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Original research
Five-year outcome of respiratory muscle weakness at intensive care unit discharge: secondary analysis of a prospective cohort study
  1. Nathalie Van Aerde1,
  2. Philippe Meersseman2,
  3. Yves Debaveye1,3,
  4. Alexander Wilmer1,2,
  5. Jan Gunst1,3,
  6. Michael P Casaer1,3,
  7. Joost Wauters2,4,
  8. Pieter J Wouters1,3,
  9. Rik Gosselink5,
  10. Greet Van den Berghe1,3,
  11. Greet Hermans1,2
  1. 1Cellular and Molecular Medicine, KU Leuven, Leuven, Flanders, Belgium
  2. 2Medical Intensive Care Unit, Department of General Internal Medicine, KU Leuven University Hospitals Leuven, Leuven, Flanders, Belgium
  3. 3Intensive Care Medicine, KU Leuven University Hospitals Leuven, Leuven, Flanders, Belgium
  4. 4Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Flanders, Belgium
  5. 5Rehabilitation Sciences, KU Leuven, Leuven, Flanders, Belgium
  1. Correspondence to Prof Dr Greet Hermans, Cellular and Molecular Medicine, KU Leuven, Leuven, Flanders, Belgium; Greet.Hermans{at}


Purpose To assess the association between respiratory muscle weakness (RMW) at intensive care unit (ICU) discharge and 5-year mortality and morbidity, independent from confounders including peripheral muscle strength.

Methods Secondary analysis of the prospective 5-year follow-up of the EPaNIC cohort ( NCT00512122), limited to 366 patients screened for respiratory and peripheral muscle strength in the ICU with maximal inspiratory pressure (MIP) after removal of the artificial airway, and the Medical Research Council sum score. RMW was defined as an absolute value of MIP <30 cmH2O. Associations between RMW at (or closest to) ICU discharge and all-cause 5-year mortality, and key measures of 5-year physical function, comprising respiratory muscle strength (MIP), hand-grip strength (HGF), 6 min walk distance (6MWD) and physical function of the SF-36 quality-of-life questionnaire (PF-SF-36), were assessed with Cox proportional hazards and linear regression models, adjusted for confounders including peripheral muscle strength.

Results RMW was present in 136/366 (37.2%) patients at ICU discharge. RMW was not independently associated with 5-year mortality (HR with 95% CI 1.273 (0.751 to 1.943), p=0.352). Among 156five-year survivors, those with, as compared with those without RMW demonstrated worse physical function (MIP (absolute value, cmH2O): 62(42–77) vs 94(78–109), p<0.001; HGF (%pred): 67(44–87) vs 96(68–110), p<0.001; 6MWD (%pred): 87(74–102) vs 99 (80–111), p=0.009; PF-SF-36 (score): 55 (30–80) vs 80 (55–95), p<0.001). Associations between RMW and morbidity endpoints remained significant after adjustment for confounders (effect size with 95% CI: MIP: −23.858 (−32.097 to −15.027), p=0.001; HGF: −18.591 (−30.941 to −5.744), p=0.001; 6MWD (transformed): −1587.007 (−3073.763 to −179.253), p=0.034; PF-SF-36 (transformed): 1.176 (0.144–2.270), p=0.036).

Conclusions RMW at ICU discharge is independently associated with 5-year morbidity but not 5-year mortality.

  • respiratory muscles
  • critical care
  • pulmonary rehabilitation

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  • GVdB and GH contributed equally.

  • Contributors GH and GVdB designed the study and planned the statistical analysis; data were acquired by GH, PM, YD, AW, JG, MC, NVA, GVdB and GH analysed and interpreted the data, and drafted the manuscript; critical revision of manuscript content was done by all authors, funding was obtained by MC, JG, GH, NVA and GVdB; administrative and technical support was provided by PJW.

  • Funding This work was supported by the Research Foundation – Flanders, Belgium (grant G.0399.12, Fundamental Clinical Research fellowship to GH: 1805116N, MPC: 1700111N; aspirant PhD fellowship to NVA: 1131618N), the clinical research fund (KOF) of the University Hospitals Leuven, Belgium (postdoctoral research fellowship to JG); the Methusalem programme of the Flemish Government (METH/08/07, renewed as METH/14/06 via KU Leuven) to GVdB; the European Research Council ERC Advanced grants (AdvG-2012-321670 from the Ideas Program of the EU FP7 and AdvG-2017-785809 from the Horizon 2020 Programme of the EU) to GVdB. An unrestricted and non-conditional research grant was given to KULeuven by Baxter between 2007 and 2010.

  • Disclaimer The authors have no conflict of interest with the sponsors of the study.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol and informed consents of EPaNIC and its long-term follow-up were approved by the Ethical Committee Research UZ/KU Leuven (ML4190).

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

  • Data availability statement Data are available on reasonable request. Data sharing is considered under the format of collaborative projects. Proposals can be directed to the senior authors (GH and GVdB).

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