RT Journal Article
T1 Non-selective beta-blockers impair global circulatory homeostasis and renal function in cirrhotic patients with refractory ascites
T2 Non-selective beta-blockers impair global circulatory homeostasis and renal function in cirrhotic patients with refractory ascites
A1 Tellez, Luis
A1 Ibañez Samaniego, Luis
A1 Pérez del Villar, Candelas
A1 Yotti, Raquel
A1 Martínez, Javier
A1 Carrión, Laura
A1 Rodríguez de Santiago, Enrique
A1 Rivera, Maite
A1 González Mansilla, Ana
A1 Pastor, Óscar
A1 Bermejo Thomas, Francisco Javier
A1 Bañares Cañizares, Rafael
A1 Albillos, Agustín
AB Background & aims: The safety of non-selective β-blockers (NSBBs) has been questioned in refractory ascites (RA). We studied the effects of NSBBs on cardiac systolic function, systemic hemodynamics, and renal perfusion pressure (RPP) and function in patients with diuretic-responsive ascites (DRA) and RA.Methods: We performed a prospective pre-post repeated-measures study in cirrhotic patients, 18 with DRA and 20 with RA on NSBBs for variceal bleeding prophylaxis. Systolic function (by ejection intraventricular pressure difference [EIVPD]), hepatic venous pressure gradient (HVPG), cardiopulmonary pressures, RPP, and sympathetic activation were measured at baseline and after 4 weeks of propranolol.Results: EIVPD was elevated at baseline (RA 4.5 [2.8-5.7] and DRA 4.2 [3.1-5.7] mmHg; normal 2.4-3.6 mmHg) and directly related to the severity of vasodilation and sympathetic activation. NSBBs led to similar reductions in heart rate and HVPG in both groups. NSBBs reduced EIPVD in RA but not in DRA (-20% vs. -2%, p <0.01). In RA, the NSBB-induced reduction in EIPVD correlated with the severity of vasodilation and with higher plasma nitric oxide, norepinephrine and IL-6 (r >0.40, all p <0.05). NSBBs reduced RPP in both groups, but impaired renal function only in patients with RA. Reduced EIPVD correlated with decreases in RPP and estimated glomerular filtration rate (r >0.40, all p <0.01). After NSBB treatment, RPP dropped below the threshold of renal flow autoregulation in 11 of the 20 (55%) patients with RA, including the 4 fulfilling the criteria for HRS-AKI.Conclusion: Renal perfusion and function depend critically on systolic function and sympathetic hyperactivation in RA. NSBBs blunt the sympathetic overdrive, hamper cardiac output, lower RPP below the critical threshold and impair renal function. β-blockade should be used cautiously or even avoided in patients with RA.Lay summary: We have identified the mechanisms by which non-selective beta-blockers could impair survival in patients with refractory ascites. We show that peripheral vasodilation and sympathetic activation lead to increased left ventricle systolic function in patients with cirrhosis and ascites, which acts as an adaptive mechanism to maintain renal perfusion. When ascites becomes refractory, this compensatory cardiac response to vasodilation is critically dependent on sympathetic hyperactivation and is hardly able to maintain renal perfusion. In this setting, β-blockade blunts the sympathetic overdrive of cardiac function, hampers cardiac output, lowers renal perfusion pressure below the critical threshold and impairs renal function.
PB Elsevier
SN 0168-8278
YR 2020
FD 2020-12-01
LK https://hdl.handle.net/20.500.14352/98625
UL https://hdl.handle.net/20.500.14352/98625
LA eng
NO Tellez, Luis; Ibanez-Samaniego, Luis; Perez del Villar, Candelas; Yotti, Raquel; Martinez, Javier; Carrion, Laura; Rodriguez de Santiago, Enrique; Rivera, Maite; Gonzalez-Mansilla, Ana; Pastor, Oscar; Bermejo, Javier; Banares, Rafael; Albillos, Agustin. Non-selective beta-blockers impair global circulatory homeostasis and renal function in cirrhotic patients with refractory ascites. JOURNAL OF HEPATOLOGY 2020; 73: 1404-1414
NO En este estudio, en el cual el solicitante es autor senior (co-último autor) se pretendía responder a una de las preguntas más relevantes en el tratamiento de los pacientes con cirrosis y ascitis: si el uso de betabloqueantes es seguro en este grupo de enfermos. En este estudio multicéntrico se analizó exhaustivamente una cohorte de pacientes con ascitis y ascitis refractaria, incluyendo una valoracion hemodinámica invasiva hepatica y cardiopulmonar y no invasiva, evaluando índices de funcion sistólica ecocardiográficos descritos por el grupo. En el estudio se demostró la estrecha relación entre la función sistólica y la hiperactividad simpática y el complejo balance entre la presión de perfusión renal y la hiperactividad simpática. El estudio pone las bases fisiopatológicas que sustentan la necesidad de tener una precaucion especial en el uso de betabloqueantes en aquellos pacientes con ascitis refractaria. Desde el punto de vista clínico el estudio da respuesta a una pregunta de gran relevancia, facilitando el tratamiento de los pacientes. Por otra parte, el trabajo representa la continuación de una línea de trabajo colaborativo con el Servicio de Cardiología (Yotti et al Hepatology 2017; Ripoll et al J Hepatol) Este estudio además formó parte además de la tesis doctoral del primer firmante del artículo.
DS Docta Complutense
RD 10 abr 2025