Neural Respiratory Drive Research Articles

Neural respiratory drive assessment and its correlation with inspiratory muscle strength in patients undergoing open-heart surgery: A cross-sectional study.

Pulmonary dysfunction and inspiratory muscle weakness are frequently observed after cardiac surgery. Understanding the load on and capacity of respiratory muscles can provide valuable insights into the overall respiratory mechanics and neural regulation of breathing. This study aimed to assess the extent of neural respiratory drive (NRD) and determine whether admission-to-discharge differences in NRD were associated with inspiratory muscle strength changes among patients undergoing open-heart surgery. This cross-sectional study was conducted on 45 patients scheduled for coronary artery bypass graft or heart valve surgery. NRD was measured using a surface parasternal intercostal electromyogram during resting breathing (sEMGpara tidal) and maximal inspiratory effort (sEMGpara max). Maximal inspiratory pressure (MIP) was used to determine inspiratory muscle strength. Evaluations were performed on the day of admission and discharge. There was a significant increase in sEMGpara tidal (6.9±3.6μV, p<0.001), sEMGpara %max (13.7±11.2%, p=0.008), and neural respiratory drive index (NRDI, the product of EMGpara %max and respiratory rate) (337.7±286.8%.breaths/min, p<0.001), while sEMGpara max (-43.6±20.4μV, p<0.01) and MIP (-24.4±10.7, p<0.001) significantly decreased during the discharge period. Differences in sEMGpara tidal (r=-0.369, p=0.045), sEMGpara %max (r=-0.646, p=0.001), and NRDI (r=-0.639, p=0.001) were significantly associated with a reduction in MIP. The findings indicate that NRD increases after open-heart surgery, which corresponds to a decrease in inspiratory muscle strength.

RESPIRATORY MECHANICS AND NEURAL RESPIRATORY DRIVE OF UNTREATED GASPING DURING CARDIAC ARREST IN A PORCINE MODEL.

Introduction: Although the effects on hemodynamics of gasping during cardiac arrest (CA) have received a lot of attention, less is known about the respiratory mechanics and physiology of respiration in gasping. This study aimed to investigate the respiratory mechanics and neural respiratory drive of gasping during CA in a porcine model. Method: Pigs weighing 34.9 ± 5.7 kg were anesthetized intravenously. Ventricular fibrillation (VF) was electrically induced and untreated for 10 min. Mechanical ventilation (MV) was ceased immediately after the onset of VF. Hemodynamic and respiratory parameters, pressure signals, diaphragmatic electromyogram data, and blood gas analysis data were recorded. Results: Gasping was observed in all the animals at a significantly lower rate (2-5 gaps/min), with higher tidal volume ( VT ; 0.62 ± 0.19 L, P < 0.01), and with lower expired minute volume (2.51 ± 1.49 L/min, P < 0.001) in comparison with the baseline. The total respiratory cycle time and the expiratory time tended to be lengthened. Statistically significant elevations in transdiaphragmatic pressure, the pressure-time product of diaphragmatic pressure, and the mean of root mean square diaphragmatic electromyogram values (RMSmean) were observed ( P < 0.05, P < 0.05, and P < 0.001, respectively); however, VT /RMSmean and transdiaphragmatic pressure/RMSmean were reduced at all time points. The partial pressure of oxygen showed a continuous decline after VF to reach statistical significance in the 10th minute (9.46 ± 0.96 kPa, P < 0.001), whereas the partial pressure of carbon dioxide tended to first rise and then fall. Conclusions: Gasping during CA was characterized by high VT , extremely low frequency, and prolonged expiratory time, which may improve hypercapnia. During gasping, increased work of breathing and insufficient neuromechanical efficacy of neural respiratory drive suggested the necessity of MV and appropriate management strategies for MV during resuscitation after CA.

