Over the last few years, the number of research publications about the role of catecholamines (epinephrine, norepinephrine, and dopamine) in the development of liver diseases such as liver fibrosis, fatty liver diseases, or liver cancers is constantly increasing. However, the mechanisms involved in these effects are not well understood. In this review, we first recapitulate the way the liver is in contact with catecholamines and consider liver implications in their metabolism. A focus on the expression of the adrenergic and dopaminergic receptors by the liver cells is also discussed. Involvement of catecholamines in physiological (glucose metabolism, lipids metabolism, and liver regeneration) and pathophysiological (impact on drug-metabolizing enzymes expression, liver dysfunction during sepsis, fibrosis development, or liver fatty diseases and liver cancers) processes are then discussed. This review highlights the importance of understanding the mechanisms through which catecholamines influence liver functions in order to draw benefit from the adrenergic and dopaminergic antagonists currently marketed. Indeed, as these molecules are well-known drugs, their use as therapies or adjuvant treatments in several liver diseases could be facilitated.
IntroductionIncidence of delirium after cardiac surgery remains high and delirium has a significant burden on short-term and long-term outcomes. Multiple causes can trigger delirium occurence, and it has been hypothesised that sleep disturbances can be one of them. Preserving the circadian rhythm with overnight infusion of low-dose dexmedetomidine has been shown to lower the occurrence of delirium in older patients after non-cardiac surgery. However, these results remain controversial. The aim of this study was to demonstrate the usefulness of sleep induction by overnight infusion of dexmedetomidine to prevent delirium after cardiac surgery.Methods and analysisDexmedetomidine after Cardiac Surgery for Prevention of Delirium is an investigator-initiated, randomised, placebo-controlled, parallel, multicentre, double-blinded trial. Nine centres in France will participate in the study. Patients aged 65 years or older and undergoing cardiac surgery will be enrolled in the study. The intervention starts on day 0 (the day of surgery) until intensive care unit (ICU) discharge; the treatment is administered from 20:00 to 08:00 on the next day. Infusion rate is modified by the treating nurse or the clinician with an objective of Richmond Agitation and Sedation Scale score from −1 to +1. The primary outcome is delirium occurrence evaluated with confusion assessment method for the ICU two times per day during 7 days following surgery. Secondary outcomes include incidence of agitation related events, self-evaluated quality of sleep, cognitive evaluation 3 months after surgery and quality of life 3 months after surgery. The sample size is 348.Ethics and disseminationThe study was approved for all participating centers by the French Central Ethics Committee (Comité de Protection des Personnes Ile de France VI, registration number 2018-000850-22). The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03477344.
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