Skeletal muscle quality as assessed by CT-derived skeletal muscle density is associated with 6-month mortality in mechanically ventilated critically ill patients

Wilhelmus G P M Looijaard, Ingeborg M Dekker, Sandra N Stapel, Armand R J Girbes, Jos W R Twisk, Heleen M Oudemans-van Straaten, Peter J M Weijs, Wilhelmus G P M Looijaard, Ingeborg M Dekker, Sandra N Stapel, Armand R J Girbes, Jos W R Twisk, Heleen M Oudemans-van Straaten, Peter J M Weijs

Abstract

Background: Muscle quantity at intensive care unit (ICU) admission has been independently associated with mortality. In addition to quantity, muscle quality may be important for survival. Muscle quality is influenced by fatty infiltration or myosteatosis, which can be assessed on computed tomography (CT) scans by analysing skeletal muscle density (SMD) and the amount of intermuscular adipose tissue (IMAT). We investigated whether CT-derived low skeletal muscle quality at ICU admission is independently associated with 6-month mortality and other clinical outcomes.

Methods: This retrospective study included 491 mechanically ventilated critically ill adult patients with a CT scan of the abdomen made 1 day before to 4 days after ICU admission. Cox regression analysis was used to determine the association between SMD or IMAT and 6-month mortality, with adjustments for Acute Physiological, Age, and Chronic Health Evaluation (APACHE) II score, body mass index (BMI), and skeletal muscle area. Logistic and linear regression analyses were used for other clinical outcomes.

Results: Mean APACHE II score was 24 ± 8 and 6-month mortality was 35.6%. Non-survivors had a lower SMD (25.1 vs. 31.4 Hounsfield Units (HU); p < 0.001), and more IMAT (17.1 vs. 13.3 cm2; p = 0.004). Higher SMD was associated with a lower 6-month mortality (hazard ratio (HR) per 10 HU, 0.640; 95% confidence interval (CI), 0.552-0.742; p < 0.001), and also after correction for APACHE II score, BMI, and skeletal muscle area (HR, 0.774; 95% CI, 0.643-0.931; p = 0.006). Higher IMAT was not significantly associated with higher 6-month mortality after adjustment for confounders. A 10 HU increase in SMD was associated with a 14% shorter hospital length of stay.

Conclusions: Low skeletal muscle quality at ICU admission, as assessed by CT-derived skeletal muscle density, is independently associated with higher 6-month mortality in mechanically ventilated patients. Thus, muscle quality as well as muscle quantity are prognostic factors in the ICU.

Trial registration: Retrospectively registered (initial release on 06/23/2016) at ClinicalTrials.gov: NCT02817646 .

Keywords: CT; Computed tomography; Intensive care unit; Intermuscular adipose tissue; Mortality; Muscle; Muscle quality; Myosteatosis; Outcome; Skeletal muscle density.

Figures

Fig. 1
Fig. 1
Example of CT scan analysis. This image shows CT scans at the level of lumbar vertebra 3 of two patients both un-analysed (upper row) and analysed (lower row). The analysed images show muscle tissue (red) and intermuscular adipose tissue (IMAT, green). The patient on the left has more muscle (165 vs. 120 cm2), less IMAT (10 vs. 19.5 cm2), and higher mean skeletal muscle density (42 vs. 18 Hounsfield Units) than the patient on the right
Fig. 2
Fig. 2
Consort diagram showing the inclusion process. CT computed tomography, ICU intensive care unit
Fig. 3
Fig. 3
Kaplan-Meier plots. These graphs illustrate mortality for groups below and above median skeletal muscle density (SMD) (29.2 Hounsfield Units) and median intermuscular adipose tissue (IMAT) (13.6 cm2). ICU intensive care unit

