Intravenous administration of halogenated inhaled anesthetics—research tool or real application?

Myocardial infarction is a major perioperative complication that is associated with significant morbidity and mortality. Therefore, the development of strategies and interventions that are designed to decrease the risk of perioperative cardiovascular complications has been the focus of intensive research. Inhaled halogenated anesthetics have repeatedly been shown to protect the heart against myocardial ischemia and reperfusion. This anesthetic-induced pharmacological preconditioning has been the subject of considerable research and has been shown to protect the heart against myocardial infarction in a variety of experimental animal models as well as in humans. In the current issue of the Journal, Hu et al. report on the protective effects of emulsified isoflurane against myocardial ischemia, using an in vivo model of regional myocardial ischemia and reperfusion in rats. Intravenous administration of emulsified isoflurane, prior to ischemia and reperfusion, reduced myocardial infarct size by approximately 40% and decreased apoptotic cell death. The authors also reported an increased expression of the anti-apoptotic protein, BCL-2, while the expression of the pro-apoptotic protein, BAX, decreased, thus shifting the cell towards a more anti-apoptotic phenotype. These cardioprotective effects, however, were not observed in the control non-preconditioned animals that received 30% intralipid. Intravenous delivery of drugs with little or no aqueous solubility has been a focus area of pharmaceutical research. In the late 1970s, ethoxylated castor oil (Cremophor ) was used as a solubilizing agent for alphaxolone and was a notorious failure due to frequent anaphylaxis. However, the longstanding availability of safe and well-recognized lipid emulsions, such as Intralipid , has expanded the intravenous use of hydrophobic compounds and is a phenomenon in the commercial formulation of propofol in 10% Intralipid with which we are all familiar. Thus, the idea of intravenous administration of inhaled anesthetic gases, although somewhat foreign in concept, has previously been suggested by others and may have clinical applicability in myocardial protection (or protection of other vital organs such as the brain) outside the operating room, particularly in high-risk patients undergoing procedures such as coronary catheterization or interventional neuroradiological procedures. As was pointed out in an excellent editorial published by Lucchinetti et al., intravenous administration of halogenated anesthetics has several advantages compared to the traditional method of administering these agents. First, the intravenous route eliminates the need for a ventilatory delivery system, although several intensive care unit ventilator systems have the ability to deliver anesthetic gases using conventional vaporizers. Second, intravenous anesthetic administration is independent of the respiratory system and, therefore, less isoflurane is required (both for induction and for maintenance) to achieve organ-protective effects and anesthetic effects that are similar to those obtained via the conventional inhalational administration route, thus leading to marked hemodynamic stability. Third, Zhang et al. have reported that both the induction and the recovery from intravenous emulsified isoflurane are more rapid than with other intravenous anesthetics such as propofol. Fourth, since the amount of isoflurane that is needed via the intravenous route to maintain similar effects is significantly less than that required via the inhalation J. Raphael, MD (&) C. Lynch III, MD, PhD Department of Anesthesiology, University of Virginia Health Sciences Center, PO Box 800710, Charlottesville, VA 22908, USA e-mail: jr5ef@virginia.edu