and mortality in hemodialysis (HD) patients. However, whether diaphragm dysfunction predicts clinical outcomes in HD patients is unknown. This was a prospective cohort study of 103 HD patients. After assessment of diaphragm function by ultrasonography and collection of other baseline data, a 36-month follow-up was then initiated. Participants were divided into diaphragm dysfunction (DD+) group and normal diaphragm function (DD−) group, according to cutoff value of thickening ratio (i.e. the change ratio of diaphragm thickness) at force respiration. The primary endpoint was the first nonfatal CV event or all-cause mortality. A secondary endpoint was less serious CV events (LSCEs, a composite of heart failure readmission, cardiac arrhythmia or myocardial ischemia needed pharmacological intervention in hospital). 98 patients were eligible to analysis and 57 (58.16%) were men. 28 of 44 patients(63.64%) in DD+ group and 23 of 54 patients (42.59%) in DD− group had at least one nonfatal CV event or death (p = 0.038). Compared to DD− group, DD+ group had significantly higher incidence of LSCEs (21 vs.14, p = 0.025) and shorter survival time (22.02 ± 12.98 months vs. 26.74 ± 12.59 months, p = 0.046). Kaplan–Meier analysis revealed significantly higher risks of primary endpoint (p = 0.039), and LSCEs (p = 0.040) in DD+ group. Multivariate hazard analysis showed that DD+ group had significantly higher risk of primary endpoint [hazard ratio (HR) 1.59; 95% confident interval (CI) 1.54–1.63], and LSCEs (HR 1.47; 95%CI 1.40–1.55). Ultrasound-assessed diaphragm dysfunction predicts clinical outcomes in HD patients.Trial registration: This study was registered with Chinese Clinical Trials Registry (www.chictr.org.cn) as ChiCTR1800016500 on Jun 05, 2018.

SHRINKING LUNG SYNDROME IN SYSTEMIC LUPUS ERYTHEMATOSUS: DIAGNOSIS OF RARE ENTITY

SHRINKING LUNG SYNDROME IN SYSTEMIC LUPUS ERYTHEMATOSUS: DIAGNOSIS OF RARE ENTITY

The impact of Diaphragmatic Dysfunction assessed by chest ultrasound on noninvasive ventilation outcome in patients with acute exacerbation of chronic obstructive pulmonary disease.

The impact of Diaphragmatic Dysfunction assessed by chest ultrasound on noninvasive ventilation outcome in patients with acute exacerbation of chronic obstructive pulmonary disease.

PO251 / #854 NONINVASIVE CLOSED LOOP DIAPHRAGM STIMULATION FOR VENTILATED ICU PATIENTS: E-POSTER VIEWING

Many COVID-19 patients need prolonged artificial ventilation. Skeletal muscle wastes rapidly when deprived of neural activation, and in ventilated patients the diaphragm muscle begins to atrophy within 24 hours (ventilator induced diaphragmatic dysfunction, VIDD). This profoundly weakens the diaphragm, complicating the weaning of the patient off the ventilator, and increasing the risk of complications such as bacterial pneumonia. 40% of the total duration of mechanical ventilation in ITU patients is accounted for by the weaning period, after the initial illness has resolved.

CAUGHT IN THE FRAY: NEUROSARCOIDOSIS PRESENTING AS CHRONIC RESPIRATORY FAILURE

CAUGHT IN THE FRAY: NEUROSARCOIDOSIS PRESENTING AS CHRONIC RESPIRATORY FAILURE

Cardiorespiratory consequences of obesity: a tale of two pumps.

