Citation Information :
Mahale N, Godavarthy P, Marreddy S, Gokhale SD, Funde P, Rajhans PA, Akole PV, Pawar B, Bhurke B, Dalvi P, Marudwar P, Gugale S, Shahane MS, Kshirsagar SN, Jog SA. Intravenous Methylene Blue as a Rescue Therapy in the Management of Refractory Hypoxia in COVID-19 ARDS Patients: A Case Series. Indian J Crit Care Med 2021; 25 (8):934-938.
Objectives: To describe the clinical outcomes of hypoxic coronavirus disease 2019 (COVID-19) patients treated with intravenous methylene blue (MB) in a tertiary care hospital.
Materials and methods: We conducted a case series of 50 patients with hypoxic COVID-19 treated with intravenous MB admitted to our hospital between June 01 and September 10, 2020. Intravenous MB was administered as rescue therapy in dosage of 1 mg/kg body weight, with a maximum of five doses, to patients with high oxygen requirements (SpO2/FiO2 <200) apart from the standard of care after obtaining G6PD levels. Data were abstracted from multiple electronic data sources or patient charts to provide information on patient characteristics, clinical and laboratory variables and outcomes.
Results: The median age of the patients was 53.3 (range 25–74 years) and most patients (74%) were men. About 68% of patients had pre-existing comorbidity. Median SpO2/FiO2 ratio progressively improved from 132.5 (predose) to 284 before the terminal event (death or discharge), ventilator-free days, and decrease in the proinflammatory biochemical parameter was significantly higher after the second dose of MB. A total of six patients out of 50 required invasive mechanical ventilation (IMV). Thirty patients were discharged with a recovery rate of 60%, while 20 patients succumbed to the illness. There was no major side effect or adverse event reported in any of the patients.
Conclusion: MB due to its polypharmacological action against SARS-CoV-2, an inexpensive and widely available drug with minimal side effects, has a significant potential in the treatment of COVID-19.
van de Veerdonk F, Netea MG, van Deuren M, van der Meer JW, de Mast Q, Bruggemann RJ, et al. Kinins and cytokines in COVID-19: a comprehensive pathophysiological approach. Preprints 2020. DOI: 10.20944/preprints202004.0023.v1.
Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020;368(6490):473–474. DOI: 10.1126/science.abb8925.
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ‘cytokine storm’ in COVID-19. J Infect 2020;80(6):607–613. DOI: 10.1016/j.jinf. 2020.03.037.
Salvi R, Patankar P. Emerging pharmacotherapies for COVID-19. Biomed Pharmacother 2020;128:110267. DOI: 10.1016/j. biopha.2020.110267.
Kwok ES, Howes D. Use of methylene blue in sepsis: a systematic review. J Intensive Care Med 2006;21(6):359–363. DOI: 10.1177/0885066606290671.
Bistas E, Sanghavi D. Methylene Blue. [Updated 2020 Jul 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557593/
Clifton J II, Leikin JB. Methylene blue. Am J Therapeut 2003;10(4): 289–291. DOI: 10.1097/00045391-200307000-00009.
Schenk P, Madl C, Rezaie-Majd S, Lehr S, Müller C. Methylene blue improves the hepatopulmonary syndrome. Ann Intern Med 2000;133(9):701–706. DOI: 10.7326/0003-4819-133-9-200011070-00012.
Mayer B, Brunner F, Schmidt K. Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol 1993;45(2):367–374. DOI: 10.1016/0006-2952(93)90072-5.
Ghahestani SM, Shahab E, Karimi S, Madani MH. Methylene blue may have a role in the treatment of COVID-19. Med Hypotheses 2020;144:110163. ISSN 0306-9877. DOI: 10.1016/j.mehy.2020.110163.
Floyd RA, Schinazi RF. Antiviral therapy using thiazine dyes. Google Patents 2002:6346529. Available from: http://www.freepatentsonline.com/6346529.html.
Henry M, Summa M, Patrick L, Schwartz L. A cohort of cancer patients with no reported cases of SARS-CoV-2 infection: the possible preventive role of Methylene Blue. Substantia 2020;4(1):888. DOI: 10.13128/Substantia-888.
Yu B, Jin C, Zhang J, Wu H, Zhou X, Yao H, et al. Methylene blue photochemical treatment as a reliable SARS-CoV-2 plasma virus inactivation method for blood safety and convalescent plasma therapy for the COVID-19 outbreak. BMC Infect Dis 2021;21(1):357. DOI: 10.1186/s12879-021-05993-0.
Cagno V, Medaglia C, Cerny A, Cerny T, Tapparel C, Cerny E. Methylene blue has a potent antiviral activity against SARS-CoV-2 in the absence of UV-activation in vitro. bioRxiv 2020. DOI: 10.1101/2020.08.14.251090.
Bojadzic D, Alcazar O, Buchwald P. Methylene Blue inhibits the SARS-CoV-2 Spike–ACE2 Protein–Protein interaction – a mechanism that can contribute to its antiviral activity against COVID-19. Front Pharmacol 2021;11:600372. DOI: 10.3389/fphar.2020.600372.
Alamdari DH, Moghaddam AB, Amini S, Keramati MR, Zarmehri AM, Alamdari AH, et al. Application of methylene blue-vitamin C-Nacetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial. Eur J Pharmacol 2020;885:173494. DOI: 10.1016/j.ejphar.2020.173494.
Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB. Comparison of the SpO2/FiO2 ratio and the PaO2/FiO2 ratio in patients with acute lung injury or ARDS. Chest 2007;132(2):410–417. DOI: 10.1378/chest.07-0617.
Pisani L, Roozeman JP, Simonis FD, Giangregorio A, van der Hoeven SM, Schouten LR, et al. Risk stratification using SpO2/FiO2 and PEEP at initial ARDS diagnosis and after 24 h in patients with moderate or severe ARDS. Ann Intensive Care 2017;7(1):108. DOI: 10.1186/s13613-017-0327-9.
Brown SM, Grissom CK, Moss M, Rice TW, Schoenfeld D, Hou PC, et al. NIH/NHLBI PETAL Network Collaborators. Nonlinear imputation of PaO2/FiO2 from SpO2/FiO2 among patients with acute respiratory distress syndrome. Chest 2016;150(2):307–313. DOI: 10.1016/j.chest.2016.01.003. PMID:26836924.
Golwalkar D. Treatment for COVID-19 using methylene blue. Medium. 2020. Available at: https://email@example.com/treatment-for-covid-19-using-methylene-blue-d23fc5a31a4d [Accessed April 12, 2020].
Gendrot M, Andreani J, Duflot I, Boxberger M, Bideau ML, Mosnier J, et al. Methylene blue inhibits replication of SARS-CoV-2 in vitro. Int J Antimicrob Agents 2020;56:106202. DOI: 10.1016/j.ijantimicag.2020.106202.
Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 2006;439(7077):682–687. DOI: 10.1038/nature04444.
Vardhana SA, Wolchok JD. The many faces of the anti-COVID immune response. J Exp Med 2020;217(6):e20200678. DOI: 10.1084/jem.20200678.