Cisatracurium, but not mivacurium, induces apoptosis in human umbilical vein endothelial cells in vitro.

BACKGROUND AND OBJECTIVE: Cisatracurium is an intermediate acting, non-depolarizing neuromuscular blocking agent. Previous reports have indicated a growth-inhibitory effect of the isoforms cisatracurium and atracurium on two human cell lines in vitro. These effects were ascribed to oxidative stress elicited by acrylate esters formed during cisatracurium breakdown. Oxidative stress is a potent precipitator of apoptosis. Therefore, the aim of the present study was to investigate whether the growth-inhibitory effects of cisatracurium could be explained by initiation of apoptosis. METHODS: Human umbilical vein endothelial cells were incubated with cisatracurium at concentrations of 0.96, 3.2, 9.6, 32 and 96 micromol for 24 h. DNA fragmentation was measured using the Cell Death Detection ELISA Plus assay (Roche Diagnostics, Mannheim, Germany). RESULTS: There was a dose dependency of cisatracurium with respect to the rate of apoptosis in human umbilical vein endothelial cells. Programmed cell death could be demonstrated at concentrations encountered in human plasma after single-bolus injections of cisatracurium. Apoptosis was attenuated by the concomitant administration of glutathione. CONCLUSIONS: These findings strongly support the hypothesis that acrylate esters, breakdown products of cisatracurium, induce oxidative stress and, subsequently, apoptosis.

Sevoflurane in exhaled air of operating room personnel.

UNLABELLED: Evidence on potential health hazards arising from exposure to volatile anesthetics remains controversial. Exposure may, in principle, be supervised by monitoring of ambient air or, alternatively, in vivo. We used the Proton Transfer Reaction-Mass Spectrometry to screen the breath of 40 operating room staff members before operating room duty, 0, 1, 2, and 3 h after duty, and before commencing duty on the consecutive day, and control persons. Staff members exhibited significantly increased sevoflurane levels in exhaled air after duty, with a mean of 0.80 parts per billion as compared with baseline values of 0.26 parts per billion (P < 0.05). Analysis of variance with adjustment for within correlation (repeated measurements) showed a statistically significant time-effect (P < 0.001). We conclude that (a) Proton Transfer Reaction-Mass Spectrometry biomonitoring of exhaled sevoflurane can serve as a simple and rapid method to determine volatile anesthetic excretion after occupational exposure, and (b) significant concentrations of sevoflurane may be continuously present in persons exposed to sevoflurane on a daily basis. IMPLICATIONS: The present study depicts the profile of volatile anesthetics, isoflurane and sevoflurane, in exhaled air of ambulatory patients. Biomonitoring of expired anesthetic concentrations is a noninvasive and rapid method to determine volatile anesthetic excretion.