Airway Occlusion Pressure Research Articles

Monitoring and modulating respiratory drive in mechanically ventilated patients.

Respiratory drive is frequently deranged in the ICU, being associated with adverse clinical outcomes. Monitoring and modulating respiratory drive to prevent potentially injurious consequences merits attention. This review gives a general overview of the available monitoring tools and interventions to modulate drive. Airway occlusion pressure (P0.1) is an excellent measure of drive and is displayed on ventilators. Respiratory drive can also be estimated based on the electrical activity of respiratory muscles and measures of respiratory effort; however, high respiratory drive might be present in the context of low effort with neuromuscular weakness. Modulating a deranged drive requires a multifaceted intervention, prioritizing treatment of the underlying cause and adjusting ventilator settings for comfort. Additional tools include changes in PEEP, peak inspiratory flow, fraction of inspired oxygen, and sweep gas flow (in patients receiving extracorporeal life-support). Sedatives and opioids have differential effects on drive according to drug category. Monitoring response to any intervention is warranted and modulating drive should not preclude readiness to wean assessment or delay ventilation liberation. Monitoring and modulating respiratory drive are feasible based on physiological principles presented in this review. However, evidence arising from clinical trials will help determine precise thresholds and optimal interventions.

Propofol and Fentanyl Pharmacokinetics and Pharmacodynamics in Extracorporeal Membrane Oxygenation.

Despite the potential risks associated with sedation, there is a paucity of pharmacokinetic/pharmacodynamic (PK/PD) data for propofol and fentanyl in patients supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO). Describe propofol and fentanyl PK/PD profiles in V-V ECMO patients. Prospective, single-center, open-label PK/PD study at the Toronto General Hospital ICU between July 2022 and January 2023. Using high-performance liquid chromatography-tandem mass spectrometry, propofol and fentanyl total concentrations were measured during V-V ECMO. Sequential PK/PD modeling, using sex as a covariate, was conducted with processed electroencephalography (PSI) for sedation, and expiratory occlusion pressure (Pocc), and airway occlusion pressure during the first 0.1 seconds (P0.1) for respiratory effort. Eleven patients underwent 106 evaluations over a median (IQR) follow-up of 146 (116-146) hours. Patient's average (±SD) age was 43 (±13) years, and 55% were female. Propofol and fentanyl PK were best described by a two-compartment model. Propofol-PSI PD was described using an effect compartment, with a coefficient of determination (ρ2) of 0.78. There was a significant increase in propofol (p=0.01) and fentanyl (p=0.03) clearance within 10 minutes of ECMO initiation, plateauing after 8 hours of ECMO support. Despite this, patient over-sedation (PSI<40) occurred in 74% of the observations. Females exhibited higher sedative central volume of distribution and lower propofol clearance. ECMO initiation resulted in a time-limited increased sedative clearance. PSI accurately described sedative PD, but variable respiratory effort was observed irrespective of sedative plasma concentrations. Sex-based differences were found in sedative PK/PD parameters.

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

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 100ms 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. 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. 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). 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. NCT03266016; August 23, 2017.

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.

The effects of real-time waveform analysis software on patient ventilator synchronization during pressure support ventilation: a randomized crossover physiological study

