Association of SOFA Score with Severity of Muscle Wasting in Critically Ill Patients: A Prospective Observational Study

HIGHLIGHTS

Muscle wasting is a notorious complication in the critically ill. The more the severity of illness, the higher the chances of wasting.

INTRODUCTION

The incidence of muscle wasting, in critically ill patients requiring admission in intensive care units (ICUs) can be up to 2% per day.¹ It adversely affects both immediate and long-term outcomes. Muscle wasting is greatest in patients with multiorgan dysfunction and occurs early (first 10 days).² Intensive care units acquired muscle weakness adversely affects recovery and it independently predicts 1 year mortality.^2–4

Immobilization, inflammation, stress response, infection, nutritional deficiency, inadequate glycemic control, drugs mainly steroids, neuromuscular blocking agents, etc. are the various causes of muscle weakness.⁵ Numerous studies have debunked the association of lean body mass depletion and nutritional support.⁶ Increasing the nutrition delivery is not found to prevent the decrease in muscle mass.²

Ultrasound (USG) is a novel noninvasive tool used for the evaluation of muscle wasting. A systemic review of seven studies suggested the potential and appreciable reliability of muscle USG.⁷ B mode ultrasonographic evaluation of rectus femoris is a dependable tool to assess muscle wasting. The USG measurements of muscles have been found to correlate well with magnetic resonance imaging (MRI) and computerized tomography (CT) measurements.^8,9

Sequential organ failure assessment (SOFA) score is a tool to assess organ dysfunction or failure. Studies have validated the SOFA score, maximum SOFA during ICU stay, and change in the SOFA over a period of time for assessing morbidity in critical illnesses.^10,11 The highest, mean or the total maximum SOFA scores are indicative of cumulative organ dysfunction.¹⁰ A SOFA score ≥2 is indicative of organ dysfunction and confers a mortality of 10%.¹²

In this study, we evaluated muscle wasting in ICU patients by measuring the thickness of the rectus femoris muscle on the day of admission day 1 and day 7, using a USG. The severity of illness in these patients was calculated using daily SOFA scores till day 7. This study aimed to determine the occurrence of muscle wasting in critically ill patients, and if so, its relationship with the severity of illness defined by the highest SOFA score during the study period. The primary objective was to assess if rectus femoris (RF) thickness, as measured by ultrasound, on day 1 and day 7 of ICU admission, can be an indicator of muscle wasting. The secondary objective was to determine the relation between muscle wasting and SOFA score.

MATERIALS AND METHODS

We conducted a prospective, observational study in a multidisciplinary ICU at a tertiary care center in Thiruvananthapuram. The study was carried out between April 2020 and December 2021. All the patients admitted to the ICU, with an expected length of stay of at least 7 days and willing to consent were enrolled in the study. Patients aged <18 years and >65 years, pregnant patients, patients with a history of neuromuscular disorders, bedridden patients, those on long-term corticosteroids, patients with amputated limbs or admitted with burn injury, those referred from other ICUs, unwilling to consent or patients who were shifted out or died within 7 days in the ICU were excluded.

RESULTS

This prospective study was done on 50 patients, of whom 33 were males and 17 were females. The majority were in the age-group 61–70 years (48%). Mean ± SD was 56.4 ± 9.7 (Table 1).

The mean height of the study population was 168.9 ± 8.2 cm (range 153–182 cm). The mean ideal body weight was 63.5 ± 9.2 kg (range 46 and 76.9 kg) (Table 2).

About 36 patients in the sample (72%) received mechanical ventilation while 14 (28%) did not receive mechanical ventilation (Fig. 1).

The mean rectus femoris thickness on day 1 was 1.32 ± 0.06 cm and on day 7 was 1.16 ± 0.08 cm. The mean difference in the thickness of the rectus femoris on day 1 and day 7 was 0.16 cm. The difference was statistically significant (t = 11.99, p < 0.01) (Table 3).

There was a statistically significant positive correlation between the highest SOFA score during the study period and the difference in rectus femoris thickness (r = 0.886, p < 0.01) (Fig. 2).