Noninvasive Assessment of Neuromechanical and Neuroventilatory Coupling in COPD

This study explored the use of parasternal second intercostal space and lower intercostal space surface electromyogram (sEMG) and surface mechanomyogram (sMMG) recordings (sEMGpara and sMMGpara, and sEMGlic and sMMGlic, respectively) to assess neural respiratory drive (NRD), neuromechanical (NMC) and neuroventilatory (NVC) coupling, and mechanical efficiency (MEff) noninvasively in healthy subjects and chronic obstructive pulmonary disease (COPD) patients. sEMGpara, sMMGpara, sEMGlic, sMMGlic, mouth pressure (Pmo), and volume (Vi) were measured at rest, and during an inspiratory loading protocol, in 16 COPD patients (8 moderate and 8 severe) and 9 healthy subjects. Myographic signals were analyzed using fixed sample entropy and normalized to their largest values (fSEsEMGpara%max, fSEsMMGpara%max, fSEsEMGlic%max, and fSEsMMGlic%max). fSEsMMGpara%max, fSEsEMGpara%max, and fSEsEMGlic%max were significantly higher in COPD than in healthy participants at rest. Parasternal intercostal muscle NMC was significantly higher in healthy than in COPD participants at rest, but not during threshold loading. Pmo-derived NMC and MEff ratios were lower in severe patients than in mild patients or healthy subjects during threshold loading, but differences were not consistently significant. During resting breathing and threshold loading, Vi-derived NVC and MEff ratios were significantly lower in severe patients than in mild patients or healthy subjects. sMMG is a potential noninvasive alternative to sEMG for assessing NRD in COPD. The ratios of Pmo and Vi to sMMG and sEMG measurements provide wholly noninvasive NMC, NVC, and MEff indices that are sensitive to impaired respiratory mechanics in COPD and are therefore of potential value to assess disease severity in clinical practice.

Limitations of surface EMG estimate of parasternal intercostal to infer neural respiratory drive

BackgroundRecently, surface EMG of parasternal intercostal muscle has been incorporated in the "ERS Statement of Respiratory Muscle Testing" as a clinical technique to monitor the neural respiratory drive (NRD). However, the anatomy of the parasternal muscle risks confounding EMG "crosstalk" activity from neighboring muscles. ObjectivesTo determine if surface “parasternal” EMG: 1) reliably estimates parasternal intercostal EMG activity, 2) is a valid surrogate expressing neural respiratory drive (NRD). MethodsFine wire electrodes were implanted into parasternal intercostal muscle in 20 severe COPD patients along with a pair of surface EMG electrodes at the same intercostal level. We recorded both direct fine wire parasternal EMG (EMGPARA) and surface estimated “parasternal” EMG (SurfEMGpara) simultaneously during resting breathing, volitional inspiratory maneuvers, apnoea with extraneous movement of upper extremity, and hypercapnic ventilation. ResultsSurface estimated “parasternal” EMG showed spurious "pseudobreathing" activity without any airflow while real parasternal EMG was silent, during apnoea with body extremity movement. Surface estimated “parasternal” EMG did not faithfully represent real measured parasternal EMG. Surface estimated “parasternal” EMG was significantly less active than directly measured parasternal EMG during all conditions including baseline, inspiratory capacity and hypercapnic ventilation. Bland-Altman analysis showed consistent bias between direct parasternal EMG recording and surface estimated EMG during stimulated breathing. ConclusionSurface “parasternal” EMG does not consistently or reliably express EMG activity of parasternal intercostal as recorded directly by implanted fine wires. A chest wall surface estimate of parasternal intercostal EMG may not faithfully express NRD and is of limited utility as a biomarker in clinical applications.

Autotitrating external positive end-expiratory airway pressure to abolish expiratory flow limitation during tidal breathing in patients with severe COPD: a physiological study.