BackgroundPatient-ventilator asynchrony commonly occurs during pressure support ventilation (PSV). IntelliSync + software (Hamilton Medical AG, Bonaduz, Switzerland) is a new ventilation technology that continuously analyzes ventilator waveforms to detect the beginning and end of patient inspiration in real time. This study aimed to evaluate the physiological effect of IntelliSync + software on inspiratory trigger delay time, delta airway (Paw) and esophageal (Pes) pressure drop during the trigger phase, airway occlusion pressure at 0.1 s (P0.1), and hemodynamic variables.MethodsA randomized crossover physiologic study was conducted in 14 mechanically ventilated patients under PSV. Patients were randomly assigned to receive conventional flow trigger and cycling, inspiratory trigger synchronization (I-sync), cycle synchronization (C-sync), and inspiratory trigger and cycle synchronization (I/C-sync) for 15 min at each step. Other ventilator settings were kept constant. Paw, Pes, airflow, P0.1, respiratory rate, SpO2, and hemodynamic variables were recorded. The primary outcome was inspiratory trigger and cycle delay time between each intervention. Secondary outcomes were delta Paw and Pes drop during the trigger phase, P0.1, SpO2, and hemodynamic variables.ResultsThe time to initiate the trigger was significantly shorter with I-sync compared to baseline (208.9±91.7 vs. 301.4±131.7 msec; P = 0.002) and I/C-sync compared to baseline (222.8±94.0 vs. 301.4±131.7 msec; P = 0.005). The I/C-sync group had significantly lower delta Paw and Pes drop during the trigger phase compared to C-sync group (-0.7±0.4 vs. -1.2±0.8 cmH2O; P = 0.028 and − 1.8±2.2 vs. -2.8±3.2 cmH2O; P = 0.011, respectively). No statistically significant differences were found in cycle delay time, P0.1 and other physiological variables between the groups.ConclusionsIntelliSync + software reduced inspiratory trigger delay time compared to the conventional flow trigger system during PSV mode. However, no significant improvements in cycle delay time and other physiological variables were observed with IntelliSync + software.Trial registrationThis study was registered in the Thai Clinical Trial Registry (TCTR20200528003; date of registration 28/05/2020).

Accuracy of respiratory muscle assessments to predict weaning outcomes: a systematic review and comparative meta-analysis

BackgroundSeveral bedside assessments are used to evaluate respiratory muscle function and to predict weaning from mechanical ventilation in patients on the intensive care unit. It remains unclear which assessments perform best in predicting weaning success. The primary aim of this systematic review and meta-analysis was to summarize and compare the accuracy of the following assessments to predict weaning success: maximal inspiratory (PImax) and expiratory pressures, diaphragm thickening fraction and excursion (DTF and DE), end-expiratory (Tdiee) and end-inspiratory (Tdiei) diaphragm thickness, airway occlusion pressure (P0.1), electrical activity of respiratory muscles, and volitional and non-volitional assessments of transdiaphragmatic and airway opening pressures.MethodsMedline (via Pubmed), EMBASE, Web of Science, Cochrane Library and CINAHL were comprehensively searched from inception to 04/05/2023. Studies including adult mechanically ventilated patients reporting data on predictive accuracy were included. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate the SROC curves of each assessment method. Meta-regression was used to compare SROC curves. Sensitivity analyses were conducted by excluding studies with high risk of bias, as assessed with QUADAS-2. Direct comparisons were performed using studies comparing each pair of assessments within the same sample of patients.ResultsNinety-four studies were identified of which 88 studies (n = 6296) reporting on either PImax, DTF, DE, Tdiee, Tdiei and P0.1 were included in the meta-analyses. The sensitivity to predict weaning success was 63% (95% CI 47–77%) for PImax, 75% (95% CI 67–82%) for DE, 77% (95% CI 61–87%) for DTF, 74% (95% CI 40–93%) for P0.1, 69% (95% CI 13–97%) for Tdiei, 37% (95% CI 13–70%) for Tdiee, at fixed 80% specificity. Accuracy of DE and DTF to predict weaning success was significantly higher when compared to PImax (p = 0.04 and p < 0.01, respectively). Sensitivity and direct comparisons analyses showed that the accuracy of DTF to predict weaning success was significantly higher when compared to DE (p < 0.01).ConclusionsDTF and DE are superior to PImax and DTF seems to have the highest accuracy among all included respiratory muscle assessments for predicting weaning success. Further studies aiming at identifying the optimal threshold of DTF to predict weaning success are warranted.Trial registration: PROSPERO CRD42020209295, October 15, 2020.

High Airway Occlusion Pressure Is Associated with Dyspnea and Increased Mortality in Critically Ill Mechanically Ventilated Patients.

