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.

Sex differences in spontaneous respiratory recovery following chronic C2 hemisection.

Respiratory deficits after C2 hemisection (C2Hx) have been well documented through single-sex investigations. Although ovarian sex hormones enable enhanced respiratory recovery observed in females 2 wk post-C2Hx, it remains unknown if sex impacts spontaneous respiratory recovery at chronic time points. We conducted a longitudinal study to provide a comprehensive sex-based characterization of respiratory neuromuscular recovery for 8 wk after C2Hx. We recorded ventilation and chronic diaphragm electromyography (EMG) output in awake, behaving animals, phrenic motor output in anesthetized animals, and performed diaphragm muscle histology in chronically injured male and female rodents. Our results show that females expressed a greater recovery of tidal volume and minute ventilation compared with males during subacute and chronic time points. Eupneic diaphragm EMG amplitude during wakefulness and phrenic motor amplitude are similar between sexes at all time points after injury. Our data also suggest that females have a greater reduction in ipsilateral diaphragm EMG amplitude during spontaneous deep breaths (e.g., sighs) compared with males. Finally, we show evidence for atrophy and remodeling of the fast, fatigable fibers ipsilateral to injury in females, but not in males. To our knowledge, the data presented here represent the first study to report sex-dependent differences in spontaneous respiratory recovery and diaphragm muscle morphology following chronic C2Hx. These data highlight the need to study both sexes to inform evidence-based therapeutic interventions in respiratory recovery after spinal cord injury (SCI).NEW & NOTEWORTHY In response to chronic C2 hemisection, female rodents display increased tidal volume during eupneic breathing compared with males. Females show a greater reduction in diaphragm electromyography (EMG) amplitude during spontaneous deep breaths (e.g., sighs) and atrophy and remodeling of fast, fatigable diaphragm fibers. Given that most rehabilitative interventions occur in the subacute to chronic stages of injury, these results highlight the importance of considering sex when developing and evaluating therapeutics after spinal cord injury.

Diaphragm weakness in late-onset Pompe disease: A complex interplay between lower motor neuron and muscle fibre degeneration.

BACKGROUND: Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients. MATERIAL AND METHODS: A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed. RESULTS: Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited. CONCLUSIONS: Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.

Is phrenic nerve conduction affected in patients with difficult-to-treat asthma? / A neurocondução do nervo frênico está alterada na asma de difícil controle?

ABSTRACT Objective The aim of this study was to obtain data on phrenic neuroconduction and electromyography of the diaphragm muscle in difficult-to-treat asthmatic patients and compare the results to those obtained in controls. Methods The study consisted of 20 difficult-to-treat asthmatic patients compared with 27 controls. Spirometry, maximal inspiratory and expiratory pressure, chest X-ray, phrenic neuroconduction and diaphragm electromyography data were obtained. Results The phrenic compound motor action potential area was reduced, compared with controls, and all the patients had normal diaphragm electromyography. Conclusion It is possible that a reduced phrenic compound motor action potential area, without electromyography abnormalities, could be related to diaphragm muscle fiber abnormalities due to overload activity.

RESUMO Objetivo O objetivo do presente estudo foi obter dados da neurocondução do frênico e exame com agulha do diafragma em pacientes com asma de difícil controlee comparar com um grupo normal. Métodos O estudo consiste em realizar radiografia de tórax, espirometria, pressão máxima inspiratória e expiratória, neurocondução do nervo frênico e eletromiografia do músculo diafragma em 20 pacientes asmáticos de difícil controle e comparar com 27 controles. Resultados Encontramos redução da área do potencial de ação muscular composto do nervo frênico e a eletromiografia do musculo diafragma estava normal em todos os pacientes. Conclusão É possível que a redução da área do potencial de ação muscular composto do nervo frênico nos pacientes com asma de difícil controle associado a eletromiografia normal do músculo diafragma esteja relacionada as alterações da fibra muscular do mesmo devido à sobrecarga de atividade.

