Sarcopenia is the independent predictor of mortality in critically ill patients with cirrhosis

Background: Sarcopenia is strongly associated with poor outcome in cirrhosis. There is little prospective data that sarcopenia influences outcomes in critically ill cirrhotics (CICs). Computed tomography (CT) is the gold standard for sarcopenia assessment in the ICU, as it is independent of hydration status.
Aim: To assess the prevalence of sarcopenia and study its impact on clinical outcomes in CICs.
Methods: In this prospective observational study, CICs admitted to the liver ICU (LICU) were enrolled, if meeting inclusion (age 18-70 years, abdominal CT scan within three months prior to ICU admission) and exclusion criteria (survival likely to be <24 hours, coexisting chronic diseases). Clinical, hemodynamic, biochemical, nutritional parameters, including length of stay (LOS), duration of mechanical ventilation (MV), development of new-onset infections (NOI), incidence of new-onset AKI and overall survival were recorded. CT images at the L3 level were analyzed using Slice-O-Matic V4.3 software to assess the skeletal muscle index (SMI)- expressed as skeletal muscle area (cm2)/height (m2). Sarcopenia was defined if SMI was <50 cm2/m2- males and <39 cm2/m2- females. Data were analyzed using SPSS version 22.
Results: Altogether 111 patients [M-83.8%; age 48.4±11.3 years; etiology: Alcohol- 56 (50.5%), NASH-27 (24.3%), Viral-12 (10.8%), Others-16 (14.4%); CTP-11.9±1.8; MELD-27.8±7.3; SOFA-10.5±4.1; APACHE-23±8; MV-54(48.6%)] were enrolled. Of these, 76 (68.5%) were sarcopenic and 35 (31.5%) non-sarcopenic. Sarcopenic CICs had higher overall mortality (72.4%) compared to non-sarcopenics (40%) [p=0.001, OR (95% CI)- 3.93 (1.69-9.12)], and higher prevalence of sepsis at ICU admission [53.9% vs. 31.4%, p=0.027, OR (95% CI)- 1.7 (1.0-2.92)] than non-sarcopenics. LOS, duration of MV, incidence of NOI, and development of new-onset AKI were comparable between groups. Multivariate binary logistic regression showed that sarcopenia, sepsis, and APACHE II score were independently associated with mortality.
Conclusion: Two-thirds of critically ill cirrhotics have sarcopenia at ICU admission, making them 1.7 times more susceptible to sepsis and increasing the risk of mortality by almost four-fold in the ICU.
Relevance for patients: Almost 70 % of patients with chronic liver disease admitted to the ICU have low muscle mass (sarcopenia). The presence of sarcopenia per se makes them highly prone to infections and increases the chances of death by almost four-fold; thus, highlighting the importance of nutrition optimization in this patient group.
[1] Nadim MK, Durand F, Kellum JA, Levitsky J, O’Leary JG, Karvellas CJ, et al. Management of the Critically Ill Patient with Cirrhosis: A Multidisciplinary Perspective. J Hepatol 2016;64:717-35.
[2] Dasarathy S. Cause and Management of Muscle Wasting in Chronic Liver Disease. Curr Opin Gastroenterol 2016;32:159-65.
[3] Topan MM, Sporea I, Dănilă M, Popescu A, GhiuchiciAM, Lupusoru R, et al. Impact of Sarcopenia on Survival and Clinical Outcomes in Patients With Liver Cirrhosis. Front Nutr 2021;8:766451.
[4] Ando Y, Ishigami M, Ito T, Ishizu Y, Kuzuya T, Honda T, et al. Sarcopenia Impairs Health-related Quality of Life in Cirrhotic Patients. Eur J Gastroenterol Hepatol 2019;31:1550-6.
[5] Welch N, Attaway A, Bellar A, Alkhafaji H, Vural A, Dasarathy S. Compound Sarcopenia in Hospitalized Patients with Cirrhosis Worsens Outcomes with Increasing Age. Nutrients 2021;13:659.
