Metoprolol’ün Covid-19 Hastalarındaki Potansiyel Yararları

Year 2022, Volume: 19 Issue: 1, 22 - 29, 28.04.2022

Mustafa Ahmet Huyut , Gersi Alisha Betül Çetintulum Huyut , Alida Alıyeva

https://doi.org/10.35440/hutfd.933801

Abstract

Amaç: Bu çalışmada, ilaca bağlı uzun QT (di-LQTc) aralığı saptanmış olan COVID-19 hastalarında aldıkları tedavilere eklenen metoprololün potansiyel yararlı etkilerini bulmayı amaçladık.
Yöntem: Bu çalışma geriye dönük yapılmış bir çalışmadır. Bu çalışmadaki veriler, 1 Nisan ile 1 Haziran 2020 tarihleri arasında serviste yatırılmış, gerçek zamanlı polimeraz zincir reaksiyonu (RT-PCR) ile hastalığı doğrulanan 160 adet Covid-19 pozitif hastanın dosyaları taranarak elde edildi. Di-LQTc'li toplam 52 hastanın dosyaları taranıp metoprolol grubuna dahil edildi ve normal QTc düzeyleri olan toplam 108 hasta da metoprolol tedavisi almayan grup olarak belirlendi.
Bulgular: Ortalama yaş 48.58±16.52 (% 48.75 erkek) olarak saptandı. Hastane içi ölüm oranı %3.125 (n = 5) olarak bulundu. Takip sırasında metoprolol grubunda herhangi ölümcül aritmi görülmedi. Metoprolol grubunda, metoprolol tedavisi öncesi hastalarda pik Qtc 466.50 (458.75-477.50) msn iken, taburculukta 443 (428.75-453) msn'ye düştü. İleri koşullu lojistik regresyon analizi ile, Covid-19 hastalarında bazal C-reaktif protein’in (CRP) (OR = 1.031,% 95 CI: 1.001-1.062, p = 0.043) di-LQTc'nin bağımsız prediktörü olduğunu saptadık.
Sonuç: Di-LQTc'li COVID-19 hastalarının tedavi protokolüne metoprolol eklenerek uzun Qt durumunun geriye döndürülebilir olduğunu düşünmekteyiz.

Keywords

COVID-19, hidroksiklorokin, ilaca bağlı uzamış QTc, metoprolol tartarat

Supporting Institution

yok

Project Number

yok

Metoprolol‘s Potential Beneficial Effects On Covid-19 Patients

Abstract

Background: We aimed to find the potential beneficial effects of metoprolol, which was added to the treatment of COVID-19 patients with drug-induced long corrected QT (di-LQTc) interval. Materials and Methods: This study was a retrospective study. Hospitalized patient files were scanned, and the data of 160 Covid-19 positive patients who were confirmed by real-time polymerase chain reaction (RT-PCR) between April 1 and June 1, 2020, were analyzed. A total of 52 patients’ data with CoVID-19 patients with di-LQTc were scanned and collected in the metoprolol group, and a total of 108 patients’ data with CoVID-19 with normal QTc levels were collected in the non-metoprolol group.
Results: The mean age was 48.58±16.52 (48.75% male). The in-hospital mortality rate was 3.125% (n=5). We did not see any malignant arrhythmias in the groups during follow-up. In the metoprolol group, the peak Qtc was 466.50 (458.75-477.50) msec in patients before metoprolol treatment, whereas it decreased to 443 (428.75-453) msec at discharge. Forward conditional logistic regression analysis demonstrated that basal C-reactive protein (CRP) (OR=1.031, 95%CI: 1.001-1.062, p=0.043) was the independent predictor of di-LQTc in Covid-19 patients.
Conclusion: COVID-19 patients with di-LQTc could be treated and we thought we could reverse the QT prolongation by adding metoprolol to the treatment protocol.

