Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

BACKGROUND: Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100 ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. METHODS: Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. RESULTS: We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). CONCLUSIONS: In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. TRIAL REGISTRATION: NCT03266016; August 23, 2017.

Advanced waveform analysis of diaphragm surface EMG allows for continuous non-invasive assessment of respiratory effort in critically ill patients at different PEEP levels.

BACKGROUND: Respiratory effort should be closely monitored in mechanically ventilated ICU patients to avoid both overassistance and underassistance. Surface electromyography of the diaphragm (sEMGdi) offers a continuous and non-invasive modality to assess respiratory effort based on neuromuscular coupling (NMCdi). The sEMGdi derived electrical activity of the diaphragm (sEAdi) is prone to distortion by crosstalk from other muscles including the heart, hindering its widespread use in clinical practice. We developed an advanced analysis as well as quality criteria for sEAdi waveforms and investigated the effects of clinically relevant levels of PEEP on non-invasive NMCdi. METHODS: NMCdi was derived by dividing end-expiratory occlusion pressure (Pocc) by sEAdi, based on three consecutive Pocc manoeuvres at four incremental (+ 2 cmH2O/step) PEEP levels in stable ICU patients on pressure support ventilation. Pocc and sEAdi quality was assessed by applying a novel, automated advanced signal analysis, based on tolerant and strict cut-off criteria, and excluding inadequate waveforms. The coefficient of variations (CoV) of NMCdi after basic manual and automated advanced quality assessment were evaluated, as well as the effect of an incremental PEEP trial on NMCdi. RESULTS: 593 manoeuvres were obtained from 42 PEEP trials in 17 ICU patients. Waveform exclusion was primarily based on low sEAdi signal-to-noise ratio (Ntolerant = 155, 37%, Nstrict = 241, 51% waveforms excluded), irregular or abrupt cessation of Pocc (Ntolerant = 145, 35%, Nstrict = 145, 31%), and high sEAdi area under the baseline (Ntolerant = 94, 23%, Nstrict = 79, 17%). Strict automated assessment allowed to reduce CoV of NMCdi to 15% from 37% for basic quality assessment. As PEEP was increased, NMCdi decreased significantly by 4.9 percentage point per cmH2O. CONCLUSION: Advanced signal analysis of both Pocc and sEAdi greatly facilitates automated and well-defined identification of high-quality waveforms. In the critically ill, this approach allowed to demonstrate a dynamic NMCdi (Pocc/sEAdi) decrease upon PEEP increments, emphasising that sEAdi-based assessment of respiratory effort should be related to PEEP dependent diaphragm function. This novel, non-invasive methodology forms an important methodological foundation for more robust, continuous, and comprehensive assessment of respiratory effort at the bedside.

A novel positive end-expiratory pressure titration using electrical impedance tomography in spontaneously breathing acute respiratory distress syndrome patients on mechanical ventilation: an observational study from the MaastrICCht cohort.

There is no universally accepted method for positive end expiratory pressure (PEEP) titration approach for patients on spontaneous mechanical ventilation (SMV). Electrical impedance tomography (EIT) guided PEEP-titration has shown promising results in controlled mechanical ventilation (CMV), current implemented algorithm for PEEP titration (based on regional compliance measurements) is not applicable in SMV. Regional peak flow (RPF, defined as the highest inspiratory flow rate based on EIT at a certain PEEP level) is a new method for quantifying regional lung mechanics designed for SMV. The objective is to study whether RPF by EIT is a feasible method for PEEP titration during SMV. Single EIT measurements were performed in COVID-19 ARDS patients on SMV. Clinical (i.e., tidal volume, airway occlusion pressure, end-tidal CO2) and mechanical (cyclic alveolar recruitment, recruitment, cumulative overdistension (OD), cumulative collapse (CL), pendelluft, and PEEP) outcomes were determined by EIT at several pre-defined PEEP thresholds (1-10% CL and the intersection of the OD and CL curves) and outcomes at all thresholds were compared to the outcomes at baseline PEEP. In total, 25 patients were included. No significant and clinically relevant differences were found between thresholds for tidal volume, end-tidal CO2, and P0.1 compared to baseline PEEP; cyclic alveolar recruitment rates changed by -3.9% to -37.9% across thresholds; recruitment rates ranged from - 49.4% to + 79.2%; cumulative overdistension changed from - 75.9% to + 373.4% across thresholds; cumulative collapse changed from 0% to -94.3%; PEEP levels from 10 up to 14 cmH2O were observed across thresholds compared to baseline PEEP of 10 cmH2O. A threshold of approximately 5% cumulative collapse yields the optimum compromise between all clinical and mechanical outcomes. EIT-guided PEEP titration by the RPF approach is feasible and is linked to improved overall lung mechanics) during SMV using a threshold of approximately 5% CL. However, the long-term clinical safety and effect of this approach remain to be determined.

Impairment of Inspiratory Muscle Function after COVID-19.

