Aufwachzeiten, Kreislaufverhalten und unerwünschte Wirkungen bei Anwendung von Sevofluran und Isofluran

Zusammenfassung.

Im Rahmen einer multizentrischen Studie, deren Ziel die Zulassung von Sevofluran in Europa und den USA ist, führten wir bei 50 Patienten eine offene, randomisierte, prospektive und vergleichende Untersuchung von Sevofluran und Isofluran hinsichtlich Aufwachzeiten, postoperativer Befindlichkeit, Hämodynamik und unerwünschter Wirkungen durch. Die Patientengruppen waren abgesehen von der Geschlechtsverteilung, die ohne Einfluß auf die Aufwachzeit ist, vergleichbar. Die applizierte Dosis betrug für beide Inhalationsanästhetika ca. 1.3 MAC-h (Berechnung für eine F_IO₂ von 1,0) bzw. 3,1 MAC-h (Berechnung für eine F_IO₂ von 0,4 und eine F_IN₂O von 0,6). Sevofluran wurde signifikant schneller pulmonal eliminiert und führte zu einem signifikant schnelleren Erwachen (7 min für Sevofluran vs. 11,5 min für Isofluran). Der postoperative Zustand der Patienten war in beiden Gruppen gleich gut. Herzfrequenz und Blutdruck zeigten im Verlauf keine Unterschiede zwischen Sevofluran und Isofluran. Unerwünschte Wirkungen, für die ein möglicher Kausalzusammenhang mit dem verwendeten Inhalationsanästhetikum herzustellen war, traten in beiden Gruppen auf (Tabelle 4).

Abstract.

Sevoflurane is a "new" volatile inhaled anaesthetic that is currently undergoing phase III clinical trial in Europe and the United States. Owing to the low blood solubility, rapid induction of anaesthesia and emergence from anaesthesia would be expected. In this study, we compared emergence times and haemodynamics in patients receiving either sevoflurane or isoflurane. Furthermore, all adverse effects were recorded and the relationship to the drug administered was rated. Methods. Fifty ASA physical status I and II patients were studied in an open, prospective, randomised clinical trial. Anaesthesia was induced with fentanyl, thiopentone, and vecuronium for facilitating endotracheal intubation and maintained with sevoflurane or isoflurane, 60% nitrous oxide (N₂O) in oxygen (O₂), and additional doses of fentanyl (1 – 2 µg/kg⋅h). The electrocardiogram, blood pressure (non-invasive), O₂ saturation, temperature, and end-tidal concentrations of sevoflurane or isoflurane, N₂O, and carbon dioxide were monitored continuously. At the end of surgery, administration of sevoflurane or isoflurane and N₂O was discontinued without tapering and emergence times were recorded. All adverse events that occurred until the 3rd postoperative day were recorded and the relationship to the inhaled anaesthetic was rated as "none", "unlikely", "possible", "probable", or "highly probable". Results. With the exception of gender, the two patient groups were comparable (Tables 1 and 2). Due to the higher MAC value, mean end-tidal concentrations were higher for sevoflurane (0.82% vs. 0.59% for isoflurane). The duration of anaesthetic exposure was 1.3 MAC h (calculation with FIO₂=1.0 MAC value) and 3.1 MAC h (calculation with FIO₂=0.4 in N₂O MAC value), respectively, for both inhaled anaesthetics. Pulmonary elimination was faster (Fig. 1) and emergence time shorter (7 min vs. 11.5 min, Table 3) with sevoflurane. There was no difference in the time courses of heart rate and mean arterial blood pressure (Figs. 2 and 3). No adverse effects with a "probable" or "highly probable" relationship to the inhaled anaesthetic were observed. Table 4 shows the adverse events with a possible relationship to the drug administered. Further evaluations of nausea, vomiting, and dizziness are shown in Table 5. Discussion. Emergence time after inhalation anaesthesia depends on pulmonary elimination and MAC_awake, that is, the end-tidal concentration that would allow opening of the eyes on verbal command. Pulmonary elimination depends on dose applied (MAC h), alveolar ventilation, and blood-gas solubility coefficient. Due to the lower blood-gas solubility coefficient (0.6 – 0.7 for sevoflurane vs. 1.3 – 1.4 for isoflurane) and in accordance with the investigations of Frink et al. [4] and Smith et al. [16], emergence time was significantly shorter with sevoflurane. Gender, the only difference between the two patient groups, does not influence pulmonary elimination and MAC_awake[8]. Supplementing inhalation anaesthesia with fentanyl, there was no difference in the time courses of heart rate and mean arterial blood pressure between sevoflurane and isoflurane. Adverse events with a possible relationship to the inhaled anaesthetic occurred in both groups.