Skip to main content

Advertisement

Log in

Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Purpose

To assess the independent association between ICU-acquired neuromuscular complications and 5-year mortality and morbidity. To explore the optimal threshold of the Medical Research Council (MRC) sum score, assessing weakness, for the prediction of 5-year outcomes.

Methods

Sub-analyses of a prospective, 5-year follow-up study including 883 EPaNIC patients (Early versus Late Parenteral Nutrition in Intensive Care) (Clinicaltrials.gov:NCT00512122), systematically screened in ICU for neuromuscular complications with MRC sum score (‘MRC-cohort’, N = 600), electrophysiology on day 8 ± 1 to quantify compound muscle action potential (‘CMAP-cohort’, N = 689), or both (‘MRC&CMAP-cohort’, N = 415). Associations between ICU-acquired neuromuscular complications and 5-year mortality, hand-grip strength (HGF, %predicted), 6-min-walk distance (6-MWD, %predicted) and physical function of the SF-36 quality-of-life questionnaire (PF-SF-36) at 5-years were assessed with Cox regression and linear regression, adjusted for confounders. The optimal threshold for MRC at ICU discharge to predict 5-year outcomes was determined by martingale residual plots (survival) and scatterplots (morbidity).

Results

Both lower MRC sum score at ICU discharge, indicating less strength [HR, per-point-increase: 0.946 (95% CI 0.928–0.968), p = 0.001], and abnormal CMAP, indicating nerve/muscle dysfunction [HR: 1.568 (95% CI 1.165–2.186), p = 0.004], independently associated with increased 5-year mortality. In the MRC&CMAP-cohort, MRC [HR: 0.956 (95% CI 0.934–0.980), p = 0.001] but not CMAP [HR: 1.478 (95% CI 0.875–2.838), p = 0.088] independently associated with 5-year mortality. Among 205 survivors, low MRC independently associated with low HGF [0.866 (95% CI 0.237–1.527), p = 0.004], low 6-MWD [105.1 (95% CI 12.1–212.9), p = 0.043] and low PF-SF-36 [− 0.119 (95% CI − 0.186 to − 0.057), p = 0.002], whereas abnormal CMAP did not correlate with these morbidity endpoints. Exploratory analyses suggested that MRC ≤ 55 best predicted poor long-term morbidity and mortality. Both MRC ≤ 55 and abnormal CMAP independently associated with 5-year mortality.

Conclusions

ICU-acquired neuromuscular complications may impact 5-year morbidity and mortality. MRC sum score, even if slightly reduced, may affect long-term mortality, strength, functional capacity and physical function, whereas abnormal CMAP only related to long-term mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Batt J, Herridge MS, dos Santos CC (2019) From skeletal muscle weakness to functional outcomes following critical illness: a translational biology perspective. Thorax 74:1091–1098

    Article  PubMed  Google Scholar 

  2. Latronico N, Herridge M, Hopkins RO, Angus D, Hart N, Hermans G, Iwashyna T, Arabi Y, Citerio G, Ely EW (2017) The ICM research agenda on intensive care unit-acquired weakness. Intensive Care Med 43:1270–1281

    Article  PubMed  Google Scholar 

  3. Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, Casaer MP, Meersseman P, Debaveye Y, Van Cromphaut S, Wouters PJ, Gosselink R, Van den Berghe G (2014) Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med 190:410–420

    Article  PubMed  Google Scholar 

  4. Hermans G, Van Mechelen H, Bruyninckx F, Vanhullebusch T, Clerckx B, Meersseman P, Debaveye Y, Casaer MP, Wilmer A, Wouters PJ, Vanhorebeek I, Gosselink R, Van den Berghe G (2015) Predictive value for weakness and 1-year mortality of screening electrophysiology tests in the ICU. Intensive Care Med 41:2138–2148

    Article  PubMed  Google Scholar 

  5. Dinglas VD, Friedman LA, Colantuoni E, Mendez-Tellez PA, Shanholtz CB, Ciesla ND, Pronovost PJ, Needham DM (2017) Muscle weakness and 5-year survival in acute respiratory distress syndrome survivors. Crit Care Med 45:446

