Transdiaphragmatic Pressure Research Articles

Unilateral diaphragmatic paralysis: inspiratory muscles, breathlessness and exercise capacity.

BackgroundPatients with unilateral diaphragmatic paralysis (UDP) may present with dyspnoea without specific cause and limited ability to exercise. We aimed to investigate the diaphragm contraction mechanisms and nondiaphragmatic inspiratory muscle activation during exercise in patients with UDP, compared with healthy individuals.MethodsPulmonary function, as well as volitional and nonvolitional inspiratory muscle strength were evaluated in 35 patients and in 20 healthy subjects. Respiratory pressures and electromyography of scalene and sternocleidomastoid muscles were continuously recorded during incremental maximal cardiopulmonary exercise testing until symptom limitation. Dyspnoea was assessed at rest, every 2 min during exercise and at the end of exercise with a modified Borg scale.Main resultsInspiratory muscle strength measurements were significantly lower for patients in comparison to controls (all p<0.05). Patients achieved lower peak of exercise (lower oxygen consumption) compared to controls, with both gastric (−9.8±4.6 cmH2O versus 8.9±6.0 cmH2O) and transdiaphragmatic (6.5±5.5 cmH2O versus 26.9±10.9 cmH2O) pressures significantly lower, along with larger activation of both scalene (40±22% EMGmax versus 18±14% EMGmax) and sternocleidomastoid (34±22% EMGmax versus 14±8% EMGmax). In addition, the paralysis group presented significant differences in breathing pattern during exercise (lower tidal volume and higher respiratory rate) with more dyspnoea symptoms compared to the control group.ConclusionThe paralysis group presented with exercise limitation accompanied by impairment in transdiaphragmatic pressure generation and larger accessory inspiratory muscles activation compared to controls, thereby contributing to a neuromechanical dissociation and increased dyspnoea perception.

Diaphragm Dysfunction as a Determinant of Persisting Dyspnoea in Patients One Year after Invasive Mechanical Ventilation Due to COVID-19 Related ARDS

Background: Some patients with coronavirus disease 2019 (COVID-19) experience prolonged fatigue and dyspnoea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a possible pathophysiological correlate after severe COVID-19 acute respiratory distress syndrome (ARDS).Methods:Ten patients with severe COVID-19 ARDS treated with invasive mechanical ventilation (IMV) (6 female, age 56±14 years, 63±45 days of IMV) and ten matched healthy controls underwent pulmonary function tests (PFTs), 6-minute walk test, echocardiography, diaphragm ultrasound, and invasive recording of twitch transdiaphragmatic pressure (twPdi) following magnetic diaphragm stimulation. Twitch interpolation was used to determine the diaphragm voluntary activation index (DVAI); reflecting central diaphragm activation.Findings: One year post discharge, neither PFTs nor echocardiography were indicative of significant abnormalities in severe COVID-19 survivors. However, six patients reported persisting dyspnoea on exertion (severe in two, moderate in four). On ultrasound, the diaphragm thickening ratio was lower in patients versus controls (1.87±0.37 vs. 2.76±0.72; pInterpretation: Inspiratory muscle dysfunction with impaired central voluntary activation of the diaphragm is present one year after severe COVID-19 ARDS treated with IMV, and relates to dyspnoea.Trial Registration: This prospective case-control study was registered with number, (NCT04854863)Funding: None to declare. Declaration of Interest: The authors have no conflicts of interest to disclose.Ethical Approval: This study was approved by the local ethics committee (Ethikkommission an der Medizinischen Fakultät der Rheinisch-Westfälischen Technischen Hochschule Aachen, CTCA-A-Nr. 20-515, AZ EK 443/20).

Phrenic nerve conduction study to diagnose unilateral diaphragmatic paralysis.

Unilateral diaphragmatic paralysis (UDP) has major clinical and etiological implications and, therefore, is important to diagnose. Lung function tests and invasive transdiaphragmatic pressure (Pdi) measurements are widely used to this end but, contrary to phrenic nerve conduction study (NCS), they require volitional maneuvers and/or may be poorly tolerated by patients. The purpose of this study was to compare the diagnostic accuracy of Pdi and phrenic NCS for UDP. We retrospectively reviewed 28 patients with suspected UDP. The diagnosis established during a multidisciplinary meeting was the reference standard. Phrenic NCS correlated well with Pdi (r = 0.82, P < .005), and the two tests showed good agreement (κ = 0.82, P < .005). Phrenic NCS and Pdi measurements both had 95% sensitivity, 87.5% specificity, 95% positive predictive, and 87.5% negative predictive values. Both tests were highly sensitive and specific. Phrenic NCS measurement is a simple, reproducible, noninvasive method whose results correlate well with Pdi and provide insight into the UDP mechanism. In the most difficult cases, combining lung function tests, respiratory muscle assessments, and phrenic NCS can help to establish the diagnosis.