Parálisis diafragmática unilateral tras colecistectomía laparoscópica / Unilateral diaphragmatic paralysis after laparoscopic cholecystectomy

La colecistectomía laparoscópica supone hoy en día el tratamiento gold estándar de la patología aguda de la vía biliar. A pesar de las numerosas ventajas que presenta respecto a la cirugía abierta clásica, no está exenta de complicaciones. Presentamos el caso de un paciente varón de 82 años que tras el diagnóstico de colecistitis gangrenosa es intervenido de urgencia de colecistectomía laparoscópica, presentando en las primeras 24h del postoperatorio un episodio de insuficiencia respiratoria aguda, motivo por el cual ingresa en reanimación. Los estudios realizados a posteriori mostraron una parálisis del hemidiafragma derecho, probablemente relacionada con la cirugía

Laparoscopic cholecystectomy is currently the gold standard treatment for acute biliary tract pathology. Despite its many advantages compared to open surgery, it is not without complications. We present the case of an 82-year-old man who, after a diagnosis of gangrenous cholecystitis, underwent urgent laparoscopic cholecystectomy. During the first 24hours after the surgery, he had an episode of acute respiratory failure, for which he was admitted to the critical care unit. Studies performed later showed paralysis of the right diaphragm that was probably related to the surgery

Utilidad de la ecografía diafragmática en el diagnóstico precoz de parálisis frénica tras cirugía de hombro para prevenir complicaciones respiratorias postoperatorias / Usefulness of diaphragmatic ultrasound in the early diagnosis of phrenic nerve palsy after shoulder surgery in the prevention of post-operative respiratory complications

El bloqueo del nervio frénico es una complicación que puede producirse tras la anestesia del plexo braquial por encima de la clavícula. La principal consecuencia de este bloqueo es la parálisis diafragmática ipsolateral, que en ocasiones puede suponer aparición de complicaciones respiratorias postoperatorias. Presentamos un caso clínico de una mujer que tras ser intervenida de una prótesis total de hombro presentó disnea en la unidad de recuperación posquirúrgica. Se realizó una ecografía diafragmática que permitió un diagnóstico rápido de parálisis completa del hemidiafragma ipsolateral. Ante la sospecha de bloqueo del nervio frénico, la ecografía ha demostrado ser una herramienta diagnóstica rápida con alta sensibilidad y especificidad. Su empleo puede anticipar el posible desarrollo de complicaciones inmediatas, y orientarnos para escoger la estrategia terapéutica adecuada para cada caso de una manera precoz. En nuestro caso nos permitió tratar de forma precoz mediante oxigenoterapia, retirada de catéter interescalénico y vigilancia intensiva

Phrenic nerve block is a complication that can occur after brachial plexus anaesthesia above the clavicle. The main consequence of this blockage is ipsolateral diaphragmatic paralysis, which can sometimes lead to the appearance of post-operative respiratory complications. A case is presented on a woman, who after having undergone a total shoulder prosthesis, presented with dyspnoea in the post-operative recovery unit. A diaphragmatic ultrasound was performed that enabled a rapid diagnosis to be made of a complete paralysis of the ipsolateral hemi-diaphragm. Given the suspicion of phrenic nerve block, ultrasound has proven to be a rapid diagnostic tool with high sensitivity and specificity. Its use can anticipate the possible development of immediate complications, and act as a guide in choosing the appropriate therapeutic strategy for each case in an early manner. In this case it enabled us to treat early with oxygen therapy, interscalene catheter removal, and intensive surveillance

Effectiveness of diaphragmatic stimulation with single-channel electrodes in rabbits / Efetividade da estimulacao diafragmatica com eletrodos monocanais em coelhos

Every year, a large number of individuals become dependent on mechanical ventilation because of a loss of diaphragm function. The most common causes are cervical spinal trauma and neuromuscular diseases. We have developed an experimental model to evaluate the performance of electrical stimulation of the diaphragm in rabbits using single-channel electrodes implanted directly into the muscle. Various current intensities (10, 16, 20, and 26 mA) produced tidal volumes above the baseline value, showing that this model is effective for the study of diaphragm performance at different levels of electrical stimulation.

A cada ano um grande número de pessoas perde a função do diafragma tornando-se dependentes de ventilação mecânica. As principais causas são o trauma raquimedular da região cervical e as doenças neuromusculares. Desenvolvemos um modelo experimental para avaliar o desempenho da estimulação elétrica do diafragma em coelhos com eletrodos monocanais implantados diretamente neste músculo. Foram aplicadas diferentes intensidades de correntes (10, 16, 20 e 26 mA), as quais geraram volumes correntes acima dos valores basais, mostrando que este modelo é eficaz para estudar o desempenho do diafragma sob diferentes tipos de estimulação elétrica.

