Irisin attenuates ventilator-induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK.

Mechanical ventilation (MV) is an essential life-saving technique, but prolonged MV can cause significant diaphragmatic dysfunction due to atrophy and decreased contractility of the diaphragm fibres, called ventilator-induced diaphragmatic dysfunction (VIDD). It is not clear about the mechanism of occurrence and prevention measures of VIDD. Irisin is a newly discovered muscle factor that regulates energy metabolism. Studies have shown that irisin can exhibit protective effects by downregulating endoplasmic reticulum (ER) stress in a variety of diseases; whether irisin plays a protective role in VIDD has not been reported. Sprague-Dawley rats were mechanically ventilated to construct a VIDD model, and intervention was performed by intravenous administration of irisin. Diaphragm contractility, degree of atrophy, cross-sectional areas (CSAs), ER stress markers, AMPK protein expression, oxidative stress indicators and apoptotic cell levels were measured at the end of the experiment.Our findings showed that as the duration of ventilation increased, the more severe the VIDD was, the degree of ER stress increased, and the expression of irisin decreased.ER stress may be one of the causes of VIDD. Intervention with irisin ameliorated VIDD by reducing the degree of ER stress, attenuating oxidative stress, and decreasing the apoptotic index. MV decreases the expression of phosphorylated AMPK in the diaphragm, whereas the use of irisin increases the expression of phosphorylated AMPK. Irisin may exert its protective effect by activating the phosphorylated AMPK pathway.

The effect of respiratory muscle training on respiratory muscle strength, diaphragm thickness/mobility, and exercise capacity in patients with systemic lupus erythematosus and associated shrinking lung syndrome.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can impact any organ in the body. The pathophysiology of shrinking lung syndrome (SLS), a rare pulmonary complication of SLE, remains unknown. The objective of the current case series was to investigate the effects of inspiratory muscle training (IMT) on diaphragm thickness/mobility, respiratory muscle strength, peripheral muscle thickness/strength, and functional exercise capacity in patients with SLE and associated SLS. Three patients with SLE were included in the case series. Respiratory muscle strength, peripheral muscle strength, peripheral muscle thickness, diaphragm muscle thickness, diaphragm muscle mobility, functional exercise capacity, and pulmonary function test were assessed. A significant improvement has been determined in respiratory muscle strength, functional exercise capacity, peripheral muscle strength, peripheral muscle thickness, diaphragm muscle thickness, and diaphragm muscle mobility. This is the first case series showing the beneficial effects of IMT on respiratory muscle strength, diaphragm thickness/mobility, peripheral muscle thickness/strength, and exercise capacity in patients with SLE.

Oleothorax: An Ultrasound Sign of an Old Practice.

INTRODUCTION: The high morbidity and mortality of tuberculosis has led to the development of numerous therapeutic interventions during the pre-antibiotic era. In 1894, Forlanini proposed the technique of collapse therapy, using spontaneous pneumothorax. In 1926, Bernou developed the oleothorax technique to induce an iatrogenic collapse of the lung through the instillation of oil into the pleural cavity, which was subsequently removed. Nowadays, there are few patients that still represent a living testimony of this historic technique and have been described through traditional radiology. CASE PRESENTATION: We report the case of a patient with evidence of a right oleothorax that was investigated not only with traditional radiology but also with the use of chest ultrasonography. Ultrasounds were able to show peculiar characteristics of the oleothorax, including its particular echogenicity, the rigidity and static nature of the collection, the presence of peripheral calcifications, and the negative impact of the collection on diaphragmatic mobility and excursion. CONCLUSION: To our knowledge, this is the first report of an ultrasound description of oleothorax. We have observed that ultrasound examination, in cases of basal oleothorax, is able to add information regarding its radiological appearance and physiopathological implications on ventilatory mechanics and diaphragmatic distress.

Association of diaphragmatic dysfunction with duration of mechanical ventilation in patients in the pediatric intensive care unit: a prospective cohort study.

