Should I continue nadolol in my patient with cirrhosis and refractory ascites?

Under certain circumstances, you may need to! Although nonselective beta blockers (NSBBs), such as nadolol and propranolol, have been the cornerstone of medical treatment of portal hypertension in preventing variceal bleeding in patients with cirrhosis for decades, recent reports of their association with worsening survival, increased risk of hepatorenal syndrome and acute kidney injury in patients with refractory ascites or spontaneous bacterial peritonitis [SBP]) 1,2 have added controversy to their routine use in end-stage cirrhosis.

This is because patients with end-stage cirrhosis may be highly dependent on their cardiac output (particularly the heart rate) in maintaining an adequate arterial blood pressure 3-5 and the negative inotropic and chronotropic effects of NSBBs blunt this compensatory mechanism. The result is a drop in the cardiac output that may be particularly significant in the presence of conditions already associated with hypotension, such as sepsis, spontaneous bacterial peritonitis (SBP), or hemorrhage, further increasing the risk of renal hypoperfusion and hepatorenal syndrome.3

Although 2 meta-analysis studies failed to find an association between NSBBs and increased mortality among patients with cirrhosis and ascites, 6,7 serious concerns over the adverse effects of these drugs in at least a subset of patients has not waned.  Some have recommended reducing NSBB dose or discontinuing treatment in patients with refractory ascites or SBP and any of the following parameters: 4

  • Systolic blood pressure <90 mmHg
  • Serum creatinine >1.5 mg/dL
  • Hyponatremia <130 mmol/L

Similar recommendations were made by a 2015 consensus conference on individualizing the care of patients with portal hypertension.

In the absence of randomized-controlled studies, it seems prudent to proceed with more caution when using NSBBs in patients with end-stage cirrhosis and watch closely for any signs of hypotension or renal function deterioration.

References

  1. Serste T, Njimi H, Degre D, et al. The use of beta-lackers is associated with the occurrence of acute kidney injury in severe hepatitis. Liver In 2015;35:1974-82. https://www.ncbi.nlm.nih.gov/pubmed/25611961
  2. Mandorfer M, Bota S, Schwabl P, et al. Nonselective beta blockers increase risk of hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterol 2014;146:1680-90. https://www.sciencedirect.com/science/article/pii/S0016508514003060?via%3Dihub
  3. Garcia-Tsao G. The use of nonselective beta blockers for treatment of portal hypertension. Gastroenterol Hepatol 2017;13: 617-19. http://www.gastroenterologyandhepatology.net/archives/october-2017/the-use-of-nonselective-beta-blockers-for-treatment-of-portal-hypertension/
  4. Reiberger T, Mandorfer M. Beta adrenergic blockade and decompensated cirrhosis. J Hepatol 2017;66: 849-59. https://www.ncbi.nlm.nih.gov/pubmed/27864004
  5. Giannelli V, Lattanzi, Thalheimer U, et al. Beta-blockers in liver cirrhosis. Ann Gastroenterol 2014;27:20-26. https://www.ncbi.nlm.nih.gov/pubmed/24714633
  6. Facciorusso A, Roy S, Livadas S, et al. Nonselective beta-blockers do not affect survival in cirrhotic patients with ascites. Digest Dis Sci 2018;63:1737-46. https://link.springer.com/article/10.1007%2Fs10620-018-5092-6
  7. Njei B, McCarty TR, Garcia-Tsao G. Beta-blockers in patients with cirrhosis and ascites: type of betablocker matters. Gut 206;65:1393-4. https://gut.bmj.com/content/gutjnl/65/8/1393.full.pdf
  8. De Franchis R. Expanding consensus in portal hypertension. Report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension.  J Hepatol 2015;63:743-52.  https://www.ncbi.nlm.nih.gov/pubmed/26047908  

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Should I continue nadolol in my patient with cirrhosis and refractory ascites?

Should I consider octreotide in my patient with non-variceal upper GI bleed?

Octreotide is routinely used in the treatment of variceal bleeding due to its vasoconstrictive effects on the splanchnic vasculature.1 In non-variceal upper GI bleed (NVUGB), however, the evidence for routine use of octreotide is hard to come by with an international consensus panel recommending its use only on a case-by-case basis in patients with very active bleeding while awaiting endoscopy or surgery.2,3

These recommendations are based on the failure of several randomized controlled trials in demonstrating the superiority of octreotide in NVUGB over placebo, either alone or with ranitidine, except in a small subset of patients with actively oozing ulcers.4-6 Although a meta-analysis has suggested that octreotide may reduce the risk of continued bleeding in NVUGB,7 the validity of some of the included studies has been questioned.8

On the other hand, octreotide decreases gastric mucosal blood flow and inhibits acid and pepsin secretion, which may potentially benefit patients who are actively bleeding.9

Final fun fact: Did you know that octreotide may be effective in the treatment of chylothorax?

 

References

  1. Avgerinos A, Armonis A, Raptis S. Somatostatin and octreotide in the management of acute variceal hemorrhage. Hepatogastroenterology 1995;42:145-50. http://europepmc.org/abstract/med/7672763
  2. Barkun AN, Barrdou M, Kulpers EJ, et al. International concensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2010;152:101-113. http://annals.org/aim/article/745521/international-consensus-recommendations-management-patients-nonvariceal-upper-gastrointestinal-bleeding
  3. Barkun A, Bardou M, Marshall JK, Nonvariceal Upper GIBCCG Consensus Conference Group. Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2003;139:843–857. https://www.ncbi.nlm.nih.gov/pubmed/14623622
  4. Nikolopoulou VN, Thomopoulos KC, Katsakoulis EC, et al. The effect of octreotide as an adjunct treatment in active nonvariceal upper gastrointestinal bleeding. J Clin Gastroenterol 2004;38:243-7. http://journals.lww.com/jcge/Abstract/2004/03000/The_Effect_of_Octreotide_as_an_Adjunct_Treatment.9.aspx
  5. Archimandritis A, Tsirantonaki M, Tryphonos M, et al. Ranitidine versus ranitidine plus octreotide in the treatment of acute non-variceal upper gastrointestinal bleeding: a prospective randomized study. Curr Med Res Opin. 2000;16(3):178-83. http://www.tandfonline.com/doi/abs/10.1185/0300799009117023
  6. Okan A, Simsek I, Akpinar H, et al. Somatostatin and ranitidine in the treatment of non-variceal upper gastrointestinal bleeding: a prospective, randomized, double-blind, controlled study. Hepatogastroenterology 2000;47:1325-7. http://europepmc.org/abstract/med/11100343
  7. Imperiale TF, Birgisson S. Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Ann Intern Med 1997;127:1062–1071. http://annals.org/aim/article/711021/somatostatin-octreotide-compared-h-2-antagonists-placebo-management-acute-nonvariceal
  8. Palmer KR. Non-variceal upper gastrointestinal haemorrhage: guidelines. Gut. 2002;51 (Suppl 4): iv1–iv6. http://gut.bmj.com/content/51/suppl_4/iv1.short
  9. Sgouros SN, Bergele C, Viazis N, et al. Somatostatin and its analogues in peptic ulcer bleeding: facts and pathophysiological aspects. Dig Liver Dis. 2006;38:143-8. http://www.sciencedirect.com/science/article/pii/S1590865805002434

 

Contributed byAlice Choi, Medical Student, Harvard Medical School

 

Should I consider octreotide in my patient with non-variceal upper GI bleed?