Primary prophylaxis with nadolol in cirrhotic patients: Doppler patterns of splanchnic hemodynamics in good and poor responders

Background/Aims

We aimed to characterize by echo-color-Doppler the splanchnic hemodynamics of patients good and poor responders to primary prophylaxis with nadolol.

Methods

Thirty cirrhotic patients (Child-score 7.0±1.8) with medium/large esophageal varices without previous bleedings were consecutively enrolled. At inclusion and after 3 months of treatment with nadolol, they underwent a splanchnic echo-color-Doppler study and a measurement of hepatic venous pressure gradient (HVPG).

Results

Nadolol (60±36 mg/day; range 20–160) induced a significant reduction of HVPG (16.6±6.1 vs. 19.4±4.6 mmHg, P<0.0001). 13 patients (43.3%) were hemodynamic responders. Responders and Poor-responders had similar baseline clinical characteristics. Poor-responders at baseline were characterized by lower impedance indexes in superior mesenteric artery (SMA) (PI 2.29±0.45 vs. 2.74±0.46; P=0.01; RI 0.83±0.04 vs. 0.86±0.03; P=0.02), hepatic artery (HA) (PI 1.41±0.19 vs. 1.79±0.48; P=0.03; RI 0.71±0.05 vs. 0.80±0.07; P=0.02), and splenic artery (SA) (PI 1.18±0.27 vs. 1.73±0.40; P=0.01; RI 0.66±0.07 vs. 0.73±0.09; P=0.02), and by higher mean flow velocity of HA (52.6±21.6 vs. 26.5±9.5 cm/s; P=0.02) and SMA (49.7±14.5 vs. 33.9±13.1 cm/s; P=0.06).

Conclusions

Cirrhotic patients poor-responders to nadolol show a pronounced arterial splanchnic vasodilatation at a baseline echo-color-Doppler study. This can be considered a non-invasive clue for the a priori identification of this subgroup of patients.

Introduction

Non-selective beta-blockers, such as propranolol and nadolol, are the first-line prophylactic treatment for cirrhotic patients with esophageal varices at medium–high risk of bleeding [1], since they decrease portal pressure by reducing cardiac index via β-1 adrenoceptors blockade and increasing splanchnic vasoconstriction via β-2 adrenoceptors blockade [2]. In conditions of increased sinusoidal resistance, portal pressure can be reliably estimated by its equivalent hepatic venous pressure gradient (HVPG), which is measured during hepatic veins' catheterization [3]. Variceal bleeding can occur when HVPG increases over 12 mmHg [4], [5]. It has been previously demonstrated that cirrhotic patients who had never bled from varices and who show a decrease of HVPG under 12 mmHg or ≥20% vs. baseline during chronic treatment with beta-blockers, are protected from the risk of first bleeding from varices [6], [7]; when beta-blockers are given for the prevention of rebleeding, a reduction of HVPG ≥20% reduces both the risk of bleeding [8] and that of developing of other complications of portal hypertension [9]. Patients showing this reduction in HVPG during pharmacological treatment are therefore considered hemodynamic responders. Patients who do not respond to beta-blockers are still at risk of variceal rupture, and it has been recently suggested that these patients may be shifted to endoscopic banding ligation [10], making noteworthy to know whether a patient is or not a responder to pharmacological treatment.

At the moment, the only method to define the hemodynamic response to beta-blockers is the repeat measurement of HVPG, since clinical and laboratory data do not predict beta-blockers' effect on portal pressure [3]. Nonetheless, the need for researching non-invasive methods to obtain such information has been stated during the last consensus conference on portal hypertension [1], since this would simplify the clinical management of portal hypertensive cirrhotic patients.

Echo-color-Doppler is a non-invasive technique, which allows the study of splanchnic circulation. To date, only one study examined the usefulness of repeat measurements of Doppler variables in patients undergoing as well HVPG measurements during chronic administration of beta-blockers [11]. In that study, Merkel and colleagues could not demonstrate any predictive value of Doppler changes on hemodynamic response to therapy; however the study was carried out both in patients who where receiving nadolol or nadolol+nitrates, and only portal blood flow and portal vein congestion index changes were evaluated.

The aim of this prospective study was to characterize the splanchnic hemodynamics by echo-color-Doppler in a consecutive series of cirrhotic patients undergoing a primary prophylaxis with nadolol and repeated HVPG measurement.