Diuretic window hypothesis in cirrhosis: Changing the point of view

Table 1 Non-selective beta-blockers “window therapy” hypothesis-studies analyses

	Aims	Conclusions	Diuretic effect analysis	Observations
Ruiz-del-Arbol et al[3], 2003	To investigate the pathogenesis of circulatory dysfunction in SBP and to assess whether impaired circulatory function is associated with increased portal pressure	SBP patients frequently develop progressive impairment in systemic hemodynamics, leading to severe renal and hepatic failure, aggravation of portal hypertension, encephalopathy, and death.	Not Performed	The group that developed renal injury presented with:
				Decreased liver function;
				BUN/creatinine ratio of almost 40:1, suggesting the presence of pre-renal injury by hypovolemia.
				The suggestion that renal failure would be caused by a decrease in CO has some critical aspects:
				CO decreased, but remained in the normal range, not explaining a renal failure per se.
				If a decrease in CO directly causes renal failure, an increase in pulmonary pressure is expected but was not observed, suggesting a reduction in plasma volume – diuretic effect?
Ruiz-del-Arbol et al[4], 2005	To investigate circulatory function in cirrhosis before and after the development of hepatorenal syndrome	Hepatorenal syndrome is the result of decreased cardiac output in the setting of severe arterial vasodilation	Not performed	The group developing HRS (old criteria of 1996) presented:
				Decreased basal renal function
				Hemodynamic values were characteristics of hypovolemia: low CO, but also low pulmonary pressures with low stroke volume. Diuretic effect?
Krag et al[5], 2009	To investigate the relationship between cardiac and renal function in patients with cirrhosis and ascites and the impact of cardiac systolic function on survival	Development of renal failure and poor outcome in patients with advanced cirrhosis and ascites seem to be related to a cardiac systolic dysfunction	Not performed	Cardiac index by gated myocardial perfusion imaging with an extreme low value of 1.5 L/min/m2 as cut-off.
				Body surface area needed to calculate CI with the Dubois formula, which contains weight, overestimated by ascites, resulting in lower CI. A CI less than 2.2 L/min/m2 is defined as cardiogenic shock, turning the 1.5 L/min/m2 cut-off into an underestimation or defining a very severe heart failure group.
				The group with lower CI was using 30 mg more furosemide and had higher creatinine levels, with 50% already presenting HRS-2 at baseline, compromising any survival analysis.
Sersté et al[10], 2010	To evaluate the effect of the administration of beta-blockers on long-term survival in patients with cirrhosis and refractory ascites	Treatment with beta-blockers is associated with poor survival in patients with refractory ascites. These results suggest that beta-blockers should be contraindicated in these patients	Not performed	There were 70% of patients with intractable ascites by renal injury at the time of inclusion. There is no description about NSBB use among these patients.
				Patients in the NSBB group had more advanced disease than the group that had not taken NSBBs.
				The independent variables with higher HR to predict death were hyponatremia and renal injury, which could be related to diuretic use. Diuretic use was not included in the analyzed model.
Sersté et al[11], 2011	To investigate the incidence of PICD before and after discontinuation of beta-blockers in patients with cirrhosis and refractory ascites. A self control cross-over study	The use of beta-blockers may be associated with a high risk of PICD in patients with cirrhosis and refractory ascites	Not performed	Small number of patients. Ten patients with refractory ascites, six were diuretic-resistant ascites. No information about diuretic dosage during the assessment.

BUN: Blood urea nitrogen; CI: Cardiac index; CO: Cardiac output; HR: Hazard ratio; HRS: Hepatorenal syndrome; NSBB: Non-selective beta-blockers; PICD: Paracentesis-induced circulatory dysfunction; SBP: Spontaneous bacterial peritonitis.