Obesity decreases respiratory compliance, increasing energy expenditure and fatigue during breathing, contributing to perceived shortness of breath, elevating respiratory drive in an exhaustive positive feedback manner. The additional demand on the diaphragm can contribute to increased production of reactive oxygen species deleterious to function. Similarly, obesity drives cardiac morphological abnormalities, for example, fatty infiltration, fibrosis and cardiac hypertrophy, which can cause pulmonary congestion, contributing to dyspnoea and thus more work. In this issue of Experimental Physiology, Kelley et al. (2022) investigated in rats the effects of an obesogenic diet (high saturated fat/high sucrose) on the structure and function of the dual pumps of life. The ‘cafeteria’ diet was adequate to provoke morphological and functional changes in the heart characterised by hypertrophy, hypercontractility and diastolic dysfunction; however, interestingly, no changes were observed in the diaphragm. Dietary supplementation with N-acetylcysteine partially or fully prevented cardiac remodelling pointing to redox mechanisms as pivotal to obesity-related morbidity. N-acetylcysteine is a substrate for endogenous glutathione production, and it also has general widespread antioxidant effects. The cardiorespiratory systems are centred on dual pumps working interdependently to maintain systemic oxygen delivery and metabolic waste removal. Reciprocal interactions between the pumps are at play in health and disease. People with end-stage heart failure often manifest diaphragm dysfunction characterized by deleterious morphological and functional changes culminating in atrophy and diminished contractile function (Ahn et al., 2017; van Hees et al., 2007). The increased burden is associated with elevated levels of reactive oxygen species, a key factor manifesting skeletal muscle atrophy and dysfunction. Cardiac dysfunction can also alter endocrine signalling, for example leading to increased circulating cytokines and angiotensin II, activating diaphragm NAD(P)H oxidase 2/4 and contributing to aberrant redox modulation of respiratory pump function (Ahn et al., 2017). It is therefore surprising that Kelley et al. (2022) noted differential outcomes in heart and diaphragm with an apparently greater resilience to stress in the respiratory pump. As noted by the authors, the lack of observed change in the diaphragm likely resulted from an insufficient metabolic stressor, as previous literature suggests a positive correlation between obesity and both cardiac and diaphragm dysfunction. Of interest, a relative resilience to stressors in diaphragm compared with other skeletal muscles is reported in the literature, but perhaps more striking is the wide range of diseases associated with diaphragm dysfunction revealing an inherent vulnerability in the principal muscle of breathing, which is often masked, owing to the large ventilatory reserve of the diaphragm, until the emergence of end-stage respiratory failure. Importantly, N-acetylcysteine also has established anti-inflammatory effects. The cytokine tumour necrosis factor α is elevated in the circulation of people with congestive heart failure, contributing to elevated levels of reactive oxygen species. Advanced congestive heart failure can also lead to elevated angiotensin II associated with increased expression of atrophy-associated genes (atrogin-1 and MuRF-1), leading to diaphragmatic atrophy (Rezk et al., 2012). Several studies, in various models of disease, have shown that N-acetylcysteine abrogates increased levels of cytokines, angiotensin II and reactive oxygen species. Moreover, should diaphragm dysfunction present either directly or indirectly in the setting of obesity, it is worth noting that N-acetylcysteine protects diaphragm force-generating capacity (O'Halloran & Lewis, 2017). The twinned pumps governing cardiorespiratory function are remarkable in their enduring capabilities subserving whole-body health. Yet, inevitably, there are inherent limitations that extend to the dysfunctional consequences of metabolic excess. Whilst remedies for obesity-related morbidity require a multimodal approach, it is encouraging that N-acetylcysteine, which is approved for use in humans, offers a potential adjunctive therapeutic option. Both authors have read and approved the final version of this manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. A.L.M. is funded by Science Foundation Ireland SFI FFP/19/6628 INSPIRE DMD. Open access funding provided by IReL. None.

The role of functional tests in the diagnosis of paresis of the diaphragm

The article presents a clinical case of diaphragm dysfunction caused by damage to the diaphragmatic nerve in a 35-year-old patient after a war wound to the chest. Imaging methods coupled with electromyography make it possible to diagnose this disease and its cause, while lung function tests make it possible to clarify pulmonary disorders due to diaphragm dysfunction. Тhere is a restrictive type of ventilation disorders due to limited mobility of the chest in particular, as well as gas exchange disorders due to hypoventilation in the basal parts of the lungs in the patient under discussion. These changes determine the strategy of long-term clinical follow-up of such patients, the need to involve pharmacotherapy and rehabilitation programs. Given the urgency of this problem, the data obtained broaden our understanding of the problem and require the creation of algorithms for the examination of patients who have received a chest wound, taking into account ventilation and diff usion capacity abnormalities, the need for clinical follow-up and the creation of medical rehabilitation programs.

