Фибрилляция предсердий при сепсисе и потенциальные возможности пропафенона и левокарнитина

Сегодня сепсис представляет одну из важнейших проблем здравоохранения, поскольку заболеваемость им в мире высока и продолжает расти, а летальность достигает 40–60%, особенно при развитии септического шока. Частое поражение сердца при сепсисе – септическая кардиомиопатия (неустоявшийся термин, обозначающий сепсис-обусловленный синдром острой сердечной дисфункции, не связанной с ишемией вследствие поражения венечных артерий) – нередко осложняется возникновением сердечных аритмий. Желудочковые аритмии при этом возникают редко, а фибрилляция предсердий развивается в 20–30% случаев, достигая 45% при септическом шоке. При этом летальность увеличивается примерно в 2–3 раза в случае безуспешности попыток кардиоверсии. Вместе с тем вопросы антиаритмической терапии до сих пор не отрегулированы. Российские и Евразийские клинические рекомендации по лечению фибрилляции предсердий (2025 г.) не содержат упоминаний о сепсисе. А рекомендации Европейских кардиологического общества и ассоциации кардиоторакальных хирургов (2024 г.), дополненные Европейской ассоциацией сердечного ритма (2025 г.), всего лишь констатируют, что сепсис является триггером возникновения фибрилляции предсердий и фактором риска последующего ее рецидивирования почти у половины выписанных пациентов с сепсисом, причем степень воспаления коррелирует с частотой развития и рецидивирования. Обычно используемые для купирования препараты – бета-адреноблокаторы, антагонисты кальция, амиодарон – способны ухудшить ситуацию, отрицательно влияя на гемодинамику септических больных, особенно при шоке. Виновниками гипотензивного действия амиодарона, в частности, является присутствие в его составе эмульгатора полисорбата-80 и бензилового спирта. В статье на основании анализа актуальных клинических исследований и собственного клинического опыта рассматривается применение в этом случае пропафенона, лишенного кардиодепрессивных свойств. Целесообразно также адъювантное использование левокарнитина, обладающего положительными инотропными и антиоксидантными свойствами, а также способного противостоять воспалительным и проаритмическим звеньям патогенеза сепсиса и предотвращать рецидивирование.

1. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395(10219): 200–211. https://doi.org/10.1016/S0140-6736(19)32989-7.

2. Fleischmann-Struzek C, Mellhammar L, Rose N, Cassini A, Rudd KE, Schlattmann P et al. Incidence and mortality of hospitaland ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Intensive Care Med. 2020;46:1552–1562. https://doi.org/10.1007/s00134-020-06151-x.

3. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–810. https://doi.org/10.1001/jama.2016.0287.

4. Gonzalez MA, Ochoa CD. Multiorgan System Failure in Sepsis. In: Ortiz-Ruiz G, Dueñas-Castell C (eds.). Sepsis. New York, NY: Springer; 2018, pp. 67–71. https://doi.org/10.1007/978-1-4939-7334-7_6.

5. Wiersinga WJ, Seymour CW (eds.). Handbook of sepsis. Cham: Springer; 2018. 267 p. https://doi.org/10.1007/978-3-319-73506-1.

6. Vieillard-Baron A, Caille V, Charron C, Belliard G, Page B, Jardin F. Actual incidence of global left ventricular hypokinesia in adult septic shock. Crit Care Med. 2008;36(6):1701–1706. https://doi.org/10.1097/CCM.0b013e318174db05.

7. Ehrman RR, Sullivan AN, Favot MJ, Sherwin RL, Reynolds CA, Abidov A, Levy PD. Pathophysiology, echocardiographic evaluation, biomarker findings, and prognostic implications of septic cardiomyopathy: a review of the literature. Crit. Care. 2018;22:112. https://doi.org/10.1186/s13054-018-2043-8.

