ICU-acquired weakness in critically ill patients at risk of malnutrition: risk factors, biomarkers, and early enteral nutrition impact

doi:10.5847/wjem.j.1920-8642.2025.020

Abstract

Abstract:

BACKGROUND This study aimed to explore the risk factors associated with intensive care unit-acquired weakness (ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nutrition (EEN) and the role of biomarkers in managing ICU-AW.

METHODS: This retrospective, observational cohort study included 180 patients at risk of malnutrition admitted to the emergency intensive care unit of the First Affiliated Hospital of Xiamen University Hospital from January 2022 to December 2023. Patients were divided into ICU-AW group and non-ICU-AW group according to whether they developed ICU-AW, or categorized into EEN and parenteral nutrition (PN) groups according to nutritional support. ICU-AW was diagnosed using the Medical Research Council score. The primary outcome was the occurrence of ICU-AW.

RESULTS: The significant factors associated with ICU-AW included age, sex, type of nutritional therapy, mechanical ventilation (MV), body mass index (BMI), blood urea nitrogen (BUN), and creatinine (Cr) levels (P<0.05). The PN group developed ICU-AW earlier than did the EEN group, with a significant difference observed (log-rank P<0.001). Among biomarkers for ICU-AW, the mean prealbumin (PAB)/C-reactive protein (CRP) ratio had the highest diagnostic accuracy (area under the curve [AUC] 0.928, 95% confidence interval [95% CI] 0.892-0.946), surpassing the mean Cr/BUN ratio (AUC 0.740, 95% CI 0.663-0.819) and mean transferrin levels (AUC 0.653, 95% CI 0.574-0.733).

CONCLUSION: Independent risk factors for ICU-AW include female sex, advanced age, PN, MV, lower BMI, and elevated BUN and Cr levels. EEN may potentially delay ICU-AW onset, and the PAB/CRP ratio may be an effective diagnostic marker for this condition.

Key words: Intensive care units, Muscular weakness, Hospital-acquired condition, Enteral nutrition, Biomarkers, Risk factors

Qingliu Zheng, Changyun Liu, Lingying Le, Qiqi Wu, Zhihong Xu, Jiyan Lin, Qiuyun Chen. ICU-acquired weakness in critically ill patients at risk of malnutrition: risk factors, biomarkers, and early enteral nutrition impact[J]. World Journal of Emergency Medicine, 2025, 16(1): 51-56.

Figures/Tables 5

Table 1.

Table 2.

Table 3.

Figure 1.

Figure 2.

