Diaphragmatic Activity Research Articles

Endobronchial valve treatment improves diaphragm function in severe emphysema patients

Rationale and aimDiaphragm dysfunction is common in severe emphysema patients, primarily due to hyperinflation, placing the diaphragm at a mechanical disadvantage. Endobronchial valve (EBV) treatment is a bronchoscopic procedure to reduce hyperinflation, and thus potentially restore diaphragm function in this patient population. Our aim was to investigate the effect of EBV treatment on diaphragm function.Patients and methodsA prospective cohort study was performed in which diaphragm function was measured at baseline and 6 weeks after EBV treatment by ultrasonic assessment to measure diaphragm motion and diaphragm thickening fraction (dTF), surface electromyography (sEMG) to quantify diaphragm activity, and maximal inspiratory pressure (MIP) to assess diaphragm strength.ResultsTwenty-five patients were included, with a mean age of 64±7 years. Residual volume (−0.85±0.49 Liter, p<0.001) decreased significantly post EBV treatment, with a significant increase in MIP (+0.6 kPa, range −1.2–2.8, p=0.001). Diaphragm motion on the treated side during tidal breathing significantly decreased (−3.3 mm, range −24.7–14.6, p=0.023). There were no significant changes in dTF on the treated side. Diaphragm activity (sEMG) for tidal breathing (−1.7 µV, p=0.004, range −8.8–5.8), maximal inspiration (−4.1 µV, p=0.004, range −42.3–16.0), and sniff manoeuvre (−6.1 µV, p=0.027, range −42.2–24.2) all significantly decreased.ConclusionOur results show that diaphragm function significantly improves after EBV treatment in severe emphysema patients. This emphasizes the physiological interaction between hyperinflation and diaphragm function, suggesting that reducing hyperinflation can at least partially reverse diaphragm dysfunction.

Effects of Inspiratory Muscle Training in Patients with COPD Exacerbations: A Randomized Controlled Trial

Abstract Objective Pulmonary rehabilitation (PR) is considered for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the impact of adding inspiratory muscle training (IMT) to PR on inspiratory muscle function is underexplored. This study aimed to evaluate the effects of IMT in addition to PR on inspiratory muscle function, functional exercise capacity (FEC), and quality of life (QoL) in patients with AECOPD. Design 16 patients with AECOPD and a maximal inspiratory pressure (PImax) < 80 cmH2O were randomized into the experimental (PR + IMT) or the control (PR + sham IMT) group for an eight-week intervention. Inspiratory muscle activation was measured using surface electromyography, FEC was examined by six-minute walk distance (6MWD), and QoL was assessed with COPD Assessment Test (CAT). Results The experimental group showed sustained and significant improvements in inspiratory muscle function, 6MWD, and QoL after intervention (all p < 0.05). The experimental group had higher PImax with less diaphragm activation (both p < 0.001) and more improvements in 6MWD and QoL after intervention (both p < 0.05). Conclusions Adding IMT to PR resulted in more improvements in inspiratory muscle function, FEC, and QoL for patients with AECOPD, suggesting IMT as a beneficial addition to PR.

Recruitment of the diaphragm and sternocleidomastoid muscle during increasing inspiratory pressure loads in healthy young adults

