Comparative Effect of High-Frequency Nasal Cannula and Noninvasive Ventilation on the Work of Breathing and Postoperative Pulmonary Complication after Pediatric Congenital Cardiac Surgery: A Prospective Randomized Controlled Trial.

BACKGROUND: Various forms of commonly used noninvasive respiratory support strategies have considerable effect on diaphragmatic contractile function which can be evaluated using sonographic diaphragm activity parameters. OBJECTIVE: To compare the magnitude of respiratory workload decreased as assessed by thickening fraction of the diaphragm and longitudinal diaphragmatic strain while using high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) modes [nasal intermittent positive pressure ventilation (NIPPV) and bilevel positive airway pressure (BiPAP)] in pediatric patients after cardiothoracic surgery. METHODOLOGY: This prospective randomized controlled trial was performed at a tertiary care surgical intensive care unit in postcardiac surgery patients aged between 1 and 48 months, who were randomly allocated into three groups: 1) HFNC (with flows at 2 L/kg/min), 2) NIPPV via RAMS cannula in PSV mode (pressure support 8 cmH2O, PEEP 5 cmH2O), and 3) BiPAP in nCPAP mode (CPAP of 5 cmH2O). Measurements were recorded at baseline after extubation (R0) and subsequently every 12 hourly (R1, R2, R3, R4, R5) at 12, 24, 36, 48, and 60 hours respectively until therapy was discontinued. RESULTS: Sixty patients were included, with 20 patients each in the NIPPV group, HFNC group, and BiPAP group. Longitudinal strain at crura of diaphragm was lower in the BiPAP group as compared to HFNC group at R2-R4 [R2 (-4.27± -2.73 vs - 8.40± -6.40, P = 0.031), R3 (-5.32± -2.28 vs -8.44± -5.6, P = 0.015), and R4 (-3.8± -3.42 vs -12.4± -7.12, P = 0.040)]. PFR was higher in HFNC than NIPPV group at baseline and R1-R3[R0 (323 ± 114 vs 264 ± 80, P = 0.008), R1 (311 ± 114 vs 233 ± 66, P = 0.022), R2 (328 ± 116 vs 237 ± 4, P = 0.002), R3 (346 ± 112 vs 238 ± 54, P = 0.001)]. DTF and clinical parameters of increased work of breathing remain comparable between three groups. The rate of reintubation (within 48 hours of extubation or at ICU discharge) was 0.06% (1 in NIPPV, 1 in BiPAP, 2 in HFNC) and remain comparable between groups (P = 1.0). CONCLUSION: BiPAP may provide better decrease in work of breathing compared to HFNC as reflected by lower crural diaphragmatic strain pattern. HFNC may provide better oxygenation compared to NIPPV group, as reflected by higher PFR ratio. Failure rate and safety profile are similar among different methods used.

Breath-by-breath comparison of a novel percutaneous phrenic nerve stimulation approach with mechanical ventilation in juvenile pigs: a pilot study.

About one in three critically ill patients requires mechanical ventilation (MV). Prolonged MV, however, results in diaphragmatic weakness, which itself is associated with delayed weaning and increased mortality. Inducing active diaphragmatic contraction via electrical phrenic nerve stimulation (PNS) not only provides the potential to reduce diaphragmatic muscular atrophy but also generates physiological-like ventilation and therefore offers a promising alternative to MV. Reasons why PNS is not yet used in critical care medicine are high procedural invasiveness, insufficient evidence, and lack of side-by-side comparison to MV. This study aims to establish a minimal-invasive percutaneous, bilateral electrode placement approach for sole PNS breathing and thereby enable, for the first time, a breath-by-breath comparison to MV. Six juvenile German Landrace pigs received general anesthesia and orotracheal intubation. Following the novel ultrasound-guided, landmark-based, 4-step approach, two echogenic needles per phrenic nerve were successfully placed. Stimulation effectiveness was evaluated measuring tidal volume, diaphragmatic thickening and tomographic electrical impedance in a breath-by-breath comparison to MV. Following sufficient bilateral phrenic nerve stimulation in all pigs, PNS breaths showed a 2.2-fold increase in diaphragmatic thickening. It induced tidal volumes in the lung-protective range by negative pressure inspiration and improved dorso-caudal regional ventilation in contrast to MV. Our study demonstrated the feasibility of a novel ultrasound-guided, percutaneous phrenic nerve stimulation approach, which generated sufficient tidal volumes and showed more resemblance to physiological breathing than MV in a breath-by-breath comparison.