    Article  PubMed  PubMed Central  Google Scholar 

  6. Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM, Group CCCT (2011) Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 364:1293–1304

    Article  Google Scholar 

  7. Herridge MS, Moss M, Hough CL, Hopkins RO, Rice TW, Bienvenu OJ, Azoulay E (2016) Recovery and outcomes after the acute respiratory distress syndrome (ARDS) in patients and their family caregivers. Intensive Care Med 42:725–738

    Article  PubMed  Google Scholar 

  8. Pfoh ER, Wozniak AW, Colantuoni E, Dinglas VD, Mendez-Tellez PA, Shanholtz C, Ciesla ND, Pronovost PJ, Needham DM (2016) Physical declines occurring after hospital discharge in ARDS survivors: a 5-year longitudinal study. Intensive Care Med 42:1557–1566

    Article  PubMed  Google Scholar 

  9. Kress JP, Hall JB (2014) ICU-acquired weakness and recovery from critical illness. N Engl J Med 371:287–288

    Article  PubMed  Google Scholar 

  10. Puthucheary Z, Prescott H (2017) Skeletal muscle weakness is associated with both early and late mortality after ARDS. Crit Care Med 45:563

    Article  PubMed  PubMed Central  Google Scholar 

  11. Needham DM, Wozniak AW, Hough CL, Morris PE, Dinglas VD, Jackson JC, Mendez-Tellez PA, Shanholtz C, Ely EW, Colantuoni E, Hopkins RO, Network NIoHNA (2014) Risk factors for physical impairment after acute lung injury in a national, multicenter study. Am J Respir Crit Care Med 189:1214–1224

    Article  PubMed  PubMed Central  Google Scholar 

  12. Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G (2011) Early versus late parenteral nutrition in critically ill adults. N Engl J Med 365:506–517

    Article  CAS  PubMed  Google Scholar 

  13. Hermans G, Casaer MP, Clerckx B, Güiza F, Vanhullebusch T, Derde S, Meersseman P, Derese I, Mesotten D, Wouters PJ, Van Cromphaut S, Debaveye Y, Gosselink R, Gunst J, Wilmer A, Van den Berghe G, Vanhorebeek I (2013) Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. Lancet Respir Med 1:621–629

    Article  PubMed  Google Scholar 

  14. Hermans G, Van Aerde N, Meersseman P, Van Mechelen H, Debaveye Y, Wilmer A, Gunst J, Casaer MP, Dubois J, Wouters P (2019) Five-year mortality and morbidity impact of prolonged versus brief ICU stay: a propensity score matched cohort study. Thorax 74:1037–1045

    Article  PubMed  Google Scholar 

  15. ATS, ERS (2002) ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med 166:518–624

    Article  Google Scholar 

  16. Ware J, Snow K, Kosinski M, Gandek B (1993) SF-36 Health Survey: Manual & Interpretation Guide. Nimrod Press, Boston

    Google Scholar 

  17. Ware J, Kosinski M, Gandek B (2005) SF-36 health survey : manual and interpretation guide. Lincoln, Boston

    Google Scholar 

  18. Van der Schaaf M, Dettling DS, Beelen A, Lucas C, Dongelmans DA, Nollet F (2008) Poor functional status immediately after discharge from an intensive care unit. Disabil Rehabil 30:1812–1818

    Article  PubMed  Google Scholar 

  19. Collin C, Wade D, Davies S, Horne V (1988) The Barthel ADL Index: a reliability study. Int Disabil Stud 10:61–63

    Article  CAS  PubMed  Google Scholar 

  20. Lederer DJ, Bell SC, Branson RD, Chalmers JD, Marshall R, Maslove DM, Ost DE, Punjabi NM, Schatz M, Smyth AR (2019) Control of confounding and reporting of results in causal inference studies. Guidance for authors from editors of respiratory, sleep, and critical care journals. Ann Am Thorac Soc 16:22–28

    Article  PubMed  Google Scholar 

  21. De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand-Zaleski I, Boussarsar M, Cerf C, Renaud E, Mesrati F, Carlet J, Raphaël JC, Outin H, Bastuji-Garin S, GdRedEdNe R (2002) Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 288:2859–2867