References 35

1	Jolley SE, Bunnell AE, Hough CL. ICU-acquired weakness. Chest. 2016; 150(5):1129-40. doi: S0012-3692(16)47575-6 pmid: 27063347
2	Kress JP, Hall JB. ICU-acquired weakness and recovery from critical illness. N Engl J Med. 2014; 370(17): 1626-35.
3	Piva S, Fagoni N, Latronico N. Intensive care unit-acquired weakness: unanswered questions and targets for future research. F1000Res. 2019; 8: F1000FacultyRev-508.
4	Dres M, Jung B, Molinari N, Manna F, Dubé BP, Chanques G, et al. Respective contribution of intensive care unit-acquired limb muscle and severe diaphragm weakness on weaning outcome and mortality: a post hoc analysis of two cohorts. Crit Care. 2019; 23(1):370.
5	Vanhorebeek I, Latronico N, BergheVan den G. ICU-acquired weakness. Intensive Care Med. 2020; 46(4):637-53. doi: 10.1007/s00134-020-05944-4 pmid: 32076765
6	Nakae R, Sekine T, Tagami T, Kodani E, Warnock G, Igarashi Y, et al. Rapidly progressive brain atrophy in ventilated patients: a retrospective descriptive study. Sci Rep. 2024; 14(1): 29729.
7	Li Y, Xie YP, Li XM, Lu T. Effects of early standardized enteral nutrition on preventing acute muscle loss in the acute exacerbation of chronic obstructive pulmonary disease patients with mechanical ventilation. World J Emerg Med. 2023; 14(3): 193-7. doi: 10.5847/wjem.j.1920-8642.2023.046 pmid: 37152533
8	Zhang B, Xu HQ, Xiao QG, Wei WZ, Ma YF, Chen XL, et al. Machine learning predictive model for aspiration risk in early enteral nutrition patients with severe acute pancreatitis. Heliyon. 2024; 10(23): e40236.
9	Khalil A, Alamri RA, Aljabri GH, Shahat EA, Almughamsi RI, Almeshhen WA. A cross-sectional study of the impact of ICU-acquired weakness: prevalence, associations, and severity. Cureus. 2023; 15(12): e49852.
10	Nakamura K, Nakano H, Ikechi D, Mochizuki M, Takahashi Y, Ogawa Y, et al. Coagulopathy correlates with muscle titin injury in critically ill patients. J Crit Care. 2023; 74: 154234.
11	OLSEN CW. Lesions of peripheral nerves developing during coma. J Am Med Assoc. 1956; 160(1):39-41. doi: 10.1001/jama.1956.02960360041008 pmid: 13271159
12	Zhou WD, Yu LL, Fan YY, Shi BS, Wang XH, Chen TL, et al. Effect of early mobilization combined with early nutrition on acquired weakness in critically ill patients (EMAS): a dual-center, randomized controlled trial. PLoS One. 2022; 17(5): e0268599.
13	Wang WK, Xu CJ, Ma XL, Zhang XM, Xie P. Intensive care unit-acquired weakness: a review of recent progress with a look toward the future. Front Med (Lausanne). 2020; 7: 559789.
14	Tortuyaux R, Davion JB, Jourdain M. Intensive care unit-acquired weakness: questions the clinician should ask. Rev Neurol (Paris). 2022; 178(1-2):84-92.
15	Liu JJ, Xu ZX, Luo SH, Bai YJ, Feng J, Li FX. Risk factors for ICU-acquired weakness in sepsis patients: a retrospective study of 264 patients. Heliyon. 2024; 10(11): e32253.
16	Sinha RK, Sinha S, Nishant P, Morya AK. Intensive care unit-acquired weakness and mechanical ventilation: a reciprocal relationship. World J Clin Cases. 2024; 12(18): 3644-7. doi: 10.12998/wjcc.v12.i18.3644 pmid: 38983411
17	Yang Z, Wang XH, Wang FY, Peng ZY, Fan YY. A systematic review and meta-analysis of risk factors for intensive care unit acquired weakness. Medicine (Baltimore). 2022; 101(43): e3140.
18	Sakamoto K, Kurokawa J. Pathophysiology of skeletal muscle during sepsis. Nihon Yakurigaku Zasshi. 2024; 159(2):112-7. doi: 10.1254/fpj.23040 pmid: 38432919
19	Chen J, Huang M. Intensive care unit-acquired weakness: Recent insights. J Intensive Med. 2023; 4(1): 73-80.
20	Xie J, Gao J, Yang M, Zhang T, Liu Y, Chen Y, et al. Prediction of sepsis within 24 hours at the triage stage in emergency departments using machine learning. World J Emerg Med. 2024; 15(5):379-85. doi: 10.5847/wjem.j.1920-8642.2024.074 pmid: 39290601
21	He Y, Duan WR, Xu P, Lin TP, Xiang Q, Dong BR, et al. Exploring the impact of interleukins on sarcopenia development: a systematic review and meta-analysis. Exp Gerontol. 2024; 193:112480.
22	Nakamura K, Hatakeyama J, Liu K, Yamakawa K, Nishida T, Ohshimo S, et al. Relationship between critical care nutrition and post-intensive care syndrome in surviving ventilated patients with COVID-19: a multicenter prospective observational study. J Clin Biochem Nutr. 2024; 74(1): 74-81. doi: 10.3164/jcbn.23-66 pmid: 38292118
23	Abe R, Shimazui T, Sugo M, Ogawa A, Namekawa M, Kitamura N, Kido S. Achievement of adequate nutrition contributes to maintaining the skeletal muscle area in patients with sepsis undergoing early mobilization: a retrospective observational study. BMC Nutr. 2024; 10(1):32.
24	McNelly AS, Bear DE, Connolly BA, Arbane G, Allum L, Tarbhai A, et al. Effect of intermittent or continuous feed on muscle wasting in critical illness: a phase 2 clinical trial. Chest. 2020; 158(1): 183-94. doi: S0012-3692(20)30584-5 pmid: 32247714
25	Liu Y, Zhao W, Chen W, Shen X, Fu R, Zhao Y, et al. Effects of early enteral nutrition on immune function and prognosis of patients with sepsis on mechanical ventilation. J Intensive Care Med. 2020; 35(10):1053-61. doi: 10.1177/0885066618809893 pmid: 30384813
26	Fan E, Cheek F, Chlan L, Gosselink R, Hart N, Herridge MS, et al. An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. Am J Respir Crit Care Med. 2014 ; 190(12):1437-46.
27	Li Y, Cheng JX, Yang HH, Chen LP, Liu FJ, Wu Y, et al. Transferrin receptor 1 plays an important role in muscle development and denervation-induced muscular atrophy. Neural Regen Res. 2021; 16(7): 1308-16. doi: 10.4103/1673-5374.301024 pmid: 33318410
28	Wu WB, Guo XL, Qu TQ, Huang YJ, Tao J, He J, et al. The combination of lactoferrin and creatine ameliorates muscle decay in a sarcopenia murine model. Nutrients. 2024; 16(12):1958.
29	Kobak K, Kasztura M, Dziegala M, Bania J, Kapuśniak V, Banasiak W, et al. Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions. Int J Mol Med. 2018; 41(5):2678-86. doi: 10.3892/ijmm.2018.3481 pmid: 29436580
30	Huang MY, Xu BQ, Xu YH, Zhang KY, Zhu WY, Lian XY, et al. Serum iron level is independently associated with sarcopenia: a retrospective study. Sci Rep. 2024; 14(1): 10554. doi: 10.1038/s41598-024-61429-0 pmid: 38719903
31	Ma J, Xia Y, Wang T, Chen J, Yang H, Ding H. Dynamic changes of diaphragm and limb skeletal muscle in patients with sepsis assessed by bedside ultrasound and their correlation with blood urea/creatinine ratio. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2024; 36(6):643-648. Chinese.
32	Araújo VA, Souza JS, Giglio BM, Lobo PCB, Pimentel GD. Association of calf circumference with clinical and biochemical markers in older adults with COVID-19 admitted at intensive care unit: a retrospective cross-sectional study. Diseases. 2024; 12(5):97.
33	Shah NS, Khan SS, Carnethon MR, Bacong AM, Palaniappan LP. Diabetes-related cardiovascular and all-cause mortality in asian american subgroups. JACC Asia. 2023; 3(3):365-72.
34	Yang X, Wang Y, Zhao S, Huang X, Tian B, Yu R, et al. Clinical characteristics and prognosis of Klebsiella pneumoniae meningitis in adults. Heliyon. 2024; 10(7):e28010.
35	Wang X, Wang J, He S, Li J, Chen X, Ma T, et al. The clinical characteristics of non-cystic fibrosis bronchiectasis patients with positive serum tumor markers: a retrospective study. BMC Pulm Med. 2024; 24(1):20. doi: 10.1186/s12890-023-02816-7 pmid: 38191360