Identification of the co-differentially expressed hub genes involved in the endogenous protective mechanism against ventilator-induced diaphragm dysfunction

BackgroundIn intensive care units (ICU), mechanical ventilation (MV) is commonly applied to save patients’ lives. However, ventilator-induced diaphragm dysfunction (VIDD) can complicate treatment by hindering weaning in critically ill patients and worsening outcomes. The goal of this study was to identify potential genes involved in the endogenous protective mechanism against VIDD.MethodsTwelve adult male rabbits were assigned to either an MV group or a control group under the same anesthetic conditions. Immunostaining and quantitative morphometry were used to assess diaphragm atrophy, while RNA-seq was used to investigate molecular differences between the groups. Additionally, core module and hub genes were analyzed using WGCNA, and co-differentially expressed hub genes were subsequently discovered by overlapping the differentially expressed genes (DEGs) with the hub genes from WGCNA. The identified genes were validated by western blotting (WB) and quantitative real-time polymerase chain reaction (qRT–PCR).ResultsAfter a VIDD model was successfully built, 1276 DEGs were found between the MV and control groups. The turquoise and yellow modules were identified as the core modules, and Trim63, Fbxo32, Uchl1, Tmprss13, and Cst3 were identified as the five co-differentially expressed hub genes. After the two atrophy-related genes (Trim63 and Fbxo32) were excluded, the levels of the remaining three genes/proteins (Uchl1/UCHL1, Tmprss13/TMPRSS13, and Cst3/CST3) were found to be significantly elevated in the MV group (P < 0.05), suggesting the existence of a potential antiproteasomal, antiapoptotic, and antiautophagic mechanism against diaphragm dysfunction.ConclusionThe current research helps to reveal a potentially important endogenous protective mechanism that could serve as a novel therapeutic target against VIDD.

Effects of Unilateral Intermediate Cervical Plexus Block on the Diaphragmatic Function in Patients Undergoing Unilateral Thyroidectomy: A Randomized Controlled Study.

Background and PurposeAlthough unilateral intermediate cervical plexus block (ICPB) can be used for perioperative analgesia in neck surgery, its effect on diaphragm function remains controversial. This prospective study aimed to examine whether unilateral ICPB with different concentrations of ropivacaine resulted in the diaphragmatic dysfunction in unilateral thyroidectomy.MethodsA total of 54 patients scheduled to undergo unilateral thyroidectomy under general anesthesia were randomly allocated to receive either 10 mL of 0.3% (Group L) or 0.5% (Group H) ropivacaine for ICPB. General anesthesia was then administered for surgery. The diaphragm thickness and diaphragmatic excursion were measured at three different times: before the ICPB, at 40 min and 4 h after the block. The primary outcome was the incidence of diaphragmatic dysfunction of the block side at 40 min and 4 h after ICPB. Secondary outcomes included the maximum pain score within 24 h after the surgery, rescue analgesics within 24 h after the surgery, and time to first ambulation.ResultsThe incidence of diaphragmatic dysfunction on the block side of Group H was higher than that of Group L at 40 min after block (58% vs 29%, P = 0.01). However, the incidence of diaphragmatic dysfunction was comparable between Group H and Group L (65% vs 46%) at 4 h after block placement. Within 24 h after the operation, the maximum VAS pain score of Group H was significantly lower than Group L (P = 0.04), and fewer patients in Group H required rescue analgesics (P < 0.01).ConclusionThe ICPB with different concentrations of ropivacaine can induce the ipsilateral diaphragmatic dysfunction. The high concentration of ropivacaine results in higher incidence of diaphragmatic dysfunction at 40 min, but comparable incidence at 4 h after block compared with lower concentration of ropivacaine.Chinese Clinical Trial RegistryChiCTR2000029348.

Thoracic surgery may alter body static balance via diaphragm dysfunction.

Many diseases and conditions can alter an ability to maintain body balance. The aim of the present study was to investigate whether thoracic surgery may elicit diaphragm dysfunction thereby impairing postural stability. 40 patients qualified to video-assisted thoracoscopy (VATS) lobectomy or lobectomy via thoracotomy due to pulmonary carcinoma were examined two times: a day before lung resection and 3–5 days after surgical procedure. Diaphragm assessment was performed using ultrasonography, while postural sways were evaluated by Zebris FDM-S stabilometric platform. Thoracic surgery was associated with decrease of diaphragm thickness and movement, as well as, with deterioration of static body balance maintenance. Upper lobe resection was linked with greater diaphragm excursion restriction and worse body sway parameters than middle and lower lobe resection. VATS lobectomy was associated with better postoperative diaphragm function and better postural sway parameters than lobectomy via thoracotomy. Patients after lobectomy via thoracotomy had significantly more load on lower limb on the operated side than patients after VATS lobectomy. Impairment of diaphragm function is closely associated with equilibrium impairment after pulmonary resection. VATS lobectomy was less invasive than lobectomy via thoracotomy in terms of primary respiratory muscle function and body balance maintenance parameters.