    Article  PubMed  Google Scholar 

  22. Moss M, Yang M, Macht M, Sottile P, Gray L, McNulty M, Quan D (2014) Screening for critical illness polyneuromyopathy with single nerve conduction studies. Intensive Care Med 40:683–690

    Article  PubMed  Google Scholar 

  23. Kelmenson DA, Held N, Allen RR, Quan D, Burnham EL, Clark BJ, Ho PM, Kiser TH, Vandivier RW, Moss M (2017) Outcomes of ICU patients with a discharge diagnosis of critical illness polyneuromyopathy: a propensity-matched analysis. Crit Care Med 45:2055–2060

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ali NA, O'Brien JM, Hoffmann SP, Phillips G, Garland A, Finley JC, Almoosa K, Hejal R, Wolf KM, Lemeshow S, Connors AF, Marsh CB, Consortium MCC (2008) Acquired weakness, handgrip strength, and mortality in critically ill patients. Am J Respir Crit Care Med 178:261–268

    Article  Google Scholar 

  25. Hodgson C, Bellomo R, Berney S, Bailey M, Buhr H, Denehy L, Harrold M, Higgins A, Presneill J, Saxena M, Skinner E, Young P (2015) Early mobilization and recovery in mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study. Crit Care 19:81

    Article  PubMed  Google Scholar 

  26. Fan E, Cheek F, Chlan L, Gosselink R, Hart N, Herridge MS, Hopkins RO, Hough CL, Kress JP, Latronico N (2014) An official American thoracic society clinical practice guideline: the diagnosis of intensive care unit–acquired weakness in adults. Am J Respir Crit Care Med 190:1437–1446

    Article  PubMed  Google Scholar 

  27. Wieske L, Dettling-Ihnenfeldt DS, Verhamme C, Nollet F, van Schaik IN, Schultz MJ, Horn J, van der Schaaf M (2015) Impact of ICU-acquired weakness on post-ICU physical functioning: a follow-up study. Crit Care 19:196

    Article  PubMed  PubMed Central  Google Scholar 

  28. Thomas S, Mehrholz J (2018) Health-related quality of life, participation, and physical and cognitive function of patients with intensive care unit-acquired muscle weakness 1 year after rehabilitation in Germany: the GymNAST cohort study. BMJ open 8:e020163

    Article  PubMed  PubMed Central  Google Scholar 

  29. Fan E, Dowdy DW, Colantuoni E, Mendez-Tellez PA, Sevransky JE, Shanholtz C, Himmelfarb CR, Desai SV, Ciesla N, Herridge MS, Pronovost PJ, Needham DM (2014) Physical complications in acute lung injury survivors: a two-year longitudinal prospective study. Crit Care Med 42:849–859

    Article  PubMed  PubMed Central  Google Scholar 

  30. Needham DM, Dinglas VD, Morris PE, Jackson JC, Hough CL, Mendez-Tellez PA, Wozniak AW, Colantuoni E, Ely EW, Rice TW, Hopkins RO, Network NNA (2013) Physical and cognitive performance of patients with acute lung injury 1 year after initial trophic versus full enteral feeding. EDEN trial follow-up. Am J Respir Crit Care Med 188:567–576

    Article  PubMed  PubMed Central  Google Scholar 

  31. Semmler A, Okulla T, Kaiser M, Seifert B, Heneka MT (2013) Long-term neuromuscular sequelae of critical illness. J Neurol 260:151–157

    Article  PubMed  Google Scholar 

  32. Bohannon RW (2019) Minimal clinically important difference for grip strength: a systematic review. J Phys Therapy Sci 31:75–78

    Article  Google Scholar 

  33. Chan KS, Pfoh ER, Denehy L, Elliott D, Holland AE, Dinglas VD, Needham DM (2015) Construct validity and minimal important difference of 6-minute walk distance in survivors of acute respiratory failure. Chest 147:1316–1326

    Article  PubMed  PubMed Central  Google Scholar 

  34. Davidson TA, Caldwell ES, Curtis JR, Hudson LD, Steinberg KP (1999) Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients. JAMA 281:354–360