Parameters	ICU-AW (n=75)	Non-ICU-AW (n=105)	OR	95% CI	P-value
Male, n (%)	45 (60.0)	68 (64.8)	0.336	0.179-0.628	0.001
Age, years, median (IQR)	74.0 (67.0-84.0)	73.0 (65.5-82.0)	1.085	1.049-1.123	<0.001
BMI, kg/m², median (IQR)	19.6 (17.8-21.6)	21.0 (19.4-20.8)	0.716	0.622-0.824	<0.001
Underlying disease, n (%)
Hypertension	36 (48.0)	50 (47.6)	0.960	0.544-1.782	0.985
Diabetes	26 (34.7)	24 (22.9)	0.083	0.246-3.185	0.558
Malignant tumor	17 (22.7)	11 (10.5)	2.505	1.097-5.721	0.029
MV, n (%)	18 (24.0)	13 (12.4)	2.235	1.018-4.905	0.048
TRF, g/L, median (IQR)	2.5 (2.3-3.3)	2.6 (2.1-2.9)	0.545	0.326-0.910	0.020
PAB, mg/L, median (IQR)	110.0 (89.0-160.0)	124.0 (98.0-180.0)	0.998	0.993-1.003	0.419
ALB, g/L, median (IQR)	35.2 (33.2-37.5)	33.8 (32.5-32.7)	1.167	1.047-1.300	0.005
CRP, mg/L, median (IQR)	77.6 (65.3-89.8)	69.3 (63.3-80.0)	1.007	1.996-1.019	0.205
IL-6, pg/mL, median (IQR)	63.2 (42.3-78.3)	58.3 (36.1-66.9)	1.016	1.002-1.030	0.022
BUN, mmol/L, median (IQR)	11.8 (10.5-12.8)	9.1 (7.8-10.2)	2.548	1.903-3.411	<0.001
Cr, μmol/L, median (IQR)	124.0 (105.0-198.0)	99.0 (87.0-111.0)	1.016	1.009-1.023	<0.001
EEN, n (%)	32 (42.7)	64 (61.9)	0.477	0.261-0.871	0.016

