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  • 1
    ISSN: 1432-055X
    Keywords: Schlüsselwörter: Sevofluran – Isofluran – Aufwachzeit – Hämodynamik – Unerwünschte Wirkung ; Key words: Sevoflurane – Isoflurane – Emergence time – Haemodynamics – Adverse effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: 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 MACawake, 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 MACawake[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.
    Notes: 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 FIO2 von 1,0) bzw. 3,1 MAC-h (Berechnung für eine FIO2 von 0,4 und eine FIN2O 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).
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  • 2
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Sevofluran ; Enfluran ; Fluorid ; Nierenfunktion ; Key words Sevoflurane ; Enflurane ; Fluoride ; Renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Sevoflurane is a “new” volatile inhaled anaesthetic. Owing to its lower blood-gas solubility coefficient, emergence from anaesthesia is faster with sevoflurane than with isoflurane, enflurane, or halothane. Sevoflurane undergoes metabolic biodegradation, releasing inorganic fluoride ions that could produce nephrotoxicity. In this study, we compared serum inorganic fluoride concentrations (IFCs) in patients receiving either sevoflurane or enflurane. Furthermore, indices of renal function were evaluated until the 3rd postoperative day. Methods. Thirty patients with no history of renal or hepatic disease and with an anticipated duration of anaesthesia of at least 3 h were studied in an open, prospective, randomised clinical trial. Anaesthesia was induced with fentanyl, thiopentone, and vecuronium for facilitating endotracheal intubation. Anaesthesia was maintained with sevoflurane or enflurane, 60% nitrous oxide in oxygen, and additional doses of fentanyl. Blood samples for serum IFCs were obtained preoperatively and 2 and, if possible, 4 and 6 h after starting sevoflurane or enflurane, at the end of anaesthesia, and 1, 2, 4, 8, 12, 24, 48 and 72 h post-anaesthesia. Fluoride analysis was performed using an ion-selective electrode. Indices of renal function (serum sodium, osmolality, creatinine, urea, and uric acid, urine specific gravity, osmolality, and pH) were evaluated preoperatively, at the end of anaesthesia, and 24, 48, and 72 h post-anaesthesia. Results. The duration of anaesthetic exposure was approximately 1.65 MAC-h for both inhaled anaesthetics. Peak serum IFCs were higher with sevoflurane (34.5 μmol/l) than with enflurane (19.4 μmol/l). Fluoride levels decreased more rapidly with sevoflurane: 24 h post-anaesthesia there was no difference between sevoflurane and enflurane (Fig. 1). The area under the curve (AUC) was greater with sevoflurane (688 μmol/l·h) than with enflurane (591 μmol/l·h). For both groups correlation coefficients were higher for MAC-h and AUC than for MAC-h and peak serum IFC (Figs. 2 and 3). Indices of renal function did not change in either group. Discussion. In our study 1.69 MAC-h sevoflurane produced peak serum IFCs of 34.5 μmol/l. This is in accordance with the investigation of Frink et al. [4], who reported approximately 30 μmol/l after 1.4 MAC-h sevoflurane. Peak serum IFCs with sevoflurane were twice those with enflurane. Within the first 24 h post-anaesthesia, fluoride levels decreased more rapidly after sevoflurane. AUC may be more important than peak serum IFC in evaluating patients who are at risk for renal concentrating defects. In our study there was no evidence of renal dysfunction in either group.
