The Effectiveness of High-dose N-acetylcysteine in Severe COVID-19 Patients
Abstract
Abstract—The study's objective was to describe the effect of using high doses of N-acetylcysteine on severe COVID-19 patients. N-acetyl cysteine, known as a mucolytic agent, in high doses (>1200 mg/day) is also known as glutathione boosting treatment, that may reduce proinflammatory cytokine so it may beneficial reduce the risk of severity. This study was an observational descriptive, evaluated from the length of stay of all patients with severe COVID-19 (clinical signs of pneumonia plus severe respiratory distress) and by monitoring the drug use data, laboratory data, and clinical data at Bhayangkara H.S Samsoeri Mertojoso Hospital Surabaya. The data was collected retrospectively from patients' Health Medical Records who got high dose N-acetylcysteine in October 2020 – February 2021, with standard therapy: antivirus (Remdesivir), antibiotics, vitamins, symptomatic and comorbid therapy, anticoagulant, and corticosteroids (Dexamethasone) as inclusion criteria, then described descriptively. The observation result confirmed that the use of a high dose of N-acetylcysteine (NAC) [1 x 1200 – 5000 mg] po/iv had effective and beneficial results as seen from the patients' length of stay, which was 12 days for patients without comorbid and 14 days for patients with comorbid like diabetes and/or hypertension. The use of high dose NAC showed improvement in the patients' clinical condition that is evaluated from improved oxygen saturation by 37%. In addition, the laboratory results are shown an improvement in thorax X-ray by 69% and inflammatory markers like CRP and d-dimer by 100%. Further research that uses a prospective method is needed to get a better result on the use of high-dose NAC in patients with severe COVID-19.
Keywords: high dose, n-acetylcysteine, severe Covid-19 patient
Abstrak—Tujuan dari penelitian ini adalah untuk mendeskripsikan efek penggunaan N-acetylcysteine dalam dosis tinggi (>1200mg/hari) pada pasien COVID-19 yang parah (dengan gejala klinis pneumonia disertai dengan distress pernafasan berat) , dinilai dari lama rawat dan dengan pemantauan data penggunaan obat, data laboratorium, dan data klinis di RS Bhayangkara H.S Samsoeri Mertojoso Surabaya. Data dikumpulkan secara retrospektif dari Rekam Medis Kesehatan pasien yang mendapat N-asetilsistein dosis tinggi pada Oktober 2020 – Februari 2021, dengan terapi standar: antivirus (Remdesivir), antibiotik, vitamin, terapi simtomatik dan komorbiditas, antikoagulan, dan kortikosteroid (Dexametason) sebagai kriteria inklusi, kemudian dideskripsikan secara deskriptif. Hasil observasi menegaskan bahwa penggunaan N-acetylcystein (NAC) dosis tinggi [1 x 1200 – 5000 mg] po/iv memiliki hasil yang efektif dan memberi benefit dilihat dari lama rawat pasien yaitu 12 hari untuk pasien tanpa penyakit penyerta dan 14 hari untuk pasien dengan penyakit penyerta seperti diabetes dan/atau hipertensi. Penggunaan NAC dosis tinggi menunjukkan perbaikan kondisi klinis pasien yang dinilai dari peningkatan saturasi oksigen sebesar 37%. Selain itu, hasil laboratorium menunjukkan peningkatan seperti pada rontgen toraks sebesar 69%, dan penanda inflamasi seperti CRP dan d-dimer sebesar 100%. Diperlukan penelitian lebih lanjut yang menggunakan metode prospektif untuk mendapatkan hasil yang lebih baik pada penggunaan NAC dosis tinggi pada pasien COVID-19 berat.
Kata kunci: dosis tinggi, pasien Covid-19 parah, n-asetilsistein
Downloads
References
Alfhad, H., Saftarina, F., Kurniawan, B., 2020. The Impact of SARS-Cov-2 infection on patients with hypertension. Major. J. 9, 1–5.
