Clinical trial NCT03633812: Effect of Preoperative Beta Blocker Use Postoperative Renal Function in the Patients Undergoing Liver Transplantation
Official title: The Effect of Preoperative Beta Blocker Use on Intraoperative Hemodynamics and Postoperative Renal Function in End-stage Liver Disease Patients Undergoing Liver Transplantation
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: End Stage Liver Disease
Acute Kidney Injury
Keywords: End Stage Liver Disease
Acute Kidney Injury
Beta blocker
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2018-08-16
Enrollment: 477
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: living donor liver transplant recipients at Asan Medical Center, Seoul, Korea, Republic of

Brief summary: This is prospective cohort study of patients classified by the premedication history of beta-blocker. The investigators aim to evaluate the hemodynamic effect of beta blocker through Swan-Ganz catheter monitoring and arterial pressure waveform analysis during surgery. The investigators also plan to observe the long-term effects of beta blocker on acute renal failure, allograft failure and mortality.

Detailed description: Since beta blockers have been shown to reduce portal venous pressure in 1980, the nonselective beta blocker (NSBB) has been widely used for the last 25 years as the primary treatment for portal hypertension. NSBB, such as propranolol and nadolol, has been shown to reduce cardiac output through β1 -receptor block and to constrict visceral vessels via β2-receptor block, thereby lowering portal venous pressure in patients with chronic liver disease. NSBB contributed to reducing complications such as esophageal variceal bleeding, ascites, hepatic encephalopathy, and improving survival in patients with cirrhosis. In addition, the use of NSBB in patients with ascites has been demonstrated to reduce the digestion time of intestinal food and reduce bacterial migration into the abdominal cavity and bloodstream.

On the other hand, recent studies have shown that NSBB use in the patients with advanced cirrhosis (accompanied by refractory ascites, spontaneous peritonitis, severe alcoholic hepatitis) may increase circulatory failure, acute renal failure, and mortality. When the cardiac index was less than 1.5 L / min / m² or the mean blood pressure was less than 80 mmHg in advanced cirrhosis with ascites, 1-year survival rate was found to be about 30% lower than the control. The use of beta blockers is argued to be avoided in the cirrhotic patients with refractory ascites because the mortality rate of these patients is associated with the use of beta blockers. These studies have been questioned in terms of reliability of the setting of treatment and control groups and correction of disturbance variables.

The window hypothesis has received attention for the risk-benefit of NSBB. This means that the beta blocker may be beneficial or harmful to the cirrhotic patients depending on the stage of disease progression. In conclusion, the use of beta-blockers in patients with early cirrhosis without moderate to large varix has no effect on prevention of esophageal varices, but is associated with depression, tiredness, sexual dysfunction, decreased cardiac output, increased risk of heart failure, symptomatic bradycardia, increased airway resistance, and bronchospasm. As the cirrhosis progresses, many changes occur in the cardiovascular system. The sympathetic nervous system and resin-angiotensin-aldosterone axis are up-regulated to compensate for the lack of effective blood volume due to peripheral vascular relaxation and hypotension. It is believed that the use of beta-blockers at this time may improve survival by reducing esophageal bleeding and bacterial migration. If the liver cirrhosis progresses more, the use of beta-blockers may compromise cardiac output, blood pressure, perfusion to important organs, thereby increasing the incidence of hepatorenal syndrome and mortality. The use of beta-blockers seems to be beneficial between the point of moderate to large varix generation to the point of advanced cirrhosis with undesired hemodynamic effect (spontaneous ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, sepsis). The research is still ongoing and controversial.

As mentioned earlier, the use of beta blockers in patients with liver disease has been actively studied for the last 10 years, but most studies have been done in patients waiting for liver transplantation. Research is minimal in patients who actually undergo liver transplantation. In addition, studies have shown that beta blockers increase survival in patients waiting for liver transplantation by lowering portal venous pressure through beta 1, 2 -receptor block. But the actual research of preoperative beta blocker on perioperative hemodynamics, postoperative complications, and mortality is still lacking.

This is prospective cohort study of patients classified by the premedication history of beta-blocker. The investigators aim to evaluate the hemodynamic effect of beta blocker through Swan-Ganz catheter monitoring and arterial pressure waveform analysis during surgery. The investigators also plan to observe the long-term effects of beta blocker on acute renal failure, allograft failure and mortality.

Eligibility criteria: Inclusion Criteria:

* living donor liver transplantation recipients

Exclusion Criteria:

* previous history of acute kidney injury
* previous liver transplantation history
* Fulminant hepatic failure
* history of TIPS, transjugular intrahepatic porto-systemic shunt

Primary outcomes:
measure: Acute kidney injury
timeFrame: 1 week
Secondary outcomes:
measure: Graft failure
timeFrame: 1 year
measure: Mortality
timeFrame: 1 year
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan medical center
Study officials:
affiliation: Asan Medical Center
name: Jun Gol Song, PH.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Krag A, Wiest R, Albillos A, Gluud LL. The window hypothesis: haemodynamic and non-haemodynamic effects of beta-blockers improve survival of patients with cirrhosis during a window in the disease. Gut. 2012 Jul;61(7):967-9. doi: 10.1136/gutjnl-2011-301348. Epub 2012 Jan 10. No abstract available.
citation: Serste T, Melot C, Francoz C, Durand F, Rautou PE, Valla D, Moreau R, Lebrec D. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology. 2010 Sep;52(3):1017-22. doi: 10.1002/hep.23775.
citation: Serste T, Francoz C, Durand F, Rautou PE, Melot C, Valla D, Moreau R, Lebrec D. Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: a cross-over study. J Hepatol. 2011 Oct;55(4):794-9. doi: 10.1016/j.jhep.2011.01.034. Epub 2011 Feb 24.