    Notes: Zusammenfassung In einer offenen, randomisierten, prospektiven und vergleichenden Studie zwischen Sevofluran und Enfluran wurden bei 30 nierengesunden Patienten die Serumfluoridkonzentrationen und die exokrine Nierenfunktion bis zum 3. postoperativen Tag untersucht. Die applizierte Dosis betrug in beiden Gruppen ca. 1,65 MAC-Stunden. Die maximale Serumfluoridkonzentration war mit 34,5 μmol/l nach Sevofluran fast doppelt so hoch wie nach Enfluran (19,4 μmol/l). 24 h nach Anästhesieende war die Serumfluoridkonzentration in der Sevoflurangruppe auf ca. 25% des Maximalwerts abgefallen, in der Enflurangruppe auf ca. 40% des Maximalwerts. Ab diesem Zeitpunkt war kein Unterschied mehr zwischen den beiden Gruppen nachweisbar. Die Fluoridbelastung (Area under the curve, AUC) war nach Sevofluran (688 μmol/l·h) etwas größer als nach Enfluran (591 μmol/l·h). Die Korrelation von MAC-Stunden (applizierte Dosis) und AUC war in beiden Gruppen besser als die von MAC-Stunden und maximaler Serumfluoridkonzentration. Veränderungen von Laborvariablen (Natrium, Osmolalität, Kreatinin, Harnstoff und Harnsäure i.S., spez. Gewicht, Osmolalität und pH-Wert i.U.), die auf eine Nierenschädigung hinweisen würden, wurden nicht nachgewiesen.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Der Anaesthesist 45 (1996), S. 323-329 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Fentanyl ; Proteinbindung ; Saures α1-Glykoprotein (Orosomucoid) ; Akut-Phase-Reaktion ; Gleichgewichtsdialyse ; Key words Fentanyl ; Protein binding ; α1-Acid glycoprotein (orosomucoid) ; Acute phase reaction ; Equilibrium dialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Numerous basic drugs are extensively bound to α1-acid glycoprotein. Fentanyl, with a pKa value of 8.43, is also a basic drug. Protein binding studies have yielded contradictory results concerning binding of fentanyl to α1-acid glycoprotein. In this study we investigated time courses of serum protein concentrations and serum protein binding of fentanyl during postoperative acute phase reaction, assuming that an increase of α1-acid glycoprotein is accompanied by an increase of serum protein binding, if fentanyl is extensively bound to α1-acid glycoprotein. Fentanyl protein binding measurements using equilibrium dialysis can be affected by volume shifts and pH changes. Therefore, volume shifts from buffer to serum and the influence of various phosphate buffers on increasing pH due to loss of CO2 were also evaluated. Methods. Thirteen patients with no history of renal or hepatic disease undergoing an operation with a significant acute phase reaction were studied. Preoperatively and on the first 3 postoperative days serum concentrations of α1-acid glycoprotein, albumin, total protein and apolipoprotein A and B were determined by rocket immunoeolectrophoresis, biuret method and laser nephelometry, respectively. Corresponding serum protein binding of fentanyl was measured by adding 40 ng of fentanyl to 1 ml serum followed by equilibrium dialysis at 37° C for 4 h. A 0.167 M phosphate buffer (pH 7.27), which gave a final pH of 7.40, was used. Volume shifts from buffer to serum were measured. Fentanyl concentration in serum before dialysis (FS) was determined by gas chromatography, and fentanyl concentration in buffer after dialysis (FB) was determined by radioimmunoassay. Serum protein binding (SPB) was calculated by the formula: where c is a correction factor. Ten randomly selected patient sera were dialyzed against four phosphate buffers of different pH values and molarities, and the serum pH at the end of equilibrium dialysis was measured. Results. Postoperatively, the serum concentration of α1-acid glycoprotein rose to 151% of the control value. In contrast, serum protein binding of fentanyl did not change significantly, with a slight decrease to 96% of control value. There was a significant decrease in serum concentrations of albumin (3rd postoperative day), total protein (2nd postoperative day) and apolipoprotein B (1st–3rd postoperative day) to 85%, 90% and 75% of control values, respectively. Changes in apolipoprotein A concentration were not significant. Protein binding of fentanyl did not correlate with α1-acid glycoprotein and apolipoprotein A, but there was a positive linear relationship between protein binding of fentanyl and albumin, total protein and apolipoprotein B. At the end of equilibrium dialysis the mean volumes of the serum and buffer compartments were 1114±72 and 834±68 μl, respectively. The two phosphate buffers, with pH 7.30 (0.15 M) and pH 7.27 (0.167 M), gave final serum pH of 7.42 and 7.40, respectively. Conclusions. Present findings suggest that in contrast to other basic drugs, fentanyl binding to α1-acid glycoprotein is of minor importance. In agreement with the findings of former studies, protein binding of fentanyl depended on albumin, total protein and apolipoprotein B concentrations. Due to unspecific binding of fentanyl by hydrophobic interactions, a major role of albumin, which amounts to about 60% of total protein, seems to be evident. Determining fentanyl protein binding by equilibrium dialysis, volume shifts must be taken into account if calculation is based on fentanyl concentrations in plasma (serum) and buffer after dialysis, and an appropriate buffer must be used.