Burhan, E., Susanto, A.D., Isbaniah, F., Nasution, S.A., Ginanjar, E., Pitoyo, C.W., Susilo, A., Firdaus, I., Santoso, A., Juzar, D.A., Arif, S.K., Wulung, N.G.H., 2018. Pedoman Tatalaksana COVID-19, in: L., M., F., P., B., A., Sjakti, H.A., Prawira, Y., Putri, N.D. (Eds.), 2020. Pedoman Tatalaksana COVID-19. Edisi Ke-3. Jakarta : Perhimpunan Dokter Paru Indonesia (PDPI), Perhimpunan Dokter Spesialis Kardiovaskular Indonesia (PERKI), Perhimpunan Dokter Spesialis Penyakit Dalam Indonesia (PAPDI), Perhimpunan Dokter Anestesiol.
Bwire, G.M., 2020. Coronavirus: Why Men are More Vulnerable to Covid-19 Than Women? SN Compr. Clin. Med. 2, 874–876. https://doi.org/10.1007/s42399-020-00341-w.
Calzetta, L., Matera, M.G., Rogliani, P., Cazzola, M., 2018. Multifaceted activity of N-acetylcysteine in chronic obstructive pulmonary disease. Expert Rev. Respir. Med. 12, 693–708.
Damayanti, K., Ryusuke, O., 2017. Pneuminia, Fakultas Kedokteran Universitas Udayana.
Davies, P.D.O., 2002. Multi-drug resistant tuberculosis. CPD Infect. 3, 9–12.
De Flora, S., Balansky, R., La Maestra, S., 2020. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J. 34, 13185–13193.
Djalante, R., Lassa, J., Setiamarga, D., Sudjatma, A., Indrawan, M., Haryanto, B., Mahfud, C., Sinapoy, M.S., Djalante, S., Rafliana, I., Gunawan, L.A., Surtiari, G.A.K., Warsilah, H., 2020. Review and analysis of current responses to COVID-19 in Indonesia: Period of January to March 2020. Prog. Disaster Sci. 6, 100091. https://doi.org/https://doi.org/10.1016/j.pdisas.2020.100091
Dos, S., Wagner, G., 2020. Natural history of COVID-19 and current knowledge on treatment therapeutic options. Biomed. Pharmacother. 129, 110493. https://doi.org/10.1016/j.biopha.2020.110493
Elgendy, I.Y., Pepine, C.J., 2020. Why are women better protected from COVID-19: Clues for men? Sex and COVID-19. Int. J. Cardiol. 315, 105–106. https://doi.org/10.1016/j.ijcard.2020.05.026.
Ibrahim, H., Perl, A., Smith, D., Lewis, T., Kon, Z., Goldenberg, R., Yarta, K., Staniloae, C., Williams, M., 2020. Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous n-acetylcysteine. Clin. Immunol. 219. https://doi.org/10.1016/j.clim.2020.108544
Kamceva, G., Arsova-Sarafinovska, Z., Ruskovska, T., Zdravkovska, M., Kamceva-Panova, L., Stikova, E., 2016. Cigarette Smoking and Oxidative Stress in Patients with Coronary Artery Disease. Maced. J. Med. Sci. 4, 636–640. https://doi.org/10.3889/oamjms.2016.117.
Khaira, K., 2010. Meangkal Radikal Bebas dengan Antioksidan. J. Sainstek.
Lai, C.-C., Shih, T.-P., Ko, W.-C., Tang, H.-J., Hsueh, P.-R., 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int. J. Antimicrob. Agents 55, 105924. https://doi.org/10.1016/j.ijantimicag.2020.105924
Levani, Prastya, Mawaddatunnadila, 2021. Coronavirus Disease 2019 (COVID-19): Patogenesis, Manifestasi Klinis dan Pilihan Terapi. J. Kedokt. dan Kesehat. 17, 44–57.
Lim, S., Bae, J.H., Kwon, H.S., Nauck, MA, 2020. COVID-19 and diabetes mellitus : from pathophysiology to clinical management. Nat. Rev. https://doi.org/10.1038/s41574-020-00435-4.
