The Korean Journal of Medicine

  • 제86권1호
  • /
  • Pages.42-48
  • /
  • 2014
  • /
  • 1738-9364(pISSN)
  • /
  • 2289-0769(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
권호 표지
DOI QR코드

DOI QR Code

Propranolol의 용량에 따른 식도 정맥류 재출혈 예방

Maximally Tolerable Versus Low Doses of Propranolol in the Prevention of Esophageal Variceal Rebleeding

  • 권혁용 (대구가톨릭대학교 의과대학 내과학교실) ;
  • 하경호 (대구가톨릭대학교 의과대학 내과학교실) ;
  • 김선영 (대구가톨릭대학교 의과대학 내과학교실) ;
  • 박진홍 (대구가톨릭대학교 의과대학 내과학교실) ;
  • 김지숙 (대구가톨릭대학교 의과대학 내과학교실) ;
  • 김병석 (대구가톨릭대학교 의과대학 내과학교실) ;
  • 이창형 (대구가톨릭대학교 의과대학 내과학교실)
  • Kwon, Hyuk Yong (Department of Internal Medicine, Catholic University of Daegu School of Medicine) ;
  • Ha, Kyung Ho (Department of Internal Medicine, Catholic University of Daegu School of Medicine) ;
  • Kim, Sun Young (Department of Internal Medicine, Catholic University of Daegu School of Medicine) ;
  • Park, Jin Hong (Department of Internal Medicine, Catholic University of Daegu School of Medicine) ;
  • Kim, Ji Suk (Department of Internal Medicine, Catholic University of Daegu School of Medicine) ;
  • Kim, Byung Seok (Department of Internal Medicine, Catholic University of Daegu School of Medicine) ;
  • Lee, Chang Hyeong (Department of Internal Medicine, Catholic University of Daegu School of Medicine)
  • 투고 : 2013.03.06
  • 심사 : 2013.05.15
  • 발행 : 2014.01.01
⟨ 이전 논문 다음 논문 ⟩

초록

목적: 베타차단제는 간경변 환자의 식도 정맥류 재출혈 예방을 위해 널리 이용되어져 왔다. 하지만 베타 차단제를 사용하더라도 문맥압 감소가 충분하지 않으면 식도 정맥류의 재출혈을 유발할 수 있다. 본 연구의 목적은 최대 내약 용량군과 저용량군 사이에 식도 정맥류 재출혈률을 비교하는 것이다. 방법: 식도 정맥류 출혈로 응급 내시경적 정맥류 결찰술을 시행 후 베타차단제를 1개월 이상 복용하였던 95명이 등록되었다. 혈역학적 안정이 이루어진 뒤 모든 환자는 propranolol을 투약하였는데 49명은 최대 내약 용량($154.7{\pm}10.1mg/day$)을 나머지 46명은 저용량($39.1{\pm}5.8mg/day$)을 복용하였다. 식도 정맥류 재출혈 발생을 연구의 종료 시점으로 정하였다. 결과: 최대 내약 용량군과 저용량군 사이에 기본 특징을 비교했을 때, 나이, 성별비, 간경변의 원인, 복수와 뇌증의 유병률, 혈청 크레아티닌, 추적 기간은 차이가 없었다. 최대 내약 용량군에서 저용량군에 비해 Child-Pugh 등급, MELD 점수, 혈청 빌리루빈이 낮았고 프로트롬빈 시간은 짧았으며 베타차단제의 감량률은 높았다. 최대 내약 용량군에서 식도 정맥류 재출혈률은 저용량군에 비해 유의하게 낮았다(38.8% vs. 67.4%, p = 0.007). 식도 정맥류 재출혈에 관여하는 인자로는 Child-Pugh 등급과 propranolol의 용량이 단변량 분석에서 유의한 인자였다. 그러나 다변량 분석에서는 propranolol의 최대 내약 용량만이 식도 정맥류 재출혈을 감소시키는 유의한 인자였다. 결론: 식도 정맥류 재출혈 예방을 위한 propranolol의 효과를 용량에 따라 비교해 보았을 때 최대 내약 용량군이 저용량군보다 우수하였다. 본 연구는 식도 정맥류 재출혈을 예방하기 위해 propranolol을 최대 내약 용량으로 투약하는 것이 중요함을 보여주었다.

Background/Aims: Beta-blockers have been used extensively to prevent esophageal variceal (EV) rebleeding in patients with liver cirrhosis. The aim of this study was to compare the rate of EV rebleeding according to the dose of beta-blocker, between maximally tolerable dose (MTD) and low dose (LD) groups. Methods: A total of 95 patients, who were treated with emergent EV ligation for acute EV bleeding and have since then taken propranolol for 1 month or longer, were enrolled. Forty-nine patients took propranolol at the MTD ($154.7{\pm}10.1mg/day$), and 46 patients took propranolol at the LD ($39.1{\pm}5.8mg/day$). The end point was occurrence of EV rebleeding. Results: The MTD and LD groups were well matched for age, sex, etiologies for cirrhosis, presence of ascites or encephalopathy, serum creatinine levels, and follow-up periods. The MTD group showed relatively lower Child-Pugh scores, mode for end stage liver disease (MELD) scores, and serum bilirubin, as well as shorter prothrombin time, but a higher dose reduction rate, as compared with the LD group. The rate of EV rebleeding was lower in the MTD group than the LD group (38.8% vs. 67.4%, p = 0.007). In the univariate analysis, the risk factors for EV rebleeding were Child-Pugh classification and dose of propranolol. However, the dose of propranolol was only a significant risk factor for EV rebleeding according to the multivariate analysis. Conclusions: The effect of propranolol on the prevention of EV rebleeding was superior in the MTD group than in the LD group.