    Notes: Zusammenfassung Zahlreiche basische Arzneimittel werden an das Akut-Phase-Protein saures α 1 -Glykoprotein (sα 1 GP) gebunden. Für Fentanyl (F) liegen dazu widersprüchliche Ergebnisse vor. Bei 13 Patienten mit Baucheingriffen wurde deshalb die postoperative Akut-Phase-Reaktion mit den entsprechenden Veränderungen der Serumproteine bis zum 3. postoperativen Tag verfolgt und untersucht, ob der Anstieg von sα 1 GP von einem Anstieg der Serumproteinbinderate (SPB) von F begleitet wird. Die SPB wurde mittels Gleichgewichtsdialyse bestimmt. Dabei auftretende methodische Probleme wurden im zweiten Teil der Studie untersucht. Während die Serumkonzentration von sα 1 GP postoperativ anstieg, blieb die SPB von F unverändert, tendenziell fiel sie geringfügig. Die Konzentrationen von Albumin, Gesamteiweiß und Apolipoprotein B nahmen tendenziell, z.T. sogar signifikant ab. Für diese drei Eiweißfraktionen konnte auch eine positive Korrelation mit der SPB nachgewiesen werden. Damit ergeben sich weitere Hinweise darauf, daß Albumin, Gesamteiweiß und Apolipoprotein B für die Proteinbindung von F von Bedeutung sind. Eine Bindung an sα 1 -GP ist zwar grundsätzlich denkbar, quantitativ ist sie aber im Vergleich zu anderen basischen Arzneimitteln nur von untergeordneter Bedeutung. Während der Gleichgewichtsdialyse kommt es zu Volumenverschiebungen vom Pufferkompartiment zum Serumkompartiment und zu Veränderungen des pH-Werts, die bei der Berechnung der Proteinbinderate und der Auswahl des Puffers zu berücksichtigen sind.
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  • 4
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Inhalationsanästhetika ; Arbeitsplatzbelastung ; Gentoxizität ; Langzeitexposition ; Umweltverträglichkeit ; Schlüsselwörter Inhalation anaesthetics ; Genetic toxicity ; Long-term occupational exposure ; Environmental pollution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary There are a number of assays available to study genetic toxicity of inhalation anaesthetics. Those discussed in this review are the Ames Salmonella mutagenesis test and assays for structural chromosome aberrations, micronuclei (MN) and sister chromatid exchanges (SCEs). None of these assays showed abnormalities induced by volatile inhalation anaesthetics. Only Compound A induced a slight increase in the number of SCEs. However, the implications of this in vitro study are unclear. Results of studies focussing on the effects of long-term occupational exposure to inhalation anaesthetics are controversial. Neither harmfulness nor safety of chronic exposure to low concentrations of inhalation anaesthetics have been proven. Although there is no clear evidence of harmfulness, there is general agreement that occupational exposure should be minimized for precautionary reasons. This particularly applies to N2O. Therefore, occupational exposure standards have been established in many countries, though not yet for sevoflurane and desflurane. In Germany, occupational exposure can be kept below the threshold values, when working in operation theatres with a standard air conditioning system, a high-flow scavenging system, low leakage anaesthesia machines and preventative maintenance of equipment. Under these conditions occupational exposure is low even when using laryngeal mask airways and uncuffed tracheal tubes. Sevoflurane is a halocarbon, but is only partially halogenated and the only halogen it contains is fluorine. Sevoflurane, therefore, appears to have an insignificant effect on ozone depletion and its contribution to the greenhouse effect is negligible.