BACKGROUND: Mechanical ventilation (MV) can cause diaphragmatic injury and ventilator induced diaphragmatic dysfunction (VIDD). Diaphragm ultrasonography (DU) is increasingly used to assess diaphragmatic anatomy, function and pathology of patients receiving MV in the pediatric intensive care unit (PICU). We report the poor contractile ability of diaphragm during ventilation of critically ill patients in our PICU and the association to prolonged length of MV and PICU stay. METHODS: Patients who received MV within 24 h of admission to the PICU, expected to undergo continuous MV for more than 48 h and succeeded to extubate were included in the study. DU monitoring was performed daily after the initiation of MV until extubation. Diaphragm thickening fraction (DTF) measured by DU was used as an indicator of diaphragmatic contractile activity. Patients with bilateral DTF = 0% during DU assessment were allocated into the severe VIDD group (n = 26) and the rest were into non-severe VIDD group (n = 29). The association of severe VIDD with individual length of MV, hospitalization and PICU stay were analyzed. RESULTS: With daily DU assessment, severe VIDD occurred on 2.9 ± 1.2 days after the initiation of MV, and lasted for 1.9 ± 1.7 days. Values of DTF of all patients recovered to > 10% before extubation. The severe VIDD group had a significantly longer duration (days) of MV [12.0 (8.0-19.3) vs. 5.0 (3.5-7.5), p < 0.001] and PICU stay (days) [30.5 (14.9-44.5) vs. 13.0 (7.0-24.5), p < 0.001]. The occurrence of severe VIDD, first day of severe VIDD and length of severe VIDD were significantly positively associated with the duration of MV and PICU stay. The occurrence of severe VIDD on the second and third days after initiation of MV significantly associated to longer PICU stay (days) [43.0 (9.0-70.0) vs. 13.0 (3.0-40.0), p = 0.009; 36.0 (17.0-208.0) vs. 13.0 (3.0-40.0), p = 0.005, respectively], and the length of MV (days) was significantly longer in those with severe VIDD on the third day after initiation of MV [16.5 (7.0-29.0) vs. 5.0 (2.0-22.0), p = 0.003]. CONCLUSIONS: Daily monitoring of diaphragmatic function with bedside ultrasonography after initiation of MV is necessary in critically ill patients in PICU and the influences and risk factors of severe VIDD need to be further studied. (355 words).

Diaphragmatic dysfunction is associated with postoperative pulmonary complications and phrenic nerve paresis in patients undergoing thoracic surgery.

PURPOSE: We aimed to quantify perioperative changes in diaphragmatic function and phrenic nerve conduction in patients undergoing routine thoracic surgery. METHODS: A prospective observational study was performed in patients undergoing esophageal resection or pulmonary lobectomy. Examinations were carried out the day prior to surgery, 3 days and 10-14 days after surgery. Endpoints for diaphragmatic function included ultrasonographic measurements of diaphragmatic excursion and thickening fraction. Endpoints for phrenic nerve conduction included baseline-to-peak amplitude, peak-to-peak amplitude, and transmission delay. Measurements were assessed on both the surgical side and the non-surgical side of the thorax. RESULTS: Forty patients were included in the study. Significant reductions in diaphragmatic excursion were seen on the surgical side of the thorax for all excursion measures (posterior part of the right hemidiaphragm, p < 0.001; hemidiaphragmatic top point, p < 0.001; change in intrathoracic area, p < 0.001). Significant changes were seen for all phrenic nerve measures (baseline-to-peak amplitude, p < 0.001; peak-to-peak amplitude, p < 0.001; transmission delay, p = 0.041) on the surgical side. However, significant changes were also seen on the non-surgical side for all phrenic nerve measures (baseline-to-peak amplitude, p < 0.001; peak-to-peak amplitude, p < 0.001; transmission delay, p = 0.022). A postoperative reduction in posterior diaphragmatic excursion of more than 50% was significantly associated with postoperative pulmonary complications (coefficient: 2.69 (95% CI [1.38, 4.01], p < 0.001). CONCLUSION: Thoracic surgery caused a significant unilateral reduction in diaphragmatic excursion on the surgical side of the thorax, which was accompanied by significant changes in phrenic nerve conduction. However, phrenic nerve conduction was also significantly affected on the non-surgical side to a lesser extent, which was not mirrored in diaphragmatic excursion. Our findings suggest that phrenic nerve paresis plays a role in postoperative diaphragmatic dysfunction, which may be a contributing factor in the pathogenesis of postoperative pulmonary complications. CLINICAL TRIALS REGISTRATION NUMBER: NCT04507594.