Management of Diaphragm Tumors.

Diaphragm tumors are very rare, with secondary tumors being more common than primary tumors. The most common benign primary tumors include lipomas and cysts, and malignant primary tumors include rhabdomyosarcoma and leiomyosarcoma. Endometriosis is the most common benign secondary tumor, followed by malignant tumors with localized spread of disease. In addition, widely metastatic disease has been described. Benign lipomas and cysts can be managed conservatively, but more complex or concerning disease typically requires resection. The diaphragm can often be repaired primarily, though any large defect or tension would indicate the need for mesh or an autologous reconstruction.

Reconstructive Techniques for Diaphragm Resection.

A variety of diaphragmatic and non-diaphragmatic pathologies may require resection, reconstruction, or repair of the diaphragm. Adequate reconstruction is crucial in cases of diaphragmatic resection to prevent the herniation of abdominal organs into the chest and to maintain optimal respiratory function. This article aims to provide a detailed overview of the techniques used for surgical diaphragm reconstruction, taking into account factors such as the size and location of the defect, available options for reconstructive materials, potential challenges and pitfalls, and considerations related to the recurrence or failure of the repair.

Assessing Rat Diaphragm Motor Unit Connectivity Outcome Measures as Quantitative Biomarkers of Phrenic Motor Neuron Degeneration and Compensation.

Loss of ventilatory muscle function is a consequence of motor neuron injury and neurodegeneration (e.g., cervical spinal cord injury and amyotrophic lateral sclerosis, respectively). Phrenic motor neurons are the final link between the central nervous system and muscle, and their respective motor units (groups of muscle fibers innervated by a single motor neuron) represent the smallest functional unit of the neuromuscular ventilatory system. Compound muscle action potential (CMAP), single motor unit potential (SMUP), and motor unit number estimation (MUNE) are established electrophysiological approaches that enable the longitudinal assessment of motor unit integrity in animal models over time but have mostly been applied to limb muscles. Therefore, the objectives of this study are to describe an approach in preclinical rodent studies that can be used longitudinally to quantify the phrenic MUNE, motor unit size (represented as SMUP), and CMAP, and then to demonstrate the utility of these approaches in a motor neuron loss model. Sensitive, objective, and translationally relevant biomarkers for neuronal injury, degeneration, and regeneration in motor neuron injury and diseases can significantly aid and accelerate experimental research discoveries to clinical testing.

Surgical Diaphragm: Anatomy and Physiology.

The diaphragm is a musculoaponeurotic structure separating the thoracic and abdominal cavities. It plays important roles in both respiration and maintaining gastrointestinal function. A careful consideration of anatomy should be taken during surgical procedures to minimize injury to this crucial organ.

Management of Traumatic Diaphragmatic Injuries.

Diaphragm injuries are rarely seen injuries in trauma patients and are difficult to diagnose. With improving technology, computed tomography has become more reliable, but with increasing rates of non-operative management of both penetrating and blunt trauma, the rate of missed diaphragmatic injury has increased. The long-term complications of missed injury include bowel obstruction and perforation, which can carry a mortality rate as high as 85%. When diagnosed, injuries should be repaired to reduce the risk of future complications.

Management of Diaphragm Paralysis and Eventration.

An elevated diaphragm may be due to eventration or paralysis. Diaphragm elevation is often asymptomatic and found incidentally on imaging. Fluoroscopic testing can be used to differentiate eventration (no paradoxic motion) from paralysis (paradoxic motion). Regardless of etiology, a diaphragm plication is indicated in all symptomatic patients with an elevated diaphragm. Plication can be approached either from a thoracic or abdominal approach, though most thoracic surgeons perform minimally invasive thoracoscopic plication. The goal of plication is to improve lung volumes and decrease paradoxic elevation of the hemidiaphragm. Diaphragm plication is safe, has excellent outcomes, and is associated with symptom improvement.

Imaging of the Diaphragm: A Primer.

The diaphragm is a critical musculotendinous structure that contributes to respiratory function. Disorders of the diaphragm are rare and diagnostically challenging. Herein, the author reviews the radiologic options for the assessment of the diaphragm.

Inter-rater reliability of the dynamic neuromuscular stabilization diaphragm tests among individuals with non-specific low back pain and neck pain.