BACKGROUND: Persistent symptoms after acute coronavirus-disease-2019 (COVID-19) are common, and there is no significant correlation with the severity of the acute disease. In long-COVID (persistent symptoms >4 weeks after acute COVID-19), respiratory symptoms are frequent, but lung function testing shows only mild changes that do not explain the symptoms. Although COVID-19 may lead to an impairment of the peripheral nervous system and skeletal muscles, respiratory muscle function has not been examined in this setting. METHODS: In this study, we assessed the severity of dyspnea (NYHA-function class) in long-COVID patients and analyzed its association with body mass index (BMI), FEV1, forced vital capacity, other parameters of body plethysmography, diffusing capacity for carbon monoxide (DLCO), arterial blood gases, and inspiratory muscle function, assessed by airway occlusion pressure (P0.1) and maximal inspiratory pressure (PImax) in two respiratory clinics in Germany between Oct 2020 and Aug 2021. RESULTS: A total of 116 patients were included in the study. The mean age was 50.2 ± 14.5 years; BMI, 26.7 ± 5.87 kg/m2; NYHA class I, 19%; II, 27%; III, 41%; and IV, 14%. While lung function values and computed tomography or conventional X-ray of the chest were in the normal range, inspiratory muscle function was markedly impaired. P01 was elevated to 154 ± 83%predicted and PImax was reduced to 41 ± 25%predicted. PImax reduction was strongly associated with the severity of dyspnea but independent of BMI, time after acute COVID-19 and most of the other parameters. CONCLUSIONS: This study shows that in long-COVID patients, respiratory symptoms may be mainly caused by reduced inspiratory muscle strength. Assessment of PImax and P0.1 might better explain dyspnea than classical lung function tests and DLCO. A prospective study is needed to confirm these results.

Airway Occlusion Pressure As an Estimate of Respiratory Drive and Inspiratory Effort during Assisted Ventilation.

Rationale: Monitoring and controlling respiratory drive and effort may help to minimize lung and diaphragm injury. Airway occlusion pressure (P0.1) is a noninvasive measure of respiratory drive.Objectives: To determine 1) the validity of "ventilator" P0.1 (P0.1vent) displayed on the screen as a measure of drive, 2) the ability of P0.1 to detect potentially injurious levels of effort, and 3) how P0.1vent displayed by different ventilators compares to a "reference" P0.1 (P0.1ref) measured from airway pressure recording during an occlusion.Methods: Analysis of three studies in patients, one in healthy subjects, under assisted ventilation, and a bench study with six ventilators. P0.1vent was validated against measures of drive (electrical activity of the diaphragm and muscular pressure over time) and P0.1ref. Performance of P0.1ref and P0.1vent to detect predefined potentially injurious effort was tested using derivation and validation datasets using esophageal pressure-time product as the reference standard.Measurements and Main Results: P0.1vent correlated well with measures of drive and with the esophageal pressure-time product (within-subjects R2 = 0.8). P0.1ref >3.5 cm H2O was 80% sensitive and 77% specific for detecting high effort (≥200 cm H2O ⋅ s ⋅ min-1); P0.1ref ≤1.0 cm H2O was 100% sensitive and 92% specific for low effort (≤50 cm H2O ⋅ s ⋅ min-1). The area under the receiver operating characteristics curve for P0.1vent to detect potentially high and low effort were 0.81 and 0.92, respectively. Bench experiments showed a low mean bias for P0.1vent compared with P0.1ref for most ventilators but precision varied; in patients, precision was lower. Ventilators estimating P0.1vent without occlusions could underestimate P0.1ref.Conclusions: P0.1 is a reliable bedside tool to assess respiratory drive and detect potentially injurious inspiratory effort.

Changes in diaphragm thickness and 6-min walking distance improvement after inspiratory muscle training in patients with chronic obstructive pulmonary disease: Clinical trial.

Aim: Inspiratory muscle training (IMT) improves respiratory muscle function and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD), but the detailed mechanism is unclear. The purpose of this study is to elucidate the mechanism of functional improvement by IMT from P0.1, an index of respiratory central output, and thickness of diaphragm (Tdi), a noninvasive and reliable ultrasound examination. Methods: This clinical trial study enrolled 13 elderly patients with COPD. IMT was performed using the POWER breathe® Medic Plus breathing trainer in combination with each participant's outpatient rehabilitation regimen. Starting at 20% of the maximal inspiratory pressure (PImax) and increasing to 50%, the participants performed 30 IMT repetitions twice a day for 2 months. P0.1 is the value of airway-occlusion pressure at 0.1 s after the start of inspiratory flow, and Tdi was measured at rest and maximal breathing. Results: PImax and 6-min walking distance(6MWD) significantly increased after training. Tdi at resting inspiration and expiration, and maximal inspiration also significantly increased after training. In addition, the Borg Scale scores for dyspnea and leg fatigue and the respiratory rate of the 1-min recovery period after the 6MWD significantly decreased. There was no significant difference in P0.1. Conclusions: These results suggest that the effects of IMT may be attributed to the improved peripheral factors rather than to the central factors in elderly COPD patients.

