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Autonomic dysfunction and impaired cerebral autoregulation in cirrhosis

  • RESEARCH ARTICLE
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Abstract

Cerebral blood flow autoregulation is lost in patients with severe liver cirrhosis. The cause of this is unknown. We determined whether autonomic dysfunction was related to impaired cerebral autoregulation in patients with cirrhosis.

Fourteen patients with liver cirrhosis and 11 healthy volunteers were recruited. Autonomic function was assessed in response to deep breathing, head-up tilt and during 24-h Holter monitoring. Cerebral autoregulation was assessed by determining the change in mean cerebral blood flow velocity (MCAVm, transcranial Doppler) during an increase in blood pressure induced by norepinephrine infusion (NE). The severity of liver disease was assessed using the Child–Pugh scale (class A, mild; class B, moderate; class C, severe liver dysfunction).

NE increased blood pressure similarly in the controls (27 (24–32) mmHg) and patients with the most severe liver cirrhosis (Child–Pugh C, 31 (26–44) mmHg, p=0.405 Mann–Whitney). However, the increase in MCAVm was greater in cirrhosis patients compared to the controls (Child–Pugh C, 26 (24–39) %; controls, 3 (−1.3 to 3) %; respectively, p=0.016, Mann–Whitney). HRV during deep breathing was reduced in the cirrhosis patients (Child–Pugh C, 6.0±2.0 bpm) compared to the controls (21.7±2.2 bpm, p=0.001, Tukey’ test). Systolic blood pressure fell during head-up tilt only in patients with severe cirrhosis.

Our results imply that cerebral autoregulation was impaired in the most severe cases of liver cirrhosis, and that those with impaired cerebral autoregulation also had severe parasympathetic and sympathetic autonomic dysfunction. Furthermore, the degree of liver dysfunction was associated with increasing severity of autonomic dysfunction. Although this association is not necessarily causal, we postulate that the loss of sympathetic innervation to the cerebral resistance vessels may contribute to the impairment of cerebral autoregulation in patients with end-stage liver disease.

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Abbreviations

MAP:

Mean arterial blood pressure

MCAVm:

mean flow velocity in the middle cerebral artery

NN-intervals:

normal to normal intervals meaning all intervals between adjacent QRS complexes resulting from sinus node depolarization identified on ECG

SDNN:

the standard deviation of NN-intervals

RMSSD:

the square root of the mean squared differences of successive NN-intervals

HRV:

overall heart rate variability

VLF:

Very low frequency (0.016–0.04 Hz)

LF:

Low frequency (0.04–0.15 Hz)

HF:

High frequency (0.15–0.4 Hz)

PaCO2 :

arterial carbon dioxide tension

AlaAT:

Alanine transaminase

PT:

ratio between prothrombine time in test plasma and standard plasma

Alc:

alcoholic

PBC:

Primary biliary cirrhosis

Crypt:

cryptogenic

HepC:

Hepatitis C

bpm:

beats per minute

ms:

milliseconds

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Acknowledgments

Financial support

The study was funded by: Danish Medical Research Council. The Danish Hospital Foundation for Medical Research, Region of Copenhagen, the Faroe Islands and Greenland. Rigshospitalet. University of Copenhagen. The Laerdal Foundation for Acute Medicine. Sawmill owner Jeppe Juhl and Wife Ovita Juhls Foundation. The Novo Nordisk Foundation. The King Christian the 10th Foundation. The AP-Moeller Foundation. The Beckett Foundation.

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Authors and Affiliations

  1. Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    Vibe G. Frøkjær MD, Gitte I. Strauss & Gitte M. Knudsen

  2. Neurobiology Research Unit 9201, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Vibe G. Frøkjær MD

  3. Dept. of Hepatology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    Gitte I. Strauss & Fin S. Larsen

  4. Dept. of Clinical Physiology, Frederiksberg Hospital, Frederiksberg, Denmark

    Jesper Mehlsen

  5. Dept. of Cardiology, Hvidovre University Hospital, Hvidovre, Denmark

    Verner Rasmussen

Authors
  1. Vibe G. Frøkjær MD
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  2. Gitte I. Strauss
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  3. Jesper Mehlsen
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  4. Gitte M. Knudsen
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  6. Fin S. Larsen
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Corresponding author

Correspondence to Vibe G. Frøkjær MD.

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Financial support

The study was funded by: Danish Medical Research Council. The Danish Hospital Foundation for Medical Research, Region of Copenhagen, the Faroe Islands and Greenland. Rigshospitalet. University of Copenhagen. The Laerdal Foundation for Acute Medicine. Sawmill owner Jeppe Juhl and Wife Ovita Juhls Foundation. The Novo Nordisk Foundation. The King Christian the 10th Foundation. The AP-Moeller Foundation. The Beckett Foundation.

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Frøkjær, V.G., Strauss, G.I., Mehlsen, J. et al. Autonomic dysfunction and impaired cerebral autoregulation in cirrhosis. Clin Auton Res 16, 208–216 (2006). https://doi.org/10.1007/s10286-006-0337-4

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  • DOI: https://doi.org/10.1007/s10286-006-0337-4

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