Liskova, A., Samec, M., Koklesova, L., Samuel, S.M., Zhai, K., Al-Ishaq, R.K., Abotaleb, M., Nosal, V., Kajo, K., Ashrafizadeh, M., Zarrabi, A., Brockmueller, A., Shakibaei, M., Sabaka, P., Mozos, I., Ullrich, D., Prosecky, R., La Rocca, G., Caprnda, M., Büsselberg, D., Rodrigo, L., Kruzliak, P., Kubatka, P., 2021. Flavonoids against the SARS-CoV-2 induced inflammatory storm. Biomed. Pharmacother. 138, 111430. https://doi.org/10.1016/j.biopha.2021.111430
Liu, I.Q., 2020. The Impact of COVID-19 Pandemic on High Performance Secondary School Student-Athletes. Sport Journal.org.
Mazzaro, E., Bortolotti, U., Milano, A., Thiene, G., Casarotto, D., 1993. Long term survival without anticoagulation after aortic valve replacement with a Lillehei-Kaster prosthesis. A case report. J. Heart Valve Dis. 2, 1–8.
Medicine, J.H., 2020. Coronavirus COVID-19 (SARSCoV-2).
Moradi, F., Hadi, N., 2021. Quorum-quenching activity of some Iranian medicinal plants. New Microbes New Infect. 42, 100882. https://doi.org/10.1016/j.nmni.2021.100882
Nasi, A., McArdle, S., Gaudernack, G., Westman, G., Melief, C., Rockberg, J., Arens, R., Kouretas, D., Sjolin, J., Mangsbo, S., 2020. Reactive oxygen species as an initiator of toxic innate immune responses in retort to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention. Toxicol. Reports 7, 768–771. https://doi.org/10.1016/j.toxrep.2020.06.003.
Ochs, E., Schegloff, E.A., Thompson, S.A., 2012. Peranan Rumah Sakit. J. Public Health (Bangkok). 1–10.
Organization, WH, 2020. Naming the coronavirus disease (COVID-19) and the virus that causes it.
RI, K.K., 2020. Pedoman Pencegahan dan Pengendalian Coronavirus Disease (COVID-19. Kementerian Kesehatan RI, Jakarta.
Robert, K., 2020. Informationen und Hilfestellungen für Personen mit einem höheren Risiko für einen schweren COVID-19-Krankheitsverlauf. Risikogruppen.
Roorda, 2016. Effect of Pneumenia.
Rusdi, M.S., 2021. Mini Review: Farmakologi pada Corona Virus Disease (Covid-19). Lumbung Farm. J. Ilmu Kefarmasian 54–61.
Santus, P., Corsico, A., Solidoro, P., Braido, F., Di Marco, F., Scichilone, N., 2014. Oxidative Stress and Respiratory System : Pharmacological and Clinical Reappraisal of N-Acetylcysteine. J. Chronic Obstr. Pulm. Dis. 11, 705–717. https://doi.org/10.3109/15412555.2014.898040.
Sari, A.P., Soemantri, J.B., Retnoningsih, E., 2015. Pengaruh N–asetilsistein terhadap transpor mukosilia tuba Eustachius penderita otitis media supuratif kronis tanpa kolesteatoma. Oto Rhino Laryngol. Indones. 45, 90. https://doi.org/10.32637/orli.v45i2.113
Sari, E.F., Rumende, C.M., Harimurti, K., 2017. Faktor–Faktor yang Berhubungan dengan Diagnosis Pneumonia pada Pasien Usia Lanjut. J. Penyakit Dalam Indones. 3, 183. https://doi.org/10.7454/jpdi.v3i4.51
Spearow, J.L., Copeland, L., 2020. Review : Improving Therapeutics for COVID-19 with Glutathione-boosting Treatments that Improve Immune Responses and Reduce the Severity of Viral Infections. https://doi.org/10.31219/osf.io/y7wc2.