BackgroundInspiratory muscle training (IMT) is often employed to enhance improvement in inspiratory muscle strength. However, the relationship between inspiratory muscle recruitment patterns and increasing inspiratory load remains unclear. Furthermore, the effect of breathing instructions on diaphragm activity at various inspiratory loads is unknown. ObjectiveTo investigate the recruitment activity of the diaphragm and sternocleidomastoid (SCM) muscles under increased inspiratory pressure loading, with and without diaphragmatic breathing instructions, in healthy young adults. MethodsParticipants were invited to breathe, in random order, 6 sets of 10 breaths at inspiratory loads of 30% to 80% maximal inspiratory pressure (MIP), in 10% increments. The measurement process was repeated with a specific focus of diaphragmatic descent during inspiration. Concurrent recorded surface electromyography of the right SCM muscle and right hemi-diaphragm thickness measured by ultrasonography during each targeted breath. ResultsSixty-two adults (31 males, age: 23±3 years) participated in the study. Irrespective of breathing instructions, computed diaphragm thickening fraction (DTf) increased with increasing inspiratory load but peaked at 50%MIP and declined with increasing load to 80%MIP. SCM recruitment increased with increasing inspiratory load to 80%MIP. Forced inspiration with diaphragmatic breathing was associated with a higher DTf and lower SCM muscle activity. The above pattern was similar for both male and female participants. Female participants produced higher SCM activity compared with males but only at inspiration loads below 50%MIP. ConclusionsIn a cohort of young healthy adults, magnitude of diaphragmatic effort was greatest at 50% MIP but declined with increasing inspiratory load to 80%MIP. Forced inspiration combined with focused diaphragmatic breathing accentuated diaphragm contraction and reduced SCM muscle contribution. Our findings show that diaphragmatic muscle recruitment is non-linear and that the generic clinical prescription of an IMT program may need to be reconfigured.

Neurally Adjusted Ventilatory Assist to Monitor Diaphragmatic Activity in Infantile Botulism.

Infantile botulism is a potentially life-threatening neuromuscular disorder. It presents with descending paralysis that can involve the diaphragm and cause respiratory failure. Neurally adjusted ventilatory assist (NAVA) provides synchronized bilevel positive pressure by using electrical diaphragmatic (Edi) signals. Diaphragmatic paresis is thought to be a contraindication for using NAVA. However, the use of a NAVA catheter allows continuous assessment of diaphragm activity in infantile botulism. We discuss a case of infantile botulism in an infant from central Pennsylvania who presented with poor oral feeding, hypothermia, and lethargy and progressed to develop apnea and acute respiratory failure. The infant was intubated and mechanically ventilated. A diagnosis of infantile botulism was confirmed through the detection of botulinum toxin in the infant's stool, and the infant was treated with botulism immune globulin neutralizing antibodies. During his recovery phase, a NAVA catheter was placed, which allowed monitoring of Edi signals to gauge the return of diaphragm activity and to assist with the assessment of extubation readiness. We describe the trends in this infant's Edi signals following administration of globulin neutralizing antibodies and the successful transition to invasive, and subsequently, noninvasive NAVA. Our report demonstrates the clinical utility of monitoring diaphragmatic activity using a NAVA catheter and that NAVA provided adequate respiratory support to an infant during the recovery phase of infantile botulism.

Impact of glossopharyngeal insufflation and complete exhalation on breath-hold performance and physiological parameters in elite skin divers.

This study examined the physiological responses of ten elite divers to normal breathing (BHn), glossopharyngeal inhalation (BHi), and complete exhalation (BHe) prior to five maximal breath-hold (BH) efforts. Breath-hold time (BHT), hemological variables, mean arterial pressure (MAP), other hemodynamic indices, and diaphragmatic activity (DA) were recorded. During BHs, phases were identified as easy-going (EPh: minimal DA), struggling (SPh: increased DA), PhI (MAP transition), PhII (MAP stabilization), and PhIII (steep MAP increase). BHi significantly extended BHT (309.14 ± 12.91s) compared to BHn (288.77 ± 10.99s) and BHe (151.18 ± 10.94s) (P = 0.001). BHT, EPh, and SPh in BHi increased by 7.05%, 2.57%, and 11.08% over BHn, respectively. PhIII appeared earlier in BHe than in other conditions (P < 0.001) and accounted for 47.07%, 44.96%, and 60.18% of BHT in BHn, BHi, and BHe, respectively. SPh comprised 47.10%, 46.01%, and 45.13% of BHT in BHn, BHi, and BHe, respectively, with SPh onset coinciding with PhIII onset in BHn and BHi but not in BHe. Bradycardia was more pronounced in BHe, maintaining better stroke volume. No significant differences in red blood cells or maximal MAP were noted across conditions. Glossopharyngeal inhalation improves BHT and extends EPh and SPh durations. PhIII onset is linked to SPh in BHn and BHi but not in BHe. BHe triggers an earlier MAP rise, leading to stronger parasympathetic responses. Despite similar maximal MAP across conditions, the higher BHT and tissue hypoxemia in BHi and BHn suggest MAP is a key limiting factor in apnoea.