Diaphragm dysfunction after severe COVID-19: An ultrasound study.

BackgroundSARS-CoV-2 infection can impair diaphragm function at the acute phase but the frequency of diaphragm dysfunction after recovery from COVID-19 remains unknown.Materials and methodsThis study was carried out on patients reporting persistent respiratory symptoms 3–4 months after severe COVID-19 pneumonia. The included patients were selected from a medical consultation designed to screen for recovery after acute infection. Respiratory function was assessed by a pulmonary function test, and diaphragm function was studied by ultrasonography.ResultsIn total, 132 patients (85M, 47W) were recruited from the medical consultation. During the acute phase of the infection, the severity of the clinical status led to ICU admission for 58 patients (44%). Diaphragm dysfunction (DD) was detected by ultrasonography in 13 patients, two of whom suffered from hemidiaphragm paralysis. Patients with DD had more frequently muscle pain complaints and had a higher frequency of prior cardiothoracic or upper abdominal surgery than patients with normal diaphragm function. Pulmonary function testing revealed a significant decrease in lung volumes and DLCO and the dyspnea scores (mMRC and Borg10 scores) were significantly increased in patients with DD. Improvement in respiratory function was recorded in seven out of nine patients assessed 6 months after the first ultrasound examination.ConclusionAssessment of diaphragm function by ultrasonography after severe COVID-19 pneumonia revealed signs of dysfunction in 10% of our population. In some cases, ultrasound examination probably discovered an un-recognized pre-existing DD. COVID-19 nonetheless contributed to impairment of diaphragm function. Prolonged respiratory physiotherapy led to improvement in respiratory function in most patients.Clinical trial registration[www.cnil.fr], identifier [#PADS20-207].

Changes in diaphragm contractility in cigarette smoking-exposed and smoking cessation rats are associated with alterations in mitochondrial morphology and homeostasis.

The effects of cigarette smoking (CS) cessation on the diaphragm are unknown, as are the CS-induced diaphragmatic mitochondrial changes. We examined the changes in diaphragm contractility, as well as alterations in mitochondrial morphology, function and homoeostasis during CS exposure and after cessation. Rats were randomly divided into CS exposure and CS cessation groups: 3-month CS (S3), 6-month CS (S6), 6-month CS followed by 3-month cessation (S6N3). The changes in the diaphragm were investigated, including contractile properties, the ultrastructure, mitochondrial function and the expression of markers of mitochondrial homoeostasis. CS caused irreversible histological disruption and functional depression in the lungs, along with significantly declines in diaphragmatic contractility and more severely in extensor digitorum longus muscular contractility. Such declines were recovered after 3-month CS cessation. CS exposure disrupted the diaphragmatic mitochondrial morphology and function (S6), which was significantly alleviated in the S6N3 group. The mitochondrial homoeostasis was depressed (S6), as indicated by the downregulation of Pink1 and Mfn1. Interestingly, the Mfn1 level was recovered after smoking cessation (S6N3). In conclusion, smoking cessation eased CS-induced diaphragmatic dysfunction and mitochondrial deregulation, which are likely associated with deregulated mitochondrial homoeostasis.

Impact of intubated vs. non-intubated anesthesia on postoperative diaphragmatic function: Results from a prospective observational study.

Background: An altered diaphragmatic function was associated with the development of postoperative pulmonary complications following thoracic surgery. Methods: To evaluate the impact of different anesthetic techniques on postoperative diaphragmatic dysfunction, patients undergoing video-assisted thoracoscopic surgery (VATS) lung biopsy for interstitial lung disease were enrolled in a monocentric observational prospective study. Patients received intubated or non-intubated anesthesia according to risk assessment and preferences following multidisciplinary discussion. Ultrasound measured diaphragmatic excursion (DIA) and Thickening Fraction (TF) were recorded together with arterial blood gases and pulmonary function tests (PFT) immediately before and 12 h after surgery. Pain control and postoperative nausea and vomiting (PONV) were also evaluated. Results: From February 2019 to September 2020, 41 consecutive patients were enrolled. Five were lost due to difficulties in collecting postoperative data. Of the remaining 36 patients, 25 underwent surgery with a non-intubated anesthesia approach whereas 11 underwent intubated general anesthesia. The two groups had similar baseline characteristics. On the operated side, DIA and TF showed a lower residual postoperative function in the intubated group compared to the non-intubated group (54 vs. 82% of DIA and 36 vs. 97% of TF; p = 0.001 for both). The same was observed on the non-operated side (58 vs. 82% and 62 vs. 94%; p = 0.005 and p = 0.045, respectively, for DIA and TF). No differences were observed between groups in terms of pain control, PONV, gas exchange and PFT. Conclusion: This study suggests that maintenance of spontaneous breathing during VATS lung biopsy is associated with better diaphragmatic residual function after surgery.