Parameters	ICU-AW (n=75)	Non-ICU-AW (n =105)	OR	95% CI	P-value
Male, n	45/75	68/105	0.210	0.064-0.994	0.010
Age, years, median (IQR)	74.0 (67.0-84.0)	73.0 (65.5-82.0)	1.132	1.058-1.326	<0.001
EEN, n	32/75	64/105	0.280	0.889-0.887	0.029
MV, n	18/75	13/105	2.212	1.546-4.065	0.032
BMI, kg/m², median (IQR)	19.6 (17.8-21.6)	21.0 (19.4-20.8)	0.613	0.451-0.831	0.002
IL-6, pg/mL, median (IQR)	63.2 (42.3-78.3)	58.3 (36.1-66.9)	1.005	0.981-1.560	0.687
TRF, g/L, median (IQR)	2.5 (2.3-3.3)	2.6 (2.1-2.9)	0.327	0.126-1.099	0.741
Cr, μmol/L, median (IQR)	124.0 (105.0-198.0)	99.0 (87.0-111.0)	1.347	1.197-1.986	<0.001
BUN, mmol/L, median (IQR)	11.8 (10.5-12.8)	9.1 (7.8-10.2)	2.183	1.518-3.139	<0.001
ALB, g/L, median (IQR)	35.2 (33.2-37.5)	33.8 (32.5-32.7)	1.179	0.930-1.495	0.174

Parameters	EEN (n=96)	PN (n=84)	P-value
Male, n (%)	63 (65.63)	50 (59.52)	0.398
Age, years, median (IQR)	74.0 (67.0-82.8)	72.5 (65.3-81.8)	0.497
BMI, kg/m², median (IQR)	21.0 (19.4-20.8)	20.6 (19.2-22.1)	0.167
Underlying disease, n (%)
Hypertension	42 (43.8)	44 (52.4)	0.247
Diabetes	28 (29.2)	22 (26.2)	0.657
Malignant tumor	17 (17.7)	11 (13.1)	0.394
MV, n (%)	16 (16.7)	15 (17.9)	0.833
TRF, g/L, median (IQR)	2.6 (2.2-3.1)	2.6 (2.1-3.2)	0.447
PAB, mg/L, median (IQR)	137.9 (97.3-169.5)	144.4 (96.5-180.0)	0.673
ALB, g/L, median (IQR)	34.5 (32.5-36.5)	34.7 (32.5-36.5)	0.937
CRP, mg/L, median (IQR)	73.6 (65.1-86.5)	75.9 (62.9-89.7)	0.654
IL-6, pg/mL, median (IQR)	56.0 (42.1-68.3)	58.6 (35.7-76.9)	0.500
BUN, mmol/L, median (IQR)	10.0 (8.6-10.9)	10.5 (8.9-12.3)	0.210
Cr, μmol/L, median (IQR)	129.8 (91.3-143.3)	120.6 (95.3-124.0)	0.946