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

BackgroundMechanical 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.MethodsPatients 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.ResultsWith 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].ConclusionsDaily 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)

Post-insufflation diaphragm contractions in patients receiving various modes of mechanical ventilation

BackgroundDuring mechanical ventilation, post-insufflation diaphragm contractions (PIDCs) are non-physiologic and could be injurious. PIDCs could be frequent during reverse-triggering, where diaphragm contractions follow the ventilator rhythm. Whether PIDCs happens with different modes of assisted ventilation is unknown. In mechanically ventilated patients with hypoxemic respiratory failure, we aimed to examine whether PIDCs are associated with ventilator settings, patients’ characteristics or both.MethodsOne-hour recordings of diaphragm electromyography (EAdi), airway pressure and flow were collected once per day for up to five days from intubation until full recovery of diaphragm activity or death. Each breath was classified as mandatory (without-reverse-triggering), reverse-triggering, or patient triggered. Reverse triggering was further subclassified according to EAdi timing relative to ventilator cycle or reverse triggering leading to breath-stacking. EAdi timing (onset, offset), peak and neural inspiratory time (Tineuro) were measured breath-by-breath and compared to the ventilator expiratory time. A multivariable logistic regression model was used to investigate factors independently associated with PIDCs, including EAdi timing, amplitude, Tineuro, ventilator settings and APACHE II.ResultsForty-seven patients (median[25%-75%IQR] age: 63[52–77] years, BMI: 24.9[22.9–33.7] kg/m2, 49% male, APACHE II: 21[19–28]) contributed 2 ± 1 recordings each, totaling 183,962 breaths. PIDCs occurred in 74% of reverse-triggering, 27% of pressure support breaths, 21% of assist-control breaths, 5% of Neurally Adjusted Ventilatory Assist (NAVA) breaths. PIDCs were associated with higher EAdi peak (odds ratio [OR][95%CI] 1.01[1.01;1.01], longer Tineuro (OR 37.59[34.50;40.98]), shorter ventilator inspiratory time (OR 0.27[0.24;0.30]), high peak inspiratory flow (OR 0.22[0.20;0.26]), and small tidal volumes (OR 0.31[0.25;0.37]) (all P ≤ 0.008). NAVA was associated with absence of PIDCs (OR 0.03[0.02;0.03]; P < 0.001). Reverse triggering was characterized by lower EAdi peak than breaths triggered under pressure support and associated with small tidal volume and shorter set inspiratory time than breaths triggered under assist-control (all P < 0.05). Reverse triggering leading to breath stacking was characterized by higher peak EAdi and longer Tineuro and associated with small tidal volumes compared to all other reverse-triggering phenotypes (all P < 0.05).ConclusionsIn critically ill mechanically ventilated patients, PIDCs and reverse triggering phenotypes were associated with potentially modifiable factors, including ventilator settings. Proportional modes like NAVA represent a solution abolishing PIDCs.