Impaired diaphragmatic motility in treatment-naive adult patients with spinal muscular atrophy improved during nusinersen treatment.

INTRODUCTION/AIMS: The leading clinical feature of 5q-associated spinal muscular atrophy (SMA) is symmetric, proximal muscle weakness. Muscles involved in ventilation exhibit a specific pattern of denervation: intercostal muscles are severely atrophic, whereas the diaphragm muscle is less affected. The aim of this study was to investigate the involvement of diaphragmatic function by ultrasound imaging in adult patients with SMA and to quantify dynamics of diaphragmatic function during nusinersen treatment. METHODS: Diaphragmatic thickness, thickening, and excursion during quiet breathing were assessed in 24 adult patients with SMA type 2 and 3 by diaphragm ultrasound imaging before and during nusinersen treatment and were correlated with spirometric parameters. RESULTS: Diaphragm thickness was not reduced, but increased in a remarkable proportion of patients, whereas diaphragm thickening and excursion were reduced in about 20% to 30% of nusinersen-naive, adult patients with SMA types 2 and 3. During 26 months of nusinersen treatment, diaphragm thickening fraction and excursion improved. DISCUSSION: Diaphragm ultrasound imaging can provide disease- and treatment-relevant information that is not identified during routine clinical assessments and may therefore be a valuable complementary outcome measure.

Feasibility of transesophageal phrenic nerve stimulation.

BACKGROUND: Every year, more than 2.5 million critically ill patients in the ICU are dependent on mechanical ventilation. The positive pressure in the lungs generated by the ventilator keeps the diaphragm passive, which can lead to a loss of myofibers within a short time. To prevent ventilator-induced diaphragmatic dysfunction (VIDD), phrenic nerve stimulation may be used. OBJECTIVE: The goal of this study is to show the feasibility of transesophageal phrenic nerve stimulation (TEPNS). We hypothesize that selective phrenic nerve stimulation can efficiently activate the diaphragm with reduced co-stimulations. METHODS: An in vitro study in saline solution combined with anatomical findings was performed to investigate relevant stimulation parameters such as inter-electrode spacing, range to target site, or omnidirectional vs. sectioned electrodes. Subsequently, dedicated esophageal electrodes were inserted into a pig and single stimulation pulses were delivered simultaneously with mechanical ventilation. Various stimulation sites and response parameters such as transdiaphragmatic pressure or airway flow were analyzed to establish an appropriate stimulation setting. RESULTS: Phrenic nerve stimulation with esophageal electrodes has been demonstrated. With a current amplitude of 40 mA, similar response figures of the diaphragm activation as compared to conventional stimulation with needle electrodes at 10mA were observed. Directed electrodes best aligned with the phrenic nerve resulted in up to 16.9 % higher amplitude at the target site in vitro and up to 6 cmH20 higher transdiaphragmatic pressure in vivo as compared to omnidirectional electrodes. The activation efficiency was more sensitive to the stimulation level inside the esophagus than to the inter-electrode spacing. Most effective and selective stimulation was achieved at the level of rib 1 using sectioned electrodes 40 mm apart. CONCLUSION: Directed transesophageal phrenic nerve stimulation with single stimuli enabled diaphragm activation. In the future, this method might keep the diaphragm active during, and even support, artificial ventilation. Meanwhile, dedicated sectioned electrodes could be integrated into gastric feeding tubes.

Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients.

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

The Incidence of Diaphragmatic Dysfunction in Patients Presenting With Dyspnea in the Emergency Department.

OBJECTIVES: Diaphragmatic dysfunction has been reported as a cause of dyspnea, and its diagnosis can be made using ultrasound. Diaphragmatic ultrasound is mainly used to predict respiratory failure in chronic conditions. The use of diaphragmatic ultrasound has also risen in acute settings, such as emergency departments (EDs). However, the number of studies on its use still needs to be increased. The present study aimed to find the incidence of diaphragmatic dysfunction in the ED. METHODS: This prospective cohort study was conducted in an ED. We enrolled patients aged greater than 18 years who presented with dyspnea. Diaphragmatic excursion and diaphragmatic thickness techniques were performed. The primary outcome was the incidence of diaphragmatic dysfunction. The secondary outcomes were the associations between diaphragmatic dysfunction and the composition of respiratory therapies within 24 hours, intubation within 24 hours, and 7-day mortality. RESULTS: A total of 237 patients were analyzed. The incidences of diaphragmatic dysfunction assessed by diaphragmatic excursion and diaphragm thickness were 22.4 and 32.1%, respectively. Patients with sepsis and cancer had the highest incidences. Diaphragmatic dysfunction assessed by both techniques was not associated with the composition of respiratory support therapies within 24 hours, intubation within 24 hours, or 7-day mortality. CONCLUSIONS: The incidence of diaphragmatic dysfunction in dyspneic patients in the ED ranged from 22.4 to 32.1%, depending on the ultrasound technique. Diaphragmatic dysfunction was not associated with the composition of respiratory support therapies, intubation, or mortality.

A case report and literature review on respiratory failure with immune checkpoint inhibitors: a life-threatening adverse event.

Neuromuscular associated respiratory failure is a rare toxicity of immunotherapy for malignant tumors. In most cases, it may overlap with the symptoms of the primary disease or myocarditis, myositis and myasthenia gravis, resulting in difficult etiological diagnosis. Early detection and optimal treatment are still topics that need attention. Here, a case of 51-year-old male lung cancer patient with sintilimab-associated myasthenia gravis, myositis, and myocarditis overlap syndrome involving the diaphragm who developed severe type II respiratory failure was reported. After high-dose methylprednisolone, immunoglobulin and pyridostigmine intravenous injection with non-invasive positive pressure ventilation, the patient's symptoms improved significantly and was discharged. One year later, the patient received immunotherapy again due to tumor progression. After 53 days, he developed dyspnea again. Chest X-ray demonstrated marked elevation of the diaphragm, and the electromyogram demonstrated dysfunction of diaphragm. With rapid diagnosis and timely treatment, the patient was finally discharged safely. A comprehensive search of PubMed, EMBASE was performed to identify all previously reported cases of immune checkpoint inhibitors-associated respiratory failure. The potential mechanisms of respiratory failure caused by ICI-associated diaphragmatic dysfunction may be related to T cell-mediated immune disturbances and we proposed possible diagnostic processes. For patients with unexplained respiratory failure who are receiving immunotherapy, standardized diagnostic strategies should be implemented immediately on admission before deciding whether to conduct a more invasive diagnostic procedure or empirical treatment.

Diaphragmatic plication among lung transplant patients: A single-center experience.