[1]	Fengxia Du, Jun Zha, Yan Li, Lichao Fang, Shuyu Xia, Youjia Yu. Risk factors for postpartum posttraumatic stress disorder after emergency admission [J]. World Journal of Emergency Medicine, 2024, 15(2): 121-125.
[2]	Tian Yan, Ziyin Chen, Shengdong Zou, Zefan Wang, Quan Du, Wenhua Yu, Wei Hu, Yongke Zheng, Keyi Wang, Xiaoqiao Dong, Shuangyong Dong. A prospective cohort study on serum A20 as a prognostic biomarker of aneurysmal subarachnoid hemorrhage [J]. World Journal of Emergency Medicine, 2023, 14(5): 360-366.
[3]	Xinlei Wang, Yao Sun, Xiaoyu Ni, Shu Zhang. Development and validation of an emergency bloodstream infection score for predicting in-hospital mortality in patients with community-acquired bloodstream infections [J]. World Journal of Emergency Medicine, 2023, 14(4): 280-286.
[4]	Yue Li, Yong-peng Xie, Xiao-min Li, Tao Lu. Effects of early standardized enteral nutrition on preventing acute muscle loss in the acute exacerbation of chronic obstructive pulmonary disease patients with mechanical ventilation [J]. World Journal of Emergency Medicine, 2023, 14(3): 193-197.
[5]	Hong-yan Wei, Wen-jie Liang, Bin Li, Ling-yu Wei, An-qi Jiang, Wei-dong Chen, Peng-hao Guo, Jia Xu. Clinical characteristics and risk factors of Talaromyces marneffei infection in human immunodeficiency virus-negative patients: A retrospective observational study [J]. World Journal of Emergency Medicine, 2021, 12(4): 281-286.
[6]	Wan-qin Xie, Lin Zhou, Yong Chen, Bin Ni. Circulating microRNAs as potential biomarkers for diagnosis of congenital heart defects [J]. World Journal of Emergency Medicine, 2016, 7(2): 85-89.
[7]	Hong-wei Zhang, Li-you Wei, Gang Zhao, Ya-jing Yang, Shu-zheng Liu, Zhen-yu Zhang, Zhang Jing, Yan-ling Hu. Periplaneta americana extract used in patients with systemic inflammatory response syndrome [J]. World Journal of Emergency Medicine, 2016, 7(1): 50-54.
[8]	Gan-nan Wang, Jin-song Zhang, Wei-juan Cao, Hao Sun, Jing Zhang, Yao Wang, Hang Xiao. Association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China [J]. World Journal of Emergency Medicine, 2013, 4(1): 32-37.
[9]	Xue-zhong Xing, Yong Gao, Hai-jun Wang, Quan-hui Yang, Chu-lin Huang, Shi-ning Qu, Hao Zhang, Hao Wang, Qing-ling Xiao, Ke-lin Sun. Risk factors and prognosis of critically ill cancer patients with postoperative acute respiratory insufficiency [J]. World Journal of Emergency Medicine, 2013, 4(1): 43-47.
[10]	Yan Chen, Wei Yang, Gan-nan Wang, Jun Li, Xiao-rong Li, Jian Zhang, Wei Yuan, Dao-wu Wang, Jin-song Zhang, Ke-jiang Cao. Circulating microRNAs, novel biomarkers of acute myocardial infarction: a systemic review [J]. World Journal of Emergency Medicine, 2012, 3(4): 257-260.
[11]	Jun He, Xiang-yu Hou, Sam Toloo, Jennifer R Patrick, Gerry Fitz Gerald. Demand for hospital emergency departments: a conceptual understanding [J]. World Journal of Emergency Medicine, 2011, 2(4): 253-261.
[12]	Jing Zhang, Yao Wang, Gan-nan Wang, Hao Sun, Tao Sun, Jian-quan Shi, Hang Xiao, Jin-song Zhang. Clinical factors in patients with ischemic versus hemorrhagic stroke in East China [J]. World Journal of Emergency Medicine, 2011, 2(1): 18-23.
[13]	Yu-feng Chu, Yi Jiang, Mei Meng, Jin-jiao Jiang, Ji-cheng Zhang, Hong-sheng Ren, Chun-ting Wang. Incidence and risk factors of gastrointestinal bleeding in mechanically ventilated patients [J]. World Journal of Emergency Medicine, 2010, 1(1): 32-36.