8. Anderson BJ, Mikkelsen ME. Organ dysfunction in sepsis: brain, neuromuscular, cardio-vascular, and gastrointestinal. In: Ward NS, Levy MM. Sepsis: Definitions, Pathophysiology and the Challenge of Bedside Management. Cham: Humana Press; 2017, pp. 159–183. https://doi.org/10.1007/978-3-319-48470-9_10.

9. Balik M, Matousek V, Maly M, Brozek T. Management of arrhythmia in sepsis and septic shock. Anaesthesiol Intensive Ther. 2017;49:419–429. https://doi.org/10.5603/AIT.a2017.0061.

10. Meierhenrich R, Steinhilber E, Eggermann C, Weiss M, Voglic S, Bögelein D et al. Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: A prospective observational study. Crit Care. 2010;14:R108. https://doi.org/10.1186/cc9057.

11. Klein Klouwenberg PM, Frencken JF, Kuipers S, Ong DS, Peelen LM, van Vught LA et al. Incidence, predictors, and outcomes of new-onset atrial fibrillation in critically ill patients with sepsis a cohort study. Am J Respir Crit Care Med. 2017;195:205–211. https://doi.org/10.1164/rccm.201603-0618OC.

12. Induruwa I, Hennebry E, Hennebry J, Thakur M, Warburton EA, Khadjooi K. Sepsis-driven atrial fibrillation and ischaemic stroke. Is there enough evidence to recommend anticoagulation? Eur J Intern Med. 2022;98:32–36. https://doi.org/10.1186/cc9057.

13. Xiao F-P, Chen M-Y, Wang L, He H, Jia Z, Kuai L et al. Outcomes of newonset atrial fibrillation in patients with sepsis: A systematic review and meta-analysis of 225,841 patients. Am J Emerg Med. 2021;42:23–30. https://doi.org/10.1016/j.ajem.2020.12.062.

14. Liu WC, Lin WY, Lin CS, Huang HB, Lin TCh, Cheng SM et al. Prognostic impact of restored sinus rhythm in patients with sepsis and new-onset atrial fibrillation. Crit Care. 2016;20:373. https://doi.org/10.1186/s13054-016-1548-2.

15. Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns HJGM et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): Developed by the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC), with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Endorsed by the European Stroke Organisation (ESO). Eur Heart J. 2024;45(36):3314–3414. https://doi.org/10.1093/eurheartj/ehae176.

16. Oprea A, Marina V, Ciobotaru OR, Popescu CM. Evaluation of Amiodarone Administration in Patients with New-Onset Atrial Fibrillation in Septic Shock. Medicina. 2024;60(9):1436. https://doi.org/10.3390/medicina60091436.

17. Curran J, Ross-White A, Sibley S. Magnesium prophylaxis of new-onset atrial fibrillation: A systematic review and meta-analysis. PLoS ONE. 2023;18(10):e0292974. https://doi.org/10.1371/journal.pone.0292974.

18. Walke AJ, Evans SR, Winter MR. Practice Patterns and Outcomes of Treatments for Atrial Fibrillation during Sepsis: A Propensity-Matched Cohort Study. Crit Care. 2016;149:74–83. https://doi.org/10.1378/chest.15-0959.

19. Patel J. Don’t Rush to “Block” Atrial Fibrillation in Sepsis. Chest. 2016;149:1348. https://doi.org/10.3390/medicina60091436.

20. Balik M, Maly M, Brozek T, Rusilek J, Porizka M, Sachl R et al. Propafenone versus amiodarone for supraventricular arrhythmias in septic shock: A randomised controlled trial. Intensive Care Med. 2023;49:1283–1292. https://doi.org/10.1007/s00134-023-07208-3.

21. Taha HS, Youssef G, Omar RM. Efficacy and speed of conversion of recent onset atrial fibrillation using oral propafenone versus parenteral amiodarone: A randomized controlled comparative study. Indian Heart J. 2022;74:212–217. https://doi.org/10.1016/j.ihj.2022.04.006.