    Notes: Zusammenfassung Testsysteme, die zur Untersuchung gentoxischer Effekte herangezogen werden können, sind der Ames-Test, die Erfassung von Chromosomenaberrationen, Mikrokernen (MN) und Schwesterchromatidaustauschen (SCE). Die Ergebnisse in diesen Testverfahren sind für die volatilen Inhalationsanästhetika, einschließlich Sevofluran negativ. Für Compound A wurde in vitro ein geringgradiger Anstieg der SCE beschrieben, dessen Bedeutung allerdings unklar ist. Die Ergebnisse von Studien, die Effekte der Langzeitexposition gegenüber Spurenkonzentrationen von Inhalationsanästhetika am Arbeitsplatz untersuchen, sind widersprüchlich. Weder die Schädlichkeit noch die Unbedenklichkeit einer chronischen Exposition gegenüber Spurenkonzentrationen von Inhalationsanästhetika gilt als bewiesen. Im Sinne einer vorsorglichen Maßnahme wird aber eine weitestgehende Reduktion der Arbeitsplatzbelastung durch Inhalationsanästhetika angestrebt. Dies gilt insbesondere für N2O. Hierbei stellen die MAK-Werte (maximale Arbeitsplatzkonzentration) verbindliche Grenzwerte dar. Für Sevofluran ist noch kein MAK-Wert festgelegt worden. Durch lüftungs-, geräte- und meßtechnische Maßnahmen bzw. Standards ist heute die Raumluftbelastung durch die halogenierten Inhalationsanästhetika nur noch gering. Dies gilt auch für die Anwendung ungeblockter Tuben und der Larynxmaske. Sevofluran besitzt als teilhalogenierter Kohlenwasserstoff nur Fluor und trägt deshalb vermutlich nur unwesentlich zur Zerstörung der Ozonschicht bei. Beim Treibhauseffekt kommt ihm eine völlig untergeordnete Bedeutung zu.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 54 (1999), S. 843-845 
    ISSN: 1432-1041
    Keywords: Key words Piritramide ; Protein binding ; Acute phase response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Piritramide is a lipophilic opioid, which is widely used for postoperative analgesia and analgosedation in Europe. In this study we investigated the influence of various protein concentrations (total protein, 1-acid glycoprotein, albumin) and the postoperative acute phase response on the protein binding of piritramide. Methods: The influence of various protein concentrations on the protein binding of piritramide was investigated by either diluting the serum samples of five volunteers with isotonic saline or by adding different amounts of 1-acid glycoprotein. Albumin binding was measured in a 5% human albumin solution. The impact of the postoperative acute phase response was investigated by obtaining daily serum samples from 18 surgical patients until the third postoperative day, and measuring piritramide protein binding, 1-acid glycoprotein, total protein and albumin. Results: There was a significant relationship between piritramide protein binding and the concentrations of total protein and 1-acid glycoprotein. The binding to albumin was 88%. During the postoperative acute phase response, the protein binding of piritramide did not change. Serum concentrations of 1-acid glycoprotein increased, whereas total protein and albumin decreased. Conclusion: Although there were significant changes in the piritramide-binding proteins, 1-acid glycoprotein and albumin, during the postoperative acute phase response, the protein binding of piritramide did not change. Therefore, a change in protein binding, which might be one factor to be considered in determining piritramide dosage in the postoperative period, does not have to be taken into account.
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  • 6
    ISSN: 1432-1246
    Keywords: Key words Occupational exposure ; Inhalation anaesthetics (nitrous oxide ; halothane ; isoflurane) ; Operating room personnel ; Eastern European hospital
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Although no dose-response relationship exists for the health risks associated with the occupational exposure to inhaled anaesthetics, public health authorities recommend threshold values. The aim of the present study was to assess whether and to what extent these threshold values are exceeded in surgeons and circulating nurses of an Eastern European university hospital, before and after measures had been taken to reduce occupational exposure. Methods: At nine workplaces, occupational exposure to nitrous oxide and the volatile anaesthetic used (halothane or isoflurane) was measured within the breathing zones of surgeons and circulating nurses by means of photoacoustic infrared spectrometry. The measurements were carried out in 1996 and were repeated in 1997 after the installation of active scavenging devices at five workplaces, and an air-conditioning system at one workplace. Results: Occupational exposure to nitrous oxide and halothane or isoflurane was lower in 1997 compared with that of 1996. In 1996, 89% of the nitrous oxide values were above the European threshold value of 100 ppm, whereas in 1997 approximately 50% were above this limit. In 1996 the majority of the measurements for the volatile anaesthetics were already below 5 ppm halothane and 10 ppm isoflurane and the number of measurements exceeding these limits was further reduced in 1997. Conclusion: The measures taken were effective in reducing waste gas exposure. Nevertheless, further efforts are necessary, especially for nitrous oxide, to reach Western European standards and to minimise possible health risks. These efforts comprise the installation of (active) scavenging devices, air-conditioning systems and new anaesthesia machines at all workplaces, the use of low-flow anaesthesia, the replacement of inhaled anaesthetics by intravenous anaesthetics and an appropriate working technique.
    Type of Medium: Electronic Resource
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