A Haemodynamic Analysis to Assess the Safe Dose of Carvedilol across Different Child Class of Liver Disease

Abstract

Background: Literature regarding safe dose of carvedilol is limited and also safe dose across different child classes of chronic liver disease is not very clear. Aim: We aimed primarily to study, the effect of reasonably safe dose (12.5 mg) of carvedilol in acute reduction of portal pressure and compared it with chronic reduction of portal pressure, after proper optimization of dose of carvedilol. Second aim of our study was to define predictors of response for acute and chronic reduction of portal pressure and to assess difference in dose tolerated and response across different child class on chronic basis. Methods: One hundred two consecutive patients of cirrhosis of liver with significant portal hypertension were included and hepatic venous pressure gradient was measured at the base line and after 90 minutes of administration of 12.5 mg carvedilol. After proper dose optimization of carvedilol, hepatic venous pressure gradient was again measured after 3 months to assess the chronic response. Results: The mean age of study population was 58.3±6.6 years. A total of 42.2%, 31.9% and 26.6% patients had child class A, child class B and Child class C cirrhosis, respectively. Mean pre-drug hepatic venous pressure gradient was 16.75±2.12 mmHg which dropped to 13.07±2.32 mmHg after 90 minutes of administration of 12.5 mg of carvedilol. The mean drop of hepatic venous pressure gradient was 4.5±2.2 mmHg and 2.4±1.9 mmHg among responders and non-responders, respectively. Overall, 51% showed acute response while 49% were non-responders. Low cardiac output and high mean arterial pressure were significantly predicting the acute response, while, low baseline cardiac output was found as an independent predictor. After dose optimization, number of responders increased from 52 to 62. Mean dose of carvedilol was higher in non–responders as compared to responders, though statistically insignificant (p>0.05). Mean reduction of hepatic venous pressure gradient from baseline and after 3 months was 5.5±1.7 mmHg and 2.8±1.6 mmHg among responders and non responders on chronic basis, respectively (p<0.001). Absence of any adverse events (OR 11.3, 95% CI; 1.9-67.8), and more than 2.5 mmHg fall in hepatic venous pressure gradient during acute response (OR 8.7, 95% CI; 3.1-25.3) were found as independent predictors of chronic response (p<0.05). Univariate analysis found that no adverse events, no ascites, low baseline cardiac output, more than 2.5 mmHg fall in hepatic venous pressure gradient during acute response, as predictors of chronic response. However, etiology, child class, variceal size (large vs small) and gender were not significantly associated with chronic response Conclusion: At safe dose and with proper optimization of dose, carvedilol may achieve greater response with minimum side effects among different child classes of liver disease.