The optimal noninvasive application of external positive end-expiratory pressure (EPAP) to abolish tidal-breathing expiratory flow limitation (EFLT) and minimise intrinsic positive end-expiratory pressure (PEEPi) is challenging in COPD patients. We investigated whether auto-titrating EPAP, using the forced oscillation technique (FOT) to detect and abolish EFLT, would minimise PEEPi, work of breathing and neural respiratory drive (NRD) in patients with severe COPD. Patients with COPD with chronic respiratory failure underwent auto-titration of EPAP using a FOT-based algorithm that detected EFLT. Once optimal EPAP was identified, manual titration was performed to assess NRD (using diaphragm and parasternal intercostal muscle electromyography, EMGdi and EMGpara, respectively), transdiaphragmatic inspiratory pressure swings (ΔP di), transdiaphragmatic pressure-time product (PTPdi) and PEEPi, between EPAP levels 2 cmH2O below to 3 cmH2O above optimal EPAP. Of 10 patients enrolled (age 65±6 years; male 60%; body mass index 27.6±7.2 kg.m-2; forced expiratory volume in 1 s 28.4±8.3% predicted), eight had EFLT, and optimal EPAP was 9 (range 4-13) cmH2O. NRD was reduced from baseline EPAP at 1 cmH2O below optimal EPAP on EMGdi and at optimal EPAP on EMGpara. In addition, at optimal EPAP, PEEPi (0.80±1.27 cmH2O versus 1.95± 1.70 cmH2O; p<0.05) was reduced compared with baseline. PTPdi (10.3±7.8 cmH2O·s-1 versus 16.8±8.8 cmH2O·s-1; p<0.05) and ΔP di (12.4±7.8 cmH2O versus 18.2±5.1 cmH2O; p<0.05) were reduced at optimal EPAP+1 cmH2O compared with baseline. Autotitration of EPAP, using a FOT-based algorithm to abolish EFLT, minimises transdiaphragmatic pressure swings and NRD in patients with COPD and chronic respiratory failure.

Novel method for evaluating the upper airway resistance using the ratio of neural respiratory drive to flow in OSA

Study objectivesSleep is associated with a reduction in ventilation and an increase in upper airway resistance (UAR) in patients with obstructive sleep apnea (OSA). However, there is no consensus on the standard for assessment of UAR and therefore it is important to develop a method to reliably assess UAR in patients with OSA. The purpose of the present study is to determine whether the ratio of neural respiratory drive (NRD) to flow can be used to assess changes in UAR in OSA during sleep. MethodsA total of 24 patients (21 men) with OSA and 10 normal subjects (6 males) were studied. The UAR was assessed by the ratio of NRD to flow, which measured by esophageal pressure (Poes), diaphragm electromyography (EMGdi) and superficial diaphragm electromyography (SEMGdi) in various stages including wakefulness, N2 sleep, N2 sleep with snoring, hypopneas, the in the “preapnea” states in OSA versus wakefulness, sleeponset, N2 sleep, N3 sleep in normal subjects. All subjects underwent overnight full polysomnography using standard techniques. ResultsOur study indicate that UAR was progressively higher from wakefulness to N2 sleep, N2 sleep with snoring, hypopneas, and the in the “preapnea” states in patients with OSA and had obvious difference in statistical significance (p < 0.05). We found NRD in hypopneas was lower than that in N2-snoring while the UAR in hypopneas was higher than that in N2-snoring.The UAR and NRD increased consecutively from wakefulness to N2 sleep and N3 sleep in normal subjects while the ventilation was reduced consecutively in NREM sleep. ConclusionsIt is feasible to use the ratio of neural respiratory drive to flow to assess UAR in patients with OSA during sleep.

Effect of Olfactory Stimulation by L-Menthol on Laboratory-Induced Dyspnea in COPD

Inhalation of L-menthol as a transient receptor potential melastatin 8 agonist induces a cooling sensation in the airway. This cooling sensation induced through olfactory stimulation by L-menthol (OSM) alleviates dyspnea in healthy humans. Therefore, we investigated effects of OSM on the neural respiratory drive (NRD) and multidimensional aspects of dyspnea induced by inspiratory resistive loaded breathing in COPD. In total, 28 patients with COPD and 14 control participants were included in this randomized, single-blinded, placebo-controlled, crossover study. OSM was administered using an L-menthol-scented patch, whereas placebo was administered using olfactory stimulation by strawberry-scented patch: placebo (OSP). Sham condition was measured by breathing through a face mask without a OSP. Dyspnea was evoked by breathing through the inspiratory resistance of 20 or 30cm H2O/L/s and measured using the Multidimensional Dyspnea Profile. NRD was estimated using the electromyogram activities of the parasternal intercostal muscles. Compared with sham and OSP, OSM did not alter the breathing pattern/timing and NRD during inspiratory resistive loading; however, it significantly alleviated the physical and mental breathing effort, air hunger, breathing discomfort, anxiety, and fear during inspiratory resistive loaded breathing in patients with COPD. However, although OSM reduced the air hunger, mental breathing effort, and unpleasantness, no significant improvement on affective dimension of dyspnea by OSM was observed in control participants. Our findings suggest that OSM activated the sense of inspiratory flow that achieved dyspnea relief in patients with COPD. UMIN Clinical Trials Registry (UMIN-CTR); No.: UMIN000033822; URL: https://www.umin.ac.jp/ctr/index.htm.