Expiratory and inspiratory action of transversus abdominis during eupnea and hypercapnic ventilation

BackgroundRecently, there is interest in the clinical importance of monitoring abdominal muscles during respiratory failure. The clinical interpretation relies on the assumption that expiration is a passive physiologic process and, since diaphragm and abdomen are arranged in series, any inward motion of the abdominal wall represents a sign of diaphragm dysfunction. However, previous studies suggest transversus abdominis might be active even during eupnea and is preferentially recruited over the other abdominal muscles. Objective1) Is transversus abdominis normally recruited during eupnea? 2) What is the degree of activation of transversus abdominis during hypercapnia? 3) Does the end-inspiratory length of transversus abdominis change during hypercapnia, while diaphragm function is normal? MethodsIn 30 spontaneously breathing canines, awake without confounding anesthetic, we measured directly both electrical activity and corresponding mechanical length and shortening of transversus abdominis during eupnea and hypercapnia. ResultsTransversus abdominis is consistently recruited during eupnea. During hypercapnia, transversus abdominis recruitment is progressive and significant. Throughout hypercapnia, transversus abdominis baseline end-inspiratory length is not constant: baseline length decreases progressively throughout hypercapnia.After expiration, into early inspiration, transversus abdominis shows a consistent neural mechanical post -expiratory expiratory activity (PEEA) at rest, which progressively increases during hypercapnia. ConclusionTransversus abdominis is an obligatory expiratory muscle, reinforcing the fundamental principle expiration is not a passive process. Beyond expiration, during hypercapnic ventilation, transversus abdominis contributes as an “accessory inspiratory muscle” into the early phase of inspiration. Clinical monitoring of abdominal wall motion during respiratory failure may be confounded by action of transversus abdominis.

Occurrence and Effects on Weaning From Mechanical Ventilation of Intensive Care Unit Acquired and Diaphragm Weakness: A Pilot Study.

PurposeLimb intensive care unit (ICU)-acquired weakness (ICUAW) and ICU acquired diaphragm weakness (DW) occur frequently in mechanically ventilated (MV) patients; their coexistence in cooperative and uncooperative patients is unknown. This study was designed to (1) describe the co-occurrence of the two conditions (2) evaluate the impact of ICUAW and DW on the ventilator-free days (VFDs) at 28 days and weaning success, and (3) assess the correlation between maximal inspiratory pressure (MIP) and thickening fraction (TFdi) in patients with DW.MethodsThis prospective pilot study was conducted in a single-center on 73 critically ill MV patients. Muscle weakness was defined as a Medical Research Council score < 48 in cooperative patients or a bilateral mean simplified peroneal nerve test < 5.26 mV in uncooperative patients. Diaphragm dysfunction was defined as MIP < 30 cm H2O or as a TFdi < 29%. Weaning success was defined according to weaning according to a new definition (WIND).ResultsFifty-seven patients (78%) had ICUAW and 59 (81%) had DW. The coexistence of the two conditions occurred in 48 patients (65%), without association (χ2 = 1.06, p = 0.304). In the adjusted analysis, ICUAW was independently related to VFDs at 28-days (estimate difference 6 days, p = 0.016), and WIND (OR of 3.62 for having WIND different than short weaning), whereas DW was not. The linear mixed model showed a significant but weak correlation between MIP and TFdi (p < 0.001).ConclusionThis pilot study is the first to explore the coexistence of ICUAW and DW in both cooperative and uncooperative patients; a lack of association was found between DW and ICUAW when considering both cooperative and uncooperative patients. We found a strong correlation between ICUAW but not DW with the VFDs at 28 days and weaning success. A future larger study is warranted in order to confirm our results, and should also investigate the use of transdiaphragmatic twitch pressure measurement during bilateral anterior magnetic phrenic nerve stimulation for the diagnosis of DW.