Rationale: Airway occlusion pressure at 100 ms (P0.1) reflects central respiratory drive. Objectives: We aimed to assess factors associated with P0.1 and whether an abnormally low or high P0.1 value is associated with higher mortality and longer duration of mechanical ventilation (MV). Methods: We performed a secondary analysis of a prospective cohort study conducted in 10 ICUs in France to evaluate dyspnea in communicative MV patients. In patients intubated for more than 24 hours, P0.1 was measured with dyspnea as soon as patients could communicate and the next day. Measurements and Main Results: Among 260 patients assessed after a median time of ventilation of 4 days, P0.1 was 1.9 (1-3.5) cm H2O at enrollment, 24% had P0.1 values >3.5 cm H2O, 37% had P0.1 values between 1.5 and 3.5 cm H2O, and 39% had P0.1 values <1.5 cm H2O. In multivariable linear regression, independent factors associated with P0.1 were the presence of dyspnea (P = 0.037), respiratory rate (P < 0.001), and PaO2 (P = 0.008). Ninety-day mortality was 33% in patients with P0.1 > 3.5 cm H2O versus 19% in those with P0.1 between 1.5 and 3.5 cm H2O and 17% in those with P0.1 < 1.5 cm H2O (P = 0.046). After adjustment for the main risk factors, P0.1 was associated with 90-day mortality (hazard ratio per 1 cm H2O, 1.19 [95% confidence interval, 1.04-1.37]; P = 0.011). P0.1 was also independently associated with a longer duration of MV (hazard ratio per 1 cm H2O, 1.10 [95% confidence interval, 1.02-1.19]; P = 0.016). Conclusions: In patients receiving invasive MV, abnormally high P0.1 values may suggest dyspnea and are associated with higher mortality and prolonged duration of MV.

Estimation of inspiratory effort using airway occlusion maneuvers in ventilated children: a secondary analysis of an ongoing randomized trial testing a lung and diaphragm protective ventilation strategy

BackgroundMonitoring respiratory effort in ventilated patients is important to balance lung and diaphragm protection. Esophageal manometry remains the gold standard for monitoring respiratory effort but is invasive and requires expertise for its measurement and interpretation. Airway pressures during occlusion maneuvers may provide an alternative, although pediatric data are limited. We sought to determine the correlation between change in esophageal pressure during tidal breathing (∆Pes) and airway pressure measured during three airway occlusion maneuvers: (1) expiratory occlusion pressure (Pocc), (2) airway occlusion pressure (P0.1), and (3) respiratory muscle pressure index (PMI) in children. We also sought to explore pediatric threshold values for these pressures to detect excessive or insufficient respiratory effort.MethodsSecondary analysis of physiologic data from children between 1 month and 18 years of age with acute respiratory distress syndrome enrolled in an ongoing randomized clinical trial testing a lung and diaphragm protective ventilation strategy (REDvent, R01HL124666). ∆Pes, Pocc, P0.1, and PMI were measured. Repeated measure correlations were used to investigate correlation coefficients between ∆Pes and the three measures, and linear regression equations were generated to identify potential therapeutic thresholds.ResultsThere were 653 inspiratory and 713 expiratory holds from 97 patients. Pocc had the strongest correlation with ∆Pes (r = 0.68), followed by PMI (r = 0.60) and P0.1 (r = 0.42). ∆Pes could be reliably estimated using the regression equation ∆Pes = 0.66 times Pocc (R2 = 0.82), with Pocc cut-points having high specificity and moderate sensitivity to detect respective ∆Pes thresholds for high and low respiratory effort. There were minimal differences in the relationship between Pocc and ∆Pes based on age (infant, child, adolescent) or mode of ventilation (SIMV versus Pressure Support), although these differences were more apparent with P0.1 and PMI.ConclusionsAirway occlusion maneuvers may be appropriate alternatives to esophageal pressure measurement to estimate the inspiratory effort in children, and Pocc represents the most promising target.Trial registration: NCT03266016; August 23, 2017.

Sensory interventions to relieve dyspnoea in critically ill mechanically ventilated patients.