Correlations between change in neural respiratory drive and heart rate variability in patients submitted to open-heart surgery.

Respiratory muscle dysfunction after open-heart surgery may influence the cardiopulmonary interactions. The purpose of this study was to examine the correlation between change in the neural respiratory drive (NRD) and change in heart rate variability (HRV) in patients submitted to open-heart surgery. An observational cross-sectional study was conducted among 32 participants. NRD was assessed via a surface electromyogram of the parasternal intercostal muscle (sEMGpara). Polar heart rate monitor was used to measure HRV during the deep breathing maneuver. Evaluations were performed on the day of admission and discharge. There were statistically significant differences in NRD and HRV indices between admission and discharge periods (P<0.05). The difference in peak root mean square of sEMGpara recorded during resting (ΔRMS sEMGpara tidal), during maximal inspiratory maneuver (ΔsEMGpara max), and its normalized values (ΔRMS sEMGpara%max) were significantly correlated with the difference in total power (ΔTotal power), mean of heart rate (ΔMeanHR), and mean of R to R intervals (ΔMeanRR) (r=−0.844, P=0.004, r=−0.835, P=0.005, and r=0.643, P=0.043, respectively). It can be concluded that NRD correlated well with HRV in patients who had undergone open-heart surgery.

Neural respiratory drive predicts long-term outcome following admission for exacerbation of COPD: a post hoc analysis

Neural respiratory drive (NRD), as reflected by change in parasternal muscle electromyogram (EMGpara), predicts clinical deterioration and safe discharge in patients admitted to hospital with an acute exacerbation of COPD...

Quantitative assessment of nocturnal neural respiratory drive in children with and without obstructive sleep apnoea using surface EMG.

What is the central question of this study? Recent studies have suggested potential utility of non-normalized respiratory muscle EMG as an index of neural respiratory drive (NRD). Whether NRD measured using non-normalized surface EMG of the lateral chest wall overlying the diaphragm (sEMGcw) recorded during nocturnal clinical polysomnography can differentiate children with and without obstructive sleep apnoea (OSA) is not known. What is the main finding and its importance? Non-normalized sEMGcw was increased in children with OSA and an additional group of snoring children without OSA but subjectively increased respiratory effort compared with primary snorers. The sEMGcw has potential clinical utility in evaluation of children with sleep-disordered breathing as an objective, non-invasive, non-volitional marker of NRD. Our aim was to investigate whether neural respiratory drive measured by non-normalized surface EMG recorded from the chest wall overlying the diaphragm (sEMGcw) differentiates children with and without obstructive sleep apnoea (OSA). Polysomnography data of children aged 0-18 years were divided into the following three groups: (i) primary snorers (PS); (ii) snoring children without OSA but with increased work of breathing (incWOB; subjective physician report of increased respiratory effort during sleep); and (iii) children with OSA [obstructive apnoea-hypopnoea index (OAHI)>1h-1 ]. Excerpts of sEMGcw obtained during tidal unobstructed breathing from light, deep and rapid eye movement sleep were exported for quantitative analysis. Overnight polysomnography data from 45 PS [median age 4.4 years (interquartile range 3.0-7.7years), OAHI 0h-1 (0.0-0.2h-1 )], 19 children with incWOB [age 2.8years (2.4-5.7years), OAHI 0.1h-1 (0.0-0.4h-1 )] and 27 children with OSA [age 3.6 years (2.6-6.2years), OAHI 3.7h-1 (2.3-6.9h-1 )] were analysed. The sEMGcw was higher in those with OSA [8.47μV (5.98-13.07μV); P<0.0001] and incWOB [8.97μV (5.94-13.43μV); P<0.001] compared with PS [4.633μV (2.98-6.76μV)]. There was no significant difference in the sEMGcw between children with incWOB and OSA (P=0.78). Log sEMGcw remained greater in children with OSA and incWOB compared with PS after age, body mass index centiles, sleep stages and sleep positions were included in the mixed linear models (P<0.0001). The correlation between sEMGcw and OAHI in children without OSA was small (rs =0.254, P=0.04). The sEMGcw is increased in children with OSA and incWOB compared with PS.

