Autonomic dysfunction measured by baroreflex sensitivity in markedly abnormal in stable cirrhosis despite minimal haemodynamic changes.

Abstract

Introduction: Autonomic dysfunction occurs in 43-80% of cases of cirrhosis, but is usually asymptomatic. The baroreflex arc is an important component of the autonomic nervous system main- taining cardiovascular status both at rest and during physio- logical stress. Baroreceptor sensitivity (BRS) is impaired in cirrhosis and correlates with disease severity. It has been stud- ied extensively in advanced disease, especially pre-transplan- tation, where impairment of BRS correlates with the presence of ascites, encephalopathy, and the hyperdynamic circulation. Impaired BRS is associated with a five-fold increase in mortal- ity predominantly from sepsis and variceal bleeding, inde- pendent of the stage of liver disease. Manipulation by ACE inhibitors, aldosterone antagonists and liver transplantation all improve BRS. The aim of this study was to determine the preva- lence of BRS abnormalities in a stable population with well compensated disease. Methods: We studied 11 stable cirrhotic patients. Spontaneous BRS was assessed in the supine position on two different days using software studying the relationship between inter-beat variability and beat-to-beat changes in sys- tolic blood pressure. Systemic haemodynamics (heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), stroke vol- ume (SV), peripheral vascular resistance (PVR)) were assessed non-invasively using the Finometer®. Portal pressure was assessed by measurement of the hepatic venous pressure gra- dient (HVPG). Results: Median age 46 (30-67) years, 64% male, median Child-Pugh (CP) score 6 and MELD 11. Median haemodynamic data as follows: systolic BP 147 (115-169) mmHg, diastolic BP 82 (73-103) mmHg, MAP 103 (87-131) mmHg, HR 90 (63-110) bpm, SV 87 (38-141) ml, CO 8.0 (3.5-10.1) lpm, PVR 0.96 (0.64-2.14) MU, HVPG 18 (12-26)mmHg. 9/11 (82%) had abnormal BRS (normal 8- 10ms/mmHg) with median BRS 2.58 (1.14-9.46) ms/mmHg. Sequential BRS readings were not significantly different (2.58 vs 3.26 ms/mmHg, p=0.8). BRS did not correlate with disease severity (CP A 2.58 vs CP B 3.80 ms/mmHg, p=0.9), systemic haemodynamics, HVPG or serum sodium. Systemic haemody- namics were not significantly different in patients with impaired BRS compared to those with normal BRS. Conclusions: Auto- nomic function as assessed by BRS is markedly abnormal in sta- ble well compensated cirrhosis. Abnormalities are not specific to advanced disease as previously thought and in our group are not associated with marked hyperdynamic changes. Our data suggest that it is predominantly the vagal aspect that is impaired in well compensated disease. The long-term outcome of these patients needs to be assessed.