22. Balik M, Waldauf P, Maly M. Efficacy and safety of 1C class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone: Protocol of a prospective randomised doubleblind study. BMJ Open. 2019;9:e031678. https://doi.org/10.1136/bmjopen-2019-031678.

23. Аракелян МС, Потешкина НГ, Могутова ПА. Современный взгляд на проблему фибрилляции предсердий и ее рецидивирования. Клиницист. 2011;5(3):10–18. Режим доступа: https://klinitsist.abvpress.ru/Klin/article/view/94.

24. Balik M, Matousek V, Maly M, Brozek T. Management of arrhythmia in sepsis and septic shock. Anaesthesiol Intensive Ther. 2017;49:430–440. https://doi.org/10.5603/AIT.a2017.0061.

25. Keller M, Meierhenrich R. New onset atrial fibrillation in patients with sepsis. Anaesthesist. 2017;66:786–794. https://doi.org/10.1007/s0010-017-0334-0.

26. Waldauf P, Porizka M, Horejsek J, Otahal M. The outcomes of patients with septic shock treated with propafenone compared to amiodarone for supraventricular arrhythmias are related to end-systolic left atrial volume. Eur Heart J Acute Cardiovasc Care. 2024;13:414–422. https://doi.org/10.1093/ehjacc/zuae023.

27. Balik M, Kolnikova I, Maly M, Waldauf P, Tavazzi G, Kristof J. Propafenone for supraventricular arrhythmias in septic shock-Comparison to amiodarone and metoprolol. J Crit Care. 2017;41:16–23. https://doi.org/10.1016/j.jcrc.2017.04.027.

28. Balik M, Matousek V, Maly M, Brozek T. Management of arrhythmia in sepsis and septic shock. Anaesthesiol Intensive Ther. 2017;49:430–440. https://doi.org/10.5603/AIT.a2017.0061.

29. Mackin C, DeWitt ES, Black KJ, Tang X, Polizzotti BD, van den Bosch SJ et al. Intravenous amiodarone and sotalol impair contractility and cardiac output, but procainamide does not: A Langendorff study. J Cardiovasc Pharmacol Ther. 2020;24:288–297. https://doi.org/10.1177/1074248418810811.

30. Jaiswal P, Attar BM, Yap JE, Devani K, Jaiswal R, Wang Y et al. Acute liver failure with amiodarone infusion: A case report and systematic review. J Clin Pharm Ther. 2017;43:129–133. https://doi.org/10.1111/jcpt.12594.

31. Singh VK, Maheshwari V. Acute respiratory distress syndrome complicated by amiodarone induced pulmonary fibrosis: Don’t let your guard down. J Clin Diagn Res. 2017;11:UD01–UD02. https://doi.org/10.7860/JCDR/2017/24710.9674.

32. Somberg JC, Cvetanovic I, Ranade V, Molnar J. Comparative effects of rapid bolus administration of aqueous amiodarone versus 10-minute cordarone I.v. infusion on mean arterial blood pressure in conscious dogs. Cardiovasc Drugs Ther. 2004;18(5):345–351. https://doi.org/10.1007/s10557-005-5058-8.

33. Path GJ, Dai XZ, Schwartz JS, Benditt DG, Bache RJ. Effects of amiodarone with and without polysorbate 80 on myocardial oxygen consumption and coronary blood flow during treadmill exercise in the dog. J Cardiovasc Pharmacol. 1991;18(1):11–16. https://doi.org/10.1097/00005344-199107000-00003.

34. Leite HP, deLima LF. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic? J Thorac Dis. 2016;8(7):552–557. https://doi.org/10.21037/jtd.2016.05.37.

35. Alhasaniah AH. l-Carnitine: nutrition, pathology, and health benefits. Saudi J Biol Sci. 2023;30(2):103555. https://doi.org/10.1016/j.sjbs.2022.103555.