Intrinsic Dynamic Positive End-Expiratory Pressure in Stable Patients with Chronic Obstructive Pulmonary Disease

Background: Assessment of intrinsic dynamic positive end-expiratory pressure (PEEPi,dyn) may be clinically important in stable patients with chronic obstructive pulmonary disease (COPD), but epidemiological data are scant. Objectives: The aim of our study was (i) to assess the PEEPi,dyn in a large population of stable patients with COPD and (ii) to evaluate the correlations with some noninvasive measurements routinely assessed. Method: Retrospective analysis of lung mechanics, dynamic volumes, arterial blood gases, dyspnoea by means of the Medical Research Council (MRC) scale, the COPD Assessment Test score, and maximal inspiratory/expiratory pressures in 87 hypercapnic and 62 normocapnic patients. Results: The mean PEEPi,dyn was significantly higher in hypercapnic than normocapnic patients (2.8 ± 2.2 vs. 1.9 ± 1.6 cm H₂O, respectively, p = 0.0094). PEEPi,dyn did not differ according to Global Initiative for Chronic Obstructive Lung Disease stage, MRC score, or use or not of long-term oxygen therapy. There were significant although weak correlations between PEEPi,dyn and airway obstruction, hyperinflation, respiratory muscle function, arterial CO₂ tension, and number of exacerbations/year. The transdiaphragmatic pressure was the strongest variable associated to PEEPi,dyn (R = 0.5713, p = 0.001). Conclusion: In stable patients with COPD, PEEPi,dyn is higher in hypercapnic patients and weakly correlated to noninvasive measures of lung and respiratory muscle function.

Sex differences in diaphragmatic fatigue: Effects of hypoxia during inspiratory loading.

Under normoxic conditions, both healthy female and male diaphragms fatigue at a similar degree when matched for absolute diaphragmatic work during inspiratory loading. We investigated whether similarities in diaphragm fatigability persist under acute hypoxic conditions. We found that, in acute hypoxia, fatigue of the diaphragm is greater in women compared to men, whereas the magnitude of fatigue in normoxia did not differ between sexes. When matched for maximal diaphragm strength, women and men had a similar pressor response to work-matched inspiratory loading, independent of oxygen availability. In normoxia, women and men display a comparable magnitude of diaphragmatic fatigue (DF) after work-matched inspiratory loading. Whether these sex similarities are maintained under acute hypoxic conditions is unknown. We investigated the influence of acute hypoxia during work-matched inspiratory pressure-threshold loading (PTL) on DF in healthy women (n=8) and men (n=8). Two 5min isocapnic PTL tasks targeting a transdiaphragmatic pressure (Pdi ) of 92cmH2 O in normoxia and hypoxia (8% O2 ) were performed on separate days (≥48h). DF was quantified by twitch Pdi (Pdi,tw ) via cervical magnetic stimulation post-PTL. Women and men had similar maximal Pdi (Pdi,max ; women: 171±16, men: 178±20cmH2 O) and relative target workload (women: 54±5%, men: 53±6% Pdi,max ). The absolute cumulative diaphragmatic work did not differ between sexes in normoxia (women: 12,653±1796cmH2 Os-1 , men: 13,717±1231cmH2 Os-1 ; P=0.202) or hypoxia (women: 11,624±1860cmH2 Os-1 , men: 12 722±1502cmH2 Os-1 ; P=0.189). In normoxia, the magnitude of reduction in Pdi,tw post-PTL was similar between sexes (women: -21.1±8.4%, men: -22.5±4.9 %; P=0.193); however, a higher degree of DF was observed in women compared to men following PTL in acute hypoxia (women: -27.6±7.7%, men: -23.4±9.6%, P=0.019). We conclude that the female diaphragm is more susceptible to fatigue after inspiratory loading under acute hypoxic conditions. This finding may be related to sex differences in diaphragm muscle metabolism, such as fibre type composition, contractile properties, substrate utilisation and blood perfusion.