DISCUSSION

This study included 50 patients, all of whom stayed in the ICU for at least 7 days and received the standard prescribed nutrition as per the ICU protocol. The mean age-group of the sample was 56.4 ± 9.7 years and 48% of them were between 60 and 65 years. Males constituted 66% of the population and females accounted for 34%. The mean height was 168.9 ± 8.2 cm and median height was 169 (163.5–176.25) cm. The mean ideal body weight was 63.5 ± 9.2 kg and the median ideal body weight was 65.11 (56.04–71.7) kg. During the study period, 72% of the sample was on invasive ventilation. The highest SOFA score was 17. This study showed a significant difference in rectus femoris thickness between day 1 and day 7, indicating the occurrence of muscle wasting and there was a positive correlation between the wasting and the highest SOFA score during the study period. The mean RF thickness on day 1 was 1.32 ± 0.06 and on day 7 was 1.16 ± 0.08. The mean difference was 0.16 cm which was statistically significant (p < 0.01). This established the occurrence of muscle wasting in the critically ill population. It was found to have a positive correlation with the highest SOFA score during the study period (r = 0.886, p < 0.01).

In the study by Katari et al.,¹⁴ on day 3, the RF thickness was 1.26 ± 0.41 as compared to 1.37 ± 0.41 on day 1 (p < 0.001). On day 7, the thickness was 1.22 ± 0.47. This difference was highly significant (p < 0.001). The mean RF thickness difference in the same study was 0.149 cm and was statistically significant. Puthucheary et al.¹⁶ in their study found that RF thickness underestimated muscle wasting, while rectus femoris cross-sectional area (CSA) had a better correlation with muscle wasting. A study by Pardo et al.¹⁷ showed that the median thickness on admission was 1.72 cm (95% CI, 1.62; 2.13) and 1.45 cm on day 7 (95% CI, 1.24; 1.665), which corresponded to a 16% significant variation in muscle thickness [− 0.32 cm (95% CI, − 0.43; − 0.2), p < 0.01]. They continued the study up to 21 days and the median thickness reduced to 1.3 cm on day 21 [95% CI, 0.80; 1.48] which signaled a total loss of 24% of muscle thickness [− 0.6 cm, (95% CI, -0.76; −0.42), p < 0.01]. The difference in the muscle thickness on admission between our study participants and the above can be attributed to the physical difference in the population. Arai et al.¹⁸ found that the thickness of the rectus femoris had the discriminative power to assess sarcopenia at the area under the curve (AUC) of 0.84 (95% CI, 0.74–0.94).

Lower limb muscles are prone to early atrophy. Studies have shown a greater decrease in the thickness of the lower limbs within the first 5 days of admission to the ICU as compared to the upper limbs.¹⁹ Rectus femoris is easy to identify and measure compared to quadriceps. A systematic review showed that the most common method of assessing musculature using USG in the literature is muscle layer thickness (MLT), and not CSA.²⁰ The advantage of MLT is that it can be obtained easily at the bedside.²¹ Another flaw highlighted by the review was the inconsistency in the landmarks for measuring the RF thickness.²⁰ The majority of the studies measured the distance between the anterior superior iliac spine (ASIS) and the patella, but we measured it between the anterior inferior iliac spine (AIIS) and patella as it fell in the midline. There was no consensus on the site of measurement also. Some measured at midpoint, some at 2/3rd. We preferred the 2/3rd point and the measurement on day 7 was also done at the exact same point. Pardo et al. showed that the 2/3rd point was more accurate than the midpoint.¹⁷

SOFA ≥ 2 signifies multiorgan dysfunction. We found that there was a significant positive correlation between the highest SOFA score and a decrease in RFT. Pearson correlation value was 0.886, p < 0.01. This shows that the more the severity of the illness, more the occurrence of muscle wasting or muscle wasting increases with each organ involvement. Even though 72% of the study population was mechanically ventilated, the effect of ventilation on wasting was not studied. Similarly, many of the patients were on vasopressors and renal replacement therapy. Whether this had any predominant contribution to muscle wasting is yet to be studied.