BACKGROUND: The Dynamic Neuromuscular Stabilization (DNS) diaphragm test and intra-abdominal pressure regulation test (IAPRT) are qualitative clinical tests that assess postural stability provided by the diaphragm. OBJECTIVE: Evaluate the inter-rater reliability of the diaphragm test and IAPRT between an experienced and novice DNS clinician among individuals with non-specific low back pain (LBP) and neck pain. METHODS: Forty-five participants with non-specific LBP and/or neck pain were assessed by an experienced and novice DNS physiotherapist in the diaphragm test and IAPRT, and scored on a visual analog scale (VAS) according to five different criteria. RESULTS: Moderate reliability was noted when assessing LBP and neck pain patients in the diaphragm test and IAPRT (p < 0.001). Moderate reliability also existed when assessing only LBP (p < 0.001) or neck pain (p = 0.002, p = 0.009) independently. Patients with lower pain (NPRS score of 5 or < ) demonstrated lower intra-class correlation coefficients, yet still moderate reliability in the diaphragm test (p = 0.004) and IAPRT (p = 0.001). Patients with higher pain (NPRS score of 6 or > ) demonstrated greater intra-class correlation coefficients, with the diaphragm test resulting in good reliability (p < 0.001). CONCLUSIONS: The diaphragm test and IAPRT demonstrate moderate reliability between an experienced and novice DNS clinician when evaluating LBP and neck pain patients, with a greater degree of reliability noted in patients suffering from higher reported pain.

Protective role of pretreatment with Anisodamine against sepsis-induced diaphragm atrophy via inhibiting JAK2/STAT3 pathway.

There is an increasing tendency for sepsis patients to suffer from diaphragm atrophy as well as mortality. Therefore, reducing diaphragm atrophy could benefit sepsis patients' prognoses. Studies have shown that Anisodamine (Anis) can exert antioxidant effects when blows occur. However, the role of Anisodamine in diaphragm atrophy in sepsis patients has not been reported. Therefore, this study investigated the antioxidant effect of Anisodamine in sepsis-induced diaphragm atrophy and its mechanism. We used cecal ligation aspiration (CLP) to establish a mouse septic mode and stimulated the C2C12 myotube model with lipopolysaccharide (LPS). After treatment with Anisodamine, we measured the mice's bodyweight, diaphragm weight, fiber cross-sectional area and the diameter of C2C12 myotubes. The malondialdehyde (MDA) levels in the diaphragm were detected using the oxidative stress kit. The expression of MuRF1, Atrogin1 and JAK2/STAT3 signaling pathway components in the diaphragm and C2C12 myotubes was measured by RT-qPCR and Western blot. The mean fluorescence intensity of ROS in C2C12 myotubes was measured by flow cytometry. Meanwhile, we also measured the levels of Drp1 and Cytochrome C (Cyt-C) in vivo and in vitro by Western blot. Our study revealed that Anisodamine alleviated the reduction in diaphragmatic mass and the loss of diaphragmatic fiber cross-sectional area and attenuated the atrophy of the C2C12 myotubes by inhibiting the expression of E3 ubiquitin ligases. In addition, we observed that Anisodamine inhibited the JAK2/STAT3 signaling pathway and protects mitochondrial function. In conclusion, Anisodamine alleviates sepsis-induced diaphragm atrophy, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway.

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.

Association between nutritional risk status and both diaphragmatic dysfunction and diaphragm atrophy in medical intensive care unit patients / Asociación entre el estado de riesgo nutricional y la disfunción diafragmática y la atrofi a del diafragma en pacientes de la unidad de cuidados intensivos médicos

Aim: critical illness often leads to malnutrition and diaphragmatic dysfunction (DD), common in intensive care units (ICU). Ultrasonography (US) is a potent tool for detecting DD. This study examines the connection between malnutrition risk and DD in ICU patients using ultrasonographic diaphragm measurements in medical ICU patients. Methods: we assessed nutritional risk using risk screening tools and mid-upper arm circumference measurements (MUAC). Diaphragm atrophy (DA) and DD were evaluated by measuring diaphragmatic excursion (DE), thickness, and thickening fraction (TF) by US. We then compared these diaphragmatic measurements in patients based on their nutritional risk scores. Results: of the fifty patients studied, 54 % to 78 % were at risk of malnutrition, 28 % exhibited diaphragm atrophy (DA), and 24 % showed DD upon ICU admission. Malnutrition risk diagnosed by all nutritional risk screening tools was significantly more frequent in patients with DD, while diagnosed by MUAC was considerably higher in patients with DA. A total of 16 patients (32 %) died during their ICU stay, with DD, DA, and malnutrition risks (as identified by the mNUTRIC Score) being more prevalent among non-survivors (p < 0.05). Malnutrition risk (as determined by the mNUTRIC Score) was an independent risk factor for DD [OR (95 % CI): 6.6 (1.3-34), p = 0.03]. Conclusion: malnutrition risk may be significantly associated with DD and DA in medical ICU patients upon ICU admission.(AU)