Continuous assessment of neuro-ventilatory drive during 12\xa0h of pressure support ventilation in critically ill patients

IntroductionPressure support ventilation (PSV) should allow spontaneous breathing with a “normal” neuro-ventilatory drive. Low neuro-ventilatory drive puts the patient at risk of diaphragmatic atrophy while high neuro-ventilatory drive may causes dyspnea and patient self-inflicted lung injury. We continuously assessed for 12 h the electrical activity of the diaphragm (EAdi), a close surrogate of neuro-ventilatory drive, during PSV. Our aim was to document the EAdi trend and the occurrence of periods of “Low” and/or “High” neuro-ventilatory drive during clinical application of PSV.MethodIn 16 critically ill patients ventilated in the PSV mode for clinical reasons, inspiratory peak EAdi peak (EAdiPEAK), pressure time product of the trans-diaphragmatic pressure per breath and per minute (PTPDI/b and PTPDI/min, respectively), breathing pattern and major asynchronies were continuously monitored for 12 h (from 8 a.m. to 8 p.m.). We identified breaths with “Normal” (EAdiPEAK 5–15 μV), “Low” (EAdiPEAK < 5 μV) and “High” (EAdiPEAK > 15 μV) neuro-ventilatory drive.ResultsWithin all the analyzed breaths (177.117), the neuro-ventilatory drive, as expressed by the EAdiPEAK, was “Low” in 50.116 breath (28%), “Normal” in 88.419 breaths (50%) and “High” in 38.582 breaths (22%). The average times spent in “Low”, “Normal” and “High” class were 1.37, 3.67 and 0.55 h, respectively (p < 0.0001), with wide variations among patients. Eleven patients remained in the “Low” neuro-ventilatory drive class for more than 1 h, median 6.1 [3.9–8.5] h and 6 in the “High” neuro-ventilatory drive class, median 3.4 [2.2–7.8] h. The asynchrony index was significantly higher in the “Low” neuro-ventilatory class, mainly because of a higher number of missed efforts.ConclusionsWe observed wide variations in EAdi amplitude and unevenly distributed “Low” and “High” neuro ventilatory drive periods during 12 h of PSV in critically ill patients. Further studies are needed to assess the possible clinical implications of our physiological findings.

Heart Failure Results in Inspiratory Muscle Dysfunction Irrespective of Left Ventricular Ejection Fraction

Background: Exercise intolerance in heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) results from both cardiac dysfunction and skeletal muscle weakness. Respiratory muscle dysfunction with restrictive ventilation disorder may be present irrespective of left ventricular ejection fraction and might be mediated by circulating pro-inflammatory cytokines. Objective: To determine lung and respiratory muscle function in patients with HFrEF/HFpEF and to determine its associations with exercise intolerance and markers of systemic inflammation. Methods: Adult patients with HFrEF (n = 22, 19 male, 61 ± 14 years) and HFpEF (n = 8, 7 male, 68 ± 8 years) and 19 matched healthy control subjects underwent spirometry, measurement of maximum mouth occlusion pressures, diaphragm ultrasound, and recording of transdiaphragmatic and gastric pressures following magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots. New York Heart Association (NYHA) class and 6-min walking distance (6MWD) were used to quantify exercise intolerance. Levels of circulating interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured using ELISAs. Results: Compared with controls, both patient groups showed lower forced vital capacity (FVC) (p < 0.05), maximum inspiratory pressure (PI_max), maximum expiratory pressure (PE_max) (p < 0.05), diaphragm thickening ratio (p = 0.01), and diaphragm strength (twitch transdiaphragmatic pressure in response to supramaximal cervical magnetic phrenic nerve stimulation) (p = 0.01). In patients with HFrEF, NYHA class and 6MWD were both inversely correlated with FVC, PI_max, and PE_max. In those with HFpEF, there was an inverse correlation between amino terminal pro B-type natriuretic peptide levels and FVC (r = −0.77, p = 0.04). In all HF patients, IL-6 and TNF-α were statistically related to FVC. Conclusions: Irrespective of left ventricular ejection fraction, HF is associated with respiratory muscle dysfunction, which is associated with increased levels of circulating IL-6 and TNF-α.

Ultrafast ultrasound coupled with cervical magnetic stimulation for non-invasive and non-volitional assessment of diaphragm contractility.