Clinically significant muscle wasting has not been defined. Critically ill patients develop muscle wasting but the cut-off value beyond which it becomes significant is not known. There is a scarcity of data in this aspect. Bloch et al. classified those with more than 9.24% muscle loss as clinically significant.²²

Most of the studies have utilized CSA or MLT as a measure of wasting. Puthucheary et al. opined that CSA is superior to MLT.¹⁶ The limitation of CSA is that it is technically difficult to obtain a full view of CSA with conventional linear frequency probes. Another parameter that can be used is muscle echogenicity. Parry et al. showed that muscle echogenicity scores increase in quadriceps muscle.²³ Muscle depth, compared between obese, overweight, and normal weight populations using ultrasound was used as a measure of muscle wasting. Muscle depth loss was found to be comparable but not statistically significant.²⁴

Many studies have shown the occurrence of muscle wasting in the critically ill. Studies comparing SOFA scores and muscle wasting are limited in the literature. This study conveys that by daily calculation of SOFA score, we can predict the chances of muscle wasting early. Higher the SOFA score, more the muscle wasting. In such patients, targeted interventions to prevent muscle wasting can be adopted. Those include early goal-directed mobilization, early muscle stimulation, adequate pain control, optimizing tissue oxygenation, minimizing the use of drugs causing muscle weakness, early enteral nutrition, correction of electrolyte disturbances, etc. Annetta et al. opined that “immobilization and inflammation rather than inadequate nutritional support might be major determinants of loss of muscle”.²⁵ Inactivity and inflammatory states favor muscle protein breakdown proteolysis.²⁶

CONCLUSION

This study demonstrates that there is the occurrence of significant muscle wasting in the critically ill population and the muscle wasting positively correlates with the SOFA score which defines the severity of illness. This study also highlights the role of bedside ultrasound in detecting muscle wasting.

ETHICS COMMITTEE APPROVAL

The questionnaire and methodology for this study were approved by the Human Research Ethics Committee of KIMSHEALTH (KIMS/IHEC/CCM-02/2021).

ORCID

Kiran Rajagopal https://orcid.org/0000-0002-4613-2696

Deepak Vijayan https://orcid.org/0000-0002-5468-5928

Sujith M Thomas https://orcid.org/0000-0002-2758-5702

REFERENCES

1. Wandrag L, Brett SJ, Frost GS, Bountziouka V, Hickson M. Exploration of muscle loss and metabolic state during prolonged critical illness: Implications for intervention? PLoS ONE 2019;14(11):e0224565. DOI: 10.1371/journal.pone.0224565.

2. Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA 2013;310(15):1591–1600. DOI: 10.1001/jama.2013.278481.

3. Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, et al. 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 2014;190(4):410–420. DOI: 10.1164/rccm.201312-2257OC.

4. 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(1):R12. DOI: 10.1186/cc13189.

5. 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):1437–1446. DOI: 10.1164/rccm.201411-2011ST.

6. Streat SJ, Beddoe AH, Hill GL. Aggressive nutritional support does not prevent protein losses despite fat gain in septic intensive care patients. J Trauma 1987;27(3):262–266. DOI: 10.1097/00005373-198703000-00006.

7. Connolly B, MacBean V, Crowley C, Lunt A, Moxham J, Rafferty GF, et al. Ultrasound for the assessment of peripheral skeletal muscle architecture in critical illness: A systematic review. Crit Care Med 2015;43(4):897–905. DOI: 10.1097/CCM.0000000000000821.

8. Reeves ND, Maganaris CN, Narici MV. Ultrasonographic assessment of human skeletal muscle size. Eur J Appl Physiol 2004;91(1):116–118. DOI: 10.1007/s00421-003-0961-9.

9. Sahathevan S, Khor B, Yeong CH, Tan TH, Meera Mohaideen AK, Ng HM, et al. Validity of ultrasound imaging in measuring quadriceps muscle thickness and cross sectional area in patients receiving maintenance hemodialysis. J Parenter Enter Nutr 2021; 45(2):422–426.DOI: 10.1002/jpen.1867.

10. Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 2001;286(14):1754–1758. DOI: 10.1001/jama.286.14.1754.

11. Lie KC, Lau C-Y, Van Vinh Chau N, West TE, Limmathurotsakul D, for Southeast Asia Infectious Disease Clinical Research N. Utility of SOFA score, management and outcomes of sepsis in Southeast Asia: A multinational multicenter prospective observational study. J Intensive Care 2018;6:9. DOI: 10.1186/s40560-018-0279-7.

12. Lambden S, Laterre PF, Levy MM, Francois B. The SOFA score—development, utility and challenges of accurate assessment in clinical trials. Crit Care 2019;23(1):374. DOI: 10.1186/s13054-019-2663-7.

