[The action of flumazenil in combination with fentanyl on spontaneous respiration].
Whereas the efficacy of flumazenil (Fl) for improving vigilance in the presence of other benzodiazepine agonists (BZA) is undoubted, its effect on BZA- and/or opioid agonists (OA)-induced respiratory depression is the subject of controversies. Some authors describe an improvement of a midazolam (Mi)-induced increase in paCO2, whereas others cannot find any influence on diazepam-induced respiratory depression. In two studies in which Fl was used to antagonize Mi/Fentanyl (Fe) anaesthesia we found even worse oxygen saturation values than with placebo (Pl). All our previous studies indicate a slight intrinsic activity of Fl on respiration in the presence of opioids. We therefore investigated the influence of Fl and Pl on expiratory pCO2 and oxygen saturation (SAT). METHODS. A group of 15 male, healthy volunteers aged 20-30 years gave written informed consent to participate in this double blind study, which was approved by our Institutional Review Board. Each subject received 3 micrograms/kg body wt. Fe + 0.5 mg Fl and 1 week later 3 micrograms/kg body wt. Fe + 5 ml NaCl 0.9% (Pl) i.v., in random order. They were undisturbed and breathed spontaneously. The following parameters were measured: SAT, pCO2 and heart rate (HR) continuously, using a pulse oximeter (SAT, H) and CO2 infrared absorption monitor (Oscar, Messrs., Datex). The blood pressure was recorded before and after a 5-min preinjection period (baseline) and at the end of the procedure (25 min). The data were stored in a microcomputer (Multitalent, Messrs. ZAK) and transmitted to a PC after each trial. STATISTICS. The groups were compared with the Wilcoxon rank sum test. P less than 0.05 is significant. RESULTS. In trials 1 and 2 there was an increase of pCO2 and a drop in SAT. The changes in pCO2 and SAT were more pronounced after Fe+Fl in 12 subjects (80%), as against 1 subject with the opposite result. There were 2 subjects who showed no difference between trials 1 and 2. The combination of Fe and Fl caused significantly higher increases in pCO2 (P = 0.007) and more pronounced decreases in SAT (P = 0.04) than Fe and Pl. DISCUSSION. These results indicate a slight enhancement of Fe-induced respiratory depression by Fl. In a previous study it could be shown that Fl antagonized the respiratory depressive effect of Mi, but baseline paCO2 was not completely recovered. In previous studies respiratory function impaired by Mi+Fe was initially improved by Fl, but rebound effects on SAT were observed, which were more pronounced than those after Pl. Therefore, respiratory function must be closely monitored in Fl-antagonized patients after Mi/Fe anaesthesia.
Tolksdorf
W
W
Klinik für Anästhesiologie, Medizinische Fakultät, RWTH Aachen.
Prag
H
H
Vorwold
M
M
Amberger
M
M
D000328:Adult; D003864:Depression, Chemical; D004311:Double-Blind Method; D004338:Drug Combinations; D005283:Fentanyl / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology*; D006801:Humans; D008297:Male; D012119:Respiration / Q000187:drug effects*
D004338:Drug Combinations; D005442:Flumazenil; D005283:Fentanyl
Die Wirkung von Flumazenil in Kombination mit Fentanyl auf die Spontanatmung.