Reply to: Isoflurane is not necessarily the only cause of cognitive deficits

Editor, We thank Braunecker and Hinkelbein1 for their interest in our recent manuscript.2 We made no claim that our findings with isoflurane anaesthetic in young adult and middle-aged rats were completely novel. Braunecker and Hinkelbein1 are correct in stating that previous studies have indeed reported enduring effects of isoflurane and other anaesthetic gases on the brain. However, the studies to which Braunecker and Hinkelbein refer have not investigated any physiological or behavioural consequences of anaesthetic-induced protein changes in the brain. We are primarily concerned with postoperative cognitive dysfunction and whether exposure to anaesthetics may be a causative factor. From this vantage point relating changes in the brain to the observed deficit is the secondary outcome measure. Certainly, the protein changes observed by authors such as Kalenka et al. 3,4 may provide clues to the mechanism of action of isoflurane and other volatile anaesthetic agents on cognition. We did not expose our sham rats to 100% oxygen for the full 4 h and we do not believe this carrier gas is responsible for the observed deficit. Other researchers have reported deficits in cognition after exposure to isoflurane but have not employed 100% oxygen as the carrier. Isoflurane (1.2%) in 30% oxygen and 70% nitrous oxide impaired performance in the radial arm maze in both adult and aged rats.5,6 A recent study in mice found low concentrations of isoflurane (1%) delivered in 100% oxygen impaired, whereas high concentrations (1.5 and 2%) improved learning and memory in the Morris water maze.7 Given that there are diametrically opposed outcomes reported following isoflurane exposure, future studies must surely include cognitive outcome in conjunction with brain analyses. The protein changes detected after isoflurane and/or 100% oxygen exposure are without significance until they can be related in some way to a physiological response.