Jamal Mawlood KHALAF, Ismail Ibrahim HUSSEIN, Marwan Salih AL-NIMER

Aminophylline as anti-hypoxic add-on therapy in the management of COVID-19 in Baghdad: An experience from single center report case study

Coronavirus has affected people of all ages, gender, and various health status. Persons with chronic diseases or other health conditions may have severe illness from COVID-19. There is no specific drug targeting the coronavirus. Aminophylline is a phosphodiesterase enzyme inhibitor that stimulates the respiratory center and peripherally relaxes the bronchial smooth muscle, which explain its anti-hypoxic effect. This study aimed to show the effect of aminophylline as an anti-hypoxic agent as add-on therapy to the high flow rate oxygen in COVID-19 patients who presented with low blood oxygen. This case managemnt study was carried out in the Army Force HospitalRespiratory Centre from 10th April-20thAugest 2020. Thirty-one patients with severe COVID-19 illness were treated with aminophylline (250-500 mg, slow intravenous infusion, per day) after 2-5 days of respiratory distress. Aminophylline therapy is effective in relieving the hypoxia by elevating the blood saturation with oxygen in 100% (10 out of 10 patients) in COVID-19 patients without evidence of risk factors or concomitant diseases. The effectiveness of aminophylline declined to 81.9% in patients with concomitant diseases, and it was ineffective in 4 patients, three of them survived with artificial ventilation, and one of them was died despite using all supportive measures. In conclusion, Aminophylline as anti-hypoxic agent is associated with improved outcome in severe COVID-19. Its effect is extended to patients with risk factors or concomitant diseases.

PDF

___

[1] Esposito S, Noviello S, Pagliano P. Update on treatment of COVID-19: ongoing studies between promising and disappointing results. Infez Med. 2020; 28(2): 198-211.
[2] Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): A review. JAMA. 2020; 324(8): 782-793.
[3] Wong AW, Fidler L, Marcoux V, Johannson KA, Assayag D, Fisher JH, Hambly N, Kolb M, Morisset J, Shapera S, Ryerson CJ. Practical considerations for the diagnosis and treatment of fibrotic interstitial lung disease during the coronavirus disease 2019 pandemic. Chest. 2020; 158(3): 1069-1078.
[4] Mo X, Jian W, Su Z, Chen M, Peng H, Peng P, Lei C, Chen R, Zhong N, Li S. Abnormal pulmonary function in COVID19 patients at time of hospital discharge. Eur Respir J. 2020; 55(6): 2001217.
[5] Elbeddini A. Sterilization plan of the used metered dose inhalers (MDI) to avoid wastage amid COVID-19 pandemic drug shortage. J Pharm Policy Pract. 2020; 13: 19.
[6] Di Marco F, Guazzi M, Sferrazza Papa GF, Vicenzi M, Santus P, Busatto P, Piffer F, Blasi F, Centanni S. Salmeterol improves fluid clearance from alveolar-capillary membrane in COPD patients: a pilot study. Pulm Pharmacol Ther. 2012; 25(1): 119-123.
[7] Ye ZW, Jin DY. Diagnosis, treatment, control and prevention of SARS-CoV-2 and coronavirus disease 2019: back to the future. Sheng Wu Gong Cheng Xue Bao. 2020; 36(4): 571-592.
[8] Luo WJ, Ling X, Huang RM. Effects of aminophylline on cytokines and pulmonary function in patients undergoing valve replacement. Eur J Cardiothorac Surg. 2004; 25(5): 766-771.
[9] Yang B, Wang GY, Chen B, Qin RB, Xi SL, Chen L. Anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high-altitude exposure. Chin Med Sci J. 2007; 22(1): 62-65.
[10] Schroeder T, Piantadosi CA, Natoli MJ, Autmizguine J, Cohen-Wolkowieczs M, Hamilton KL, Bell C, Klawitter J, Christians U, Irwin DC, Noveck RJ. Safety and ergogenic properties of combined aminophylline and ambrisentan in hypoxia. Clin Pharmacol Ther. 2018; 103(5): 888-898.
[11] Yokoba M, Katagiri M, Ichikawa T, Takakura A, Ishii N, Kurosaki Y, Yamada Y, Tsukushi T, Masuda N, Easton PA, Nishii Y, Okada Y, Abe T. Aminophylline increases respiratory muscle activity during hypercapnia in humans. Pulm Pharmacol Ther. 2015; 30: 96-101.
[12] Dima M, Enatescu I, Craina M, Petre I, Iacob ER, Iacob D. First neonates with severe acute respiratory syndrome coronavirus 2 infection in Romania: Three case reports. Medicine (Baltimore). 2020; 99(3): e21284.
[13] Shao JI, Lin CH, Yang YH, Jeng MJ. Effects of intravenous phosphodiesterase inhibitors and corticosteroids on severe meconium aspiration syndrome. J Chin Med Assoc. 2019; 82: 568-575.
[14] Nair P, Milan SJ, Rowe BH. Addition of intravenous aminophylline to inhaled beta(2)-agonists in adults with acute asthma. Cochrane Database Syst Rev 2012; 12(12): CD002742.
[15] McGonagle D, Sharif K, O'Regan A, Bridgewood C. The role of cytokines including interleukin-6 in covid-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020; 19(6): 102537.
[16] Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. 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.
[17] Tamburro RF, Thomas NJ, Ceneviva GD, Dettorre MD, Brummel GL, Lucking SE. A prospective assessment of the effect of aminophylline therapy on urine output and inflammation in critically ill children. Front Pediatr. 2014; 2: 59.
[18] Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr. 2020; 14(4): 303-310.
[19] AlAjmi MF, Azhar A, Owais M, Rashid S, Hasan S, Hussain A, Rehman MT. Antiviral potential of some novel structural analogs of standard drugs repurposed for the treatment of COVID-19. J Biomol Struct Dyn. 2020; 39(17): 6676-6688.
[20] Sarma P, Shekhar N, Prajapat M, Avti P, Kaur H, Kumar S, Singh S, Kumar H, Prakash A, Dhibar DP, Medhi B. Insilico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain). J Biomol Struct Dyn. 2020: 39(8): 2724-2732.