Taquipnea en un recién nacido macrosómico. Parálisis diafragmática de causa obstétrica / Macrosomic newborn tachypnea. Diaphragmatic paralysis

La parálisis diafragmática está originada por una lesión del nervio frénico, y su causa predominante en pediatría es el traumatismo durante el parto, especialmente en fetos macrosómicos. La asociación con la parálisis braquial orienta la sospecha diagnóstica, pero hay que tener en cuenta que hasta un 25% de los casos se presentan sin daño en el plexo braquial. Los síntomas pueden ser variables y aparecer inmediatamente tras el parto o durante el periodo neonatal. La radiografía muestra una elevación del hemidiafragma afectado, aunque el diagnóstico de confirmación se realiza con la ecografía en modo M. El manejo habitualmente es conservador, con aportes suplementarios de oxígeno o ventilación no invasiva (CPAP), y los pacientes e recuperan espontáneamente en la mayoría de los casos, aunque en ocasiones es necesario el tratamiento quirúrgico (plicatura) (AU)

The diaphragmatic paralysis is caused by a lesion of the phrenic nerve, being the predominant cause in pediatrics during birth, especially in macrosomic fetus. The relationship with brachial palsy, aids the diagnostic suspicion, but we have to take into account that up to 25% of the cases are shown without brachial plexus injury. Symptoms are variable and may appear immediately after delivery or later in the neonatal period. Chest x-rays show an elevation of the affected hemi-diaphragm. The diagnosis is confirmed by M-mode sonography. The management commonly is conservative (oxygen or CPAP), with spontaneous recovery in most cases, although surgical plication is required in some cases (AU)

Parálisis diafragmática unilateral dolorosa como única manifestación de la neuralgia amiotrófica / Unilateral Painful Diaphragm Paralysis as the Only Sign of Amyotrophic Neuralgia

La neuralgia amiotrófica es una neuropatía inflamatoria e idiopática que se caracteriza por dolor neuropático. Se describió por primera vez en 1948 como una afectación sólo del plexo braquial y se denominó síndrome de Parsonage-Turner. Aunque este síndrome es más frecuente en el plexo braquial, puede afectar de forma concomitante o aislada al nervio frénico, y en esta circunstancia el diagnóstico es muy difícil si no hay alta sospecha clínica.Presentamos el caso de un paciente con neuralgia amiotrófica cuya única manifestación fue la afectación frénica izquierda, y destacamos la refractariedad del dolor a los analgésicos, así como la persistencia de los síntomas y de la alteración diafragmática durante más de 6 meses(AU)

Amyotrophic neuralgia is an inflammatory and idiopathic neuropathy which is characterised by neuropathic pain. It was described for the first time in 1948 as condition that only affected the brachial plexus and was called Parsonage-Turner syndrome. Although this syndrome is more common in the brachial plexus, it can concomitantly, or in isolation affect the phrenic nerve, and in this case the diagnosis is very difficult if there is no high clinical suspicion.We present a case of a patient with amyotrophic neuralgia in which the only sign was left phrenic involvement, and we highlight the resistance of the pain to analgesics, as well as the persistence of the symptoms and diaphragm problems for over 6 months(AU)

Enfermedad respiratoria y parálisis diafragmática en la enfermedad de Charcot-Marie-Tooth / Respiratory disease and diaphragm paralysis in Charcot-Marie-Tooth disease

La disfunción diafragmática bilateral es una entidad infrecuente. Dentro del ámbito pediátrico las causas más comunes son las asociadas a traumatismo obstétrico o cirugía cardiovascular. En el diagnóstico diferencial se incluye la enfermedad de Charcot-Marie-Tooth (CMT).Si bien en esta enfermedad es infrecuente, la afectación de la musculatura respiratoria, por su carácter distal, está descrita su asociación con neumopatía restrictiva secundaria a una disfunción del nervio frénico con paresia diafragmática bilateral o anomalías de la pared torácica. Presentamos 2 casos de CMT que ingresaron en la Unidad de Cuidados Intensivos con fallo respiratorio tipo II. En ambos casos el tratamiento con ventilación no invasiva produjo una mejoría clínica significativa. A destacar el hecho de que en uno de los pacientes la evidencia de una afectación frénica sirvió como signo guía para el diagnóstico de su enfermedad de base (AU)