BACKGROUND: There is lack of data reporting outcomes among patients needing diaphragmatic plication (DP) during or after lung transplantation (LT). We sought to assess the association of DP with post-transplant spirometry among other outcomes. METHODS: We included all patients who underwent LT between 2012 and 2016 (n = 324, mean age 56.3±13.4 years; M:F 198:126). We compared early and late outcomes based on the need for DP. RESULTS: The frequency of diaphragmatic dysfunction (DD) on pre-transplant fluoroscopy was 52.2%. A total of 38 DP procedures were performed among 37 patients (11.4% of LT patients). DP was done for anatomic (sizing or spacing issues) or functional indications (symptomatic DD). While patients with DP had significantly lower spirometry throughout the 3-year follow-up period, their slope of decline, functional assessments at the first annual visit, the risk of CLAD, and mortality were similar to patients without DP. A sub-group analysis limited to patients with restrictive lung diseases as the transplant indication had similar findings. CONCLUSIONS: Pre-transplant DD is common among LT candidates although it did not predict the need for DP. DP may be performed for functional or anatomic indications especially for addressing the donor-recipient size mismatch. Despite the lack of favorable effect on post-transplant spirometry, patients undergoing DP have acceptable and comparable early and late outcomes.

Shear Wave Elastography, a New Tool for Diaphragmatic Qualitative Assessment: A Translational Study.

Rationale: Prolonged mechanical ventilation is often associated with either a decrease (known atrophy) or an increase (supposed injury) in diaphragmatic thickness. Shear wave elastography is a noninvasive technique that measures shear modulus, a surrogate of tissue stiffness and mechanical properties. Objectives: To describe changes in shear modulus (SM) during the ICU stay and the relationship with alterations in muscle thickness. To perform a comprehensive ultrasound-based characterization of histological and force production changes occurring in the diaphragm. Methods: Translational study using critically ill patients and mechanically ventilated piglets. Serial ultrasound examination of the diaphragm collecting thickness and SM was performed in both patients and piglets. Transdiaphragmatic pressure and diaphragmatic biopsies were collected in piglets. Measurements and Main Results: We enrolled 102 patients, 88 of whom were invasively mechanically ventilated. At baseline, SM was 14.3 ± 4.3 kPa and diaphragm end-expiratory thickness was 2.0 ± 0.5 mm. Decrease or increase by more than 10% from baseline was reported in 86% of the patients for thickness and in 92% of the patients for SM. An increase in diaphragmatic thickness during the stay was associated with a decrease in SM (ß = -9.34 ± 4.41; P = 0.03) after multivariable analysis. In the piglet sample, a decrease in SM over 3 days of mechanical ventilation was associated with loss of force production, slow and fast fiber atrophy, and increased lipid droplets accumulation. Conclusions: Increases in diaphragm thickness during critical illness is associated with decreased tissue stiffness as demonstrated by shear wave ultrasound elastography, consistent with the development of muscle injury and weakness. Clinical trial registered with www.clinicaltrials.gov (NCT03550222).

Diaphragmatic Dysfunction due to Neuralgic Amyotrophy After SARS-CoV-2 Vaccination: A Case Report.

Neuralgic amyotrophy is an idiopathic neuropathy characterized by acute-onset pain, typically in the upper extremity or shoulder, followed by weakness of the associated muscles. Phrenic nerve involvement is rare. We report a 63-year-old man who presented with dyspnea and right shoulder pain after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. His chest radiograph showed an elevated right hemidiaphragm that was absent before vaccination. A pulmonary function test showed a restrictive pattern with a significant reduction (40%) in forced vital capacity in the supine position. Diaphragm ultrasonography revealed a reduction in both diaphragmatic excursion and a thickening fraction of the right hemidiaphragm. Electrophysiological studies suggested a right upper brachial plexopathy. Considering the temporal relationship between the vaccination and absence of other causes, SARS-CoV-2 vaccination was thought to be the reason for neuralgic amyotrophy with diaphragmatic dysfunction. As there was no evidence of hypoventilation or sleep disturbance that may require noninvasive ventilation, the patient was followed with conservative treatment with analgesics. During 8 months of follow-up, his shoulder pain was relieved significantly but dyspnea improved only slightly. Neuralgic amyotrophy is an under-diagnosed etiology of diaphragmatic dysfunction and should be considered in patients with dyspnea and shoulder pain.