In critically ill patients receiving mechanical ventilation, dyspnoea is frequent, severe and associated with an increased risk of neuropsychological sequelae. We evaluated the efficacy of sensory interventions targeting the brain rather than the respiratory system to relieve dyspnoea in mechanically ventilated patients. Patients receiving mechanical ventilation for ≥48 h and reporting dyspnoea (unidimensional dyspnoea visual analogue scale (Dyspnoea-VAS)) first underwent increased pressure support and then, in random order, auditory stimulation (relaxing music versus pink noise) and air flux stimulation (facial versus lower limb). Treatment responses were assessed using Dyspnoea-VAS, the Multidimensional Dyspnea Profile and measures of the neural drive to breathe (airway occlusion pressure (P 0.1) and electromyography of inspiratory muscles). We included 46 patients (tracheotomy or intubation n=37; noninvasive ventilation n=9). Increasing pressure support decreased Dyspnoea-VAS by median 40 mm (p<0.001). Exposure to music decreased Dyspnoea-VAS compared with exposure to pink noise by median 40 mm (p<0.001). Exposure to facial air flux decreased Dyspnoea-VAS compared with limb air flux by median 30 mm (p<0.001). Increasing pressure support, but not music exposure and facial air flux, reduced P 0.1 by median 3.3 cmH2O (p<0.001). In mechanically ventilated patients, sensory interventions can modulate the processing of respiratory signals by the brain irrespective of the intensity of the neural drive to breathe. It should therefore be possible to alleviate dyspnoea without resorting to pharmacological interventions or having to infringe the constraints of mechanical ventilation lung protection strategies by increasing ventilatory support.

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

AimInspiratory 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. MethodsThis 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. ResultsPImax 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. ConclusionsThese 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.

Inspiratory effort impacts the accuracy of pulse pressure variations for fluid responsiveness prediction in mechanically ventilated patients with spontaneous breathing activity: a prospective cohort study

BackgroundPulse pressure variation (PPV) is unreliable in predicting fluid responsiveness (FR) in patients receiving mechanical ventilation with spontaneous breathing activity. Whether PPV can be valuable for predicting FR in patients with low inspiratory effort is unknown. We aimed to investigate whether PPV can be valuable in patients with low inspiratory effort.MethodsThis prospective study was conducted in an intensive care unit at a university hospital and included acute circulatory failure patients receiving volume-controlled ventilation with spontaneous breathing activity. Hemodynamic measurements were collected before and after a fluid challenge. The degree of inspiratory effort was assessed using airway occlusion pressure (P0.1) and airway pressure swing during a whole breath occlusion (ΔPocc) before fluid challenge. Patients were classified as fluid responders if their cardiac output increased by ≥ 10%. Areas under receiver operating characteristic (AUROC) curves and gray zone approach were used to assess the predictive performance of PPV.ResultsAmong the 189 included patients, 53 (28.0%) were defined as responders. A PPV > 9.5% enabled to predict FR with an AUROC of 0.79 (0.67–0.83) in the whole population. The predictive performance of PPV differed significantly in groups stratified by the median value of P0.1 (P0.1 < 1.5 cmH2O and P0.1 ≥ 1.5 cmH2O), but not in groups stratified by the median value of ΔPocc (ΔPocc < − 9.8 cmH2O and ΔPocc ≥ − 9.8 cmH2O). Specifically, in patients with P0.1 < 1.5 cmH2O, PPV was associated with an AUROC of 0.90 (0.82–0.99) compared with 0.68 (0.57–0.79) otherwise (p = 0.0016). The cut-off values of PPV were 10.5% and 9.5%, respectively. Besides, patients with P0.1 < 1.5 cmH2O had a narrow gray zone (10.5–11.5%) compared to patients with P0.1 ≥ 1.5 cmH2O (8.5–16.5%).ConclusionsPPV is reliable in predicting FR in patients who received controlled ventilation with low spontaneous effort, defined as P0.1 < 1.5 cmH2O.Trial registration NCT04802668. Registered 6 February 2021, https://clinicaltrials.gov/ct2/show/record/NCT04802668

The combined use of parasternal intercostal muscle thickening fraction and P0.1 for prediction of weaning outcomes