    Article  CAS  PubMed  Google Scholar 

  35. Latronico N, Bolton CF (2011) Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. Lancet Neurol 10:931–941

    Article  PubMed  Google Scholar 

  36. Leijten FS, Harinck-de Weerd JE, Poortvliet DC, de Weerd AW (1995) The role of polyneuropathy in motor convalescence after prolonged mechanical ventilation. JAMA 274:1221–1225

    Article  CAS  PubMed  Google Scholar 

  37. Fletcher SN, Kennedy DD, Ghosh IR, Misra VP, Kiff K, Coakley JH, Hinds CJ (2003) Persistent neuromuscular and neurophysiologic abnormalities in long-term survivors of prolonged critical illness. Crit Care Med 31:1012–1016

    Article  PubMed  Google Scholar 

  38. Guarneri B, Bertolini G, Latronico N (2008) Long-term outcome in patients with critical illness myopathy or neuropathy: the Italian multicentre CRIMYNE study. J Neurol Neurosurg Psychiatry 79:838–841

    Article  CAS  PubMed  Google Scholar 

  39. Fan E, Herridge MS (2015) Finally, a time and place for electrophysiological testing in critically ill patients? Intensive Care Med 41:2221–2223

    Article  PubMed  Google Scholar 

  40. Intiso D, Amoruso L, Zarrelli M, Pazienza L, Basciani M, Grimaldi G, Iarossi A, Di Rienzo F (2011) Long-term functional outcome and health status of patients with critical illness polyneuromyopathy. Acta Neurol Scand 123:211–219

    Article  CAS  PubMed  Google Scholar 

  41. Koch S, Spuler S, Deja M, Bierbrauer J, Dimroth A, Behse F, Spies CD, Wernecke K-D, Weber-Carstens S (2011) Critical illness myopathy is frequent: accompanying neuropathy protracts ICU discharge. J Neurol Neurosurg Psychiatry 82:287–293

    Article  PubMed  Google Scholar 

  42. Koch S, Wollersheim T, Bierbrauer J, Haas K, Morgeli R, Deja M, Spies CD, Spuler S, Krebs M, Weber-Carstens S (2014) Long-term recovery In critical illness myopathy is complete, contrary to polyneuropathy. Muscle Nerve 50:431–436

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are indebted to all patients and controls for their participation in this study, to Helena Van Mechelen, Tine Vanhullebusch, Sanne Verweyen, and Tim Van Assche for acquisition of data, to Helena Van Mechelen, Tine Vanhullebusch, Sanne Verweyen, Tim Van Assche, Alexandra Hendrickx, Heidi Utens, and Sylvia Van Hulle for their technical and administrative support and to Steffen Fieuws for his statistical advice.

Funding

This work was supported by the Research Foundation—Flanders, Belgium (Grant G.0399.12 to GH; Fundamental Clinical Research fellowship to GH: 1805116N, to MC: 1700111N; aspirant PhD fellowship to NVA: 1131618N), the Clinical Research and Education Council (KOOR) of the University Hospitals Leuven, Belgium (postdoctoral research fellowship to JG); the Methusalem program of the Flemish Government (METH/08/07 which has been 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 Program of the EU) to GVdB. Baxter provided an unrestricted and non-conditional research grant to KULeuven between 2007 and 2010.

Author information

Authors and Affiliations

Authors

Contributions

Study concept and design: GH and GB. Acquisition of data: GH, PM, FB, YD, AW, JG, and PJW. Analysis and interpretation of data: NA, GB, and GH. Drafting of the manuscript: NA, GB, and GH. Critical revision of the manuscript for important intellectual content: NA, PM, FB, YD, AW, JG, MPC, RG, PJW, GB, and GH. Statistical analysis: GH, NA, and GB. Obtained funding: GH, NA, and GB. Administrative and technical support: PJW. Study supervision: GH, PJW, and GB.

Corresponding author

Correspondence to Greet Hermans.

Ethics declarations

Conflicts of interest

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

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 513 kb)

Supplementary file2 (DOCX 29 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Van Aerde, N., Meersseman, P., Debaveye, Y. et al. Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. Intensive Care Med 46, 1184–1193 (2020). https://doi.org/10.1007/s00134-020-05927-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-020-05927-5

Keywords

Navigation