Assessment of Diaphragm in Hemiplegic Patients after Stroke with Ultrasound and Its Correlation of Extremity Motor and Balance Function.

Background: A variety of functional disorders can be caused after stroke, among which impairment of respiratory function is a frequent and serious complication of stroke patients. The aim of this study was to examine diaphragmatic function after stroke by diaphragm ultrasonography and then to apply to explore its correlation with extremity motor function and balance function of the hemiplegia patients. Methods: This cross-sectional observational study recruited 48 hemiplegic patients after stroke and 20 matched healthy participants. The data of demographic and ultrasonographic assessment of all healthy subjects were recorded, and 45 patients successfully underwent baseline data assessment in the first 48 h following admission, including post-stroke duration, stroke type, hemiplegia side, pipeline feeding, pulmonary infection, ultrasonographic assessment for diaphragm, Fugl–Meyer Motor Function Assessment Scale (FMA Scale), and Berg Balance Scale assessment. Ultrasonographic assessment parameters included diaphragm mobility under quiet and deep breathing, diaphragm thickness at end-inspiratory and end-expiratory, and calculated thickening fraction of the diaphragm. The aim was to analyze the diaphragm function of hemiplegic patients after stroke and to explore its correlation with extremity motor function and balance function. Results: The incidence of diaphragmatic dysfunction under deep breath was 46.67% in 45 hemiplegia patients after stroke at the convalescent phase. The paralyzed hemidiaphragm had major impairments, and the mobility of the hemiplegic diaphragm was significantly reduced during deep breathing (p < 0.05). Moreover, the thickness fraction of hemiplegic side was extremely diminished when contrasted with the healthy control and non-hemiplegic side (p < 0.05). We respectively compared the diaphragm mobility under deep breath on the hemiplegic and non-hemiplegic side of patients with left and right hemiplegia and found there was no significant difference between the hemiplegic side of right and left hemiplegia (p > 0.05), but the non-hemiplegic side of right hemiplegia was significantly weaker than that of left hemiplegia patients (p < 0.05). The diaphragm mobility of stroke patients under quiet breath was positively correlated with age and FMA Scale score (R2 = 0.296, p < 0.05), and significant positive correlations were found between the diaphragm mobility under deep breath and Berg Balance Scale score (R2 = 0.11, p < 0.05), diaphragm thickness at end-inspiratory and FMA Scale score (R2 = 0.152, p < 0.05), and end-expiratory thickness and FMA Scale score (R2 = 0.204, p < 0.05). Conclusions: The mobility and thickness fraction of the hemiplegic diaphragm after stroke by diaphragm ultrasonography were significantly reduced during deep breathing. Diaphragm mobility on bilateral sides of the right hemiplegia patients were reduced during deep breathing. Moreover, the hemiplegic diaphragmatic function was positively correlated with extremity motor and balance function of the hemiplegia patients.

Ultrasound imaging of diaphragmatic motion.

The diaphragm is the key muscle of respiration, especially in infants. Diaphragmatic dysfunction and paralysis can have significant implications for medical management and treatment, and they can be challenging to diagnose by clinical parameters alone. Multiple imaging modalities are useful for assessing the diaphragm, but US - specifically M-mode US - offers several distinct advantages and few limitations compared to fluoroscopy, radiography, CT and MRI. The purpose of this manuscript is to discuss the pathophysiology of the diaphragm, review common indications for dynamic diaphragmatic US, describe optimal imaging technique, and discuss how to avoid imaging pitfalls.

Diaphragm Dysfunction after Cardiac Surgery: Insights from Ultrasound Imaging during Cardiac Rehabilitation.