BackgroundA variety of parameters and diaphragmatic ultrasound in ventilator weaning has been studied extensively, and the findings yield inconsistent conclusions. The parasternal intercostal muscle holds important substantial respiratory reserve capacity when the central drive is enhanced, the predictive value of combining parasternal intercostal muscle ultrasound parameters with P0.1(airway occlusion pressure at 100 msec) in assessing ventilator weaning outcomes is still unknown. ObjectivesOur study aimed to evaluate the predictive efficacy of parasternal intercostal muscle ultrasound in conjunction with P0.1 in determining weaning failure. MethodsWe recruited patients who had been admitted to ICU and had been receiving mechanical ventilation for over two days. All patients underwent a half-hour spontaneous breathing trial (SBT) with low-level pressure support ventilation (PSV). They were positioned semi-upright for parasternal intercostal muscle ultrasound evaluations, including parasternal intercostal muscle thickness (PIMT), and parasternal intercostal muscle thickening fraction (PIMTF); P0.1 was obtained from the ventilator. Weaning failure was defined as the need for non-invasive positive pressure ventilation or re-intubation within 48 h post-weaning. ResultsOf the 56 enrolled patients with a mean age of 63.04 ± 15.80 years, 13 (23.2%) experienced weaning failure. There were differences in P0.1 (P = .001) and PIMTF (P = .017) between the two groups, but also in patients with a diaphragm thickness ≥ 2 mm. The predictive threshold values were PIMTF ≥ 13.15% and P0.1 ≥ 3.9 cmH2O for weaning failure. The AUROC for predicting weaning failure was 0.721 for PIMTF, 0.792 for P0.1, and 0.869 for the combination of PIMTF and P0.1. ConclusionsThe parasternal intercostal muscle thickening fraction and P0.1 are independently linked to weaning failure, especially in patients with normal diaphragm thickness. The combination of parasternal intercostal muscle thickening fraction and P0.1 can serve as a valuable tool for the precise clinical prediction of weaning outcomes. Trial registrationChinese Clinical Trial Registry website (ChiCTR2200065422).

Pulmonary function testing in patients with liver cirrhosis (Review).

Liver cirrhosis is a common long-term outcome of chronic hepatic inflammation. Patients with liver cirrhosis may also have pulmonary complications. There are several reasons for pulmonary dysfunction in liver cirrhosis, including intrinsic cardiopulmonary dysfunction unrelated to liver disease and specific disorders related to the presence of liver cirrhosis and/or portal hypertension. The most prevalent and clinically significant pulmonary complications are hepatic hydrothorax, hepatopulmonary syndrome, spontaneous pulmonary empyema and portopulmonary hypertension. Pulmonary function tests (PFTs) have traditionally been used to assess the lung function of patients with liver cirrhosis. To the best of our knowledge, the present review is the first to detail all types of PFTs performed in patients with liver cirrhosis and discuss their clinical significance. Patients with liver cirrhosis have reduced values of spirometric parameters, diffusion capacity for carbon monoxide (DLCO), lung volumes, maximal inspiratory pressure and maximal expiratory pressure. Furthermore, they have a higher closing volume, a greater airway occlusion pressure 0.1 sec after the onset of inspiratory flow and greater exhaled nitric oxide values. In order to improve pulmonary function, patients with ascites may require therapeutic paracentesis. Such findings should be considered when evaluating individuals with liver disease, particularly those who may require surgery. Poor lung function, particularly restrictive lung disease, can have an impact on post-transplant outcomes, such as ventilator time, length of hospital duration and post-operative pulmonary complications; thus, the transplant care team needs to be aware of its prevalence and relevance.

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

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. 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. 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). 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 effectiveness of the respiratory muscles in children with oncohematological diseases after hematopoietic stem cell transplantation

The article analyzes the effectiveness of the respiratory muscles by measuring inspiratory mouth occlusion pressure at 0.1 seconds during quiet breathing (P0.1) and maximum voluntary ventilation maneuver (P0.1 max ) in children with acute leukemia and acquired idiopathic aplastic anemia after allogeneic hematopoietic stem cell transplantation (HSCT). We carried out a comparative analysis of the Р0.1 and Р0.1 max values measured before HSCТ and on days +30, +90, +180 and +360. In a group of patients with acquired idiopathic aplastic anemia, we revealed a significant decrease in these values starting from day +30, followed by a recovery to baseline values by one year of follow-up. In children with acute leukemia, effectiveness of the respiratory muscles was increased after 360 days of transplantation as a result of the aggravation of impaired ventilation. This method for measuring airway occlusion pressure can be used in a comprehensive assessment of the functional state of the respiratory system for the timely diagnosis of pulmonary complications after HSCT. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation.