Diaphragmatic bilateral palsy is uncommon in children. The most important etiologies are thoracic surgery and obstetric trauma. Respiratory muscle impairment is a rare phenomenon in patients with Charcot-Marie-Tooth disease (CMT). However, it can be associated with restrictive pulmonary impairment, phrenic nerve dysfunction or thoracic cage abnormalities. We report two paediatric cases of CMT disease with type 2 respiratory failure due to diaphragmatic dysfunction. In both cases treatment with non-invasive mechanical ventilation resulted in satisfactory clinical improvement. Evidence of phrenic damage was the main clue in one patient in order to obtain an accurate diagnostic of her disease (AU)

Tres casos de parálisis diafragmática: utilidad del estudio electromiográfico / Three cases of diaphragmatic paralysis: the utility of electromyographic studies

La parálisis diafragmática (PD) es poco frecuente en pediatría y su adecuado manejo es importante por el potencial compromiso respiratorio. La PD es sospechada por la radiografía de tórax y confirmada por la ultrasonografía. Ultimamente la electromiografía (EMG) ha mostrado utilidad en la evaluación funcional del diafragma y del nervio frénico (NF), en especial a lo que se refiere a su pronóstico y reversibilidad. Objetivo: Reportar la utilidad de la EMG en 3 pacientes con PD. Pacientes y Método: Caso 1, lactante con PD bilateral secundaria a enfermedad neuromuscular adquirida y distrés respiratorio, la EMG mostró denervación y se indicó ventilación permanente. Caso 2: lactante con PD derecha secundaria a cirugía del plexo braquial, el seguimiento electromiográfico permitió tratamiento conservador. Caso 3: preescolar portadora de cardiopatia compleja, PD bilateral post cirugía cardiaca y dependencia de ventilación mecánica (VM), se realizó plicatura diafragmática bilateral, presentó recidiva, necesitó nueva plicatura izquierda por amplitud muy disminuida en la respuesta diafragmática al estudiar conducción de NF. Conclusión: La EMG determinó la disfunción del NF y permitió una conducta conservadora en estos pacientes evitando la cirugía. Sugerimos que la EMG es una herramienta útil en el estudio de pacientes con PD y en la determinación de su conducta terapéutica.

Electrophysiological and ultrastructural analysis of the neuromuscular blockade and miotoxicity induced by the Micrurus nigrocinctus snake venom

Micrurus nigrocinctus is the most abundant coral snake in Central America. The venom of this specie induced a concentration-dependent (10-20 mug/ml) depolarization in the isolated mouse phrenic nerve-diaphragm preparations incubated ate 37 degree. D-Tubocurrarine (10 mug/ml) and alpha betaungarotoxin (3-5 mug/ml) were able to partially protect against the depolarization induced by the venom (10 mug/ml), suggesting the involvement of subsynaptic cholinergic receptors. This venom (10 mug/ml) also increased the frequency and amplitude of miniature end-plate potentials (mepps) during the first 10-20 min of incubation. Subsequently, the mepps progressively decreased and disappeared after 60 min. These responses were accompanied by ultrastructural changes involving the nerve terminals, the subsynaptic junctional folds and the muscle mitochondria. The synaptic gutter was shallow and, very often, "shrunken" terminal with omega-shaped axolemmal identations and a decreased number of synaptic vecicles were present. A common finding was the presence of numerous finger-like, membrane-bounded bodies interposed between the terminal and the Schwann cells or postsynaptic sarcolemma. The preincubation of the venom with specific antivenom or the incubation of the preparations at room temperature (24-26 degree) reduced the number and intensity of the ultrastructural alterations. The last finding suggests the involvement of a enzymatic process, probably a phospholipase A2, present in the venom. There was a good correlation between the electrophysiological and ultrastructural effects induced by the venom which allow us to conclude that M. nigrocinctus venom has a presynaptic action in the initial stages of intoxication followed by sub- and postsynaptic effects, the last being the most important cause of neuromuscular blockade. A direct action of the venom on muscle fibers may also contributes to the irreversible blockade.