13. Hulley SB, Cummings SR, Browner WS, Grady D, Newman clinical research: An epidemiologic approach, 4th edition. Philadelphia: L & Wilkins; 2013. Appendix 6C, p. 79.

14. Katari Y, Srinivasan R, Arvind P, Hiremathada S. Point-of-care ultrasound to evaluate thickness of rectus femoris, vastus intermedius muscle, and fat as an indicator of muscle and fat wasting in critically ill patients in a multidisciplinary intensive care unit. Indian J Crit Care Med 2018;22(11):781–788. DOI: 10.4103/ijccm.IJCCM_394_18.

15. Galindo Martín CA, Ubeda Zelaya RDC, Monares Zepeda E, Lescas Méndez OA. ROUNDS studies: Relation of outcomes with nutrition despite severity—round one: Ultrasound muscle measurements in critically ill adult patients. J Nutr Metab 2018;2018:7142325. DOI: 10.1155/2018/7142325.

16. Puthucheary ZA, McNelly AS, Rawal J, Connolly B, Sidhu PS, Rowlerson A, et al. Rectus femoris cross-sectional area and muscle layer thickness: Comparative markers of muscle wasting and weakness. Am J Respir Crit Care Med 2017;195(1):136–138. DOI: 10.1164/rccm.201604-0875LE.

17. Pardo E, El Behi H, Boizeau P, Verdonk F, Alberti C, Lescot T. Reliability of ultrasound measurements of quadriceps muscle thickness in critically ill patients. BMC Anesthesiol 2018;18(1):205. DOI: 10.1186/s12871-018-0647-9.

18. Arai Y, Nakanishi N, Ono Y, Inoue S, Kotani J, Harada M, et al. Rectus femoris muscle mass measured by ultrasound is an indicator of whole-body muscle mass at intensive care unit admission: A Retrospective Study. Research Square 2021. DOI: 10.21203/rs.3.rs-501371/v1.

19. Turton P, Hay R, Taylor J, McPhee J, Welters I. Human limb skeletal muscle wasting and architectural remodeling during five to ten days intubation and ventilation in critical care – An observational study using ultrasound. BMC Anesthesiol 2016;16(1):119. DOI: 10.1186/s12871-016-0269-z.

20. Weinel LM, Summers MJ, Chapple LA. Ultrasonography to measure quadriceps muscle in critically ill patients: A literature review of reported methodologies. Anaesth Intensive Care 2019;47(5):423–434. DOI: 10.1177/0310057X19875152.

21. Paris MT, Mourtzakis M, Day A, Leung R, Watharkar S, Kozar R, et al. Validation of bedside ultrasound of muscle layer thickness of the quadriceps in the critically ill patient (VALIDUM Study). JPEN J Parenter Enteral Nutr 2017;41(2):171–180. DOI: 10.1177/0148607116637852.

22. Bloch SA, Lee JY, Wort SJ, Polkey MI, Kemp PR, Griffiths MJ. Sustained elevation of circulating growth and differentiation factor-15 and a dynamic imbalance in mediators of muscle homeostasis are associated with the development of acute muscle wasting following cardiac surgery. Crit Care Med 2013;41:982–989. DOI: 10.1097/CCM.0b013e318274671b.

23. 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(5):1151e9–e14. DOI: 10.1016/j.jcrc.2015.05.024.

24. Segaran E, Wandrag L, Stotz M, Terblanche M, Hickson M. Does body mass index impact on muscle wasting and recovery following critical illness? A pilot feasibility observational study. J Hum Nutr Diet 2017;30(2):227–235. DOI: 10.1111/jhn.12401.

25. Annetta MG, Pittiruti M, Silvestri D, Grieco DL, Maccaglia A, La Torre MF, et al. Ultrasound assessment of rectus femoris and anterior tibialis muscles in young trauma patients. Ann Intensive Care 2017;7(1):104. DOI: 10.1186/s13613-017-0326-x.

26. Reid MB, Moylan JS. Beyond atrophy: redox mechanisms of muscle dysfunction in chronic inflammatory disease. J Physiol 2011;589(Pt 9):2171–2179. DOI: 10.1113/jphysiol.2010.203356.