Sujana, K.S., Maulida, M., 2021. Efektivitas N-Acetylsistein pada Pasien COVID-19 48, 416–418.
Suprabawati, D.G.A., 2020. Panduan Praktik Klinis Coronavirus Disease 2019 (COVID-19. Ed. 1 1.
Suryadinata, R.V., 2018. Pengaruh Radikal Bebas Terhadap Proses Inflamasi pada Penyakit Paru Obstruktif Kronis (PPOK). Amerta Nutr. 2, 317. https://doi.org/10.20473/amnt.v2i4.2018.317-324
Susilo, A., Rumende, C.M., Pitoyo, C.W., Santoso, W.D., Yulianti, M., Herikurniawan, H., Sinto, R., Singh, G., Nainggolan, L., Nelwan, E.J., Chen, L.K., Widhani, A., Wijaya, E., Wicaksana, B., Maksum, M., Annisa, F., Jasirwan, C.O.M., Yunihastuti, E., 2020. Coronavirus Disease 2019: Tinjauan Literatur Terkini. J. Penyakit Dalam Indones. 7, 45. https://doi.org/10.7454/jpdi.v7i1.415
Sweetman, S.C. (Ed.), 2009. Martindale : The Complete Drug Reference, 36th ed. Pharmaceutical Press, London.
Tian, H., Zhou, Y., Tang, L., Wu, F., Deng, Z., Lin, B., Huang, P., Wei, S., Zhao, D., Zheng, J., Zhong, N., Ran, P., 2020. High-dose N-acetylcysteine for long-term, regular treatment of early-stage chronic obstructive pulmonary disease (GOLD I-II): Study protocol for a multicenter, double-blinded, parallel-group, randomized controlled trial in China. Trials 21, 1–10. https://doi.org/10.1186/s13063-020-04701-8
Vivianni, A., Farhanah, N., 2016. Faktor  Faktor Prediktor Mortalitas Sepsis Dan Syok Sepsis Di Icu Rsup Dr Kariadi. Diponegoro Med. J. (Jurnal Kedokt. Diponegoro) 5, 504–517.
Whittle, J.S., Pavlov, I., Sacchetti, A.D., Atwood, C., Rosenberg, M.S., 2020. Respiratory support for adult patients with COVID‐19. J. Am. Coll. Emerg. Physicians Open 1, 95–101. https://doi.org/10.1002/emp2.12071.
Yuliana, Y., 2020. Corona virus diseases (Covid-19): Sebuah tinjauan literatur. Wellness Heal. Mag. 2, 187–192. https://doi.org/10.30604/well.95212020
Zheng, Z., Peng, F., Xu, B., Zhao, J., Liu, H., Peng, J., Li, Q., Jiang, C., Zhou, Y., Liu, S., Ye, C., Zhang, P., Xing, Y., Guo, H., Tang, W., 2020. Risk factors of critical & mortal COVID-19 cases : A systematic literature review and meta-analysis. J. Infect. 81, 16– 25. https://doi.org/10.1016/j.jinf.2020.04.021.
Zhou, Yang, Wang, 2020. Mengenal Seputar Corona Virus Diseases (Covid-19). Clin. Manag. 21, 1–9.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
- Articles published in Keluwih: JKK are licensed under a Creative Commons Attribution-ShareAlike 4.0 International license. You are free to copy, transform, or redistribute articles for any lawful purpose in any medium, provided you give appropriate credit to the original author(s) and the journal, link to the license, indicate if changes were made, and redistribute any derivative work under the same license.
- Copyright on articles is retained by the respective author(s), without restrictions. A non-exclusive license is granted to Kluwih: JKK to publish the article and identify itself as its original publisher, along with the commercial right to include the article in a hardcopy issue for sale to libraries and individuals.
- By publishing in Keluwih: JKK, authors grant any third party the right to use their article to the extent provided by the Creative Commons Attribution-ShareAlike 4.0 International license.