36. Li X, Zhang C, Zhang X, Wang S, Meng Q, Wu S et al. An acetyl-l-carnitine switch on mitochondrial dysfunction and rescue in the metabolomics study on aluminum oxide nanoparticles. Part Fibre Toxicol. 2015;13(1):4–23. https://doi.org/10.1186/s12989-016-0115-y.

37. Zhang ZY, Fan ZK, Cao Y, Jia ZQ, Li G, Zhi XD, Yu DS, Lv G. Acetyl-l-carnitine ameliorates mitochondrial damage and apoptosis following spinal cord injury in rats. Neurosci Lett. 2015;604:18–23. https://doi.org/10.1016/j.neulet.2015.06.021.

38. Tebay LE, Robertson H, Durant ST, Vitale SR, Penning TM, Dinkova-Kostova AT, Hayes JD. Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic Biol Med. 2015;88(Pt B):108–146. https://doi.org/10.1016/j.freeradbiomed.2015.06.021.

39. Lohninger A, Pittner G, Pittner F. L-Carnitine: New Aspects of a Known Compound – A Brief Survey. Monatsh Chem. 2005;136(8):1255–1268. https://doi.org/10.1007/s00706-005-0339-2.

40. Zhang L, Xiu L, Wang T, Zhao D. Effect of L-carnitine in Ameliorating Lipopolysaccharide-Induced Cardiomyocyte Injury via MAPK Signaling. Mol Biotechnol. 2024;66(1):79–89. https://doi.org/10.1007/s12033-023-00731-0.

41. Zhao M, Jiang Q, Wang W. The Roles of Reactive Oxygen Species and Nitric Oxide in Perfluorooctanoic Acid-Induced Developmental Cardiotoxicity and l-Carnitine Mediated Protection. Int J Mol Sci. 2017;18(6):1229. https://doi.org/10.3390/ijms18061229.

42. Fan Z, Han Y, Ye Y, Liu C, Cai H. L-Carnitine preserves cardiac function by activating p38 MAPK/Nrf2 signalling in hearts exposed to irradiation. Eur J Pharmacol. 2017;804:7–12. https://doi.org/10.1016/j.ejphar.2017.04.003.

43. Cui YJ, Song CL, Chen F, Li P, Cheng YB. Myocardial protective effect of L-carnitine in children with hand, foot and mouth disease caused by Coxsackie A16 virus. Zhongguo Dang Dai Er Ke Za Zhi. 2017;19(8):908–912. https://doi.org/10.7499/j.issn.1008-8830.2017.08.012.

44. Mohammadi M, Hajhossein Talasaz A, Alidoosti M. Preventive effect of l-carnitine and its derivatives on endothelial dysfunction and platelet aggregation. Clin Nutr ESPEN. 2016;15:1–10. https://doi.org/10.1016/j.clnesp.2016.06.009.

45. Keshani M, Alikiaii B, Babaei Z, Askari G, Heidari Z, Sharma M, Bagherniya M. The effects of l-carnitine supplementation on inflammation, oxidative stress, and clinical outcomes in critically Ill patients with sepsis: a randomized, double-blind, controlled trial. Nutr J. 2024;23:31. https://doi.org/10.1186/s12937-024-00934-4.

46. Jing L, Zhou LJ, Li WM, Zhang FM, Yuan L, Li S et al. Carnitine regulates myocardial metabolism by Peroxisome Proliferator-Activated Receptoralpha (PPARalpha) in alcoholic cardiomyopathy. Med Sci Monit. 2011;17(1):BR1–9. https://doi.org/10.12659/msm.881311.

47. Lewis RJ, Viele K, Broglio K, Berry SM, Jones AE. An adaptive, phase II, dosefinding clinical trial design to evaluate L-carnitine in the treatment of septic shock based on efficacy and predictive probability of subsequent phase III success. Crit Care Med. 2013;41(7):1674–1678. https://doi.org/10.1097/CCM.0b013e318287f850.

