Optimizing high-flow nasal cannula flow settings in adult hypoxemic patients based on peak inspiratory flow during tidal breathing

Background Optimal flow settings during high-flow nasal cannula (HFNC) therapy are unknown. We investigated the optimal flow settings during HFNC therapy based on breathing pattern and tidal inspiratory flows in patients with acute hypoxemic respiratory failure (AHRF). Methods We conducted a prospective clinical study in adult hypoxemic patients treated by HFNC with a fraction of inspired oxygen (FIO2) ≥ 0.4. Patient’s peak tidal inspiratory flow (PTIF) was measured and HFNC flows were set to match individual PTIF and then increased by 10 L/min every 5–10 min up to 60 L/min. FIO2 was titrated to maintain pulse oximetry (SpO2) of 90–97%. SpO2/FIO2, respiratory rate (RR), ROX index [(SpO2/FIO2)/RR], and patient comfort were recorded after 5–10 min on each setting. We also conducted an in vitro study to explore the relationship between the HFNC flows and the tracheal FIO2, peak inspiratory and expiratory pressures. Results Forty-nine patients aged 58.0 (SD 14.1) years were enrolled. At enrollment, HFNC flow was set at 45 (38, 50) L/min, with an FIO2 at 0.62 (0.16) to obtain an SpO2/FIO2 of 160 (40). Mean PTIF was 34 (9) L/min. An increase in HFNC flows up to two times of the individual patient’s PTIF, incrementally improved oxygenation but the ROX index plateaued with HFNC flows of 1.34–1.67 times the individual PTIF. In the in vitro study, when the HFNC flow was set higher than PTIF, tracheal peak inspiratory and expiratory pressures increased as HFNC flow increased but the FIO2 did not change. Conclusion Mean PTIF values in most patients with AHRF were between 30 and 40 L/min. We observed improvement in oxygenation with HFNC flows set above patient PTIF. Thus, a pragmatic approach to set optimal flows in patients with AHRF would be to initiate HFNC flow at 40 L/min and titrate the flow based on improvement in ROX index and patient tolerance. Trial registration: ClinicalTrials.gov (NCT03738345). Registered on November 13th, 2018. https://clinicaltrials.gov/ct2/show/NCT03738345?term=NCT03738345&draw=2&rank=1

Monitoring Adult Subglottic Stenosis With Spirometry and Dyspnea Index: A Novel Approach

Objective The aim was to examine the correlations among the anatomic Cotton-Myer classification, pulmonary function tests (PFTs), and patient-perceived dyspnea or dysphonia in patients with subglottic stenosis and identify measurements accurately reflecting treatment effects. Study Design Prospective cohort study. Setting Tertiary referral center. Method Fifty-two adults receiving endoscopic treatment for isolated subglottic stenosis were consecutively included. Correlations were calculated among the preoperative Cotton-Myer scale, PFTs, the Dyspnea Index (DI), and the Voice Handicap Index. Receiver operating characteristic curves were determined for PFT, DI, and Voice Handicap Index pre- and postoperative measurements. Results The Cotton-Myer classification correlated weakly with peak expiratory flow ( r = −0.35, P = .012), expiratory disproportion index ( r = 0.32, P = .022), peak inspiratory flow ( r = −0.32, P = .022), and total peak flow ( r = −0.36, P = .01). The DI showed an excellent area under the curve (0.99, P < .001), and among PFTs, the expiratory disproportion index demonstrated the best area under the curve (0.89, P < .001), followed by total peak flow (0.88, P < .001), peak expiratory flow (0.87, P < .001), and peak inspiratory flow (0.84, P < .001). Patients treated endoscopically with balloon dilatation showed a 53% decrease in expiratory disproportion index (95% CI, 41%-66%; P < .001) and a 37% improvement in peak expiratory flow (95% CI, 31%-43%; P < .001). Conclusion Expiratory disproportion index or peak expiratory flow combined with DI was a feasible measurement for the monitoring of adult subglottic stenosis. The percentage deterioration of peak expiratory flow and increase in expiratory disproportion index correlated significantly with a proportional percentage increase in DI.

