The Effect of N-Acetylcysteine as Adjuvant Therapy of Hypoxemia in COVID-19 Patients, Assessed by Interleukin-6 Level and PaO2/FiO2 Ratio

Simon Petrus Hardiyanto Rumaratu, Ngakan Putu Parsama Putra, Yani Jane Sugiri, Susanthy Djajalaksana, Aditya Sri Listyoko, Harun al Rasyid

Abstract


Background: Interleukin 6 (IL-6) is a cytokine that plays an essential role in lung damage and mortality. Arterial-to-inspired oxygen (PaO2/FiO2) ratio, also known as the Horowitz index, is a measure of hypoxemia in respiratory failure. N-Acetylcysteine (NAC) might be helpful in managing coronavirus disease 2019 (COVID-19) patients by decreasing the cytokine storm, which will lead to a decrease in disease severity. This study aims to analyze the effect of NAC as adjuvant therapy on IL-6 level and PaO2/FiO2 ratio in COVID-19 patients.

Methods: This is a quasi-experimental, non-equivalent control group designed study of confirmed COVID-19 patients moderate to critical in Saiful Anwar Hospital Malang. Seventy-five patients received NAC intravenously 5000mg/72 hours as adjuvant therapy for seven days, and 16 subjects in the control group. IL-6 level and PaO2/FiO2 ratio were measured on day one and day 8 in both groups from blood samples. Wilcoxon, Mann-Whitney U Test, and Pearson correlation were conducted for statistical analysis.

Results: The decrease in IL-6 level on days 1 to 8 in the NAC group is significantly lower (94.49±253.51) than in the control group (P=0.002). The increase in PaO2/FiO2 ratio from day 1 to day 8 in the NAC group is significantly improving (126.94±76.05), the same as the control group (P<0.001). There is a weak correlation between IL-6 level and PaO2/FiO2 ratio after administration of NAC (r=0.154, P=0.186).

Conclusion: There is a significant decrease in IL-6 level after administration of NAC. NAC has no significant effect on hypoxemia in COVID-19 patients.


Keywords


IL-6, N-acetylcysteine, PaO2/FiO2 ratio

Full Text:

PDF

References


World Health Organization. COVID-19 clinical management: living guidance, 25 January 2021. Geneva: World Health Organization; 2021.

Zhou P, Yang X Lou, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–3.

Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109:102433.

Kementrian Kesehatan Republik Indonesia. Situasi terkini perkembangan coronavirus disease (COVID-19) 10 maret 2021 [Internet]. Infeksi Emerging. 2021 [cited 2020 Oct 20]. Available from: https://infeksiemerging.kemkes.go.id/situasi-infeksi-emerging/situasi-terkini-perkembangan-coronavirus-disease-covid-19-10-maret-2021

Abbasifard M, Khorramdelazad H. The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics. Life Sci. 2020;257:118097.

Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust. 2020;213(2):54-56.e1.

Pallás Beneyto LA, Rodríguez Luis O, Saiz Sánchez C, Coltell O, Bautista Rentero D, Miguel Bayarri V. [Prognostic value of interleukin 6 for death of patients with sepsis]. Med Clin (Barc). 2016;147(7):281–6.

Chen LYC, Hoiland RL, Stukas S, Wellington CL, Sekhon MS. Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome. Vol. 56, The European respiratory journal. 2020. p. 2003006.

Coomes EA, Haghbayan H. Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol. 2020;30(6):1–9.

Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239–42.

Unhale SS, Ansar QB, Sanap S, Thakhre S, Wadatkar S, Bairagi R, et al. A review on corona virus and covid-19. World J Pharm Life Sci. 2020;6(4):109–15.

Suter PM, Domenighetti G, Schaller MD, Laverrière MC, Ritz R, Perret C. N-acetylcysteine enhances recovery from acute lung injury in man. A randomized, double-blind, placebo-controlled clinical study. Chest. 1994;105(1):190–4.

Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A Review on Various Uses of N-Acetyl Cysteine. Cell J. 2017;19(1):11–7.

Guo L, Zhang H, Li W, Zhan D, Wang M. N-acetyl cysteine inhibits lipopolysaccharide-mediated induction of interleukin-6 synthesis in MC3T3-E1 cells through the NF-kB signaling pathway. Arch Oral Biol. 2018;93:149–54.

Qiu P, Zhou Y, Wang F, Wang H, Zhang M, Pan X, et al. Clinical characteristics, laboratory outcome characteristics, comorbidities, and complications of related COVID-19 deceased: a systematic review and meta-analysis. Aging Clin Exp Res. 2020;32(9):1869–78.

Baradaran A, Ebrahimzadeh MH, Baradaran A, Kachooei AR. Prevalence of Comorbidities in COVID-19 Patients: A Systematic Review and Meta-Analysis. Arch bone Jt Surg. 2020;8(Suppl 1):247–55.

Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9(1):1123–30.

Patanavanich R, Glantz SA. Smoking Is Associated With COVID-19 Progression: A Meta-analysis. Nicotine Tob Res. 2020;22(9):1653–6.

Biswas M, Rahaman S, Biswas TK, Haque Z, Ibrahim B. Association of Sex, Age, and Comorbidities with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis. Intervirology. 2021;64(1):36–47.

Abeywardena MY, Leifert WR, Warnes KE, Varghese JN, Head RJ. Cardiovascular biology of interleukin-6. Curr Pharm Des. 2009;15(15):1809–21.

Zhang C, Wu Z, Li J-W, Zhao H, Wang G-Q. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020;55(5):105954.

Wong KK, Lee SWH, Kua KP. N-Acetylcysteine as adjuvant therapy for COVID-19 - A perspective on the current state of the evidence. J Inflamm Res. 2021;14:2993–3013.

Saddadi F, Alatab S, Pasha F, Ganji MR, Soleimanian T. The effect of treatment with N-acetylcysteine on the serum levels of C-reactive protein and interleukin-6 in patients on hemodialysis. Saudi J Kidney Dis Transpl. 2014;25(1):66–72.

Petersson J, Glenny RW. Gas exchange and ventilation–perfusion relationships in the lung. Eur Respir J. 2014;44(4):1023 LP – 1041.

Shi Z, Puyo CA. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Ther Clin Risk Manag. 2020;16:1047–55.

Hagau N, Slavcovici A, Gonganau DN, Oltean S, Dirzu DS, Brezoszki ES, et al. Clinical aspects and cytokine response in severe H1N1 influenza A virus infection. Crit care. 2010;14(6):R203.

Nasonov E, Samsonov M. The role of Interleukin 6 inhibitors in therapy of severe COVID-19. Biomed Pharmacother. 2020;131:110698.




DOI: https://doi.org/10.36497/jri.v42i3.227

Refbacks

  • There are currently no refbacks.




Copyright (c) 2022 Jurnal Respirologi Indonesia

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


INDEXING & PARTNER

SINTA Garuda Indonesian Scientific Journal Database (ISJD) Indonesia One Search (IOS) Crossref

ROAD-ISSN Dimensions Google Scholar 

 

Jurnal Respirologi Indonesia
pISSN: 0853-7704 - eISSN: 2620-3162
Address: Jalan Cipinang Bunder No. 19, Cipinang, Pulogadung, Jakarta Timur, DKI Jakarta 13240, Indonesia
Phone: +62-21-2247-4845
Email: editor@jurnalrespirologi.org


An official publication by
the Indonesian Society of Respirology (ISR)

Creative Commons License
Creative Commons Attribution-NonCommercial 4.0 International License

Statcounter