Objetivo: las enfermedades graves a menudo conducen a desnutrición y disfunción diafragmática (DD), comunes en las unidades de cuidados intensivos (UCI). La ultrasonografía (US) es una herramienta poderosa para detectar la DD. Este estudio examina la conexión entre riesgo de desnutrición y DD en pacientes de UCI utilizando mediciones ultrasonográficas del diafragma.Métodos: evaluamos el riesgo nutricional utilizando herramientas de evaluación de riesgos y mediciones de la circunferencia del brazo en su punto medio superior (MUAC). La atrofia del diafragma (DA) y la DD se evaluaron midiendo la excursión diafragmática (DE), el grosor y la fracción de engrosamiento (TF) por ecografía. Luego, comparamos estas mediciones diafragmáticas en pacientes según sus puntuaciones de riesgo nutricional. Resultados: de los cincuenta pacientes estudiados, entre el 54 % y el 78 % estaban en riesgo de desnutrición, el 28 % presentaban atrofia del diafragma (DA) y el 24 % mostraban DD al ingreso en la UCI. El riesgo de desnutrición diagnosticado por todas las herramientas de evaluación del riesgo nutricional fue significativamente más frecuente en los pacientes con DD, mientras que el diagnosticado por el MUAC fue considerablemente mayor en los pacientes con DA. Un total de 16 pacientes (32 %) fallecieron durante su estancia en la UCI, siendo la DD, la DA y los riesgos de desnutrición (según lo identificado por la puntuación mNUTRIC) más prevalentes entre los no sobrevivientes (p < 0,05). El riesgo de desnutrición (según lo determinado por la puntuación mNUTRIC) fue un factor de riesgo independiente de la DD [OR (95 % CI): 6,6 (1,3-34), p = 0,03]. Conclusión: en este estudio se encontró una asociación significativa entre el riesgo de desnutrición y la disfunción diafragmática, así como con la atrofia diafragmática al ingreso en la UCI.(AU)

Dynamic equilibrium of skeletal muscle macrophage ontogeny in the diaphragm during homeostasis, injury, and recovery.

The diaphragm is a unique skeletal muscle due to its continuous activation pattern during the act of breathing. The ontogeny of macrophages, pivotal cells for skeletal muscle maintenance and regeneration, is primarily based on two distinct origins: postnatal bone marrow-derived monocytes and prenatal embryonic progenitors. Here we employed chimeric mice to study the dynamics of these two macrophage populations under different conditions. Traditional chimeric mice generated through whole body irradiation showed virtually complete elimination of the original tissue-resident macrophage pool. We then developed a novel method which employs lead shielding to protect the diaphragm tissue niche from irradiation. This allowed us to determine that up to almost half of tissue-resident macrophages in the diaphragm can be maintained independently from bone marrow-derived monocytes under steady-state conditions. These findings were confirmed by long-term (5 months) parabiosis experiments. Acute diaphragm injury shifted the macrophage balance toward an overwhelming predominance of bone marrow (monocyte)-derived macrophages. However, there was a remarkable reversion to the pre-injury ontological landscape after diaphragm muscle recovery. This diaphragm shielding method permits analysis of the dynamics of macrophage origin and corresponding function under different physiological and pathological conditions. It may be especially useful for studying diseases which are characterized by acute or chronic injury of the diaphragm and accompanying inflammation.

Dyssynchronous diaphragm contractions impair diaphragm function in mechanically ventilated patients.

