Clinical efficacy of specialized enteral tube feed with arginine, zinc and antioxidants compared with standard enteral feeds in complex pressure ulcers treatment: an open-label, real-world practice, low interventional randomized parallelgroup trial

Specialised nutritional supplements that promote wound healing shorten the duration of pressure ulcer (PU) healing, but such data are limited in tube-fed patients.

Material and methods. The effectiveness of a specialized enteral tube feed with arginine, zinc and antioxidants (Nutrison Advanced Cubison) in hospitalized patients with PUs was assessed in a multicenter, prospective, randomized, open-label, parallel-group study involving 67 adult patients with stroke or traumatic brain injury with stage 2–3 pressure ulcers. Tube feed using a specialized product (SpP) was compared with standard enteral tube feed (StdP).

Results. Over 28 days, the PU area in the SpP group decreased by an average of 76.9% while in the StdP group by 51.3%; the difference was 26% (95% CI from 5.9% to 45.3%; p = 0.013). By the end of the trial, a decrease in the average PU area by 20% and more from the initial size occurred in most patients in both groups, while the difference between the groups was statistically insignificant (SpP 86.2% vs StdP 69.2%; p > 0.05). The change in total score and components of PUSH© score over 28 days was significant for intragroup changes in both groups (p < 0.001), but intergroup change was statistically insignificant. By the end of the study, complete healing of the PU occurred in 62% of patients in the SpP group compared with 34.6% of patients in the StdP group (difference 27%, 95% CI from 1,6% to 56,5%; p = 0.04). The mean time for complete PU healing was reduced by 3.2 days (SpP 21,3 days vs StdP 24,4 days, 95% CI 1.4 to 4.9; p = 0.005).

Conclusion. Specialised enteral tube feed stimulates PU healing in hospitalised patients compared with a standard tube feed.

1. European Pressure Ulcer Advisory Panel; National Pressure Injury Advisory Panel; and Pan Pacifi c Pressure Injury Alliance. Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline. The International Guideline.; EPUAP/ NPIAP/PPPIA, 2019.

2. Chaboyer W.P., Thalib L., Harbeck E.L., Coyer F.M., Blot S., Bull C. F., Nogueira P. C., & Lin F.F. Incidence and Prevalence of Pressure Injuries in Adult Intensive Care Patients: A Systematic Review and Meta-Analysis. Critical care medicine. 2018;46(11):e1074–e1081. https://doi.org/10.1097/CCM.0000000000003366

3. Lin F.F., Liu Y., Wu Z., Li J., Ding Y., Li C., Jiang Z., Yang J., Wang K., Gao J., Li X., Xia X., Liu H., Li X., Chen X., Yang L., Fang X., Zhao R., Chen J., Labeau S., … on behalf of the DecubICUs Study China Team, the DecubICUs Study Team, and the European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators. Pressure injury prevalence and risk factors in Chinese adult intensive care units: A multi-centre prospective point prevalence study. International wound journal. 2022; 19(3):493–506. https://doi.org/10.1111/iwj.13648

4. Coyer F., Miles S., Gosley S., Fulbrook P., Sketcher-Baker K., Cook J. L., & Whitmore J. Pressure injury prevalence in intensive care versus non-intensive care patients: A state-wide comparison. Australian critical care : offi cial journal of the Confederation of Australian Critical Care Nurses. 2017;30(5):244–250. https://doi.org/10.1016/j.aucc.2016.12.003

5. Harris C. L., & Fraser C. Malnutrition in the institutionalized elderly: the eff ects on wound healing. Ostomy/wound management. 2004;50(10):54–63.

6. Scholl D., & Langkamp-Henken B. Nutrient recommendations for wound healing. Journal of intravenous nursing : the offi cial publication of the Intravenous Nurses Society. 2001;24(2):124– 132.

7. Patel G.K. The role of nutrition in the management of lower extremity wounds. The international journal of lower extremity wounds. 2005;4(1):12–22. https://doi.org/10.1177/1534734605274574

8. Meyer N.A., Muller M.J., & Herndon D.N. Nutrient support of the healing wound. New horizons (Baltimore, Md.). 1994;2(2):202– 214.

