Tatsuo Nakamoto

Propofol decreases the clearance of midazolam by inhibiting CYP3A4: an in vivo and in vitro study

To examine the effect of propofol on the pharmacokinetics of midazolam in vivo and to elucidate the mechanism of the pharmacokinetic changes of midazolam by propofol with the use of human liver microsomes and recombinant CYP3A4.

The monoethylglycinexylidide test is more useful for evaluating liver function than indocyanine green test: case of a patient with remarkably decreased indocyanine green half-life.

Lidocaine was used for evaluation of hepatic function in a patient undergoing hepatic resection. Preoperatively, half-life of indocyanine green (ICG) was 33 min after intravenous administration. Plasma concentration of the N-dealkylated metabolite of lidocaine, monoethylglycinexylidide (MEGX), was quantitatively determined to evaluate hepatic function. The patients rate of formation of MEGX at 15 min after administration of lidocaine was within normal limits, at 56 micrograms/L. These findings suggest that in this patient, hepatic cytochrome P-450IIIA activity was not impaired, but selective impairment of uptake of ICG into hepatocytes or excretion into the bile ducts was present. The rate of formation of MEGX was decreased, and plasma concentration of bilirubin was elevated postsurgically; this could have been the result of decreased cytochrome P-450IIIA activity or decreased hepatic blood flow after hepatic resection. We conclude that the rate of formation of MEGX is a better index of hepatic function than is ICG half-life.

Area under the plasma concentration-time curve of inorganic fluoride following sevoflurane anesthesia correlates with CYP2E1 mRNA level in mononuclear cells

Background Because the amount of inorganic fluoride released after anesthesia with sevoflurane depends on the dose of administered sevoflurane and cytochrome P450 (CYP) 2E1 activity in the liver, a reliable and noninvasive probe for CYP2E1 would be useful for predicting plasma inorganic fluoride levels after anesthesia. In this study, the authors evaluated the relation between plasma concentration of inorganic fluoride after sevoflurane anesthesia and CYP2E1 mRNA level in mononuclear cells. Methods Twenty patients (American Society of Anesthesiologists physical status I), aged 20–68 yr undergoing body surface surgery with general anesthesia with sevoflurane were enrolled. One milliliter of blood was obtained before administration of sevoflurane and mononuclear cells were obtained. Levels of CYP2E1 mRNA in mononuclear cells were measured by competitive reverse transcription polymerase chain reaction with a specific primer and competitor for CYP2E1 mRNA. Results There was a significant correlation between level of CYP2E1 mRNA in mononuclear cells and the area under the plasma concentration–time curve of plasma inorganic fluoride from the beginning of sevoflurane administration to infinity in uninduced and uninhibited patients (r2 = 0.56;P < 0.01). Conclusions Area under the plasma concentration–time curve of inorganic fluoride after sevoflurane anesthesia correlates with CYP2E1 mRNA in mononuclear cells in peripheral blood.

Spontaneous shutoff of desflurane vaporizer

Keywords Vaporizer Desflurane Failure EquipmentTo the Editor:We would like to report the intraoperative failure of adesflurane vaporizer. The incident occurred as a 57-year-old man underwent parathyroid surgery. After inductionand intubation, anesthesia was maintained with 5 %inhaled desflurane, using a Tec 6 Plus vaporizer (GEHealthcare Japan Co., Tokyo, Japan), via a semiclosedcircuit with a 3 l/min fresh gas flow. Approximately 7 mininto the case, the ‘‘no output’’ vaporizer alarm sounded andthe desflurane concentration in the anesthesia circuit beganto fall. We immediately turned off the vaporizer. Afterseveral seconds, the vaporizer automatically reset butwithin several minutes, the ‘‘no output’’ error occurredagain. The surgery was then completed using sevoflurane,without assessing the depth of anesthesia. The patientemerged from anesthesia uneventfully, with no recollectionof the intraoperative events.We purchased the vaporizer 2 months prior to theincident; it was used almost every day for 2 months.Although clinical engineers and anesthesiologists maintainanesthetic machines and circuits, vaporizers are notinspected usually in our operating rooms. According to themanufacturer’s technical department, 10 incidences ofinitial failure have been confirmed in 431 products sincethe vaporizer’s 2011 release in Japan. The vaporizer wasexchanged at no charge following this initial failure.Afterward, the manufacturer reported to us that the failureof an electronic pressure transducer caused this incident.They recommended the immediate use of alternativeanesthetics if the ‘‘no output’’ error recurred.Reports of spontaneous shutoff during surgery of acorrectly mounted desflurane vaporizer have not previouslybeen published [1–3]. Unlike conventional mechanicalvaporizers, the desflurane vaporizer has sophisticatedelectronic components. As a fail-safe, it completely haltsagent output if an electronic failure occurs. Since thewashout for desflurane is more rapid than that for otherinhalation agents, patients emerge from anesthesia soonafter shutoff of the vaporizer. The incidence of initialfailure reported by the manufacturer seems relatively high.This case serves to emphasize the importance of fullyunderstanding the features of equipment that is in frequentuse [4].