Respimat as the new standard for inhalation therapy devices

The effectiveness of inhalation therapy can be significantly reduced by a number of problems. For example, inhalation technique errors can reduce the dose delivered by 22-95% compared to the optimal value in patients with technical errors in the use of the inhaler. Sub-optimal inspiratory flow rates in a number of patients with chronic obstructive pulmonary disease and asthma are often the cause of technical errors during inhalation. Patient education does not produce the expected results, as the underlying cause of reduced flow is high hyperinflation and weakening of the respiratory musculature. The use of technologically outdated inhalers is another significant cause of reduced therapy effectiveness. Patient education and even conversion to a different inhaler do not always increase the effectiveness of therapy. Respimat, a brand new delivery agent introduced in 2004, allows 39% to 67% of the nominal dose to be delivered to the airways, while the degree of pulmonary deposit is independent of inspiratory flow and pulmonary drug deposit does not decrease with increasing obstruction. Compared to powder inhalers, Respimat creates less resistance to airflow on inhalation. In addition, Respimat is an active device that requires no effort on the part of the patient to move the aerosol particles. These features make Respimat the new standard for inhalation therapy. This review aims to familiarise readers with the main features of the Respimat and the latest research findings

Different Inspiratory Flow Waveform during Volume-Controlled Ventilation in ARDS Patients

The most used types of mechanical ventilation are volume- and pressure-controlled ventilation, respectively characterized by a square and a decelerating flow waveform. Nowadays, the clinical utility of different inspiratory flow waveforms remains unclear. The aim of this study was to assess the effects of four different inspiratory flow waveforms in ARDS patients. Twenty-eight ARDS patients (PaO2/FiO2 182 ± 40 and PEEP 11.3 ± 2.5 cmH2O) were ventilated in volume-controlled ventilation with four inspiratory flow waveforms: square (SQ), decelerating (DE), sinusoidal (SIN), and trunk descending (TDE). After 30 min in each condition, partitioned respiratory mechanics and gas exchange were collected. The inspiratory peak flow was higher in the DE waveform compared to the other three waveforms, and in SIN compared to the SQ and TDE waveforms, respectively. The mean inspiratory flow was higher in the DE and SIN waveforms compared with TDE and SQ. The inspiratory peak pressure was higher in the SIN and SQ compared to the TDE waveform. Partitioned elastance was similar in the four groups; mechanical power was lower in the TDE waveform, while PaCO2 in DE. No major effect on oxygenation was found. The explored flow waveforms did not provide relevant changes in oxygenation and respiratory mechanics.

Bronchodilator Delivery via High-Flow Nasal Cannula: A Randomized Controlled Trial to Compare the Effects of Gas Flows

(1) Background: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted increasing clinical interest. In vitro studies report that the ratio of HFNC gas flow to patient inspiratory flow (GF:IF) is a key factor in the efficiency of trans-nasal aerosol delivery. (2) Methods: In a randomized controlled trial, patients with a history of COPD or asthma and documented positive responses to inhaled bronchodilators in an outpatient pulmonary function laboratory were recruited. Subjects were randomized to receive inhalation at gas flow ratio settings of: GF:IF = 0.5, GF:IF = 1.0, or GF = 50 L/min. Subjects were assigned to inhale saline (control) followed by salbutamol via HFNC with cumulative doses of 0.5 mg, 1.5 mg, 3.5 mg, and 7.5 mg. Spirometry was performed at baseline and 10–12 min after each inhalation. (3) Results: 75 subjects (49 asthma and 26 COPD) demonstrating bronchodilator response were enrolled. Per the robust ATS/ERS criteria no difference was observed between flows, however using the criteria of post-bronchodilator forced expiratory volume in the first second (FEV1) reaching the screening post-bronchodilator FEV1 with salbutamol, a higher percentage of subjects receiving GF:IF = 0.5 met the criteria at a cumulative dose of 1.5 mg than those receiving GF:IF = 1.0, and GF = 50 L/min (64% vs. 29% vs. 27%, respectively, p = 0.011). Similarly at 3.5 mg (88% vs. 54% vs. 46%, respectively, p = 0.005). The effective dose at GF:IF = 0.5 was 1.5 mg while for GF = 50 L/min it was 3.5 mg. (4) Conclusions: During salbutamol delivery via HFNC, cumulative doses of 1.5 mg to 3.5 mg resulted in effective bronchodilation. Applying the robust ATS/ERS criteria no difference was observed between the flows, however using the more sensitive criteria of subjects reaching post screening FEV1 to salbutamol via HFNC, a higher number of subjects responded to the doses of 0.5 mg and 1.5 mg when HFNC gas flow was set at 50% of patient peak inspiratory flow.