Twitch transdiaphragmatic pressure elicited by cervical magnetic stimulation of the phrenic nerves is a fully non-volitional method for assessing diaphragm contractility in humans, yet it requires invasive procedures such as oesophageal and gastric catheter balloons. Ultrafast ultrasound enables a very high frame rate allowing the capture of transient events, such as muscle contraction elicited by nerve stimulation (twitch). Whether indices derived from ultrafast ultrasound can be used as an alternative to the invasive measurement of twitch transdiaphragmatic pressure is unknown. Our findings demonstrate that maximal diaphragm tissue velocity assessed using ultrafast ultrasound following cervical magnetic stimulation is reliable, sensitive to change in cervical magnetic stimulation intensity, and correlates to twitch transdiaphragmatic pressure. This approach provides a novel fully non-invasive and non-volitional tool for the assessment of diaphragm contractility in humans. Measuring twitch transdiaphragmatic pressure (Pdi,tw ) elicited by cervical magnetic stimulation (CMS) is considered as a reference method for the standardized evaluation of diaphragm function. Yet, the measurement of Pdi requires invasive oesophageal and gastric catheter-balloons. Ultrafast ultrasound is a non-invasive imaging technique enabling frame rates high enough to capture transient events such as evoked muscle contractions. This study investigated relationships between indices derived from ultrafast ultrasound and Pdi,tw , and how these indices might be used to estimate Pdi,tw . CMS was performed in 13healthy volunteers from 30% to 100% of maximal stimulator intensity in units of 10% in a randomized order. Pdi,tw was measured and the right hemidiaphragm was imaged using a custom ultrafast ultrasound sequence with 1kHz framerate. Maximal diaphragm axial velocity (Vdi ,max ) and diaphragm thickening fraction (TFdi,tw ) were computed. Intra-session reliability was assessed. Repeated-measures correlation (R) and Spearman correlation coefficients (ρ) were used to assess relationships between variables. Intra-session reliability was strong for Pdi,tw and Vdi,max and moderate for TFdi,tw . Vdi,max correlated with Pdi,tw in all subjects (0.64<ρ<1.00, R=0.75; all P < 0.05). TFdi,tw correlated with Pdi,tw in eight subjects only (0.85<ρ<0.93, R=0.69; all P<0.05). Coupling ultrafast ultrasound and CMS shows promise for the non-invasive and fully non-volitional assessment of diaphragm contractility. This approach opens up the prospect of both diagnosis and follow-up of diaphragm contractility in clinical populations.

Esophageal and transdiaphragmatic pressure swings as indices of inspiratory effort

AimTo describe the correlation between the inspiratory esophageal and transdiaphragmatic pressure swings (ΔPes and ΔPdi), easily measured indices of inspiratory effort, with the gold-standard, the transdiaphragmatic pressure time product (PTPPdi/min), and assess the accuracy of swing pressures in predicting very high or low effort. MethodRetrospective analysis of data from patients enrolled in four previous studies. ROC curves of ΔPes and ΔPdi values for specific PTPPdi/min thresholds (50, 150, 200 cmH2O × sec/min) were constructed, and the diagnostic accuracy of different thresholds of swing values were computed. ResultsA threshold of inspiratory ΔP<7cmH2O can be used to identify most patients with low effort, as lower ΔP thresholds have low sensitivity. Thresholds of inspiratory ΔP>14–18cmH2O can be used to identify patients with very high inspiratory effort (PTPPdi/min> 200 cmH2O × sec/min). ConclusionsThe results of this study can help clinicians better select and interpret thresholds of ΔP to evaluate inspiratory effort.

Trans-Diaphragmatic Pressure Differential as Determined by High Resolution Manometry

Trans-Diaphragmatic Pressure Differential as Determined by High Resolution Manometry

Reliability of diaphragm voluntary activation measurements in healthy adults

Voluntary activation can be used to assess central fatigue of the diaphragm after tasks such as exercise or inspiratory muscle loading. Cervical magnetic stimulation (CMS) of the phrenic nerves elicits an involuntary contraction, or twitch, of the diaphragm. This twitch is quantified based on a measure of transdiaphragmatic pressure and can be used to evaluate diaphragm contractile function and diaphragm voluntary activation (diaphragm-VA). The test-retest reliability of diaphragm-VA using CMS is currently unknown. Thirteen participants (4 male, 9 female; aged 25 ± 3 years) performed a series of interpolated twitch manoeuvres, which included a maximal inspiratory effort against a semi-occluded mouthpiece and 2 CMS-stimuli, 1 during the inspiratory manoeuvre and 1 after when the participant returned to functional residual capacity to quantify diaphragm-VA. Intraclass correlation coefficients (ICCs) and standard error of measurement (SEM) measured between-day and within-session reliability of diaphragm-VA, respectively. Maximal diaphragm-VA values were 91% (SD: 6; SEM: 3.9) and 92% (SD: 5; SEM: 2.2) during visits 1 and 2 (p = 0.68), respectively, and displayed "good" between-day reliability (ICC: 0.88; 95% confidence interval: 0.67-0.95; SEM: 2.7). Our results suggest that assessing diaphragm-VA using CMS is reliable in young healthy adults. Measuring diaphragm-VA may provide additional insight into the consequences and mechanisms of diaphragm fatigue. Novelty: Magnetic stimulation of the phrenic nerves can reliably measure voluntary activation of the diaphragm. Diaphragm voluntary activation can be used to provide additional insight into fatigability of the diaphragm.