References

    1. Hermans G, Van den Berghe G. Clinical review: intensive care unit acquired weakness. Crit Care. 2015;19:274. doi: 10.1186/s13054-015-0993-7.
    1. Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310:1591–1600. doi: 10.1001/jama.2013.278481.
    1. Ali NA, O'Brien JM, Jr, Hoffmann SP, Phillips G, Garland A, Finley JC, et al. Acquired weakness, handgrip strength, and mortality in critically ill patients. Am J Respir Crit Care Med. 2008;178:261–268. doi: 10.1164/rccm.200712-1829OC.
    1. De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand-Zaleski I, Boussarsar M, et al. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA. 2002;288:2859–2867. doi: 10.1001/jama.288.22.2859.
    1. De Jonghe B, Bastuji-Garin S, Durand MC, Malissin I, Rodrigues P, Cerf C, et al. Respiratory weakness is associated with limb weakness and delayed weaning in critical illness. Crit Care Med. 2007;35:2007–2015. doi: 10.1097/01.ccm.0000281450.01881.d8.
    1. Wieske L, Dettling-Ihnenfeldt DS, Verhamme C, Nollet F, van Schaik IN, Schultz MJ, et al. Impact of ICU-acquired weakness on post-ICU physical functioning: a follow-up study. Crit Care. 2015;19:196. doi: 10.1186/s13054-015-0937-2.
    1. Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364:1293–1304. doi: 10.1056/NEJMoa1011802.
    1. Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304:1787–1794. doi: 10.1001/jama.2010.1553.
    1. Weijs PJ, Looijaard WG, Dekker IM, Stapel SN, Girbes AR, Oudemans-van Straaten HM, et al. Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients. Crit Care. 2014;18:R12. doi: 10.1186/cc13189.
    1. Moisey LL, Mourtzakis M, Cotton BA, Premji T, Heyland DK, Wade CE, et al. Skeletal muscle predicts ventilator-free days, ICU-free days, and mortality in elderly ICU patients. Crit Care. 2013;17:R206. doi: 10.1186/cc12901.
    1. Goodpaster BH, Carlson CL, Visser M, Kelley DE, Scherzinger A, Harris TB, et al. Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study. J Appl Physiol (1985) 2001;90:2157–2165.
    1. Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol. 2013;31:1539–1547. doi: 10.1200/JCO.2012.45.2722.
    1. Antoun S, Lanoy E, Iacovelli R, Albiges-Sauvin L, Loriot Y, Merad-Taoufik M, et al. Skeletal muscle density predicts prognosis in patients with metastatic renal cell carcinoma treated with targeted therapies. Cancer. 2013;119:3377–3384. doi: 10.1002/cncr.28218.
    1. Goodpaster BH, Kelley DE, Thaete FL, He J, Ross R. Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol (1985) 2000;89:104–110.
    1. Parry SM, El-Ansary D, Cartwright MS, Sarwal A, Berney S, Koopman R, et al. Ultrasonography in the intensive care setting can be used to detect changes in the quality and quantity of muscle and is related to muscle strength and function. J Crit Care. 2015;30:1151. doi: 10.1016/j.jcrc.2015.05.024.
    1. Addison O, Marcus RL, Lastayo PC, Ryan AS. Intermuscular fat: a review of the consequences and causes. Int J Endocrinol. 2014;2014:309570. doi: 10.1155/2014/309570.
    1. Coen PM, Goodpaster BH. Role of intramyocelluar lipids in human health. Trends Endocrinol Metab. 2012;23:391–398. doi: 10.1016/j.tem.2012.05.009.
    1. MacDonald AJ, Greig CA, Baracos V. The advantages and limitations of cross-sectional body composition analysis. Curr Opin Support Palliat Care. 2011;5:342–349. doi: 10.1097/SPC.0b013e32834c49eb.
    1. Shen W, Punyanitya M, Wang Z, Gallagher D, St-Onge MP, Albu J, et al. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. J Appl Physiol (1985) 2004;97:2333–2338. doi: 10.1152/japplphysiol.00744.2004.
    1. Schweitzer L, Geisler C, Pourhassan M, Braun W, Gluer CC, Bosy-Westphal A, et al. What is the best reference site for a single MRI slice to assess whole-body skeletal muscle and adipose tissue volumes in healthy adults? Am J Clin Nutr. 2015;102:58–65. doi: 10.3945/ajcn.115.111203.
    1. Ruan XY, Gallagher D, Harris T, Albu J, Heymsfield S, Kuznia P, et al. Estimating whole body intermuscular adipose tissue from single cross-sectional magnetic resonance images. J Appl Physiol (1985) 2007;102:748–754. doi: 10.1152/japplphysiol.00304.2006.
    1. Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33:997–1006. doi: 10.1139/H08-075.