Keywords

COVID-19, drug-induced prolonged QTc, hydroxychloroquine, metoprolol tartrate

Project Number

yok

References

• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
• Huyut MA. Novel Coronavirus Pneumonia and Cardiomyopathy: A Case Report. Nova Pneumonia por Coronavírus e Miocardiopatia: Relato de Caso. Arq Bras Cardiol. 2020;114(5):843-845. doi:10.36660/abc.20200268.
• Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648.
• Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, et al. Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology. 2020 Feb 26:200642. doi: 10.1148/radiol.2020200642.
• Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 Apr;55(4):105932. doi: 10.1016/j.ijantimicag.2020.105932.
• Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020 Mar 18;6:16. doi: 10.1038/s41421-020-0156-0.
• Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20:105949. doi: 10.1016/j.ijantimicag.2020.105949.
• de Paiva MRB, Arribada RG, da Silva CN, Ribeiro MCS, Jorge R, Fialho SL, et al. Assessment of the safety of intravitreal injection of metoprolol tartrate in rabbits. Doc Ophthalmol. 2020 Jul 4. doi: 10.1007/s10633-020-09781-0. Epub ahead of print. PMID: 32623534.
• Harvey RA, Champe PA and Finkel R. Antiarrhythmic drugs. In: Lippincott’s Illustrated Review: Pharmacology. Lippincott Williams & Wilkins; 2009. p. 201.
• Al-Khatib SM, LaPointe NM, Kramer JM, Califf RM. What clinicians should know about the QT interval. JAMA. 2003 Apr 23-30;289(16):2120-7. doi: 10.1001/jama.289.16.2120.
• Armstrong C, Joint National Committee. JNC 8 Guidelines for the Management of Hypertension in Adults, Am Fam Physician 2014 Oct 1;90(7):503-504.
• Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26(Suppl 1): S5‐20.
• National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Third Report of the National Cholesterol Education Program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults final report. Circulation. 2002;106:3143‐3421.
• https://covid19.saglik.gov.tr/Eklenti/39061/0/covid-19rehberieriskinhastatedavisipdf.pdf Access date:05/05/2021
• Du RH, Liu LM, Yin W, Wang W, Guan LL, Yuan ML, et al. Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan, China. Ann Am Thorac Soc. 2020 Jul;17(7):839-846. doi: 10.1513/AnnalsATS.202003-225OC.
• Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 Apr 22;323(20):2052–9. doi: 10.1001/jama.2020.6775.
• Ocak M, Tascanov MB, Şimşek Yurt N, Yurt YC. A new predictor for indicating clinical severity and prognosis in COVID-19 patients: Frontal QRS-T angle. American Journal of Emergency Medicine 50 (2021) 631–635. doi.org/10.1016/j.ajem.2021.09.046.
• Liu W, Tao ZW, Wang L, Yuan ML, Liu K, Zhou L, et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Version 2. Chin Med J (Engl). 2020 May 5;133(9):1032-1038. doi: 10.1097/CM9.0000000000000775.
• Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2011 May 31;123(21):2434-506. doi: 10.1161/CIR.0b013e31821daaf6.
• Furian T, Aguiar C, Prado K, Ribeiro RV, Becker L, Martinelli N, et al. Ventricular dysfunction and dilation in severe sepsis and septic shock: relation to endothelial function and mortality. J Crit Care. 2012 Jun;27(3):319.e9-15.
• Nielsen J, Graff C, Kanters JK, Toft E, Taylor D, Meyer JM. Assessing QT interval prolongation and its associated risks with antipsychotics. CNS Drugs. 2011 Jun 1;25(6):473-90.
• Wu TC, Sacilotto L, Darrieux FCDC, Pisani CF, Melo SL, Hachul DT, et al. QT Interval Control to Prevent Torsades de Pointes during Use of Hydroxychloroquine and/or Azithromycin in Patients with COVID-19. Arq Bras Cardiol. 2020 Jun;114(6):1061-1066. English, Portuguese. doi: 10.36660/abc.20200389.
• Roden DM, Harrington RA, Poppas A, Russo AM. Considerations for drug interactions on QTc interval in exploratory COVID-19 treatment. Heart Rhythm. 2020 Jul;17(7):e231-e232. doi: 10.1016/j.hrthm.2020.04.016. Epub 2020 Apr 14.