Airway pressure morphology and respiratory muscle activity during end-inspiratory occlusions in pressure support ventilation

BackgroundThe driving pressure of the respiratory system is a valuable indicator of global lung stress during passive mechanical ventilation. Monitoring lung stress in assisted ventilation is indispensable, but achieving passive conditions in spontaneously breathing patients to measure driving pressure is challenging. The accuracy of the morphology of airway pressure (Paw) during end-inspiratory occlusion to assure passive conditions during pressure support ventilation has not been examined.MethodsRetrospective analysis of end-inspiratory occlusions obtained from critically ill patients during pressure support ventilation. Flow, airway, esophageal, gastric, and transdiaphragmatic pressures were analyzed. The rise of gastric pressure during occlusion with a constant/decreasing transdiaphragmatic pressure was used to identify and quantify the expiratory muscle activity. The Paw during occlusion was classified in three patterns, based on the differences at three pre-defined points after occlusion (0.3, 1, and 2 s): a “passive-like” decrease followed by plateau, a pattern with “clear plateau,” and an “irregular rise” pattern, which included all cases of late or continuous increase, with or without plateau.ResultsData from 40 patients and 227 occlusions were analyzed. Expiratory muscle activity during occlusion was identified in 79% of occlusions, and at all levels of assist. After classifying occlusions according to Paw pattern, expiratory muscle activity was identified in 52%, 67%, and 100% of cases of Paw of passive-like, clear plateau, or irregular rise pattern, respectively. The driving pressure was evaluated in the 133 occlusions having a passive-like or clear plateau pattern in Paw. An increase in gastric pressure was present in 46%, 62%, and 64% of cases at 0.3, 1, and 2 s, respectively, and it was greater than 2 cmH2O, in 10%, 20%, and 15% of cases at 0.3, 1, and 2 s, respectively.ConclusionsThe pattern of Paw during an end-inspiratory occlusion in pressure support cannot assure the absence of expiratory muscle activity and accurate measurement of driving pressure. Yet, because driving pressure can only be overestimated due to expiratory muscle contraction, in everyday practice, a low driving pressure indicates an absence of global lung over-stretch. A measurement of high driving pressure should prompt further diagnostic workup, such as a measurement of esophageal pressure.

Inhibition of central activation of the diaphragm: a mechanism of weaning failure.

During a T-tube trial following disconnection of mechanical ventilation, patients failing the trial do not develop contractile diaphragmatic fatigue despite increases in inspiratory pressure output. Studies in volunteers, patients, and animals raise the possibility of spinal and supraspinal reflex mechanisms that inhibit central-neural output under loaded conditions. We hypothesized that diaphragmatic recruitment is submaximal at the end of a failed weaning trial despite concurrent respiratory distress. Tidal transdiaphragmatic pressure (ΔPdi) and electrical activity (ΔEAdi) were recorded with esophago-gastric catheters during a T-tube trial in 20 critically ill patients. During the T-tube trial, ∆EAdi was greater in weaning failure patients than in weaning success patients (P = 0.049). Despite increases in ΔPdi, from 18.1 ± 2.5 to 25.9 ± 3.7 cm H2O (P < 0.001), rate of transdiaphragmatic pressure development (from 22.6 ± 3.1 to 37.8 ± 6.7 cm H2O/s; P < 0.0004), and concurrent respiratory distress, ∆EAdi at the end of a failed T-tube trial was half of maximum, signifying inhibition of central neural output to the diaphragm. The increase in ΔPdi in the weaning failure group, while ∆EAdi remained constant, indicates unexpected improvement in diaphragmatic neuromuscular coupling (from 46.7 ± 6.5 to 57.8 ± 8.4 cm H2O/%; P = 0.006). Redistribution of neural output to the respiratory muscles characterized by a progressive increase in rib cage and accessory muscle contribution to tidal breathing and expiratory muscle recruitment contributed to enhanced coupling. In conclusion, diaphragmatic recruitment is submaximal at the end of a failed weaning trial despite concurrent respiratory distress. This finding signifies that reflex inhibition of central neural output to the diaphragm contributes to weaning failure.NEW & NOTEWORTHY Research into pathophysiology of failure to wean from mechanical ventilation has excluded several factors, including contractile fatigue, but the precise mechanism remains unknown. We recorded transdiaphragmatic pressure and diaphragmatic electrical activity in patients undergoing a T-tube trial. Diaphragmatic recruitment was submaximal at the end of a failed trial despite concurrent respiratory distress, signifying that inhibition of central neural output to the diaphragm is an important mechanism of weaning failure.