Predictive value of diaphragm ultrasound for mechanical ventilation outcome in patients with acute exacerbation of chronic obstructive pulmonary disease.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is often combined with respiratory failure, which increases the patient's morbidity and mortality. Diaphragm ultrasound (DUS) has developed rapidly in the field of critical care in recent years. Studies with DUS monitoring diaphragm-related rapid shallow breathing index have demonstrated important results in guiding intensive care unit patients out of the ventilator. Early prediction of the indications for withdrawal of non-invasive ventilator and early evaluation of patients to avoid or reduce disease progression are very important. To explore the predictive value of DUS indexes for non-invasive ventilation outcome in patients with AECOPD. Ninety-four patients with AECOPD who received mechanical ventilation in our hospital from January 2022 to December 2023 were retrospectively analyzed, and they were divided into a successful ventilation group (68 cases) and a failed ventilation group (26 cases) according to the outcome of ventilation. The clinical data of patients with successful and failed noninvasive ventilation were compared, and the independent predictors of noninvasive ventilation outcomes in AECOPD patients were identified by multivariate logistic regression analysis. There were no significant differences in gender, age, body mass index, complications, systolic pressure, heart rate, mean arterial pressure, respiratory rate, oxygen saturation, partial pressure of oxygen, oxygenation index, or time of inspiration between patients with successful and failed mechanical ventilation (P > 0.05). The patients with successful noninvasive ventilation had shorter hospital stays and lower partial pressure of carbon dioxide (PaCO2) than those with failed treatment, while potential of hydrogen (pH), diaphragm thickening fraction (DTF), diaphragm activity, and diaphragm movement time were significantly higher than those with failed treatment (P < 0.05). pH [odds ratio (OR) = 0.005, P < 0.05], PaCO2 (OR = 0.430, P < 0.05), and DTF (OR = 0.570, P < 0.05) were identified to be independent factors influencing the outcome of mechanical ventilation in AECOPD patients. The DUS index DTF can better predict the outcome of non-invasive ventilation in AECOPD patients.

Functional and Structural Changes in Diaphragm Neuromuscular Junctions in Early Aging.

Age-related impairment of the diaphragm causes respiratory complications. Neuromuscular junction (NMJ) dysfunction can be one of the triggering events in diaphragm weaknesses in old age. Prominent structural and functional alterations in diaphragm NMJs were described in elderly rodents, but NMJ changes in middle age remain unclear. Here, we compared diaphragm muscles from young adult (3 months) and middle-aged (12 months) BALB/c mice. Microelectrode recordings, immunofluorescent staining, electron microscopy, myography, and whole-body plethysmography were used. We revealed presynaptic (i) and postsynaptic (ii) changes. The former (i) included an increase in both action potential propagation velocity and neurotransmitter release evoked by low-, moderate-, and high-frequency activity but a decrease in immunoexpression of synapsin 1 and synaptic vesicle clustering. The latter (ii) consisted of a decrease in currents via nicotinic acetylcholine receptors and the area of their distribution. These NMJ changes correlated with increased contractile responses to moderate- to high-frequency nerve activation. Additionally, we found alterations in the pattern of respiration (an increase in peak inspiratory flow and a tendency of elevation of the tidal volume), which imply increased diaphragm activity in middle-aged mice. We conclude that enhancement of neuromuscular communication (due to presynaptic mechanism) accompanied by improved contractile responses occurs in the diaphragm in early aging.

Deventilation syndrome in patients with chronic obstructive pulmonary disease using nocturnal non-invasive ventilation: what are the underlying mechanisms?

Introduction Patients with chronic obstructive pulmonary disease (COPD) commonly experience severe dyspnea after discontinuation of nocturnal non-invasive ventilation (NIV), known as deventilation syndrome (DVS), which negatively affects quality of life. Despite various hypotheses, the precise mechanisms of DVS remain unknown. Methods An observational pilot study was performed monitoring 16 stable COPD patients, before, during and after an afternoon nap on NIV. Seven patients experienced DVS (Borge dyspnea scale ≥ 5), while nine served as controls (Borg Dyspnea Scale ≤ 2). Hyperinflation was evaluated through inspiratory capacity (IC) measurements and end-expiratory lung impedance (EELI) via electrical impedance tomography. Respiratory muscle activity was assessed by diaphragmatic surface electromyography (sEMG). Results Post-NIV dyspnea scores were significantly higher in the DVS group (5[3-7] vs. 0[0-1.5], p&lt;0.001). IC values were lower in the DVS group compared to controls, both pre- (54[41-63] vs. 88[72-94] %pred., p=0.006) and post-NIV (45[40-59] vs. 76[65-82] %pred., p=0.005), while no intergroup difference was seen in IC changes pre- and post-NIV. EELI values after NIV indicated a tendency towards lower values in controls and higher values in DVS patients. sEMG amplitudes were higher in the DVS group within the first 5 minutes post-NIV (221[112-294] vs. 100[58-177]% of baseline, p=0.030). Conclusion This study suggests that it is unlikely that DVS originates from the inability to create diaphragmatic muscle activity after NIV. Instead, NIV-induced hyperinflation in individuals with static hyperinflation may play a significant role. Addressing hyperinflation holds promise in preventing DVS symptoms in COPD patients.