Neural Respiratory Drive Measured Using Surface Electromyography of Diaphragm as a Physiological Biomarker to Predict Hospitalization of Acute Exacerbation of Chronic Obstructive Pulmonary Disease Patients.

Background:Neural respiratory drive (NRD) using diaphragm electromyography through an invasive transesophageal multi-electrode catheter can be used as a feasible clinical physiological parameter in patients with chronic obstructive pulmonary disease (COPD) to provide useful information on the treatment response. However, it remains unknown whether the surface diaphragm electromyogram (EMGdi) could be used to identify the deterioration of clinical symptoms and to predict the necessity of hospitalization in acute exacerbation of COPD (AECOPD) patients.Methods:COPD patients visiting the outpatient department due to acute exacerbation were enrolled in this study. All patients who were subjected to EMGdi and classical parameters such as spirometry parameters, arterial blood gas analysis, COPD assessment test (CAT) score, and the modified early warning score (MEWS) in outpatient department, would be treated effectively in the outpatient or inpatient settings according to the Global Initiative for Chronic Obstructive Lung Disease guideline. When the acute exacerbation of the patients was managed, all the examination above would be repeated.Results:We compared the relationships of admission-to-discharge changes (Δ) in the normalized value of the EMGdi, including the change of the percentage of maximal EMGdi (ΔEMGdi%max) and the change of the ratio of minute ventilation to the percentage of maximal EMGdi (ΔVE/EMGdi%max) with the changes of classical parameters. There was a significant positive association between ΔEMGdi%max and ΔCAT, ΔPaCO2, and ΔpH. The change (Δ) of EMGdi%max was negatively correlated with ΔPaO2/FiO2 in the course of the treatment of AECOPD. Compared with the classical parameters including forced expiratory volume in 1 s, MEWS, PaO2/FiO2, the EMGdi%max (odds ratio 1.143, 95% confidence interval 1.004–1.300) has a higher sensitivity when detecting the early exacerbation and enables to predict the admission of hospital in the whole cohort.Conclusions:The changes of surface EMGdi parameters had a direct correlation with classical measures in the whole cohort of AECOPD. The measurement of NRD by surface EMGdi represents a practical physiological biomarker, which may be helpful in detecting patients who should be hospitalized timely.

Correlation of surface respiratory electromyography with esophageal diaphragm electromyography

ObjectivesTo assess the correlation between surface respiratory electromyography(sEMG) and esophageal diaphragm electromyography(EMGdi) at different levels of neural respiratory drive (NRD). DesignRandomised parallel design controlled trial. SettingThe First Affiliated Hospital of Guangzhou Medical University. Participants15 healthy subjects and 1 severe to very severe stable COPD patients were studied. Interventions15 healthy subjects performed incremental inspiratory threshold loading (ILT) and 15 stable COPD patients underwent noninvasive positive pressure ventilation (NPPV).The correlation between EMGdi and sEMG at different NRD levels was analyzed. EMGdi was performed with a multi-pair esophageal electrode catheter; sEMG were was performed by surface diaphragm EMG(located in right anterior axillary line and left anterior axillary line respectively expressed as sEMGdi(r) andsEMGdi(l))、surface parasternal EMG(sEMGpara),and surface sternocleidomastoid EMG(sEMGsc).Signals were normalized using the peak EMG expressed as EMG%max. Primary and secondary outcome measuresThe mean ± standard deviation resting EMGdi%max was higher in patients with COPD than in healthy subjects (57.26%±15.45% vs13.64% ±4.96%, respectively; p < 0.001).During ILT and NPPV, EMGdi was correlated with sEMGdi (r), sEMGdi (1), sEMGpara and sEMGsc (r = 0.90, 0.87, 0.90, 0.90 and r = 0.92, 0.83, 0.92 and 0.71, respectively; all P < 0.001). ConclusionA strong relationship is present between NRD measured by EMGdi%max and NRD measured by sEMG%max. sEMG%max serves as a non-invasive marker of NRD.

Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial lung disease.