BACKGROUND: Pre-clinical studies suggest that dyssynchronous diaphragm contractions during mechanical ventilation may cause acute diaphragm dysfunction. We aimed to describe the variability in diaphragm contractile loading conditions during mechanical ventilation and to establish whether dyssynchronous diaphragm contractions are associated with the development of impaired diaphragm dysfunction. METHODS: In patients receiving invasive mechanical ventilation for pneumonia, septic shock, acute respiratory distress syndrome, or acute brain injury, airway flow and pressure and diaphragm electrical activity (Edi) were recorded hourly around the clock for up to 7 days. Dyssynchronous post-inspiratory diaphragm loading was defined based on the duration of neural inspiration after expiratory cycling of the ventilator. Diaphragm function was assessed on a daily basis by neuromuscular coupling (NMC, the ratio of transdiaphragmatic pressure to diaphragm electrical activity). RESULTS: A total of 4508 hourly recordings were collected in 45 patients. Edi was low or absent (≤ 5 µV) in 51% of study hours (median 71 h per patient, interquartile range 39-101 h). Dyssynchronous post-inspiratory loading was present in 13% of study hours (median 7 h per patient, interquartile range 2-22 h). The probability of dyssynchronous post-inspiratory loading was increased with reverse triggering (odds ratio 15, 95% CI 8-35) and premature cycling (odds ratio 8, 95% CI 6-10). The duration and magnitude of dyssynchronous post-inspiratory loading were associated with a progressive decline in diaphragm NMC (p < 0.01 for interaction with time). CONCLUSIONS: Dyssynchronous diaphragm contractions may impair diaphragm function during mechanical ventilation. TRIAL REGISTRATION: MYOTRAUMA, ClinicalTrials.gov NCT03108118. Registered 04 April 2017 (retrospectively registered).

Ampakines increase diaphragm activation following mid-cervical contusion injury in rats.

Ampakines are positive allosteric modulators of AMPA receptors. We hypothesized that low-dose ampakine treatment increases diaphragm electromyogram (EMG) activity after mid-cervical contusion injury in rats. Adult male and female Sprague Dawley rats were implanted with in-dwelling bilateral diaphragm EMG electrodes. Rats received a 150 kDyn C4 unilateral contusion (C4Ct). At 4- and 14-days following C4Ct, rats were given an intravenous bolus of ampakine CX717 (5 mg/kg, n = 10) or vehicle (2-hydroxypropyl-beta-cyclodextrin; HPCD; n = 10). Diaphragm EMG was recorded while breathing was assessed using whole-body plethysmography. At 4-days, ampakine administration caused an immediate and sustained increase in bilateral peak inspiratory diaphragm EMG bursting and ventilation. The vehicle had no impact on EMG bursting. CX717 treated rats were able to increase EMG activity during a respiratory challenge to a greater extent vs. vehicle treated. Rats showed a considerable degree of spontaneous recovery of EMG bursting by 14 days, and the impact of CX717 delivery was blunted as compared to 4-days. Direct recordings from the phrenic nerve at 21-24 days following C4Ct confirmed that ampakines stimulated bilateral phrenic neural output in injured rats. We conclude that low-dose intravenous treatment with a low-impact ampakine can enhance diaphragm activation shortly following mid-cervical contusion injury, when deficits in diaphragm activation are prominent.

The Application of Diaphragm Ultrasound in Chronic Obstructive Pulmonary Disease: A Narrative Review.

Chronic Obstructive Pulmonary Disease (COPD) is a prevalent condition that poses a significant burden on individuals and society due to its high morbidity and mortality rates. The diaphragm is the main respiratory muscle, its function has a direct impact on the quality of life and prognosis of COPD patients. This article aims to review the structural measurement and functional evaluation methods through the use of diaphragmatic ultrasound and relevant research on its application in clinical practice for COPD patients. Thus, it serves to provide valuable insights for clinical monitoring of diaphragm function in COPD patients, facilitating early clinical intervention and aiding in the recovery of diaphragm function.

[Traumatic damage to the diaphragm in children]. / Travmaticheskie povrezhdeniya diafragmy u detei.

OBJECTIVE: To analyze treatment outcomes in children with traumatic injuries of the diaphragm. MATERIAL AND METHODS: We followed-up 14 children aged 3-18 years with traumatic injuries of the diaphragm. Diagnostic measures included anamnesis, physical examination, pleural and abdominal puncture, bladder catheterization, ultrasound and X-ray examination including CT. RESULTS: Traumatic brain injury and thoracoabdominal trauma prevailed in children with traumatic injuries of the diaphragm. In 8 children, diaphragm injury was the result of a traffic accident. Of these, 5 ones died at the scene due to traumatic brain injury. In 3 children, diaphragm injury was associated with penetration of an iron pin through the perineum, pelvic cavity, abdominal and chest cavities when falling from a height (n=1) and sledding (n=2). Two children were littered with a pile of bricks and building materials. One girl suffered a diaphragm injury as a result of a stab wound. CONCLUSION: Combined damage to the diaphragm, TBI, chest and abdominal organs are serious injuries. Signs of shock, internal bleeding, respiratory failure and bone fractures come to the fore. Assistance to these children should be carried out in specialized hospitals.