Inspiratory Muscle Fatigue Is Not Different In Response To Long Vs. Short-duration High-intensity Exercise

Maximal isokinetic power (PISO) at the limit of short duration (<6 min) high-intensity constant-power exercise (TlimSHORT) is not different from task power. Conversely, PISO at the limit of long duration (>7 min) high-intensity constant-power exercise (TlimLONG) exceeds task power. This suggests that while TlimSHORT is predominantly limited by locomotor neuromuscular fatigue, other physiological mechanisms contribute to exercise limitation in TlimLONG. One possibility for this difference in the mechanism of exercise intolerance is that the severity of exercise-induced inspiratory muscle fatigue is greater in TlimLONG vs. TlimSHORT due to a larger cumulative work of breathing in the longer-duration task. PURPOSE: To determine whether the magnitude of exercise-induced inspiratory muscle fatigue is greater in TlimLONG vs. TlimSHORT. METHODS: Ten healthy adults (3 females; 25 ± 3 yr) completed a maximal ramp-sprint test (RIT) to determine critical power (CP), V̇O2peak and peak ramp power (RITpeak). Maximal constant-power exercise was then performed at 1) 50% (TlimSHORT), and 2) 25 % (TlimLONG) of the difference between CP and RITpeak. PISO (6 s effort at 80 r/min) was measured at intolerance. Inspiratory muscle fatigue was assessed as the pre- to post-test reduction in magnetically evoked transdiaphragmatic (Pditw) twitch pressure. RESULTS: TlimLONG was longer than TlimSHORT (10.3 ± 2.6 vs. 5.2 ± 1.1 min; P < 0.001), but V̇O2peak was not different between tests (3.7 ± 0.8 vs. 3.7 ± 0.8 L/min; P > 0.05). PISO at intolerance was not different from task power in TlimSHORT (294 ± 101 vs. 241 ± 58 W; P = 0.11). Conversely, PISO at intolerance was greater than task power in TlimLONG (341 ± 106 vs. 215 ± 53 W; P = 0.008). Cumulative diaphragm pressure-time product was higher in TlimLONG vs. TlimSHORT (5945 ± 1956 vs. 2729 ± 1004 cmH2O/s; P < 0.001). Both TlimLONG and TlimSHORT induced a reduction in Pditw (-15 ± 13% vs. -19 ± 13%, respectively; P < 0.05). However, the magnitude of exercise-induced inspiratory muscle fatigue was not different between tests (P > 0.05). CONCLUSIONS: Despite PISO at intolerance being greater than task power in TlimLONG but not TlimSHORT, inspiratory muscle fatigue was not different between tests and therefore may not contribute to differences in exercise limitation in TlimLONG vs. TlimSHORT.

The Effect Of Exercise Intensity On The Development Of Diaphragm And Expiratory Abdominal Muscle Fatigue

Exhaustive high-intensity exercise (85-95% of V̇O2peak) elicits respiratory muscle fatigue, likely due to a high work of breathing (WoB) combined with a competition for available cardiac output (Q̇). However, the WoB associated with submaximal heavy-intensity exercise (≤75% V̇O2peak) makes insufficient demands for V̇O2 and Q̇ to engender a substantial competition for available blood flow. Whether the respiratory muscles fatigue in response to exhaustive heavy-intensity exercise remains unclear. PURPOSE: To investigate the effect of exercise intensity on the presence and severity of exercise-induced diaphragm and expiratory muscle fatigue in healthy humans. METHODS: Ten healthy adults (25 ± 3 y, 3 females) performed a ‘ramp sprint’ test to determine critical power (CP), peak ramp power (Ppeak) and V̇O2peak (54 ± 9 ml/kg/min). The subjects then performed two constant-power cycling tests to exhaustion: 1) 5% < CP (173 ± 50 W, heavy intensity); 2) ~25% of the difference between CP and Ppeak (215 ± 53 W, severe intensity). Diaphragm and expiratory muscle fatigue were quantified as the pre- to post-exercise reduction in the transdiaphragmatic (Pditw) and gastric (Pgatw) twitch pressure response to magnetic stimulation of the cervical and thoracic nerves, respectively. RESULTS: Exercise time was longer for heavy vs. severe exercise (36 ± 6 vs. 10 ± 3 min, P < 0.05). Final min V̇O2 was lower during heavy (3.12 ± 0.74 L/min; 82 ± 5% of V̇O2peak) vs. severe exercise (3.60 ± 0.83 L/min; 95 ± 4% of V̇O2peak) (P < 0.05). Both heavy and severe exercise elicited a significant reduction in Pditw (−13 ± 11% and -19 ± 13%) and Pgatw (−23 ± 20% vs. -24 ± 17%) (both P < 0.05); however, the magnitude of exercise-induced respiratory muscle fatigue was not different between trials (P > 0.05). The cumulative diaphragm and gastric pressure-time products were greater for heavy vs. severe exercise (PTPdi: 16790 ± 6727 vs. 5945 ± 1956 cmH2O/s; PTPga: 7818 ± 3368 vs. 2595 ± 1233 cmH2O/s; both P < 0.05). CONCLUSION: The diaphragm and expiratory muscles fatigue in response to exhaustive heavy- and severe-intensity exercise in healthy humans. The magnitude of exercise-induced respiratory muscle fatigue between trials was not different despite a substantially greater cumulative PTPdi and PTPga for heavy- vs. severe-intensity exercise.