Diaphragm dysfunction is common after cardiac surgery and can be evaluated with ultrasonography (US). We aimed at assessing with US the incidence of diaphragmatic dysfunction and the impact of cardiovascular rehabilitation (CR) on its recovery. A single-center cohort study was performed. Patients were enrolled after cardiac surgery. The 6-min walking test (6MWT) and diaphragm US were performed at CR admission and after 10 rehabilitative sessions. One hundred eighty-five patients were eligible for final analysis. One hundred thirty-one patients (70.8%) were found to have diaphragm dysfunction (excursion <2 cm). After CR, 68 patients regained normal diaphragmatic function; those with persistent dysfunction had a lower level of functional performance on the 6MWT (metabolic equivalents of tasks: 3.3 vs. 3.6, p =0.013). The patients who underwent combined surgery (adjusted odds ratio [aOR]=4.09, p=0.001) and those with post-operative pneumothorax (aOR=3.02, p=0.042) were at increased risk of failure to improve diaphragmatic excursion. US parameters were more powerful tools in predicting diaphragmatic evolution compared with the 6MWT indexes: baseline diaphragm excursion and thickening fraction were associated with complete diaphragmatic functional recovery after CR (aOR=9.101, p < 0.001, and aOR=1.058, p=0.020 respectively). US is a valuable tool for the assessment of post-operative diaphragmatic dysfunction and can identify patients at risk of diaphragmatic recovery failure.

Diaphragm dysfunction: a comprehensive review from diagnosis to management.

Although the diaphragm represents a critical component of the respiratory pump, the clinical presentations of diaphragm dysfunction are often non-specific and can be mistaken for other more common causes of dyspnoea. While acute bilateral diaphragm dysfunction typically presents dramatically, progressive diaphragm dysfunction associated with neuromuscular disorders and unilateral hemidiaphragm dysfunction may be identified incidentally or by recognising subtle associated symptoms. Diaphragm dysfunction should be considered in individuals with unexplained dyspnoea, restrictive respiratory function tests or abnormal diaphragm position on plain chest imaging. A higher index of suspicion should occur for individuals with profound orthopnoea, those who have undergone procedures in proximity to the phrenic nerve(s) or those with co-morbid conditions that are associated with diaphragm dysfunction, particularly neuromuscular disorders. A systematic approach to the evaluation of diaphragm function using non-invasive diagnostic techniques such as respiratory function testing and diaphragm imaging can often confirm a diagnosis. Neurophysiological assessment may confirm diaphragm dysfunction and assist in identifying an underlying cause. Identifying those with or at risk of respiratory failure can allow institution of respiratory support, while specific cases may also benefit from surgical plication or phrenic nerve pacing techniques.

Endoplasmic Reticulum Stress Contributes to Ventilator-Induced Diaphragm Atrophy and Weakness in Rats

Background: Accumulating evidence indicates that endoplasmic reticulum (ER) stress plays a critical role in the regulation of skeletal muscle mass. In recent years, much attention has been given to ventilator-induced diaphragm dysfunction (VIDD) because it strongly impacts the outcomes of critically ill patients. Current evidence suggests that the enhancement of oxidative stress is essential for the development of VIDD, but there are no data on the effects of ER stress on this pathological process. Methods: VIDD was induced by volume-controlled mechanical ventilation (MV) for 12 h; Spontaneous breathing (SB, for 12 h) rats were used as controls. The ER stress inhibitor 4-phenylbutyrate (4-PBA), the antioxidant N-acetylcysteine (NAC), and the ER stress inducer tunicamycin (TUN) were given before the onset of MV or SB. Diaphragm function, oxidative stress, and ER stress in the diaphragms were measured at the end of the experiments. Results: ER stress was markedly increased in diaphragms relative to that in SB after 12 h of MV (all p < 0.001). Inhibition of ER stress by 4-PBA downregulated the expression levels of proteolysis-related genes in skeletal muscle, including Atrogin-1 and MuRF-1, reduced myofiber atrophy, and improved diaphragm force-generating capacity in rats subjected to MV (all p < 0.01). In addition, mitochondrial reactive oxygen species (ROS) production and protein level of 4-HNE (4-hydroxynonenal) were decreased upon 4-PBA treatment in rats during MV (all p < 0.01). Interestingly, the 4-PBA treatment also markedly increased the expression of peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1α) (p < 0.01), a master regulator for mitochondrial function and a strong antioxidant. However, the antioxidant NAC failed to reduce ER stress in the diaphragm during MV (p > 0.05). Finally, ER stress inducer TUN largely compromised diaphragm dysfunction in the absence of oxidative stress (all p < 0.01). Conclusion: ER stress is induced by MV and the inhibition of ER stress alleviates oxidative stress in the diaphragm during MV. In addition, ER stress is responsible for diaphragm dysfunction in the absence of oxidative stress. Therefore, the inhibition of ER stress may be another promising therapeutic approach for the treatment of VIDD.