[6] Kalafateli M, Mantzoukis K, Yau YC, Mohammad AO, Arora S, Rodrigues S, et al. Malnutrition and Sarcopenia Predict Post-liver Transplantation Outcomes Independently of the Model for End-stage Liver Disease Score. J Cachexia Sarcopenia Muscle 2017;8:113-21.
[7] Figueiredo F, Perez R, Freitas M, Kondo M. Comparison of Three Methods of Nutritional Assessment in Liver Cirrhosis: Subjective Global Assessment, Traditional Nutritional Parameters, and Body Composition Analysis. J Gastroenterol 2006;41:476-82.
[8] Lee SJ, Janssen I, Heymsfield SB, Ross R. Relation between Whole-body and Regional Measures of Human Skeletal Muscle. Am J Clin Nutr 2004;80:1215-21.
[9] Moisey LL, Mourtzakis M, Cotton BA, Premji T, Heyland DK, Wade CE, et al. Nutrition and Rehabilitation Investigators Consortium (NUTRIC). Skeletal Muscle Predicts Ventilator-free Days, ICU-free Days, and Mortality in Elderly ICU Patients. Crit Care 2013;17:R206.
[10] Kou HW, Yeh CH, Tsai HI, Hsu CC, Hsieh YC, Chen WT, et al. Sarcopenia is an Effective Predictor of Difficult-towean and Mortality among Critically Ill Surgical Patients. PLoS One 2019;14:e0220699.
[11] Toptas M, Yalcin M, Akkoc İ, Demir E, Metin C, Savas Y, et al. The Relation between Sarcopenia and Mortality in Patients at Intensive Care Unit. Biomed Res Int 2018;2018:5263208.
[12] Ju S, Choi SM, Park YS, Lee CH, Lee SM, Yoo CG, et al. Rapid Muscle Loss Negatively Impacts Survival in Critically Ill Patients With Cirrhosis. J Intensive Care Med 2020;35:663-71.
[13] Fleming KM, Aithal GP, Solaymani-Dodaran M, Card TR, West J. Incidence and Prevalence of Cirrhosis in the United Kingdom, 1992-2001: A General Population-based Study. J Hepatol 2008;49:732-8.
[14] Sarin SK, Kedarisetty CK, Abbas Z, Amarapurkar D, Bihari C, Chan AC, et al. Acute-on-chronic Liver Failure: Consensus Recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol Int 2014;8:453-71.
[15] Kvist H, Sjostrom L, Tylen U. Adipose Tissue Volume Determinations in Women by Computed Tomography: Technical Considerations. Int J Obes 1986;10:53-67.
[16] Carey EJ, Lai JC, Wang CW, Dasarathy S, Lobach I, Montano-Loza AJ, et al. Fitness, Life Enhancement, and Exercise in Liver Transplantation Consortium. A Multicenter Study to Define Sarcopenia in Patients with End-stage Liver Disease. Liver Transpl 2017;23:625-33.
[17] Torriani M, Hadigan C, Jensen ME, Grinspoon S. Psoas Muscle Attenuation Measurement with Computed Tomography Indicates Intramuscular Fat Accumulation in Patients with the HIV-lipodystrophy Syndrome. J Appl Physiol (1985) 2003;95:1005-10.
[18] Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med 2017;43:304-77.
[19] van Vught LA, Klein Klouwenberg PM, Spitoni C, SciclunaBP, Wiewel MA, Horn J, et al. MARS Consortium. Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit after Admission for Sepsis. JAMA 2016;315:1469-79.
[20] Acute Kidney Injury Work Group. Kidney Disease: Improving Global Outcome (KDIGO)-Clinical practical Guidelines for Acute Kidney Injury. Kidney Inter 2012;2:1-138.
[21] Nayak SL, Maiwall R, Nandwani A, Ramanarayanan S, Mathur RP, Kumar R, et al. Management of Acute Kidney Injury in Cirrhosis. Hepatol Int 2013;7:813-9.