Have a Little Heart (or Not): Highly Minimized Skeletal Muscle Regulatory Cassettes with Low or No Activity in the Heart.

Adeno-associated virus-mediated gene therapies for certain muscle disorders require regulatory cassettes that provide high-level, striated muscle-specific activity. However, cardiotoxicity has emerged as a serious concern in clinical trials for Duchenne muscular dystrophy and X-linked myotubular myopathy. While this may be caused by systemic inflammatory effects of the treatment, high transgene expression in the heart may also play a role. Thus, certain muscle disorders may require a modulated level of therapeutic expression in the heart, while others may not require any cardiac expression at all. Additionally, the size of some cargos requires regulatory cassettes to be small enough that large cDNAs and other therapeutic payloads can be accommodated. Thus, we have performed enhancer/promoter optimization to develop highly minimized regulatory cassettes that are active in skeletal muscles, with either low or no detectable activity in cardiac muscle. Our No-heart (NH) cassette is active in most skeletal muscles, but exhibits only very low activity in extensor digitorum longus (EDL), soleus, and diaphragm, and no activity in the heart. By contrast, our Have a Little Heart (HLH) cassette displays high activity in most skeletal muscles, comparable to the ∼800-bp CK8 cassette, with increased activity in EDL, soleus, and diaphragm, and low activity in the heart. Due to their small size, these cassettes can be used in therapeutic strategies with both flexible (e.g., antisense) and stringent (e.g., CRISPR/Cas or bicistronic) size limitations. Thus, our new cassettes may be useful for gene therapies of muscle disorders in which the need for low or almost no expression in cardiac muscle would outweigh the need for high levels of therapeutic product in certain skeletal muscles.

Airway mechanics alters generation of cough motor pattern.

Effects of sequential increase in airway resistance: no, low (5 kPa.s/l), high (24 kPa.s/l), and complete block in the inspiratory or expiratory phase of mechanically induced cough on the cough motor pattern were studied in 16 anesthetized (pentobarbital) spontaneously breathing cats (3.70±0.15 kg, 11♂, 5♀). Esophageal pressure and electromyographic activities of the diaphragm during inspiration and abdominal muscles during expiration were analyzed. No significant changes in the number of coughs occurred. Inspiratory occlusion caused a prolongation of cough inspiratory phase, cough inspiratory diaphragm activity, and all cough-related activity. Inspiratory occlusion along with high resistance increased inspiratory esophageal pressure amplitude, total cough cycle duration and the time between maximum activity of the diaphragm and abdominal muscles. High expiratory resistance and occlusion resulted in increased cough expiratory esophageal pressure amplitude, a longer active portion of cough expiration, and cough abdominal activity. Expiratory occlusion also prolonged cough expiratory phase, all cough activity, and total cough cycle. Significantly increased airway resistance and occlusion induce secondary, in addition to mechanical, changes in cough by significantly modulating the generated cough motor pattern. A certain level of resistance appears to be successfully compensated, resulting in minimal changes in coughing characteristics, including expiratory airflow and the rising time of the airflow. Afferent feedback from the respiratory tract, particularly volume feedback, represents a significant factor in modulating cough, mainly under various pathological conditions in the respiratory system.

Characterisation of sleep apneas and respiratory circuitry in mice lacking CDKL5.