9. Witte M.B., & Barbul A. Arginine physiology and its implication for wound healing. Wound repair and regeneration : offi cial publication of the Wound Healing Society [and] the European Tissue Repair Society. 2003;11(6):419–423. https://doi.org/10.1046/j.1524-475x.2003.11605.x

10. Stechmiller J.K. Understanding the role of nutrition and wound healing. Nutrition in clinical practice : offi cial publication of the American Society for Parenteral and Enteral Nutrition. 2010;25(1):61–68. https://doi.org/10.1177/0884533609358997

11. Gomes F., Schuetz P., Bounoure L., Austin P., BallesterosPomar M., Cederholm T., Fletcher J., Laviano A., Norman K., Poulia K.A., Ravasco P., Schneider S.M., Stanga Z., Weekes C.E., & Bischoff S.C. ESPEN guidelines on nutritional support for polymorbid internal medicine patients. Clinical nutrition (Edinburgh, Scotland). 2018;37(1):336–353. https://doi.org/10.1016/j.clnu.2017.06.025

12. Neyens J.C.L., Cereda E., Meijer E.P., Lindholm C., Schols J.M.G.A. Arginine-enriched oral nutritional supplementation in the treatment of pressure ulcers: A literature review. Wound Medicine. 2017;16:46-51. https://doi.org/10.1016/j.wndm.2016.07.002

13. Cereda E., Klersy C., Serioli M., Crespi A., D’Andrea F., & OligoElement Sore Trial Study Group. A nutritional formula enriched with arginine, zinc, and antioxidants for the healing of pressure ulcers: a randomized trial. Annals of internal medicine. 2015;162(3):167–174. https://doi.org/10.7326/M14-0696

14. Cereda E., Klersy C., Andreola M., Pisati R., Schols J. M., Caccialanza R., D’Andrea F., & OligoElement Sore Trial (OEST) Study Group. Cost-effectiveness of a disease-specific oral nutritional support for pressure ulcer healing. Clinical nutrition (Edinburgh, Scotland). 2017;36(1):246–252. https://doi.org/10.1016/j.clnu.2015.11.012

15. Cereda E., Gini A., Pedrolli C., & Vanotti A. Disease-specific, versus standard, nutritional support for the treatment of pressure ulcers in institutionalized older adults: a randomized controlled trial. Journal of the American Geriatrics Society. 2009;57(8):1395–1402. https://doi.org/10.1111/j.1532-5415.2009.02351.x

16. Li Z., Lin F., Thalib L., Chaboyer W. Global prevalence and incidence of pressure injuries in hospitalised adult patients: A systematic review and meta-analysis. International journal of nursing studies. 2020;105:103546. https://doi.org/10.1016/j.ijnurstu.2020.103546

17. Labeau S.O., Afonso E., Benbenishty J., Blackwood B., Boulanger C., Brett S.J., Calvino-Gunther S., Chaboyer W., Coyer F., Deschepper M., et al. Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study. Intensive care medicine. 2021;47:160- 169. doi: 10.1007/s00134-020-06234-9

18. van Anholt R.D., Sobotka L., Meijer E.P., Heyman H., Groen H.W., Topinková E., van Leen M., & Schols J.M. Specifi c nutritional support accelerates pressure ulcer healing and reduces wound care intensity in non-malnourished patients. Nutrition (Burbank, Los Angeles County, Calif.). 2010;26(9):867–872. https://doi.org/10.1016/j.nut.2010.05.009

19. Lew C.C.H., Yandell R., Fraser R.J.L., Chua A.P., Chong M.F.F., & Miller, M. Association Between Malnutrition and Clinical Outcomes in the Intensive Care Unit: A Systematic Review [Formula: see text]. JPEN. Journal of parenteral and enteral nutrition. 2017;41(5):744–758. https://doi.org/10.1177/0148607115625638

20. Berger M.M., Shenkin A., Schweinlin A., Amrein K., Augsburger M., Biesalski H.K., Bischoff S.C., Casaer M.P., Gundogan K., Lepp H.L., de Man A.M.E., Muscogiuri G., Pietka M., Pironi L., Rezzi S., & Cuerda C. ESPEN micronutrient guideline. Clinical nutrition (Edinburgh, Scotland). 2022;41(6):1357– 1424. https://doi.org/10.1016/j.clnu.2022.02.015

21. Bendavid I., Singer P., Theilla M., Themessl-Huber M., Sulz I., Mouhieddine M., Schuh C., Mora B., & Hiesmayr M. NutritionDay ICU: A 7 year worldwide prevalence study of nutrition practice in intensive care. Clinical nutrition (Edinburgh, Scotland). 2017;36(4):1122–1129. https://doi.org/10.1016/j.clnu.2016.07.012

22. PUSH Tool Version 3.0: 9/15/98. Available per: https://www.sralab.org/sites/default/fi les/2017-06/push3.pdf (access 19/01/2023).

23. Collier S.R., Casey D.P., & Kanaley J.A. Growth hormone responses to varying doses of oral arginine. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2005;15(2):136–139. https://doi.org/10.1016/j.ghir.2004.12.004

24. Nevzorova D.V. Guidelines for nutritional support and rehydration of adults in need of palliative care. Pallium: palliative and hospice care. 2022;4(17):12–14 (In Russ.) https://pallium.pro-hospice.ru/