Increased CaMKII-dependent pro-arrhythmic activity in a novel mouse model of obstructive sleep apnoea

Background Obstructive sleep apnoea (OSA) is frequently associated with atrial arrhythmias, but detailed mechanisms remain elusive. Most recently, we found an increased CaMKII-dependent pro-arrhythmic activity in patients with sleep apnoea. Since patients suffer from various confounding comorbidities, we have developed a novel mouse model of OSA by tongue enlargement. Purpose We tested if mice with OSA exhibit increased atrial CaMKII-dependent pro-arrhythmic activity. Methods Polytetrafluorethylene (PTFE) was injected into the tongue of 12 wild-type (WT) and 10 CaMKII knock-out (CKO) mice. 9 WT and 9 CKO mice were used as control without PTFE injection. Inspiratory flow limitations and apnoeas were monitored during murine sleep phases by whole-body plethysmography (Buxco). After eight weeks, isolated atrial cardiomyocytes were incubated with the Ca-sensitive dye FURA-2 AM for 15 min. Regular Ca transients were elicited by electrical field stimulation (1 Hz, 20 V for 4 ms) using epifluorescence microscopy. Pro-arrhythmic non-stimulated events were defined as deviations from diastolic Ca baseline between two stimulated Ca transients. Results Sonographic measurements revealed a significant increase in mean tongue diameter from (in mm) 3.7±0.1 to 5.1±0.1 after PTFE injection (n=23, p&lt;0.0001). There was a significant correlation between magnitude of tongue diameter and frequency of apnoeas in OSA mice (p=0.046, r2=0.19, Fig. 1A). Interestingly, we observed a significantly increased frequency of pro-arrhythmic events of (in s–1) 0.06±0.01 in WT OSA mice compared to 0.02±0.01 in WT control mice (p=0.047, Fig. 1B). Similar results were observed at higher stimulation frequencies (2 and 4 Hz). There was a significant correlation of pro-arrhythmic events with inspiratory flow limitations (p=0.03, r2=0.24, Fig. 1C) and with the frequency of apnoeas by strong trend (p=0.06, r2=0.18). In contrast, no increase in atrial pro-arrhythmic events was observed in CKO mice after PTFE injection (for CKO mice after PTFE vs. CKO mice without PTFE, 0.03±0.01 s–1 vs. 0.03±0.01 s–1, p=0.89, Fig. 1B). Accordingly, the correlations between pro-arrhythmic events and both inspiratory flow limitations (p=0.36, r2=0.05, Fig. 1C) and apnoeas (p=0.82, r2=0.004) were completely abolished in CKO mice. Conclusion In a novel mouse model of obstructive sleep apnoea, atrial pro-arrhythmic activity was increased in a CaMKII-dependent fashion, which may have therapeutic implications. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Benedikt Schaner / Mr., this work is supported by a research grant of the German Cardiac Society (DGK); Stefan Wagner / Professor, was funded by DFG grants Figure 1

Quantification of Airway Conductance from Non-invasive Ventilatory Drive in Patients with Sleep Apnea

Upper airway conductance, the ratio of inspiratory airflow to inspiratory effort, quantifies the degree of airway obstruction in hypopneas observed in sleep apnea. We evaluated the ratio of ventilation to non-invasive ventilatory drive as a surrogate of conductance. Further, we developed and tested a refinement of non-invasive drive to incorporate the interactions of inspiratory flow, pressure, and drive in order to better estimate conductance. Hypopneas were compiled from existing polysomnography studies with esophageal catheterization in 18 patients with known or suspected sleep apnea, totaling 1517 hypopneas during NREM sleep. For each hypopnea, reference-standard conductance was calculated as the ratio of peak inspiratory flow to esophageal pressure change during inspiration. Ventilatory drive was calculated using the algorithm developed by Terrill et al and then mathematically modified according to the presence or absence of flow limitation in order to non-invasively estimate esophageal pressure. The ratio of ventilation to ventilatory drive and the ratio of peak inspiratory flow to estimated esophageal pressure were each compared to the reference standard for all hypopneas and for median values from individual patients. Hypopnea ventilation:drive ratios were of limited correlation with the reference standard (R2 = 0.17, individual hypopneas; R2 = 0.03, median patient values). Modification of drive to estimated pressure yielded estimated conductance, which strongly correlated with reference standard conductance (R2 = 0.49, individual hypopneas; R2 = 0.77, median patient values­). We conclude that the severity of airway obstruction during hypopneas may be estimated from non-invasive drive by accounting for mechanical effects of flow on pressure.