키워드

참고문헌

  1. Giannini EG, Zaman A, Kreil A, et al. Platelet count/spleen diameter ratio for the noninvasive diagnosis of esophageal varices: results of a multicenter, prospective, validation study. Am J Gastroenterol 2006;101:2511-2519. https://doi.org/10.1111/j.1572-0241.2006.00874.x
  2. D'Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis 1999;19:475-505. https://doi.org/10.1055/s-2007-1007133
  3. Bosch J, Garcia-Pagan JC. Prevention of variceal rebleeding. Lancet 2003;361:952-954. https://doi.org/10.1016/S0140-6736(03)12778-X
  4. Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med 2010;362:823-832. https://doi.org/10.1056/NEJMra0901512
  5. Talwalkar JA, Kamath PS. An evidence-based medicine approach to beta-blocker therapy in patients with cirrhosis. Am J Med 2004;116:759-766. https://doi.org/10.1016/j.amjmed.2004.03.006
  6. Burroughs AK, Jenkins WJ, Sherlock S, et al. Controlled trial of propranolol for the prevention of recurrent variceal hemorrhage in patients with cirrhosis. N Engl J Med 1983;309:1539-1542. https://doi.org/10.1056/NEJM198312223092502
  7. Colombo M, de Franchis R, Tommasini M, Sangiovanni A, Dioguardi N. Beta-blockade prevents recurrent gastrointestinal bleeding in well-compensated patients with alcoholic cirrhosis: a multicenter randomized controlled trial. Hepatology 1989;9:433-438. https://doi.org/10.1002/hep.1840090315
  8. Lebrec D, Poynard T, Bernuau J, et al. A randomized controlled study of propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a final report. Hepatology 1984;4:355-358. https://doi.org/10.1002/hep.1840040301
  9. Wilbur K, Sidhu K. Beta blocker prophylaxis for patients with variceal hemorrhage. J Clin Gastroenterol 2005;39:435-440. https://doi.org/10.1097/01.mcg.0000159222.16032.98
  10. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W; Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46:922-938. https://doi.org/10.1002/hep.21907
  11. Groszmann RJ, Garcia-Tsao G, Bosch J, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005;353:2254-2261. https://doi.org/10.1056/NEJMoa044456
  12. Casado M, Bosch J, Garcia-Pagan JC, et al. Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings. Gastroenterology 1998;114:1296-1303. https://doi.org/10.1016/S0016-5085(98)70436-6
  13. Garcia-Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickman M. Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology 1985;5:419-424. https://doi.org/10.1002/hep.1840050313
  14. Groszmann RJ, Bosch J, Grace ND, et al. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology 1990;99:1401-1407. https://doi.org/10.1016/0016-5085(90)91168-6
  15. Bosch J, Abraldes JG. Variceal bleeding: pharmacological therapy. Dig Dis 2005;23:18-29. https://doi.org/10.1159/000084722
  16. Bosch J, Berzigotti A, Garcia-Pagan JC, Abraldes JG. The management of portal hypertension: rational basis, available treatments and future options. J Hepatol 2008;48(Suppl 1):S68-92.
  17. Hillon P, Lebrec D, Munoz C, Jungers M, Goldfarb G, Benhamou JP. Comparison of the effects of a cardioselective and a nonselective beta-blocker on portal hypertension in patients with cirrhosis. Hepatology 1982;2:528-531.
  18. Mills PR, Rae AP, Farah DA, Russell RI, Lorimer AR, Carter DC. Comparison of three adrenoreceptor blocking agents in patients with cirrhosis and portal hypertension. Gut 1984;25:73-78. https://doi.org/10.1136/gut.25.1.73
  19. Bosch J. Carvedilol for portal hypertension in patients with cirrhosis. Hepatology 2010;51:2214-2218. https://doi.org/10.1002/hep.23689
  20. Lee CH. Prevention of esophageal variceal bleeding. Korean J Gastroenterol 2010;56:155-167. https://doi.org/10.4166/kjg.2010.56.3.155
  21. Minano C, Garcia-Tsao G. Clinical pharmacology of portal hypertension. Gastroenterol Clin North Am 2010;39:681-695. https://doi.org/10.1016/j.gtc.2010.08.015
  22. Anand BS. Drug treatment of the complications of cirrhosis in the older adult. Drugs Aging 2001;18:575-585. https://doi.org/10.2165/00002512-200118080-00002
  23. Tursi T. Use of ${\beta}$-blocker therapy to prevent primary bleeding of esophageal varices. J Am Acad Nurse Pract 2010;22:640-647. https://doi.org/10.1111/j.1745-7599.2010.00567.x
  24. Garcia-Pagan JC, Feu F, Bosch J, Rodes J. Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: a randomized controlled study. Ann Intern Med 1991;114:869-873. https://doi.org/10.7326/0003-4819-114-10-869
  25. Gournay J, Masliah C, Martin T, Perrin D, Galmiche JP. Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding. Hepatology 2000;31:1239-1245. https://doi.org/10.1053/jhep.2000.8106
  26. Lebrec D, Vinel JP, Dupas JL. Complications of portal hypertension in adults: a French consensus. Eur J Gastroenterol Hepatol 2005;17:403-410. https://doi.org/10.1097/00042737-200504000-00003
  27. Abraczinskas DR, Ookubo R, Grace ND, et al. Propranolol for the prevention of first esophageal variceal hemorrhage: a lifetime commitment? Hepatology 2001;34:1096-1102. https://doi.org/10.1053/jhep.2001.29305

피인용 문헌

  1. Prevention of Variceal Rebleeding According to the Dose of Propranolol vol.86, pp.1, 2014, https://doi.org/10.3904/kjm.2014.86.1.30