48. Puskarich MA, Kline JA, Krabill V, Claremont H, Jones AE. Preliminary safety and efficacy of l-carnitine infusion for the treatment of vasopressordependent septic shock: a randomized control trial. JPEN J Parenter Enteral Nutr. 2014;38(6):736–743. https://doi.org/10.1177/0148607113495414.

49. Jones AE, Puskarich MA, Shapiro NI, Guirgis FW, Runyon M, Adams JY et al. Effect of levocarnitine vs placebo as an adjunctive treatment for septic shock: the Rapid Administration of Carnitine in Sepsis (RACE) randomized clinical trial. JAMA Netw Open. 2018;1(8):e186076. https://doi.org/10.1001/jamanetworkopen.2018.6076.

50. Sahebnasagh A, Avan R, Monajati M, Hashemi J. Habtemariam S, Negintaji S et al. L-carnitine: Searching for New Therapeutic Strategy for Sepsis Management. Curr Med Chem. 2022;29(18):3300–3323. https://doi.org/10.2174/0929867328666211117092345.

51. Noordali H, Loudon BL, Frenneaux M, Madhani M. Cardiac metabolism – a promising therapeutic target for heart failure. Pharmacol Ther. 2017;182:95–114. https://doi.org/10.1016/j.pharmthera.2017.08.001.

52. Abdollahi H, Abdolahi M, Sedighiyan M, Jafarieh A. The Effect of L-Carnitine on Mortality Rate in Septic Patients: A Systematic Review and Meta-Analysis on Randomized Clinical Trials. Endocr Metab Immune Disord Drug Targets. 2021;21(4):673–681. https://doi.org/10.2174/1871530320666200727150450.

53. Rastgoo S, Fateh ST, Nikbaf-Shandiz M, Rasaei N, Aali Y, Zamani M et al. The effects of L-carnitine supplementation on inflammatory and antiinflammatory markers in adults: a systematic review and dose-response meta-analysis. Inflammopharmacology. 2023;31(5):2173–2199. https://doi.org/10.1007/s10787-023-01323-9.

54. Abolfathi M, Mohd-Yusof BN, Hanipah ZN, Mohd Redzwan S. Zubaidah NH, Mohd R et al. The effects of carnitine supplementation on clinical characteristics of patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med. 2020;48:102273. https://doi.org/10.1016/j.ctim.2019.102273.

55. Askarpour M, Djafarian K, Ghaedi E, Sadeghi O. Sheikhi A, Shab-Bidar S. Effect of L-Carnitine Supplementation on Liver Enzymes: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Arch Med Res. 2020;51(1):82–94. https://doi.org/10.1016/j.arcmed.2019.12.005.

56. Mohammadi M, Hajhossein Talasaz A, Alidoosti M, Pour Hosseini HR, Gholami K, Jalali A, Aryannejad H. Nephroprotective Effects of L-Carnitine against Contrast-Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention: A Randomized Open-Labeled Clini cal Trial. J Tehran Heart Cent. 2017;12(2):57–64. Available at: https://pdfs.semanticscholar.org/5d4d/ea1cf4f6591a6bad93e2121725f09f83010d.pdf.

57. Khalatbari-Soltani S, Tabibi H. Inflammation and L-carnitine therapy in hemodialysis patients: a review. Clin Exp Nephrol. 2015;19(3):331–335. https://doi.org/10.1007/s10157-014-1061-3.

58. Ibarra-Sifuentes HR, Del Cueto-Aguilera Á, Gallegos-Arguijo DA, Castillo-Torres SA, Vera-Pineda R, Martínez-Granados RJ et al. Levocarnitine Decreases Intradialytic Hypotension Episodes: A Randomized Controlled Trial. Ther Apher Dial. 2017;21(5):459–464. https://doi.org/10.1111/1744-9987.12553.

59. Fukami K, Yamagishi S, Sakai K, Nasu M, Okuda S. Effects of switching from oral administration to intravenous injection of l-carnitine on lipid metabolism in hemodialysis patients. Clin Kidney J. 2014;7(5):470–474. https://doi.org/10.1093/ckj/sfu082.