Our understanding of the mechanisms of dyspnoea in fibrotic interstitial lung disease (ILD) is incomplete. The aims of this study were two-fold: 1) to determine whether dyspnoea intensity is better predicted by neural respiratory drive (NRD) or neuromechanical uncoupling (NMU) of the respiratory system in fibrotic ILD, and 2) to examine the effect of breathing 60% oxygen on NRD, NMU and dyspnoea ratings.Fourteen patients with fibrotic ILD were included. Visit 1 comprised a familiarisation incremental cycle exercise test, Visit 2 comprised a normoxic incremental cycling test to address Aim 1, and Visits 3 and 4 consisted of constant-load cycling while breathing room air or 60% oxygen to address Aim 2. Diaphragmatic electromyography (EMGdi) was used as a surrogate of NRD. NMU was calculated as the ratio between EMGdi (%max) and tidal volume (%vital capacity).On adjusted analysis, NMU and its constituents were all significantly associated with dyspnoea ratings during incremental cycling, with EMGdi having the strongest correlation. The between-treatment change in dyspnoea ratings during constant load cycling was only correlated with change in exercise endurance time and NMU.Dyspnoea more strongly reflected the level of EMGdi than NMU in fibrotic ILD. However, the improvement in dyspnoea with 60% oxygen was better predicted by improvements in NMU.

Observational Study of Neural Respiratory Drive During Sleep at High Altitude.

Ventilation at altitude changes due to altered levels of pO2, pCO2 and the effect on blood pH. Nocturnal ventilation is particularly exposed to these changes. We hypothesized that an increasing neural respiratory drive (NRD) is associated with the severity of sleep-disordered breathing at altitude. Mountaineers were studied at sea level (London, United Kingdom), and at altitude at the Aconcagua (Andes, Argentina). NRD was measured as electromyogram of the diaphragm (EMGdi) overnight by a transesophageal multi-electrode catheter; results were reported for sea level, 3,380 m, 4,370 m, and 5,570 m. Four healthy subjects (3 men, age 31(3)years, body mass index 23.6(0.9)kg/m2, neck circumference 37.0(2.7)cm, forced expiratory volume in 1 second 111.8(5.1)%predicted, and forced vital capacity 115.5(6.3)%predicted) were studied. No subject had significant sleep abnormalities at sea level. Time to ascent to 3,380 m was 1 day, to 4,370 m was 5 days, and the total nights at altitude were 21 days. The oxygen desaturation index (4% oxygen desaturation index [ODI] 0.8(0.4), 22.0 (7.2), 61.4 (26.9), 144.9/hour, respectively) and the EMGdi (5.2 (1.9), 12.8 (5.1), 14.1 (3.4), 18.5%, respectively) increased with the development of periodic breathing at altitude, whereas the average SpO2 declined (97.5 (1.3), 84.8 (0.5), 81.0 (4.1), 68.5%, respectively). The average EMGdi correlated well with the 4%ODI (r = 0.968, p = 0.032). NRD sleep increases at altitude in relation to the severity of periodic breathing.

Is parasternal intercostal EMG an accurate surrogate of respiratory neural drive and biomarker of dyspnea during cycle exercise testing?

Recent evidence suggests that surface electromyography of the parasternal intercostals (EMGpara) can be a non-invasive alternative to diaphragmatic EMG (EMGdi) for estimating neural respiratory drive (NRD) during cardiopulmonary exercise testing (CPET). The purpose of this study was to determine if non-respiratory muscles influence EMGpara by having subjects place their hands on (Hon) and off (Hoff) the handlebars during cycling-based CPET. Ten healthy adults performed an incremental cycling test until volitional exhaustion. Participants were instrumented with an esophageal electrode catheter to measure EMGdi, and surface electrodes on the 2nd intercostal space to measure EMGpara. Subjects alternated between 30s of Hon and 30s Hoff during each exercise stage. There were no differences in EMGdi across all exercise intensities. However, EMGpara was significantly greater during the Hon vs. Hoff condition at all exercise intensities (p<0.05). These results suggest that EMGpara may not be an appropriate surrogate of NRD during cycle exercise testing due to co-activation of adjacent skeletal muscles.