Deterioration of Nighttime Respiratory Mechanics in COPD: Impact of Bronchodilator Therapy

COPD is associated with nighttime respiratory symptoms, poor sleep quality, and increased risk of nocturnal death. Overnight deterioration of inspiratory capacity (IC) and FEV1 have been documented previously. However, the precise nature of this deterioration and mechanisms by which evening bronchodilation may mitigate this occurrence have not been studied. What is the effect of evening dosing of dual, long-acting bronchodilation on detailed nocturnal respiratory mechanics and inspiratory neural drive (IND)? A double-blind, randomized, placebo-controlled crossover study assessed the effects of evening long-acting bronchodilation (aclidinium bromide/formoterol fumarate dihydrate: 400/12 μg) or placebo on morning trough IC (12h after the dose; primary outcome) and serial overnight measurements of spirometry, dynamic respiratory mechanics, and IND (secondary outcomes). Twenty participants with COPD (moderate/severe airway obstruction and lung hyperinflation) underwent serial measurements of IC, spirometry, breathing pattern, esophageal and transdiaphragmatic pressures, and diaphragm electromyography (diaphragmatic electromyography as a percentage of maximum; IND) at 6 time points from 0 to 12h after the dose and compared with sleeping IND. Compared with placebo, evening bronchodilation was not associated with increased morning trough IC 12h after the dose (P= .48); however, nadir IC (lowest IC, independent of time), peak IC, area under the curve for 12h after the dose, and IC for 10h after the dose were improved (P< .05). During placebo, total airways resistance, lung hyperinflation, IND, and tidal esophageal and transdiaphragmatic pressure swings all increased significantly overnight compared with baseline evening values; however, each of these parameters improved with bronchodilator treatment (P< .05) with no change in ventilation or breathing pattern. Respiratory mechanics significantly deteriorated at night during placebo. Although the morning trough IC was unchanged, evening bronchodilator treatment was associated consistently with sustained overnight improvements in dynamic respiratory mechanics and inspiratory neural drive compared with placebo CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02429765.

Inspiratory flow-resistive breathing, respiratory muscle-induced systemic oxidative stress, and diaphragm fatigue in healthy humans.

We questioned whether the respiratory muscles of humans contribute to systemic oxidative stress following inspiratory flow-resistive breathing, whether the amount of oxidative stress is influenced by the level of resistive load, and whether the amount of oxidative stress is related to the degree of diaphragm fatigue incurred. Eight young and healthy participants attended the laboratory for four visits on separate days. During the first visit, height, body mass, lung function, and maximal inspiratory mouth and transdiaphragmatic pressure (Pdimax) were assessed. During visits 2-4, participants undertook inspiratory flow-resistive breathing with either no resistance (control) or resistive loads equivalent to 50 and 70% of their Pdimax (Pdimax50% and Pdimax70%) for 30 min. Participants undertook one resistive load per visit, and the order in which they undertook the loads was randomized. Inspiratory muscle pressures were higher (P < 0.05) during the 5th and Final min of Pdimax50% and Pdimax70% compared with control. Plasma F2-isoprostanes increased (P < 0.05) following inspiratory flow-resistive breathing at Pdimax70%. There were no increases in plasma protein carbonyls or total antioxidant capacity. Furthermore, although we evidenced small reductions in transdiapragmaic twitch pressures (PdiTW) after inspiratory flow-resistive breathing at Pdimax50% and Pdimax70%, this was not related to the increase in plasma F2-isoprostanes. Our novel data suggest that it is only when sufficiently strenuous that inspiratory flow-resistive breathing in humans elicits systemic oxidative stress evidenced by elevated plasma F2-isoprostanes, and based on our data, this is not related to a reduction in PdiTW.NEW & NOTEWORTHY We examined whether the respiratory muscles of humans contribute to systemic oxidative stress following inspiratory flow-resistive breathing, whether the amount of oxidative stress is influenced by the level of resistive load, and whether the amount of oxidative stress is related to the degree of diaphragm fatigue incurred. It is only when sufficiently strenuous that inspiratory flow-resistive breathing elevates plasma F2-isoprostanes, and our novel data show that this is not related to a reduction in transdiaphragmatic twitch pressure.