60. Aoki Y, Yamamoto T. Carnitine reduced erythropoietin dose required and improved cardiac function of patients on maintenance hemodialysis. Saudi J Kidney Dis Transpl. 2017;28(3):477–482. https://doi.org/10.4103/1319-2442.206445.

61. Dastan F, Talasaz AH, Mojtahedzadeh M, Karimi A, Salehiomran A, Bina P et al. Randomized Trial of Carnitine for the Prevention of Perioperative Atrial Fibrillation. Semin Thorac Cardiovasc Surg. 2018;30(1):7–13. https://doi.org/10.1053/j.semtcvs.2017.08.006.

62. da Silva Guimarães S, de Souza Cruz W, da Silva L, Maciel G, Huguenin AB, de Carvalho M et al. Effect of L-Carnitine Supplemen tation on Reverse Remodeling in Patients with Ischemic Heart Disease Undergoing Coronary Artery Bypass Grafting: A Randomized, Placebo-Controlled Trial. Ann Nutr Metab. 2017;70(2):106–110. https://doi.org/10.1159/000465531.

63. Li M, Xue L, Sun H, Xu S. Myocardial Protective Effects of L-Carnitine on Ischemia-Reperfusion Injury in Patients With Rheumatic Valvular Heart Disease Undergoing Cardiac Surgery. J Cardiothorac Vasc Anesth. 2016;30(6):1485–1493. https://doi.org/10.1053/j.jvca.2016.06.006.

64. Семиголовский НЮ. Применение левокарнитина при синдроме малого выброса у больных острым инфарктом миокарда. Российский семейный врач. 2013;17(1):45–49. https://doi.org/10.17816/RFD2013145-49.

65. Семиголовский НЮ, Азанов БА, Верцинский ЕК, Иванова ЕВ,Дмитриев МИ, Воронов АГ. Опыт клинического использования левокарнитина у больных с низкой фракцией выброса левого желудочка (острый инфаркт миокарда, дилатационная кардиомиопатия, тромбоэмболия легочной артерии). Клиническая больница. 2013;(1):135–136. Режим доступа: https://elibrary.ru/rcsdmr.

66. Семиголовский НЮ, Верцинский ЕК, Азанов БА, Иванова ЕВ. Положительные инотропные свойства левокарнитина при синдроме малого выброса у больных острым инфарктом миокарда. Кардиология и сердечно­сосудистая хирургия. 2013,6(3):43–46. Режим доступа: https://www.mediasphera.ru/issues/kardiologiya-i-serdechno-sosudistaya-khirurgiya/2013/3/031996-6385201338.

67. Lango R, Smolenski R, Narkiewicz M, Suchorzewska J, Lysiak-Szydlowska W. Influence of L-carnitine and its derivatives on myocardial metabolism and function in ischemic heart disease and during cardiopulmonary bypass. Cardiovasc Res. 2001;51:21–29. https://doi.org/10.1016/s0008-6363(01)00313-3.

68. Асташкин ЕИ, Глезер МГ. Роль L-карнитина в энергетическом обмене кардиомиоцитов и лечении заболеваний сердечно-сосудистой системы. Кардиология и сердечно­сосудистая хирургия. 2012;(2):58–65. Режим доступа: https://www.mediasphera.ru/issues/kardiologiya-i-serdechno-sosudistaya-khirurgiya/2012/6/031996-63852012611.

69. Roussel J, Labarthe F, Thireau J, Ferro F, Farah C, Roy J et al. Carnitine deficiency induces a short QT syndrome. Heart Rhythm. 2016;13(1):165–174. https://doi.org/10.1016/j.hrthm.2015.07.027.

70. Глезер МГ, Асташкин ЕИ, Киселева АЕ. Применение L­карнитина в каче­ стве средства снижения риска развития фатальной аритмии. Патент РФ RU 2014147357, 25.11.2014. Режим доступа: https://patents.google.com/patent/RU2014147357A/ru.