CDKL5 deficiency disorder is a rare genetic disease caused by mutations in the CDKL5 gene. Central apneas during wakefulness have been reported in patients with CDKL5 deficiency disorder. Studies on CDKL5-knockout mice, a CDKL5 deficiency disorder model, reported sleep apneas, but it is still unclear whether these events are central (central sleep apnea) or obstructive (obstructive sleep apnea) and may be related to alterations of brain circuits that modulate breathing rhythm. This study aimed to discriminate central sleep apnea and obstructive sleep apnea in CDKL5-knockout mice, and explore changes in the somatostatin neurons expressing high levels of neurokinin-1 receptors within the preBötzinger complex. Ten adult male wild-type and 12 CDKL5-knockout mice underwent electrode implantation for sleep stage discrimination and diaphragmatic activity recording, and were studied using whole-body plethysmography for 7 hr during the light (resting) period. Sleep apneas were categorised as central sleep apnea or obstructive sleep apnea based on the recorded signals. The number of somatostatin neurons in the preBötzinger complex and their neurokinin-1 receptors expression were assessed through immunohistochemistry in a sub-group of animals. CDKL5-knockout mice exhibited a higher apnea occurrence rate and a greater prevalence of obstructive sleep apnea during rapid eye movement sleep, compared with wild-type, whereas no significant difference was observed for central sleep apnea. Moreover, CDKL5-knockout mice showed a reduced number of somatostatin neurons in the preBötzinger complex, and these neurons expressed a lower level of neurokinin-1 receptors compared with wild-type controls. These findings underscore the pivotal role of CDKL5 in regulating normal breathing, suggesting its potential involvement in shaping preBötzinger complex neural circuitry and controlling respiratory muscles during sleep.

Assessing Functional Recovery of Eupneic Diaphragm Activity Following Unilateral Cervical Spinal Cord Injury in Rats.

Following cSCI, activation of the DIAm can be impacted depending on the extent of the injury. The present manuscript describes a unilateral C2 hemisection (C2SH) model of cSCI that disrupts eupneic ipsilateral diaphragm (iDIAm) electromyographic (EMG) activity during breathing in rats. To evaluate recovery of DIAm motor control, the extent of deficit due to C2SH must first be clearly established. By verifying a complete initial loss of iDIAm EMG during breathing, subsequent recovery can be classified as either absent or present, and the extent of recovery can be estimated using the EMG amplitude. Additionally, by measuring the continued absence of iDIAm EMG activity during breathing after the acute spinal shock period following C2SH, the success of the initial C2SH may be validated. Measuring contralateral diaphragm (cDIAm) EMG activity can provide information about the compensatory effects of C2SH, which also reflects neuroplasticity. Moreover, DIAm EMG recordings from awake animals can provide vital physiological information about the motor control of the DIAm after C2SH. This article describes a method for a rigorous, reproducible, and reliable C2SH model of cSCI in rats, which is an excellent platform for studying respiratory neuroplasticity, compensatory cDIAm activity, and therapeutic strategies and pharmaceuticals.

Effect of manual diaphragmatic activation on diaphragm function in patients with gastroesophageal reflux disease

Effect of manual diaphragmatic activation on diaphragm function in patients with gastroesophageal reflux disease

The diaphragmatic electrical activity during spontaneous breathing trial in patients with mechanical ventilation: physiological description and potential clinical utility

BackgroundsIncreased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure.MethodsWe conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min.ResultsOf the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p < 0.01). Early increases in EAdi were observed in SBT, which are more prominent in SBT failure group. One minute, changes in EAdi and neuro-discharge per min also predicted weaning outcome (AUROCs 0.944 and 0.918, respectively).ConclusionsEAdi-based parameters, especially neuro-excursion efficiency and changes in neuro-discharge per min, may detect impending weaning failure earlier than conventional indices. EAdi monitoring provides physiological insights and a more tailored approach to facilitate successful weaning. Further research should validate these findings and explore the utility of combined EAdi and diaphragm ultrasound assessment in weaning ICU patients from mechanical ventilation.Trial RegistrationRegistered at ClinicalTrials.gov on 20 September 2022 (Identifier: NCT05632822).

Skin-to-Skin Contact and Diaphragm Electrical Activity in Preterm Infants During Noninvasive Pressure Control.

