Journal zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Hepatology 1996; 25: 145-151 Printed in Denmark All rights reserved Munksgaard Copenhagen Copyright0 European Association for the Studyof the Liver 1996 Journal of Hepatology ISSN0168-82 78 Dissociated cerebral vasoparalysis in acute liver failure zyxwvutsrqponmlkjih A hypothesis of gradual cerebral hyperaemia Fin Stolze Larsen’, Bent Adel Hansen’, Frank Pott2, Ellen Ejlersen2, Niels H. Seche?, Olaf B. Paulson3 and Gitte Moos Knudsen3 Departments of ‘Hepatology, ‘ Anaesthesia and ‘Neurology, Rigshospitalet, University of Copenhagen, Denmark Background/Aims: Normally, cerebral blood flow responds to changes in the arterial carbon dioxide tension (PaCO,) but not to changes in mean arte- rial pressure, commonly referred to as the cere- bral CO,-reactivity and autoregulation. In patients with fulminant hepatic failure and in the rat with thioacetamide-induced liver failure, autoregulation is absent, presumably due to cere- bral vasoparalysis. Since also CO,-reactivity may then be compromised, it was studied in patients with fulminant hepatic failure and rats with thioa- cetamide-induced liver failure. Methods: In ten patients (median age 32 (range 20- 48) years)) and in ten age-matched volunteers, cer- ebral perfusion was evaluated by transcranial Doppler assessed mean flow velocity (V,,,) in the ‘middle cerebral artery during hypo- and hyper- capnia. In six rats with liver failure and in six con- trol rats, cerebral blood flow was measured re- peatedly by the intracarotid ‘33Xenon injection technique. Results: In the patients and volunteers, PaCO, was lowered from 33 (23-44) to 28 (23-39) mmHg by hypocapnia and raised to 40 (3M8) mmHg by hy- percapnia or 5 % CO, inhalation. During hypocap- nia, the CO,-reactivity did not differ significantly between patients and volunteers, 4.0 (1.1-7.4) vs. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG I N SEVERE cases of fulminant hepatic failure (FHF), cerebral oedema may cause a reduction in cere- bral blood flow (CBF) (1). Conversely, primary changes in the regulatory mechanisms of CBF may provoke altered flow dynamics, intracranial hyperten- sion and subsequent brain death (2,3). Indeed, a de- Received 4 August; revised 4 December: accepted 21 December 1995 Correspondence: Fin Stolze Larsen, MD, Division of Hepatology A-2102, Rigshospitalet, Blegdamsvej 9, DK- 2 100 Copenhagen 0, Denmark. Tel: +45 35451257. Fax: +45 35456511. 3.0 (1.7-5.0)% mmHgA, while it was reduced dur- ing hypercapnia in the patients, 2.2 (1.8-5.2) vs. 4.6 (3.0-&O)% mmHg_’ (pcO.05). In the rats, PaCO, was reduced from 39 (3740) to 30 (29-31) mmHg and then raised to 51 (41-55) mmHg. During hy pocapnia, CO,-reactivity was similar in rats with liver failure and in control rats, 2.3 vs 2.7% mmHg21, respectively. In all rats with liver failure CO,-reactivity was abolished during hypercapnia, while it was 1.5% mmHgA in the control rats (p<O.Ol). Conclusions: The finding that cerebral CO, reac- tivity is reduced in hypercapnia, while it is pre- served in hypocapnia, suggests that gradual dilata- tion of the cerebral resistance vessels develops in fulminant hepatic failure and connects previous morphological studies with changes in the regula- tion of cerebral blood flow, i.e. impaired cerebral autoregulation and blunted CO,-reactivity. Key words: Acetaminophen; Acute; Autoregula- tion; Blood pressure; Brain edema; Carbon diox- ide reactivity; Cerebral blood flow; Encephalopa- thy; Intoxication; Liver failure; Rat thioaceta- mide. crease in CBF may precede intracranial hypertension in FHF (4). CBF is subjected to regulation by several factors, most importantly by brain metabolism, mean arterial pressure, and arterial carbon dioxide tension (PaCO,). The decrease in CBF most often found in patients with FHF (5-9) may be a consequence of a reduced cerebral glucose and oxygen metabolism (5). Alternatively, impaired CBF autoregulation is dem- onstrated both for the rat with thioacetamide-induced liver failure (2) and in patients with FHF presumably due to vasoparalysis (3). This vasoparalysis may also 145