Validation of a quantitative method to measure neural respiratory drive in children during sleep

AimsQuantitatively measure and validate analysis of neural respiratory drive (NRD) using a commercial polysomnography system in children during sleep. MethodSurface electromyogram of the diaphragm (sEMGdi) recorded from primary snoring children were analysed. A subset was re-analysed to assess intra- and inter-investigator reproducibility. Effects of different band pass filter settings (20–100Hz vs 10–1000Hz) on sEMGdi amplitude were evaluated. ResultsMean sEMGdi from 45 children aged 4.38 years (median; IQR 3.00–7.96) was 5.05μV (SD 2.73). The sEMGdi had a high intra-subject intraclass correlation coefficient (ICC) of 0.88. sEMGdi analysis was reproducible with high ICC between occasions (0.99; 95% CI 0.98–0.99) and between investigators (0.98; 95% CI 0.97–0.99). There was also a high ICC (0.99, 95% CI 0.96–1.00) between the sEMGdi measured using different band-pass filter settings. Age and BMI were negative predictors of sEMGdi (p<0.0001 and p=0.0004 respectively). ConclusionNRD in children during sleep as assessed by sEMGdi can be quantified in a reliable and reproducible fashion.

Continuous Positive Airway Pressure and Breathlessness in Obese Patients with Obstructive Sleep Apnea: A Pilot Study.

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA). However, long-term compliance with CPAP is limited. We tested the hypothesis that CPAP levels routinely used during sleep increase neural respiratory drive (NRD) and breathlessness, which may discourage compliance. This was an observational physiological cohort study in a respiratory physiology and sleep unit, University Hospital. Patients with a body mass index (BMI) > 25 kg/m(2) and confirmed OSA were studied supine and awake on CPAP (4-20 cm H2O, increments of 2 cm H2O/3 min). We measured NRD during awake CPAP titration in obese subjects to quantify the response to the load of the respiratory system and compared it to the CPAP used for nocturnal treatment, with the modified Borg Scale (mBorg) for dyspnea recorded (from 0 to 10 points, with higher numbers indicating more breathlessness). Fifteen patients (age 48 ± 10 years, 12 male, BMI 38.9 ± 5.8 kg/m(2)) with OSA (AHI 32.2 ± 21.1/h, 95(th) percentile of CPAP 14.1 ± 3.8 cm H2O) were studied and NRD (electromyogram of the parasternal intercostals, EMGpara; EMG of the external oblique, EMGabdomen) was recorded (awake, supine). Awake, EMGpara declined from baseline to 70.2% ± 17.1% when CPAP of 10.7 ± 3.4 cm H2O (P = 0.026) was applied. Further increase in CPAP led to a rise in EMGpara and increased breathlessness (P = 0.02). CPAP compliance (nights used) correlated negatively with mBorg scores (r = -0.738, P = 0.006). Awake, the respiratory system is maximally offloaded with lower than therapeutic CPAP levels in obese patients with OSA. Levels of NRD observed at effective CPAP levels while asleep are associated with breathlessness which may limit long-term CPAP compliance.

Efficiency of neural respiratory drive for the assessment of bronchodilator responsiveness in patients with chronic obstructive pulmonary disease: an exploratory study.

Conventional lung function parameters, such as forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and inspiratory capacity (IC) are often used to assess the therapeutic outcomes of bronchodilators, but they lack sensitivity. A novel indicator, namely efficiency of neural respiratory drive (NRD), may objectively evaluate the physiological changes in patients with chronic obstructive pulmonary disease (COPD). We investigated whether this indicator could be used to more accurately assess the responsiveness to inhaled bronchodilators. Thirty-six subjects with moderate-to-severe COPD were randomized into group A (n=18) and group B (n=18). Participants in group A inhaled 400 µg placebo, 400 µg salbutamol and 80 µg ipratropium in sequence whereas those in group B had the salbutamol and ipratropium reversed. At different time points after administration of placebo or bronchodilators, evaluated indices included FEV1, FVC, IC, root mean square (RMS) of diaphragm electromyogram (EMGdi), and efficiency of NRD [herein defined as the ratio of minute ventilation (VE) to RMS, or VE/RMS]. FEV1, FVC, IC, RMS, and VE/RMS significantly improved after inhaled bronchodilators and VE/RMS had the largest improvement among five indices. The detection efficiency of VE/RMS was greater than FEV1, FVC, IC (all P<0.05), but not different from RMS. The accuracy and sensitivity of VE/RMS were significantly higher than FEV1, FVC, IC, and RMS (all P<0.05). Efficiency of NRD may be a sensitive tool to evaluate the efficacy of inhaled bronchodilators in COPD.