Skin-to-skin contact (SSC) is widely implemented in the neonatal intensive care unit (NICU) due to its established role in reducing mortality and morbidity. However, the impact of SSC on diaphragmatic electrical activity (Edi) in premature infants undergoing noninvasive pressure control (NIV-PC) for respiratory management remains insufficiently explored. To assess the effects of SSC on Edi and vital signs in preterm infants managed with NIV-PC. A prospective, observational, crossover study was conducted, involving preterm infants admitted to a level III NICU between May 2020 and August 2021, who were receiving respiratory support with NIV-PC. Data were collected at 3 distinct time points: before SSC (pre-SSC period), during SSC (SSC period), and after SSC (post-SSC period). Thirty-minute periods of stable data were extracted for analysis. A total of 21 SSC sessions were performed on 14 preterm infants, with a median age at the initiation of SSC of 62 days. The median (interquartile range) Edi peak (in microvolts) before, during, and after SSC was 7.1 (5.8-10.8), 6.8 (4.3-8.8), and 7.1 (5.5-8.8), respectively. No statistically significant differences were observed in Edi peak or minimum values during SSC, when compared with the periods before and after the SSC procedure. Likewise, no significant changes were noted in respiratory rate, oxygen saturation, heart rate, or the incidence of apnea. SSC in preterm infants undergoing NIV-PC does not exacerbate their clinical condition. Further investigations involving diverse patient cohorts are warranted.

Reverse triggering ? a novel or previously missed phenomenon?

Reverse triggering (RT) was described in 2013 as a form of patient-ventilator asynchrony, where patient's respiratory effort follows mechanical insufflation. Diagnosis requires esophageal pressure (Pes) or diaphragmatic electrical activity (EAdi), but RT can also be diagnosed using standard ventilator waveforms. We wondered (1) how frequently RT would be present but undetected in the figures from literature, especially before 2013; (2) whether it would be more prevalent in the era of small tidal volumes after 2000. We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, from 1950 to 2017, with key words related to asynchrony to identify papers with figures including ventilator waveforms expected to display RT if present. Experts labelled waveforms. 'Definite' RT was identified when Pes or EAdi were in the tracing, and 'possible' RT when only flow and pressure waveforms were present. Expert assessment was compared to the author's descriptions of waveforms. We found 65 appropriate papers published from 1977 to now, containing 181 ventilator waveforms. 21 cases of 'possible' RT and 25 cases of 'definite' RT were identified by the experts. 18.8% of waveforms prior to 2013 had evidence of RT. Most cases were published after 2000 (1 before vs. 45 after, p = 0.03). 54% of RT cases were attributed to different phenomena. A few cases of identified RT were already described prior to 2013 using different terminology (earliest in 1997). While RT cases attributed to different phenomena decreased after 2013, 60% of 'possible' RT remained missed. RT has been present in the literature as early as 1997, but most cases were found after the introduction of low tidal volume ventilation in 2000. Following 2013, the number of undetected cases decreased, but RT are still commonly missed. Reverse Triggering, A Missed Phenomenon in the Literature. Critical Care Canada Forum 2019 Abstracts. Can J Anesth/J Can Anesth67 (Suppl 1), 1-162 (2020). https://doi-org.myaccess.library.utoronto.ca/ https://doi.org/10.1007/s12630-019-01552-z .

Neural Respiratory Drive During Different Dyspnea Relief Positions and Breathing Exercises in Individuals With COPD.

