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High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial
  1. Michael Dreher1,
  2. Jan H Storre1,
  3. Claudia Schmoor2,
  4. Wolfram Windisch1
  1. 1Department of Pneumology, University Medical Hospital, Freiburg, Germany
  2. 2Clinical Trials Center, University Medical Center, Freiburg, Germany
  1. Correspondence to Prof Dr Wolfram Windisch, Department of Pneumology, University Hospital Freiburg, Killianstrasse 5, D-79106 Freiburg, Germany; wolfram.windisch{at}


Rationale The conventional approach of low-intensity non-invasive positive pressure ventilation (NPPV) produces only minimal physiological and clinical benefits in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD).

Objectives To determine whether the novel approach of high-intensity NPPV is superior to low-intensity NPPV in controlling nocturnal hypoventilation.

Methods A randomised controlled crossover trial comparing 6 weeks of high-intensity NPPV (using controlled ventilation with mean inspiratory pressures of 28.6±1.9 mbar) with low-intensity NPPV (using assisted ventilation with mean inspiratory pressures of 14.6±0.8 mbar) was performed in 17 patients with severe stable hypercapnic COPD.

Results Two patients refused low-intensity NPPV and two patients dropped out while on low-intensity NPPV. Thirteen patients (mean forced expiratory volume in 1 s (FEV1) 0.76±0.29 l) completed the trial. High-intensity NPPV produced higher pneumotachographically-measured expiratory volumes, with a mean treatment effect of 96 ml (95% CI 23 to 169) (p=0.015). This resulted in a mean treatment effect on nocturnal arterial carbon dioxide tension (Paco2) of −9.2 mm Hg (95% CI −13.7 to −4.6) (p=0.001) in favour of high-intensity NPPV. Daily use of NPPV was increased in high-intensity NPPV compared with low-intensity NPPV, with a mean difference of 3.6 h/day (95% CI 0.6 to 6.7) (p=0.024). In addition, compared with baseline, only high-intensity NPPV resulted in significant improvements in exercise-related dyspnoea, daytime Paco2, FEV1, vital capacity and the Severe Respiratory Insufficiency Questionnaire Summary Score.

Conclusions High-intensity NPPV is better tolerated by patients with severe chronic hypercapnic COPD and has been shown to be superior to the conventional and widely-used form of low-intensity NPPV in controlling nocturnal hypoventilation. High-intensity NPPV therefore offers a new promising therapeutic option for these patients.

  • Chronic obstructive pulmonary disease
  • mechanical ventilation
  • respiratory failure
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  • Registration number: UKF001909

  • MD and JHS contributed equally to this work.

  • Competing interests The study group received an open research grant from Breas Medical AB, Molnlycke, Sweden and from Respironics, Pittsburgh, Pennsylvania, USA. This study was supported by Respironics, Pittsburgh, Pennsylvania, USA. Neither the study design, results, interpretation of the findings nor any other subject discussed in the submitted manuscript was dependent on support.

  • Ethics approval This study was conducted with the approval of the Institutional Review Board for Human Studies at the Albert-Ludwigs University, Freiburg, Germany and was performed in accordance with the ethical standards laid down in the Declaration of Helsinki. Informed, written consent was obtained from all subjects.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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