Effects of acute intermittent hypoxia on P0.1 in humans with spinal cord injury

Spinal cord injury (SCI) disrupts neural pathways to respiratory motor neurons, diminishing respiratory drive and breathing function. Breathing impairment remains a leading cause of illness and death after SCI. Therapeutic acute intermittent hypoxia (tAIH; 15, 1-minute episodes of 9% inspired O 2 , 1.5 min normoxic intervals), a promising strategy to restore breathing function after SCI, promotes spinal neuroplasticity in rodent models. However, in humans, respiratory drive is unchanged after a single tAIH session; thus we tested the hypothesis that tAIH on five successive days increases neuromechanical respiratory drive in humans living with chronic SCI. Sixteen participants with chronic SCI (1 female; 33.5 + 15.3 years of age; 1-28 years post-SCI; 11 cervical, 5 thoracic; C1-T6 AIS A-D) were studied; their respiratory function was 52% ± 19% of age predicted expiratory pressure generation, and 123% ± 32% for inspiratory pressure. Five days of tAIH or Sham treatment were delivered in a randomized, cross-over design (minimum 3 weeks apart). Airway occlusion pressure in the first 0.1s of inspiration (P0.1), a surrogate for neuromechanical respiratory drive prior to within-breath sensory feedback, was collected at baseline and at 1, 3, and 7-days post-treatment. Repeated measures ANOVA revealed no significant effect of time (F(3)=.49; P=.69) or group (F(3)=1.33; P=.27). Despite the lack of significant differences in this preliminary analysis, P0.1 increased by 25% on day 3 versus 0.8% after Sham. Because of this change, pairwise comparisons were conducted, revealing a near significant increase in P0.1, 3 days post tAIH (MD=-.17; P =.06). Thus, although P0.1, a surrogate for neuromechanical respiratory drive, did not significantly increase after 5 days of AIH in people with SCI, the marginally significant change at day 3 suggests further investigation is warranted. Next steps include assessment in a larger sample, investigation of biomarkers for treatment effects, and examination of combinatorial interventions including task specific training and/or mild CO 2 elevations to enhance AIH-induced neuroplasticity in the drive to breathe. DoD SCIRP Clinical Trial Award W81XWH-17-SCIRP-CTA; The Craig H. Neilsen Foundation (JW); NIH T32 HL134621 (MM); and the UF McKnight Brain Institute. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ineffective Effort in Patients With Acute Brain Injury Undergoing Invasive Mechanical Ventilation.

Ineffective effort (IE) is a frequent patient-ventilator asynchrony in invasive mechanical ventilation. This study aimed to investigate the incidence of IE and to explore its relationship with respiratory drive in subjects with acute brain injury undergoing invasive mechanical ventilation. We retrospectively analyzed a clinical database that assessed patient-ventilator asynchrony in subjects with acute brain injury. IE was identified based on airway pressure, flow, and esophageal pressure waveforms collected at 15-min intervals 4 times daily. At the end of each data set recording, airway-occlusion pressure (P0.1) was determined by the airway occlusion test. IE index was calculated to indicate the severity of IE. The incidence of IE in different types of brain injuries as well as its relationship with P0.1 was determined. We analyzed 852 data sets of 71 subjects with P0.1 measured and undergoing mechanical ventilation for at least 3 d after enrollment. IE was detected in 688 (80.8%) data sets, with a median index of 2.2% (interquartile range 0.4-13.1). Severe IE (IE index ≥ 10%) was detected in 246 (28.9%) data sets. The post craniotomy for brain tumor and the stroke groups had higher median IE index and lower P0.1 compared with the traumatic brain injury group (2.6% [0.7-9.7] vs 2.7% [0.3-21] vs 1.2% [0.1-8.5], P = .002; 1.4 [1-2] cm H2O vs 1.5 [1-2.2] cm H2O vs 1.8 [1.1-2.8] cm H2O, P = .001). Low respiratory drive (P0.1 < 1.14 cm H2O) was independently associated with severe IE in the expiratory phase (IEE) even after adjusting for confounding factors by logistic regression analysis (odds ratio 5.18 [95% CI 2.69-10], P < .001). IE was very common in subjects with acute brain injury. Low respiratory drive was independently associated with severe IEE.