When the work load of the respiratory muscles increases and/or their capacity decreases in individuals with COPD, respiratory muscle activation increases to maintain gas exchange and respiratory mechanics, and perception of dyspnea occurs. The present study aimed to compare diaphragm and accessory respiratory muscle activation during normal breathing, pursed-lip breathing, and breathing control in different dyspnea relief positions, supine and side lying. A cross-sectional study design was used. Sixteen individuals with COPD age between 40-75 y were included. Pulmonary function was evaluated by spirometry, muscle activation by surface electromyography, and dyspnea by the modified Borg scale. Muscle activation was measured in the diaphragm, scalene, sternocleidomastoid, and parasternal muscles. The evaluation was made in the dyspnea relief positions (sitting leaning forward, sitting leaning forward at a table, leaning forward with back against a wall, standing leaning forward, and high lying), seated erect, supine, and side lying. There were significant differences between the 8 positions (P < .001). There was no significant difference in muscle activation between sitting leaning forward and sitting leaning forward at a table position with analyzing post hoc test results (P > .99 for each muscle). However, muscle activation was lower in these 2 positions than in the other positions (P < .001 for each muscle). Muscle activation was greater in the supine position than in the other positions (P < .001 for each muscle). No difference was observed in muscle activation between the seated erect, leaning forward with back against a wall, standing leaning forward, high-lying, or side-lying positions (P > .05 for each muscle with a minimum P value of .09). The use of sitting leaning forward and sitting leaning forward at a table positions together with breathing control may help people with COPD to achieve more effective dyspnea relief and greater energy efficiency.

TNF-a Receptor 1 Activity Is Differentially Required for Phrenic Long-term Facilitation (pLTF) Over the Course of Motor Neuron Death in Adult Rats

Intrapleural injection of cholera toxin B fragment conjugated to saporin (CTB-SAP) selectively kills respiratory motor neurons, and mimics aspects of neuromuscular disorders and neurodegenerative diseases including phrenic motor neuron death, decreased phrenic motor output, and increased microglial cell number. Over the course of motor neuron loss, enhanced A2A receptor-dependent phrenic plasticity is observed early (7d), and then constrained 5-HT receptor-dependent phrenic plasticity is observed later (28d). In addition, COX-1/2-induced inflammation differentially impacts breathing and phrenic plasticity in CTB-SAP rats, but the underlying mechanism by which COX-1/2-induced inflammation impacts breathing and plasticity over the course of motor neuron death has not been studied. We observe that increased cervical neuroinflammatory gene expression ( e.g., tumor necrosis factor-a; TNF-a) is reduced back to control levels in the presence of ketoprofen in CTB-SAP rats, and it is known that TNF-a is involved in phrenic plasticity in naïve rats. Thus, we hypothesized that acute TNF-a receptor inhibition attenuates phrenic plasticity at 7d and enhances it at 28d TNF-a following CTB-SAP-induced neuropathology. Using anesthetized, paralyzed and ventilated CTB-SAP-treated adult Sprague Dawley rats, we studied acute intermittent hypoxia (AIH; 3, 5 min bouts of 10.5% O2) induced pLTF following acute intrathecal C4 delivery of a TNF-a receptor 1 inhibitor (soluble TNFR1; sTNFR1; 0.13 ug/ul) or vehicle (aCSF) to rats that received bilateral, intrapleural injections of: 1) CTB-SAP (25ug), or 2) un-conjugated CTB and SAP (control) in rats treated 7d or 28d prior. Surprisingly, preliminary results indicate that acute sTNFR1 delivery does not affect pLTF in 7d CTB-SAP-treated rats (n=5; i.e., pLTF still enhanced) but it enhanced pLTF in 28d CTB-SAP-treated rats (n=6; p&lt;0.05) vs. controls (n=6 at 7d; n=7 at 28d) and vs. vehicle treated rats (controls n=6 for 7d and n=9 for 28d; CTB-SAP, n=4 for 7d and 28d each). These preliminary observations suggest that TNF-a does not contribute to pLTF in 7d CTB-SAP-treated rats, whereas it may undermine pLTF in 28d CTB-SAP-treated rats. Studies are underway to assess the cellular source of TNF-a and the impact of chronic sTNFR1 delivery on pLTF, diaphragm activity, and breathing. Since most patients with neuromuscular disorders or neurodegenerative disease develop respiratory insuffciency and ultimately become ventilator dependent, our long-range goal is to develop new strategies to enhance the functional capacity of spared motor neurons and reduce ventilatory compromise in motor neuron loss pathology. These novel strategies, if successful, will identify new therapeutic targets for future, translational studies to enhance breathing in patients with neuromuscular disorders. Supported by a Spinal Cord Injury and Disease Research grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.