Automonic dysfunction measured by baroreflex sensitivity is markedly abnormal in stable cirrhosis despite minimal systemic haemodynamic changes

Introduction: Baroreceptor sensitivity (BRS) is well recognised as a composite marker of the overall integrity of the autonomic nervous system, maintaining cardiovascular status both at rest and during physiological stress. Autonomic dysfunction occurs in 43–80% of cases of cirrhosis, affecting both sympathetic and parasympathetic branches. BRS impairment occurs independently of aetiology and correlates with disease severity and the hyperdynamic circulation. BRS has been studied extensively in advanced disease, especially pre-transplantation but less so in more compensated disease. Impaired BRS is associated with a 5-fold increase in mortality, independent of cirrhosis stage, yet can be improved by drugs and liver transplantation. Aims and Methods: The aim of this study was to determine the prevalence of BRS abnormalities in a stable population of cirrhotics. We studied 16 cirrhotic patients with stable disease for >6 months. Systemic haemodynamics and BRS were assessed non-invasively in the supine position on two different days using the Finometer® (TNO instruments, Amsterdam). Data were downloaded to a PC-based analysis program (Beatscope®). Spontaneous BRS was assessed using software studying the relationship between inter-beat variability and beat-to-beat changes in systolic blood pressure. Portal pressure was assessed by measurement of the hepatic venous pressure gradient (HVPG). Results: Median age 47 (30 to 67) years, 63% male, median Child–Pugh (CP) score 6 and MELD 11. 94% alcoholic aetiology, 69% abstinent. 9/16 (56%) concomitant spironolactone. Median haemodynamic data as follows: systolic BP 147 (115 to 169) mm Hg, diastolic BP 82 (65 to 103) mm Hg, MAP 104 (87 to 131) mm Hg, HR 89 (54 to 117) bpm, SV 89 (36 to 164) ml, CO 7.0 (3.5 to 12.0) lpm, PVR 0.98 (0.45 to 2.14) MU, HVPG 18 (7 to 25) mm Hg. 12/16 (75%) had abnormal BRS (normal 8 to 10 ms/mm Hg) with median BRS 3.38 (1.14 to 11.19) ms/mm Hg. Sequential BRS readings were not significantly different (3.38 vs 3.98 ms/mm Hg, p = 0.87). Systemic haemodynamics were not significantly different in patients with impaired BRS compared with those with normal BRS. BRS did not correlate with disease severity (CP A 2.96 vs CP B 3.80 ms/mm Hg, p = 1.0), systemic haemodynamics, serum sodium or variceal size. There was a significant negative correlation between BRS and HVPG (r = −0.523, p = 0.045). Conclusion: Autonomic function as assessed by BRS is frequently abnormal in stable cirrhotic patients. Abnormalities of BRS are not associated with marked haemodynamic changes, suggesting that it is predominantly the vagal aspect that is impaired in stable disease. Abnormalities of BRS are associated with HVPG which may suggest that portal pressure itself plays a pivotal role in its causation. The significance of impaired BRS in this stable group needs to be determined by assessing long-term outcome.N/