• Yazar U, Hızıroğlu S, Karahan S, Ercın ME, Güvercin AR, Ozer Yaman S. Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi. 2021; 11(1): 33-38.
• Sanfilippo F, Corredor C, Fletcher N, Landesberg G, Benedetto U, Foex P, et al. Diastolic dysfunction and mortality in septic patients: a systematic review and meta-analysis. Intensive care medicine 2015 Mar 24.
• Bergstrom A, Andersson B, Edner M, Nylander E, Persson H, Dahlstrom U. Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function. Results of the Swedish Doppler-echocardiographic study (SWEDIC). Eur J Heart Fail 2004 Jun;6(4):453-61.
• Morelli A, Donati A, Ertmer C, Rehberg S, Kampmeier T, Orecchioni A, et al. Microvascular effects of heart rate control with esmolol in patients with septic shock: a pilot study. Critical care medicine 2013 Sep; 41(9):2162-8.
• Wang JF, Meissner A, Malek S, Chen Y, Ke Q, Zhang J, et al. Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis. American journal of physiology Heart and circulatory physiology 2005 Oct;289(4): H1577-83.
• Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. The New England journal of medicine 2005 Feb 10; 352(6):539-48.
• O'Dwyer MJ, Mankan AK, Stordeur P, O'Connell B, Duggan E, White M, et al. The occurrence of severe sepsis and septic shock are related to distinct patterns of cytokine gene expression. Shock (Augusta, Ga) 2006 Dec; 26(6):544-50.
• Cavaillon JM, Adib-Conquy M, Fitting C, Adrie C, Payen D. Cytokine cascade in sepsis. Scandinavian journal of infectious diseases 2003; 35(9):535-44.
• Cain BS, Meldrum DR, Dinarello CA, Meng X, Joo KS, Banerjee A, et al. Tumor necrosis factor-alpha and interleukin-1beta synergistically depress human myocardial function. Critical care medicine 1999 Jul; 27(7):1309-18.
• Hsueh WA, Law R. The central role of fat and effect of peroxisome proliferator-activated receptor-gamma on progression of insulin resistance and cardiovascular disease. The American Journal of Cardiology 2003 Aug 18; 92(4A):3J-9J.
• de Montmollin E, Aboab J, Mansart A, Annane D. Bench-to-bedside review: Beta-adrenergic modulation in sepsis. Critical care (London, England) 2009; 13(5):230.
• Suzuki T, Morisaki H, Serita R, Yamamoto M, Kotake Y, Ishizaka A, et al. Infusion of the beta-adrenergic blocker esmolol attenuates myocardial dysfunction in septic rats. Critical care medicine 2005 Oct; 33(10):2294-301.
• Mori K, Morisaki H, Yajima S, Suzuki T, Ishikawa A, Nakamura N, et al. Beta-1 blocker improves survival of septic rats through preservation of gut barrier function. Intensive care medicine 2011 Nov;37(11):1849-56.
• Hagiwara S, Iwasaka H, Maeda H, Noguchi T. Landiolol, an ultrashort-acting beta1-adrenoceptor antagonist, has protective effects in an LPS-induced systemic inflammation model. Shock (Augusta, Ga) 2009 May;31(5):515-20.
• Ackland GL, Yao ST, Rudiger A, Dyson A, Stidwill R, Poputnikov D, et al. Cardioprotection, attenuated systemic inflammation, and survival benefit of beta1-adrenoceptor blockade in severe sepsis in rats. Critical care medicine 2010 Feb; 38(2):388-94.
• Calzavacca P, Lankadeva YR, Bailey SR, Bailey M, Bellomo R, May CN. Effects of selectivess1-adrenoceptor blockade on cardiovascular and renal function and circulating cytokines in ovine hyperdynamic sepsis. Critical care (London, England) 2014 Nov 21;18(6):610.
• Schmitz D, Wilsenack K, Lendemanns S, Schedlowski M, Oberbeck R. beta-Adrenergic blockade during systemic inflammation: impact on cellular immune functions and survival in a murine model of sepsis. Resuscitation 2007 Feb; 72(2):286-94.
• Muthu K, Deng J, Gamelli R, Shankar R, Jones SB. Adrenergic modulation of cytokine release in bone marrow progenitor-derived macrophage following polymicrobial sepsis. Journal of neuroimmunology 2005 Jan; 158(1-2):50-7.