Number of attempts required by emergency physicians to achieve competency in diaphragmatic ultrasound imaging.

PURPOSE: This research aimed to determine the number of attempts that emergency physicians need to become proficient in undertaking diaphragmatic ultrasound imaging. METHODS: A prospective observational study was conducted at the emergency department (ED) of a tertiary-care university hospital. Sixteen emergency physicians were each required to obtain a set of images of the right hemidiaphragm of five dyspneic patients using both diaphragmatic excursion and thickness techniques. The images were subsequently reviewed by a specialist using American College of Emergency Physician guidelines. If the evaluations of a physician did not reach the expected standard, the physician was to be given feedback and requested to collect images from another five patients. The process was to be repeated until such time as the images obtained by the physician were deemed to be up to standard. RESULTS: Eighty patients, twelve emergency medicine residents, and four attending physicians were enrolled. Following a didactic session on diaphragmatic ultrasound imaging and its interpretation, practicing on five patients proved sufficient to achieve an adequate level of competency in conducting diaphragmatic ultrasound examinations. CONCLUSION: Practicing on five patients is sufficient for emergency physicians to achieve an adequate level of competency in conducting right-sided diaphragmatic ultrasound examinations.

Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction.

BACKGROUND: Ventilator-induced diaphragmatic dysfunction (VIDD) is associated with weaning difficulties, intensive care unit hospitalization (ICU), infant mortality, and poor long-term clinical outcomes. The expression patterns of long noncoding RNAs (lncRNAs) and mRNAs in the diaphragm in a rat controlled mechanical ventilation (CMV) model, however, remain to be investigated. RESULTS: The diaphragms of five male Wistar rats in a CMV group and five control Wistar rats were used to explore lncRNA and mRNA expression profiles by RNA-sequencing (RNA-seq). Muscle force measurements and immunofluorescence (IF) staining were used to verify the successful establishment of the CMV model. A total of 906 differentially expressed (DE) lncRNAs and 2,139 DE mRNAs were found in the CMV group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological functions or pathways of these DE mRNAs. Our results revealed that these DE mRNAs were related mainly related to complement and coagulation cascades, the PPAR signaling pathway, cholesterol metabolism, cytokine-cytokine receptor interaction, and the AMPK signaling pathway. Some DE lncRNAs and DE mRNAs determined by RNA-seq were validated by quantitative real-time polymerase chain reaction (qRT-PCR), which exhibited trends similar to those observed by RNA-sEq. Co-expression network analysis indicated that three selected muscle atrophy-related mRNAs (Myog, Trim63, and Fbxo32) were coexpressed with relatively newly discovered DE lncRNAs. CONCLUSIONS: This study provides a novel perspective on the molecular mechanism of DE lncRNAs and mRNAs in a CMV model, and indicates that the inflammatory signaling pathway and lipid metabolism may play important roles in the pathophysiological mechanism and progression of VIDD.

Incidence of early diaphragmatic dysfunction after lung transplantation: results of a prospective observational study.

BACKGROUND: Diaphragmatic dysfunction is common after cardiothoracic surgery, but few studies report its incidence and consequences after lung transplantation. We aimed to estimate the incidence of diaphragmatic dysfunction using ultrasound in lung transplant patients up to 3 months postoperatively and evaluated the impact on clinical outcomes. METHODS: This was a single-center prospective observational cohort study of 27 lung transplant recipients using diaphragmatic ultrasound preoperatively, at 1 day, 1 week, 1 month, and 3 months postoperatively. Diaphragmatic dysfunction was defined as excursion < 10 mm in men and < 9 mm in women during quiet breathing. Clinical outcomes measured included duration of mechanical ventilation, length of stay (LOS) in Intensive Care (ICU), and hospital LOS. RESULTS: Sixty-two percentage of recipients experienced new, postoperative diaphragmatic dysfunction, but the prevalence fell to 22% at 3 months. No differences in clinical outcomes were found between those with diaphragmatic dysfunction compared to those without. Patients who experienced diaphragmatic dysfunction at 1 day postoperatively were younger and had a lower BMI than those who did not. CONCLUSIONS: Diaphragmatic dysfunction is common after lung transplant, improves significantly within 3 months, and did not impact negatively on duration of mechanical ventilation, LOS in ICU or hospital, or discharge destination.

