title: Hemodynamic effects of propranolol and nitrates in cirrhotics with transjugular intrahepatic portosystemic stent-shunt.
abstract: BACKGROUND
  The combination of tailored TIPS with vasoactive drugs might allow reduction of the rate of subsequent shunt-related sequelae.
  
  
  METHODS
  We studied cirrhotic patients 8 weeks (median) after TIPS insertion (8-10 mm) for variceal bleeding. Nitrate (0.1 mg/kg) and propranolol (0.15 mg/kg) alone or combined (same dosages) were infused (I h) sequentially at 1-h intervals (n = 17). Similarly, propranolol was randomly compared to placebo (NaCl, n = 14). We measured mean arterial pressure (MAP, mmHg), heart rate (HR) and portal pressure gradient (PPG: portal minus central venous pressure) prior to and after drugs.
  
  
  RESULTS
  Propranolol reduced PPG (mean +/- s, mmHg) significantly (14.8 +/- 3.7 versus 12.1 +/- 3.7; -21% +/- 10%; P < 0.001), while nitrates alone (14.3 +/- 3.4 versus 13.7 +/- 3.4; -11% +/- 3%; P=0.06) or nitrates plus propranolol (12.9 +/- 4 versus 12.4 +/- 4; -7% +/- 8%; P=0.2) induced only minor additive effects on portal pressure. However, nitrate reduced MAP (P < 0.001) and increased HR (P < 0.01), whereas propranolol reduced only HR (P < 0.001) with unchanged MAP, and the combination decreased MAP (P < 0.001). Compared to placebo (no effect), propranolol decreased PPG (14.4 +/- 5.6 versus 11.1 +/- 5.5; -23% +/- 11%; P < 0.001) and HR (P < 0.001). Overall, most patients (92%) responded to propranolol and 54% showed a marked PPG decrease (>20%).
  
  
  CONCLUSIONS
  Propranolol significantly reduced portal pressure in cirrhotic patients after TIPS, whereas nitrates induced only minor benefit. TIPS-treated patients might therefore profit from additive propranolol therapy allowing limited shunts to be applied initially and/or to reduce the need for TIPS revisions in the case of shunt-dysfunction during follow-up.
authors.affiliation: Dept of Internal Medicine, University of Bonn, Germany.
authors.forename: K A
authors.initials: KA
authors.lastname: Brensing
authors.forename: M
authors.initials: M
authors.lastname: Hörsch
authors.forename: J
authors.initials: J
authors.lastname: Textor
authors.forename: P
authors.initials: P
authors.lastname: Schiedermaier
authors.forename: P
authors.initials: P
authors.lastname: Raab
authors.forename: M
authors.initials: M
authors.lastname: Schepke
authors.forename: H
authors.initials: H
authors.lastname: Strunk
authors.forename: H
authors.initials: H
authors.lastname: Schild
authors.forename: T
authors.initials: T
authors.lastname: Sauerbruch
mesh_terms: D001794:Blood Pressure / Q000187:drug effects; D004338:Drug Combinations; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006975:Hypertension, Portal / Q000517:prevention & control; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use*; D017082:Portal Pressure / Q000187:drug effects; D019168:Portasystemic Shunt, Transjugular Intrahepatic; D011433:Propranolol / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D014665:Vasodilator Agents; D011433:Propranolol; D005996:Nitroglycerin