    1. Aubrey J, Esfandiari N, Baracos VE, Buteau FA, Frenette J, Putman CT, et al. Measurement of skeletal muscle radiation attenuation and basis of its biological variation. Acta Physiol (Oxf) 2014;210:489–497. doi: 10.1111/apha.12224.
    1. Baracos V, Kazemi-Bajestani SM. Clinical outcomes related to muscle mass in humans with cancer and catabolic illnesses. Int J Biochem Cell Biol. 2013;45:2302–2308. doi: 10.1016/j.biocel.2013.06.016.
    1. Delmonico MJ, Harris TB, Visser M, Park SW, Conroy MB, Velasquez-Mieyer P, et al. Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr. 2009;90:1579–1585. doi: 10.3945/ajcn.2009.28047.
    1. Manini TM, Clark BC, Nalls MA, Goodpaster BH, Ploutz-Snyder LL, Harris TB. Reduced physical activity increases intermuscular adipose tissue in healthy young adults. Am J Clin Nutr. 2007;85:377–384.
    1. Zderic TW, Hamilton MT. Physical inactivity amplifies the sensitivity of skeletal muscle to the lipid-induced downregulation of lipoprotein lipase activity. J Appl Physiol (1985) 2006;100:249–257. doi: 10.1152/japplphysiol.00925.2005.
    1. Bey L, Hamilton MT. Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity. J Physiol. 2003;551:673–682. doi: 10.1113/jphysiol.2003.045591.
    1. Hikida RS, Gollnick PD, Dudley GA, Convertino VA, Buchanan P. Structural and metabolic characteristics of human skeletal muscle following 30 days of simulated microgravity. Aviat Space Environ Med. 1989;60:664–670.
    1. Ferretti G, Antonutto G, Denis C, Hoppeler H, Minetti AE, Narici MV, et al. The interplay of central and peripheral factors in limiting maximal O2 consumption in man after prolonged bed rest. J Physiol. 1997;501(Pt 3):677–686. doi: 10.1111/j.1469-7793.1997.677bm.x.
    1. Wagenmakers AJ. A malonyl-CoA fuel sensing mechanism in muscle: effects of insulin, glucose and denervation. Clin Nutr. 1996;15:144–145. doi: 10.1016/S0261-5614(96)80041-0.
    1. Stein TP, Wade CE. Metabolic consequences of muscle disuse atrophy. J Nutr. 2005;135:1824s–8s.
    1. Lehr S, Hartwig S, Sell H. Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl. 2012;6:91–101. doi: 10.1002/prca.201100052.
    1. Khan IM, Perrard XY, Brunner G, Lui H, Sparks LM, Smith SR, et al. Intermuscular and perimuscular fat expansion in obesity correlates with skeletal muscle T cell and macrophage infiltration and insulin resistance. Int J Obes (Lond) 2015;39:1607–1618. doi: 10.1038/ijo.2015.104.
    1. Lee DE, Kehlenbrink S, Lee H, Hawkins M, Yudkin JS. Getting the message across: mechanisms of physiological cross talk by adipose tissue. Am J Physiol Endocrinol Metab. 2009;296:E1210–E1229. doi: 10.1152/ajpendo.00015.2009.
    1. Reid MB, Lannergren J, Westerblad H. Respiratory and limb muscle weakness induced by tumor necrosis factor-alpha: involvement of muscle myofilaments. Am J Respir Crit Care Med. 2002;166:479–484. doi: 10.1164/rccm.2202005.
    1. Wilcox P, Osborne S, Bressler B. Monocyte inflammatory mediators impair in vitro hamster diaphragm contractility. Am Rev Respir Dis. 1992;146:462–466. doi: 10.1164/ajrccm/146.2.462.
    1. Sharshar T, Bastuji-Garin S, Stevens RD, Durand MC, Malissin I, Rodriguez P, et al. Presence and severity of intensive care unit-acquired paresis at time of awakening are associated with increased intensive care unit and hospital mortality. Crit Care Med. 2009;37:3047–3053. doi: 10.1097/CCM.0b013e3181b027e9.
    1. Casaer MP, Langouche L, Coudyzer W, Vanbeckevoort D, De Dobbelaer B, Guiza FG, et al. Impact of early parenteral nutrition on muscle and adipose tissue compartments during critical illness. Crit Care Med. 2013;41:2298–2309. doi: 10.1097/CCM.0b013e31828cef02.
    1. McGregor RA, Cameron-Smith D, Poppitt SD. It is not just muscle mass: a review of muscle quality, composition and metabolism during ageing as determinants of muscle function and mobility in later life. Longev Healthspan. 2014;3:9. doi: 10.1186/2046-2395-3-9.
    1. Puthucheary ZA, Phadke R, Rawal J, McPhail MJ, Sidhu PS, Rowlerson A, et al. Qualitative ultrasound in acute critical illness muscle wasting. Crit Care Med. 2015;43:1603–1611. doi: 10.1097/CCM.0000000000001016.
    1. World Health Organization. Obesity: preventing and managing the global epedemic: report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i-253.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner