Volatile Anesthetics in Ischemic Liver Injury: Enemy or Friend?

Implication for health policy/practice/research/medical education: Liver surgery and perioperative care of patients with hepatic dysfunction is still moving toward better safety. Anesthesiologists play their role with judicious selection of anesthetic medications. Ischemic liver injury occurs in a variety of clinical settings such as trauma, shock, and liver surgery (1, 2). Isch-emia and subsequent reperfusion injury rapidly evolves to sinusoid endothelial cell damage, activation of Kupffer cells, inflammation, hepatocyte necrosis and finally liver dysfunction, especially in patients with preoperative liver injures (3). Liver failure is associated with a risk of poor outcome (4). Therefore, a judicious strategy for in-traoperative physical and pharmacological liver protection should be implemented. A few decades ago, postop-erative mortality following liver surgery or non-hepatic surgery in a patient with liver dysfunction was as high as 50% (5, 6). Substantial improvement in techniques of surgery and perioperative care has made surgery dramatically safer in these patients. Better knowledge of liver pathophysiology has made perioperative liver protection feasible (7, 8). Contribution of anesthesiologists to new horizons of safety deserves to be highlighted. High quality organ preservation during liver surgeries by hypothermia, management of intraoperative massive hemorrhage and blood transfusion, appropriate fluid management, postoperative pain control and stress reduction and recently preconditioning by using certain opioids (9-11) and volatile anesthetics (12) are examples of protective strategies implemented by anesthesiologists. Recent evidences suggest that an exposure to a brief period of ischemia or mild oxidative stress before a severe ischemic insult would help the organ to minimize the sequels of ischemia, a phenomenon known as precon-ditioning. Several modes of action have been proposed for preconditioning including biological adaptation to injury, direct protection by anti-inflammatory or anti-apoptotic mechanisms and finally organ priming by cellular activation of protection (e.g. hemoxygenases-1). A variety of preconditioning methods have been introduced to date such as hyperthermic, ischemic and pharmacological strategies, with variable degrees of efficacy (13). In liver surgery, evidences for less effectiveness of ischemic preconditioning as well as the possibility of increased intraoperative blood loss due to intermittent clamping has made ischemic preconditioning a less favorable choice compared with pharmacological precon-ditioning (14). Several medications have been proposed for pharmacological liver preconditioning including an-tioxidants, adenosine agonists, pentoxifylline, protease-inhibitors, anti-apoptotic substances, prostaglandins, matrix-metalloproteinases-inhibitors and inductors of hemoxygenases 1 (HO-1) (15). Recent laboratory and clinical studies demonstrated a promising role for volatile conditioning (12, 16) (Figure 1). A well-designed clinical trial reported that application of sevoflurane for 30 …