Diaphragm dysfunction detected with ultrasound to predict noninvasive mechanical ventilation failure: A prospective cohort study.

OBJECTIVE: This study aimed to examine the use of point-of-care ultrasonography (POCUS) in detecting diaphragmatic dysfunction (DD) and evaluate its ability to predict noninvasive mechanical ventilation (NIV) failure in patients presented to the emergency department with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: In this prospective cohort study, the diaphragm was examined using POCUS in patients with AECOPD. DD was defined as a diaphragm thickening fraction of less than 20% during spontaneous breathing. NIV failure was the primary outcome of the study, and duration of hospital stay and in-hospital mortality were the secondary outcomes. Specificity, sensitivity, positive predictive value, and negative predictive value were estimated for predicting NIV failure in DD and evaluating the diagnostic performance of POCUS. RESULTS: 60 patients were enrolled the study. NIV failure was found in 11 (73.3%) of 15 patients with DD and in 2 (4.4%) of 45 patients without DD. In predicting NIV failure, DD had a sensitivity of 84.6% (95% confidence interval [CI]:54.6-98.1), specificity of 91.5% (95% CI:79.6-97.6), positive predictive value of 73.3% (95% CI:51.2-87.8), and negative predictive value of 95.6% (95% CI:85.7-98.7). The duration of hospital stay was not different between groups (p = .065). No in-hospital mortality was seen in patients without DD. CONCLUSIONS: DD has high sensitivity and specificity in predicting NIV failure in patients admitted to the emergency department with AECOPD. DD can be assessed by an experienced clinician noninvasively using POCUS in emergency departments.

Diaphragm Dysfunction After Cardiac Surgery: Reappraisal.

OBJECTIVES: The aim of this study was to re-investigate the incidence, risk factors, and outcomes of postoperative diaphragmatic dysfunction (DD) with actual cardiac surgery procedures. DESIGN: Single-center, retrospective, observational study based on a prospectively collected database. SETTING: Tertiary care cardiac surgery center. PARTICIPANTS: Patients who underwent cardiac surgery between January 2016 and September 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The DD group included patients with clinically perceptible diaphragmatic paralysis, which was confirmed by chest ultrasound (amplitude of the diaphragm movement in time-motion mode at rest, after a sniff test). The primary endpoint was the incidence of DD. Among 3,577 patients included, the authors found 272 cases of DD (7.6%). Individuals with DD had more arterial hypertension (64.3% v 52.6%; p < 0.0001), higher body mass index (BMI) (28 [25-30] kg/m2v 26 [24-29] kg/m2; p < 0.0002), and higher incidence of coronary bypass grafting (CABG) (58.8% v 46.6%; p = 0.0001). DD was associated with more postoperative pneumonia (23.9% v 8.7%; p < 0.0001), reintubation (8.8% v 2.9%; p < 0.0001), tracheotomy (3.3% v 0.3%; p < 0.0001), noninvasive ventilation (45.6% v 5.4%; p < 0.0001), duration of mechanical ventilation (five [four-11] hours v four [three-six] hours; p < 0.0001), and intensive care unit and hospital stays (14 [11-17] days v 13 [11-16] days; p < 0.0001). In multivariate analysis, DD was associated with CABG (odds ratio [OR] 1.9 [1.5-2.6]; p = 0.0001), arterial hypertension (OR 1.4 [1.1-1.9]; p = 0.008), and BMI (OR per point 1.04 [1.01-1.07] kg/m2; p = 0.003). CONCLUSIONS: The incidence of symptomatic DD after cardiac surgery was 7.6%, leading to respiratory complications and increased ICU stay. CABG was the principal factor associated with DD.