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.

Oesophageal pressure and respiratory muscle ultrasonographic measurements indicate inspiratory effort during pressure support ventilation

BackgroundBedside measures of patient effort are essential to properly titrate the level of pressure support ventilation. We investigated whether the tidal swing in oesophageal (ΔPes) and transdiaphragmatic pressure (ΔPdi), and ultrasonographic changes in diaphragm (TFdi) and parasternal intercostal (TFic) thickening are reliable estimates of respiratory effort. The effect of diaphragm dysfunction was also considered. MethodsTwenty-one critically ill patients were enrolled: age 73 (14) yr, BMI 27 (7) kg m−2, and Pao2/Fio2 33.3 (9.2) kPa. A three-level pressure support trial was performed: baseline, 25% (PS-medium), and 50% reduction (PS-low). We recorded the oesophageal and transdiaphragmatic pressure–time products (PTPs), work of breathing (WOB), and diaphragm and intercostal ultrasonography. Diaphragm dysfunction was defined by the Gilbert index. ResultsPressure support was 9.0 (1.6) cm H2O at baseline, 6.7 (1.3) (PS-medium), and 4.4 (1.0) (PS-low). ΔPes was significantly associated with the oesophageal PTP (R2=0.868; P<0.001) and the WOB (R2=0.683; P<0.001). ΔPdi was significantly associated with the transdiaphragmatic PTP (R2=0.820; P<0.001). TFdi was only weakly correlated with the oesophageal PTP (R2=0.326; P<0.001), and the correlation improved after excluding patients with diaphragm dysfunction (R2=0.887; P<0.001). TFdi was higher and TFic lower in patients without diaphragm dysfunction: 33.6 (18.2)% vs 13.2 (9.2)% and 2.1 (1.7)% vs 12.7 (9.1)%; P<0.0001. ConclusionsΔPes and ΔPdi are adequate estimates of inspiratory effort. Diaphragm ultrasonography is a reliable indicator of inspiratory effort in the absence of diaphragm dysfunction. Additional measurement of parasternal intercostal thickening may discriminate a low inspiratory effort or a high effort in the presence of a dysfunctional diaphragm.

ICU outcomes can be predicted by noninvasive muscle evaluation: a meta-analysis

The relationship between muscle function in critically ill patients assessed using bedside techniques and clinical outcomes has not been systematically described. We aimed to evaluate the association between muscle weakness assessed by bedside evaluation and mortality or weaning from mechanical ventilation, and the capacity of each evaluation tool to predict outcomes. Five databases (PubMed, Embase, CINAHL, Cochrane Library, Science Direct) were searched from January 2000 to December 2018. Data were extracted and random effects meta-analyses were performed. 60 studies were analysed, including 4382 patients. Intensive care unit (ICU)-related muscle weakness was associated with an increase in overall mortality with odds ratios ranging from 1.2 (95% CI 0.60-2.40) to 4.48 (95% CI 1.49-13.42). Transdiaphragmatic twitch pressure had the highest predictive capacity for overall mortality, with a sensitivity of 0.87 (95% CI 0.76-0.93) and a specificity of 0.36 (95% CI 0.27-0.43). The area under the curve (AUC) was 0.74 (95% CI 0.70-0.78). Muscle weakness was associated with an increase in mechanical ventilation weaning failure rate with an odds ratio ranging from 2.64 (95% CI 0.72-9.64) to 19.07 (95% CI 9.35-38.9). Diaphragm thickening fraction had the highest predictive capacity for weaning failure with a sensitivity of 0.76 (95% CI 0.67-0.83) and a specificity of 0.86 (95% CI 0.78-0.92). The AUC was 0.86 (95% CI 0.83-0.89). ICU-related muscle weakness detected by bedside techniques is a serious issue associated with a high risk of death or prolonged mechanical ventilation. Evaluating diaphragm function should be a clinical priority in the ICU.