Effect of nocturnal EPAP titration to abolish tidal expiratory flow limitation in COPD patients with chronic hypercapnia: a randomized, cross-over pilot study

Emanuela Zannin, Ilaria Milesi, Roberto Porta, Simona Cacciatore, Luca Barbano, R Trentin, Francesco Fanfulla, Michele Vitacca, Raffaele L Dellacà, Emanuela Zannin, Ilaria Milesi, Roberto Porta, Simona Cacciatore, Luca Barbano, R Trentin, Francesco Fanfulla, Michele Vitacca, Raffaele L Dellacà

Abstract

Background: Tidal expiratory flow limitation (EFLT) promotes intrinsic PEEP (PEEPi) in patients with chronic obstructive pulmonary disease (COPD). Applying non-invasive ventilation (NIV) with an expiratory positive airway pressure (EPAP) matching PEEPi improves gas exchange, reduces work of breathing and ineffective efforts. We aimed to evaluate the effects of a novel NIV mode that continuously adjusts EPAP to the minimum level that abolishes EFLT.

Methods: This prospective, cross-over, open-label study randomized patients to one night of fixed-EPAP and one night of EFLT-abolishing-EPAP. The primary outcome was transcutaneous carbon dioxide pressure (PtcCO2). Secondary outcomes were: peripheral oxygen saturation (SpO2), frequency of ineffective efforts, breathing patterns and oscillatory mechanics.

Results: We screened 36 patients and included 12 in the analysis (age 72 ± 8 years, FEV1 38 ± 14%Pred). The median EPAP did not differ between the EFLT-abolishing-EPAP and the fixed-EPAP night (median (IQR) = 7.0 (6.0, 8.8) cmH2O during night vs 7.5 (6.5, 10.5) cmH2O, p = 0.365). We found no differences in mean PtcCO2 (44.9 (41.6, 57.2) mmHg vs 54.5 (51.1, 59.0), p = 0.365), the percentage of night time with PtcCO2 > 45 mm Hg was lower (62(8,100)% vs 98(94,100)%, p = 0.031) and ineffective efforts were fewer (126(93,205) vs 261(205,351) events/hour, p = 0.003) during the EFLT-abolishing-EPAP than during the fixed-EPAP night. We found no differences in oxygen saturation and lung mechanics between nights.

Conclusion: An adaptive ventilation mode targeted to abolish EFLT has the potential to reduce hypercapnia and ineffective efforts in stable COPD patients receiving nocturnal NIV.

Trial registration: ClicalTrials.gov, NCT04497090. Registered 29 July 2020-Retrospectively registered, https://ichgcp.net/clinical-trials-registry/NCT04497090 .

Keywords: Chronic obstructive pulmonary disease; Forced oscillation technique; Intrinsic PEEP; Non-invasive ventilation.

Figures

Fig. 1
Fig. 1
Study flow diagram. EFLT tidal expiratory flow limitation
Fig. 2
Fig. 2
Representative pressure and PtcCO2 tracings for the EFLT-abolishing-EPAP (black) and the fixed-EPAP nights (grey). During the fixed-EPAP night, EPAP and IPAP were kept constant at the prescribed values (horizontal dashed lines)
Fig. 3
Fig. 3
EPAP and tidal expiratory flow limitation index during the night with EFLT-abolishing-EPAP vs. fixed-EPAP. Data are reported as individual values (open symbols dotted lines) and as mean ± SD of all subjects (closed symbols). Dashed-line: tidal expiratory flow limitation threshold. EPAP: expiratory positive airway pressure. ΔXrs: difference between mean inspiratory and expiratory reactance (tidal expiratory flow limitation index). ΔXrs data for 11 subjects
Fig. 4
Fig. 4
Gas exchange during the night with EFLT-abolishing-EPAP vs. fixed-EPAP. Data are reported as individual values (open symbols dotted lines) and as mean ± SD of all subjects (closed symbols). SpO2: peripheral oxygen saturation. T90: percentage of time spent with oxygen saturation SpO2 below 90%. PtcCO2: transcutaneous partial pressure of carbon dioxide. T hypercapnia: percentage of time spent with a PtcCO2 > 45 mm Hg. T hypercapnia and ΔXrs data for 11 subjects. *p < 0.05 between nights

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