Detecting Ventilator-Induced Diaphragmatic Dysfunction Using Point-of-Care Ultrasound in Children With Long-term Mechanical Ventilation.

Long-term mechanical ventilation (MV) is defined as the use of MV for more than 6 hours per day for at least 3 weeks. Children requiring long-term MV include those with neuromuscular disease, central dysregulation, or lung dysfunction. Such children with medical complexity may be at risk for ventilator-induced diaphragmatic dysfunction. Ventilator-induced diaphragmatic dysfunction has been described in adult patients requiring acute MV with ultrasound (US). At this time, diaphragmatic US has not been evaluated in the pediatric post-acute care setting or incorporated into weaning strategies. We present 24 cases of children requiring long-term MV who underwent diaphragmatic US examinations to evaluate for ventilator-induced diaphragmatic dysfunction.

Ultrasonographic Assessment of Diaphragmatic Inspiratory Amplitude and Its Association with Postoperative Pulmonary Complications in Upper Abdominal Surgery: A Prospective, Longitudinal, Observational Study.

BACKGROUND: Diaphragmatic dysfunction following upper abdominal surgery is less recognized due to a lack of diagnostic modality for bedside evaluation. We used point-of-care ultrasound to evaluate the diaphragmatic inspiratory amplitude (DIA) in upper abdominal surgery for cancer. Our primary hypothesis was DIA would be reduced in the immediate postoperative period in patients with postoperative pulmonary complications (PPCs). Our aim was to identify an optimal cutoff of DIA for the diagnosis of PPCs. METHODS: We conducted a prospective, observational study in patients aged 18-75 years undergoing elective, upper abdominal oncological surgeries under combined general and epidural anesthesia. Ultrasound evaluation of the diaphragm was done by measuring the DIA in the right and left hemidiaphragms during quiet and deep breathing on the day before surgery and postoperative days (PODs) 1, 2, and 3. Patients were followed up for PPCs until POD 7. The linear mixed-effects model examined the association between DIA and PPCs and other perioperative factors. Receiver-operating characteristics analysis was done to determine the optimal cutoff of DIA in diagnosing PPCs. RESULTS: DIA measured in the 162 patients showed a significant decrease in their absolute values postoperatively from its preoperative baseline measurement. This decrease in DIA was significantly associated with PPC [right hemidiaphragm, ß = -0.17, 95% confidence interval (CI) -0.31 to -0.02, p = 0.001 during quiet breathing; left hemidiaphragm, ß = -0.24, 95% CI = -0.44 to -0.04, p = 0.018 and ß = -0.40, 95% CI = -0.71 to -0.09, p = 0.012 during quiet and deep breathing, respectively]. A cutoff value of DIA of left hemidiaphragm at 1.3 cm during quiet breathing and 1.6 cm during deep breathing had a sensitivity of 77 and 75%, respectively, in their ability to diagnose PPCs [left hemidiaphragm quiet breathing, area under the curve (AUC): 0.653, 95% CI 0.539-0.768, p = 0.015; left hemidiaphragm deep breathing, AUC: 0.675, 95% CI 0.577-0.773, p = 0.007]. CONCLUSION: Following upper abdominal surgery, the DIA is decreased and associated with PPCs. DIA of left hemidiaphragm less than 1.3 cm during quiet breathing and 1.6 cm during deep breathing has a sensitivity of 77 and 75%, respectively, in diagnosing PPCs following upper abdominal surgery. HOW TO CITE THIS ARTICLE: Vanamail PV, Balakrishnan K, Prahlad S, Chockalingam P, Dash R, Soundararajan DK. Ultrasonographic Assessment of Diaphragmatic Inspiratory Amplitude and Its Association with Postoperative Pulmonary Complications in Upper Abdominal Surgery: A Prospective, Longitudinal, Observational Study. Indian J Crit Care Med 2021;25(9):1031-1039.