[22] Nguyen NQ, Fraser RJ, Chapman MJ, Bryant LK, Holloway RH, Vozzo R, et al. Feed Intolerance in Critical Illness is Associated with Increased Basal and Nutrientstimulated Plasma Cholecystokinin Concentrations. Crit Care Med 2007;35:82-8.
[23] Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R. Cadaver Validation of Skeletal Muscle Measurement by Magnetic Resonance Imaging and Computerized Tomography. J Appl Physiol (1985) 1998;85:115-22.
[24] Weijs PJ, Looijaard WG, Dekker IM, Stapel SN, GirbesAR, 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.
[25] Cox MC, Booth M, Ghita G, Wang Z, Gardner A, Hawkins RB, et al. The Impact of Sarcopenia and Acute Muscle Mass Loss on Long-term Outcomes in Critically Ill Patients with Intra-abdominal Sepsis. J Cachexia Sarcopenia Muscle 2021;12:1203-13.
[26] Montano-Loza AJ, Meza-Junco J, Prado CM, Lieffers JR, Baracos VE, Bain VG, et al. Muscle Wasting is Associated with Mortality in Patients with Cirrhosis. Clin Gastroenterol Hepatol 2012;10:166-73.
[27] Kang SH, Jeong WK, Baik SK, Cha SH, Kim MY. Impact of Sarcopenia on Prognostic Value of Cirrhosis: Going Beyond the Hepatic Venous Pressure Gradient and MELD Score. J Cachexia Sarcopenia Muscle 2018;9:860-70.
[28] Montano-Loza AJ, Angulo P, Meza-Junco J, Prado CM, Sawyer MB, Beaumont C, et al. Sarcopenic Obesity and Myosteatosis are Associated with Higher Mortality in Patients with Cirrhosis. J Cachexia Sarcopenia Muscle 2016;7:126-35.
[29] Lucidi C, Lattanzi B, Di Gregorio V, Incicco S, D’Ambrosio D, Venditti M, et al. A Low Muscle Mass Increases Mortality in Compensated Cirrhotic Patients with Sepsis. Liver Int 2018;38:851-7.
[30] Kalafateli M, Konstantakis C, Thomopoulos K, Triantos C. Impact of Muscle Wasting on Survival in Patients with Liver Cirrhosis. World J Gastroenterol 2015;21:7357-61.
[31] Zhang XM, Chen D, Xie XH, Zhang JE, Zeng Y, Cheng AS. Sarcopenia as a Predictor of Mortality among the Critically Ill in an Intensive Care Unit: A Systematic Review and Meta-analysis. BMC Geriatr 2021;2:339.
[32] Kumar V, Benjamin J, Shasthry V, Bharathy KG, Sinha PK, Kumar G, et al. Sarcopenia in Cirrhosis: Fallout on Liver Transplantation. J Clin Exp Hepatol 2020;10:467-76.
[33] Wong CH, Weiss D, Sourial N, Karunananthan S, QuailJM, Wolfson C, et al. Frailty and its Association with Disability and Comorbidity in a Community-dwelling Sample of Seniors in Montreal: A Cross-sectional Study. Aging Clin Exp Res 2010;22:54-62.
[34] Meyer F, Valentini L. Disease-related Malnutrition and Sarcopenia as Determinants of Clinical Outcome. Visc Med 2019;35:282-91.
[35] Gass C, Hipskind P, Tsien C, Malin SK, KasumovT, ShahSN, et al. Sarcopenia and a Physiologically Low Respiratory Quotient in Patients with Cirrhosis: a Prospective Controlled Study. J Appl Physiol 2013;114:559-65.
[36] Peng S, Plank LD, McCall JL, Gillanders LK, McIlroy K, Gane EJ. Body Composition, Muscle Function, and Energy Expenditure in Patients with Liver Cirrhosis: A Comprehensive Study. Am J Clin Nutr 2007;85:1257-66.