The inspiratory activity of respiratory center and respiratory muscles strength after COVID-19

The respiratory pump that provides pulmonary ventilation includes the respiratory center, peripheral nervous system, chest and respiratory muscles.The aim of this study was to evaluate the activity of the respiratory center and the respiratory muscles strength after COVID-19 (COronaVIrus Disease 2019).Methods. The observational retrospective cross-sectional study included 74 post-COVID-19 patients (56 (76%) men, median age – 48 years). Spirometry, body plethysmography, measurement of lung diffusing capacity (DLCO), maximal inspiratory and expiratory pressures (MIP and MEP), and airway occlusion pressure after 0.1 sec (P0.1) were performed. In addition, dyspnea was assessed in 31 patients using the mMRC scale and muscle strength was assessed in 27 of those patients using MRC Weakness scale.Results. The median time from the COVID-19 onset to pulmonary function tests (PFTs) was 120 days. The total sample was divided into 2 subgroups: 1 – P0.1 ≤ 0.15 kPa (norm), 2 – &gt; 0.15 kPa. The lung volumes, airway resistance, MIP, and MEP were within normal values in most patients, whereas DLCO was reduced in 59% of cases in both the total sample and the subgroups. Mild dyspnea and a slight decrease in muscle strength were also detected. Statistically significant differences between the subgroups were found in the lung volumes (lower) and airway resistance (higher) in subgroup 2. Correlation analysis revealed moderate negative correlations between P0.1 and ventilation parameters.Conclusion. Measurement of P0.1 is a simple and non-invasive method for assessing pulmonary function. In our study, an increase in P0.1 was detected in 45% of post-COVID-19 cases, possibly due to impaired pulmonary mechanics despite the preserved pulmonary ventilation as well as normal MIP and MEP values.

Monitoring Respiratory Effort and Lung-distending Pressure Noninvasively during Mechanical Ventilation: Ready for Prime Time.

Monitoring Respiratory Effort and Lung-distending Pressure Noninvasively during Mechanical Ventilation: Ready for Prime Time.

Performance of noninvasive airway occlusion maneuvers to assess lung stress and diaphragm effort in mechanically ventilated critically ill patients.

Monitoring and controlling lung stress and diaphragm effort has been hypothesized to limit lung injury and diaphragm injury. The occluded inspiratory airway pressure (Pocc) and the airway occlusion pressure at 100ms (P0.1) have been used as non-invasive methods to assess lung stress and respiratory muscle effort, but comparative performance of these measures and their correlation to diaphragm effort is unknown. We hypothesized that Pocc and P0.1 correlate to diaphragm effort and lung stress, and would have strong discriminative performance in identifying extremes of lung stress and diaphragm effort. Secondary analysis of two studies. Transdiaphragmatic pressure (ΔPdi) and transpulmonary pressure (ΔPL) were obtained with double-balloon nasogastric catheters in critically ill patients (n = 38). Pocc and P0.1 were measured every 1-3 hours. Correlations between Pocc and P0.1 with ΔPL and ΔPdi were computed from patients from the first cohort. Accuracy of Pocc and P0.1 to identify patients with extremes of lung stress (ΔPL>20cmH2O) and diaphragm effort (ΔPdi <3cmH2O and >12cmH2O) in the preceding hour was assessed with area under receiver-operator characteristic curves (AUROC). Cut-offs were validated in patients from the second cohort (n = 13). Pocc and P0.1 correlate with ΔPL (r2=0.62 and 0.51, respectively) and ΔPdi (r2 = 0.53 and 0.22, respectively). AUROC to detect high lung stress is 0.90 (0.86-0.94) for Pocc and 0.88 (0.84-0.92) for P0.1. AUROC to detect low diaphragm effort is 0.97 (0.87-1.00) for Pocc and 0.93 (0.81-0.99) for P0.1. AUROC to detect high diaphragm effort is 0.86 (0.81-0.91) for Pocc and 0.73 (0.66-0.79) for P0.1. Performance was similar in the external dataset. Pocc and P0.1 correlate with lung stress and diaphragm effort in the preceding hour. Diagnostic performance of Pocc and P0.1 to detect extremes in these parameters is reasonable to excellent. Pocc is more accurate in detecting high diaphragm effort.