Bias and Precision of Continuous P0.1 Measurement by Various Ventilators: A Simulation Study.

BACKGROUND: Most ventilators measure airway occlusion pressure (occlusion P0.1) by occluding the breathing circuit; however, some ventilators can predict P0.1 for each breath without occlusion. Nevertheless, few studies have verified the accuracy of continuous P0.1 measurement. The aim of this study was to evaluate the accuracy of continuous P0.1 measurement compared with that of occlusion methods for various ventilators using a lung simulator. METHODS: A total of 42 breathing patterns were validated using a lung simulator in combination with 7 different inspiratory muscular pressures and 3 different rise rates to simulate normal and obstructed lungs. PB980 and Dräger V500 ventilators were used to obtain occlusion P0.1 measurements. The occlusion maneuver was performed on the ventilator, and a corresponding reference P0.1 was recorded from the ASL5000 breathing simulator simultaneously. Hamilton-C6, Hamilton-G5, and Servo-U ventilators were used to obtain sustained P0.1 measurements (continuous P0.1). The reference P0.1 measured with the simulator was analyzed by using a Bland-Altman plot. RESULTS: The 2 lung mechanical models capable of measuring occlusion P0.1 yielded values equivalent to reference P0.1 (bias and precision values were 0.51 and 1.06, respectively, for the Dräger V500, and were 0.54 and 0.91, respectively, for the PB980). Continuous P0.1 for the Hamilton-C6 was underestimated in both the normal and obstructive models (bias and precision values were -2.13 and 1.91, respectively), whereas continuous P0.1 for the Servo-U was underestimated only in the obstructive model (bias and precision values were -0.86 and 1.76, respectively). Continuous P0.1 for the Hamilton-G5 was mostly similar to but less accurate than occlusion P0.1 (bias and precision values were 1.62 and 2.06, respectively). CONCLUSIONS: The accuracy of continuous P0.1 measurements varies based on the characteristics of the ventilator and should be interpreted by considering the characteristics of each system. Moreover, measurements obtained with an occluded circuit could be desirable for determining the true P0.1.

The predictive value of airway occlusion pressure at 100 msec (P0.1) on successful weaning from mechanical ventilation: A systematic review and meta-analysis.

PURPOSE: The predictive value of airway occlusion pressure at 100 milliseconds (P0.1) on weaning outcome has been controversial. We performed a meta-analysis to investigate the predictive value of P0.1 on successful weaning from mechanical ventilation. MATERIALS AND METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE, and two authors independently screened articles. The pooled sensitivity, specificity and the summary receiver operating characteristic (sROC) curve were estimated. Diagnostic odds ratio (DOR) was calculated using meta-regression analysis. RESULTS: We included 12 prospective observational studies (n = 1089 patients). Analyses of sROC curves showed the area under the curve of 0.81 (95% confidence interval (CI): 0.77 to 0.84) for P0.1. The pooled sensitivity and specificity were 86% (95% CI, 72 to 94%) and 58% (95% CI, 37% to 76%) with substantial heterogeneity respectively. DOR was 20.09 (p = 0.019, 95%CI: 1.63-247.15). After filling the missing data using the trim-and-fill method to adjust publication bias, DOR was 36.23 (p = 0.002, 95%CI: 3.56-372.41). CONCLUSION: This meta-analysis suggests that P0.1 is a useful tool to predict successful weaning. To determine clinical utility, a large prospective study investigating the sensitivity and specificity of P0.1 on weaning outcomes from mechanical ventilation is warranted.

The Relationship Between Airway Occlusion Pressure and Severity of liver Cirrhosis in Candidates for Liver Transplantation.

BACKGROUND End-stage cirrhosis is an irreversible condition, and liver transplantation is the only treatment option in for the affected patients. Respiratory problems and abnormal breathing are common findings among these patients. In this study, for the first time, we examined the relationship between the severity of liver cirrhosis and respiratory drive measured by mouth occlusion pressure (P0.1). METHODS This was a cross-sectional study conducted on 50 candidates for liver transplantation who were referred to the pulmonary clinic of Imam Khomeini Hospital for pre-operative pulmonary evaluations. Arterial blood gas analysis (ABG), pulmonary function tests, and measurement of P0.1 were performed for all patients. The severity of liver disease was assessed using the Model for End-Stage Liver Disease (MELD) score. RESULTS The median P0.1 was 5 cm H2 O. P0.1 was negatively associated with PaCO2 (r = -0.466, p = 0.001) and HCO3 - (r = -0.384, p = 0.007), and was positively correlated with forced expiratory volume at 1s (FEV1 )/ forced vital capacity (FVC) (r = 0.282, p = 0.047). There was a strong correlation between P0.1 and MELD score (r = 0.750, p < 0.001). Backward multivariate linear regression revealed that a higher MELD score and lower PaCO2 were associated with increased P0.1. CONCLUSION High levels of P0.1 and strong direct correlation between P0.1 and MELD score observed in the present study are suggestive of the presence of abnormal increased respiratory drive in candidates for liver transplantation, which is closely related to their disease severity.