Blunted perception of neural respiratory drive and breathlessness in patients with cystic fibrosis.

The electromyogram recorded from the diaphragm (EMGdi) and parasternal intercostal muscle using surface electrodes (sEMGpara) provides a measure of neural respiratory drive (NRD), the magnitude of which reflects lung disease severity in stable cystic fibrosis. The aim of this study was to explore perception of NRD and breathlessness in both healthy individuals and patients with cystic fibrosis. Given chronic respiratory loading and increased NRD in cystic fibrosis, often in the absence of breathlessness at rest, we hypothesised that patients with cystic fibrosis would be able to tolerate higher levels of NRD for a given level of breathlessness compared to healthy individuals during exercise.15 cystic fibrosis patients (mean forced expiratory volume in 1 s (FEV1) 53.5% predicted) and 15 age-matched, healthy controls were studied. Spirometry was measured in all subjects and lung volumes measured in the cystic fibrosis patients. EMGdi and sEMGpara were recorded at rest and during incremental cycle exercise to exhaustion and expressed as a percentage of maximum (% max) obtained from maximum respiratory manoeuvres. Borg breathlessness scores were recorded at rest and during each minute of exercise.EMGdi % max and sEMGpara % max and associated Borg breathlessness scores differed significantly between healthy subjects and cystic fibrosis patients at rest and during exercise. The relationship between EMGdi % max and sEMGpara % max and Borg score was shifted to the right in the cystic fibrosis patients, such that at comparable levels of EMGdi % max and sEMGpara % max the cystic fibrosis patients reported significantly lower Borg breathlessness scores compared to the healthy individuals. At Borg score 1 (clinically significant increase in breathlessness from baseline) corresponding levels of EMGdi % max (20.2±12% versus 32.15±15%, p=0.02) and sEMGpara % max (18.9±8% versus 29.2±15%, p=0.04) were lower in the healthy individuals compared to the cystic fibrosis patients.In the cystic fibrosis patients EMGdi % max at Borg score 1 was related to the degree of airways obstruction (FEV1) (r=−0.664, p=0.007) and hyperinflation (residual volume/total lung capacity) (r=0.710, p=0.03). This relationship was not observed for sEMGpara % max.These data suggest that compared to healthy individuals, patients with cystic fibrosis can tolerate much higher levels of NRD before increases in breathlessness from baseline become clinically significant. EMGdi % max and sEMGpara % max provide physiological tools with which to elucidate factors underlying inter-individual differences in breathlessness perception.

Understanding Heroin Overdose: A Study of the Acute Respiratory Depressant Effects of Injected Pharmaceutical Heroin.

Opioids are respiratory depressants and heroin/opioid overdose is a major contributor to the excess mortality of heroin addicts. The individual and situational variability of respiratory depression caused by intravenous heroin is poorly understood. This study used advanced respiratory monitoring to follow the time course and severity of acute opioid-induced respiratory depression. 10 patients (9/10 with chronic airflow obstruction) undergoing supervised injectable opioid treatment for heroin addiction received their usual prescribed dose of injectable opioid (diamorphine or methadone) (IOT), and their usual prescribed dose of oral opioid (methadone or sustained release oral morphine) after 30 minutes. The main outcome measures were pulse oximetry (SpO2%), end-tidal CO2% (ETCO2%) and neural respiratory drive (NRD) (quantified using parasternal intercostal muscle electromyography). Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% < 90% for >10s and ETCO2% per breath >6.5%. Increases in ETCO2% indicated significant respiratory depression following IOT in 8/10 patients at 30 minutes. In contrast, SpO2% indicated significant respiratory depression in only 4/10 patients, with small absolute changes in SpO2% at 30 minutes. A decline in NRD from baseline to 30 minutes post IOT was also observed, but was not statistically significant. Baseline NRD and opioid-induced drop in SpO2% were inversely related. We conclude that significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction. Hypoventilation is reliably detected by capnography, but not by SpO2% alone. Chronic suppression of NRD in the presence of underlying lung disease may be a risk factor for acute opioid-induced respiratory depression.