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Mild hypothermia for the treatment of acute liver failure—what are we waiting for?

Nature Clinical Practice Gastroenterology & Hepatology volume 4, pages 528–529 (2007)Cite this article

Intracranial hypertension leading to brain herniation is a major cause of mortality in patients with acute liver failure (ALF), and reflects the limitations of conventional therapy in this setting.1 Uncontrolled clinical studies (see Supplementary Table 1 online), and a large body of experimental evidence strongly suggest that mild hypothermia (32.0–35.0°C) is effective for reducing intracranial pressure (ICP) in patients with ALF.1,2 The cerebro-protective mechanisms of mild hypothermia include a reduction in cerebral blood flow and arterial ammonia concentrations, which together result in reduced delivery of ammonia to the brain. Reduction of cerebral blood flow by hypothermia also decreases hydrostatic pressure in brain capillaries and prevents cerebral hyperemia; increased hydrostatic pressure and cerebral hyperemia are factors that accelerate the development of brain edema in patients with ALF. In addition, mild hypothermia attenuates pathophysiological events in the brain that occur downstream of ammonia exposure, such as lactate and glutamate accumulation, as well as the altered expression of a wide range of genes that encode key astrocytic and endothelial cell proteins.2 Mild hypothermia also corrects abnormalities in the concentration of organic osmolytes and pro-inflammatory cytokines in the brain of patients with ALF.

In addition to improvements in cerebral function, there is evidence to suggest that the systemic effects of mild hypothermia are beneficial in patients with ALF. Mild hypothermia facilitates the hemodynamic management of patients with ALF by counteracting the hyperdynamic circulation of these patients, reducing vasopressor requirements, and restoring cerebrovascular autoregulation.2,3,4 Furthermore, mild hypothermia attenuates ischemia-reperfusion5 and acetaminophen-induced liver injury in experimental animals,6 and apoptotic cell death in cultured hepatocytes.7

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Acknowledgements

This work was supported by a grant from the Canadian Institutes of Health Research (CIHR). J Vaquero was supported by a fellowship from the Canadian Association for the Study of the Liver (CASL)/Schering Canada.

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Authors and Affiliations

  1. J Vaquero is a Senior Post-doctoral Fellow, and RF Butterworth is Scientific Director in the Neuroscience Research Unit at the Hôpital Saint-Luc, University of Montréal, Montréal, QC, Canada.,

    Javier Vaquero & Roger F Butterworth

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  1. Javier Vaquero
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  2. Roger F Butterworth
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Correspondence to Roger F Butterworth.

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The authors declare no competing financial interests.

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Vaquero, J., Butterworth, R. Mild hypothermia for the treatment of acute liver failure—what are we waiting for?. Nat Rev Gastroenterol Hepatol 4, 528–529 (2007). https://doi.org/10.1038/ncpgasthep0927

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