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  • 1
    ISSN: 1432-055X
    Keywords: Schlüsselwörter PDE-III-Hemmer ; Hämodynamik ; Koronare Herzkrankheit ; Key words PDE-III-inhibitors ; Haemodynamics ; Ischaemic heart disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract At present, phosphodiesterase III inhibitors are commonly used for the treatment of low cardiac output states. Despite their positive inotropic and lusitropic effects, these drugs are still under discussion because of certain adverse effects like thrombopaenia, elevation of transaminases, abdominal disregulation, and excessive periphereal vasodilatation. As a consequence, more cardioselective phosphodiesterase inhibitors were developed with the aim of reducing these adverse effects. One of them, enoximone (Marion Merrell Dow, Fig. 1), an imidazole derivative, has nearly no influence on platelets and abdominal organ function. In addition, in many studies vasodilatation was found to be absent. Recently a new substance, R80122 (Janssen, Belgium, Fig. 1), was developed. First experimental studies showed high cardioselectivity of this substance. The aim of this study was to compare the haemodynamic effects of enoximone and R80122 in patients with ischaemic heart disease. Methods. This study was thoroughly discussed and approved by the local Ethics Committee; all patients gave written informed consent. Twenty male patients (Table 1) with normal left ventricular function who were about to undergo elective coronary artery bypass surgery were randomly allocated to receive a bolus of either 1.0 mg/kg enoximone or 0.3 mg/kg R80122 after induction of anaesthesia. Premedication consisted of 2 mg flunitrazepam orally the evening before and in the morning 1 h before operation. Anaesthesia was induced with 0.007 mg/kg fentanyl, 0.2 mg/kg etomidate, and 0.1 mg/kg pancuronium bromide and maintained by a continuous infusion of 0.02 mg/min fentanyl and 0.3 mg/min midazolam. After induction of anaesthesia haemodynamic measurements were performed and blood gas samples were taken preoperatively under steady-state conditions before and 5, 30, and 60 min after drug administration. Results. The results of both groups are shown in Table 2 as mean values with standard deviations. Individual changes of cardiac index (CI), mean arterial pressure (MAP), and systemic vascular resistance (SVR) are depicted in Fig. 2. Peak percentage changes of the haemodynamic parameters are shown in Fig. 3. Both substances improved cardiac function; 5 min after drug administration CI increased by 31% and 26%, respectively. This was accompanied by increases in stroke volume (13% and 14%, respectively) and heart rate (15% and 10%, respectively). At the same time, there were declines in SVR (38% and 36%, respectively) and MAP (19% and 21%, respectively). Although mean values of pulmonary arterial and wedge pressure decreased after drug administration, these changes were inconsistent and not of clinical relevance. There were no statistically significant differences between the haemodynamic effects of both substances at any time in this study. Conclusions. Both enoximone and R80122 showed the expected inotropic effects. Nevertheless, both substances have a distinct vasodilative effect, which leads to a decline in MAP. R80122 does not have higher cardioselectivity than enoximone.
    Notes: Zusammenfassung In dieser Untersuchung wurden die hämodynamischen Effekte einer Bolusinjektion von 1,0 mg/kg KG Enoximon bzw. 0,3 mg/kg KG R80122 bei jeweils 10 Patienten mit koronarer Herzkrankheit und normaler linksventrikulärer Funktion gemessen und miteinander verglichen. Die einzelnen Messungen erfolgten präoperativ nach Narkoseeinleitung unter steady state-Bedingungen. Der Herzindex stieg bereits 5 min nach Gabe des jeweiligen PDE-III-Hemmers maximal an, in der Enoximongruppe im Mittel um 31%, in der R80122-Gruppe im Mittel um 26% über die jeweiligen Ausgangswerte. Der Anstieg des Herzindex basierte bei beiden Gruppen sowohl auf einem Anstieg des Schlagvolumens, nach Enoximongabe im Mittel um 13%, nach Gabe von R80122 im Mittel um 14%, wie auch der Herzfrequenz, nach Enoximongabe im Mittel um 15%, nach Gabe von R80122 im Mittel um 10%. Gleichzeitig kam es zu einem Abfall des arteriellen Mitteldrucks, nach Enoximongabe im Mittel um 19%, nach Gabe von R80122 im Mittel um 21%. Ursache für den Abfall des arteriellen Mitteldrucks war in beiden Gruppen die Erniedrigung des peripheren Gefäßwiderstands, in der Enoximongruppe im Mittel um 38%, in der R80122-Gruppe im Mittel um 36%. Ein signifikanter Unterschied zwischen den hämodynamischen Parametern beider Gruppen lag zu keinem Meßzeitpunkt vor. Beide Substanzen zeigen in der vorgegebenen Dosierung vergleichbare hämodynamische Effekte, einen Anstieg von Herzindex, Herzfrequenz und Schlagvolumen bei gleichzeitigem Abfall des peripheren Gefäßwiderstands. Die in tierexperimentellen Untersuchungen nachgewiesene höhere Kardioselektivität von R80122 konnte unter den klinischen Bedingungen dieser Studie nicht nachgewiesen werden.
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  • 2
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Eltanolon ; Pharmakokinetik ; Konzentrationswirkungsbeziehung ; Hysterese ; Hämodynamik ; Respiration ; Key words Eltanolone ; Pharmacokinetics ; Concentration-effect relationship ; Hysteresis ; Haemodynamics ; Respiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract During the last five years several authors have reported largely satisfactory results, using the steroid intravenous anaesthetic eltanolone (pregnanolone) for induction of anaesthesia after administering a bolus dose. Until now, however, no investigations have been undertaken, dealing with the infusion pharmacokinetics of eltanolone after arterial blood sampling and using slow induction to quantify the concentration-effect relationship. Secondary objectives were to assess the haemodynamic and respiratory effects. Material and methods. Eltanolone emulsion was administered to 12 healthy male volunteers using a computer-controlled infusion device. Linearly increasing serum concentrations were generated for two consecutive times with an anticipated slope of 0.075 μg ml−1 min−1 and with a targeted concentration of 2 μg ml−1. During and following the infusion, EEG was recorded and clinical signs were assessed as measure of the hypnotic effect. Thus, the time intervals from start of infusion until the volunteers fell asleep, until they did no longer respond to loud verbal commands, until loss of the corneal reflex and until the appearance of burst suppression patterns in the EEG were recorded. The latter sign was used as endpoint for the infusion. After the cessation of the infusion the time intervals until the disappearance of burst suppression and the reappearance of the clinical signs were recorded until full orientation was regained. Arterial blood samples were frequently drawn up to 720 min following the cessation of the last infusion cycle. Eltanolone serum concentrations were measured by a specific GC-MS assay. Pharmacokinetics were analysed with NONMEM® by an open three compartment model. The serum concentrations were correlated with the corresponding clinical signs to quantify the concentration-effect relationship. Blood pressure, heart rate and oxygen saturation were measured continuously and the arterial pCO2 was analysed every 6 min. Results. The model-dependent pharmacokinetic parameters of eltanolone were characterized by a high total clearance (1.75±0.22 l min–1), small volumes of distribution (Vc=7.7±3.4 l; Vdss=92±22 l) and relatively short half-lives (t1/2α =1.5±0.6 min; t1/2β=27±5 min; t1/2γ=184±32 min) (Table 2). The clinical signs revealed a good hypnotic effect, resulting in burst suppression periods in the EEG after 19 min during the first and 15 min during the second infusion cycle. The slow induction enabled a thorough observation of the induction phase. During the first infusion cycle cessation of counting occurred after 7.7±1.3 min (mean±SD), reaction to verbal contact was lost after 10.4±1.3 min and the corneal reflex was lost only in about one half of the volunteers after 17.9±2.8. During recovery, the corneal reflex reappeared 9.4±2.4 min after stop of infusion, first reactions to loud verbal commands were recorded after 24.2±4.3 min and full orientation was regained after 34.7±6.2 min. During the second cycle all signs disappeared faster and were regained later (Table 3). The correlation between clinical signs and corresponding serum concentrations revealed, that in both cycles the disappearance occurred at clearly higher concentrations than the reappearance (Fig. 2). The decrease of the systolic arterial pressure showed a maximum of 31% compared to the baseline values, which was statistically significant (P〈0.05). Diastolic arterial blood pressure decreased of about 10%, while heart rate increased significantly of about 24% (P〈0.05) (Fig. 3 and 4). Oxygen saturation remained stable with values between 96 and 100% with the exception of one volunteer. Apnoea was not recorded during the entire observation period. The median value of all pCO2 analyses was 41 mmHg with a range of 25–60 mmHg. The only serious undesirable effect was a seizure during awakening in one volunteer which coincided with polyspike waves in his raw-EEG recordings (Fig. 5). Conclusions. Eltanolone proved to be a potent hypnotic. With regard to haemodynamics and respiration it caused relatively modest reactions. The quantification of the concentration-effect relationship revealed a time lag between serum concentration and corresponding effect that seems to exceed the effect-hysteresis of thiopentone and propofol. This hysteresis restricts the control of the substance, if the effect has to be changed rapidly, and leads to a delayed recovery. Together with its possible proconvulsant properties and increased reports of urticaria this meanwhile led to the cessation of the clinical investigations with eltanolone.
    Notes: Zusammenfassung In der vorliegenden Untersuchung wurden bei 12 jungen gesunden männlichen Probanden langsam linear ansteigende Blutspiegel mit Hilfe computergesteuerter Perfusorpumpen in jeweils zwei aufeinanderfolgenden Infusionszyklen generiert. Der Endpunkt der Infusion war durch das Auftreten von Burst-Suppression-Mustern im EEG festgelegt. Zur Beurteilung des hypnotischen Effekts wurden die Zeitpunkte erfaßt, zu denen die Probanden einschliefen resp. wieder aufwachten und zu denen die Reaktion auf Ansprache sowie der Kornealreflex ausfiel resp. wiederkam. Parallel wurden regelmäßig arterielle Serumkonzentrationen von Eltanolon bestimmt, der Blutdruck kontinuierlich arteriell gemessen und die Herzfrequenz durchgehend aufgezeichnet. Die Spontanatmung wurde pulsoximetrisch, kapnometrisch als auch klinisch beurteilt. Im Vergleich zur Bolusgabe und venöser Analytik zeigte sich eine höhere Clearance, ein niedrigeres zentrales Verteilungsvolumen, und ein niedrigeres Verteilungsvolumen im Fließgleichgewicht. Klinisch zeigte sich eine gute hypnotische Wirkung, die bei der langsamen Infusionsgeschwindigkeit nach ca. 19 min im ersten und 15 min im zweiten Zyklus zu Burst-Suppression-Mustern im EEG führte. Die Serumkonzentrationen bei Verlust einer Reaktion waren deutlich höher als bei der Wiederkehr. Hierin drückte sich eine Effekthysterese aus, die stärker ausgeprägt zu sein schien als bei anderen bekannten Hypnotika. Die hämodynamischen und respiratorischen Veränderungen fielen vergleichsweise moderat aus. Es kam zu einem dokumentierten Krampfanfall, der zusammen mit anderen Berichten über Krampfanfälle und gehäufte Meldungen von Urtikaria zur Einstellung der klinischen Prüfung von Eltanolon geführt hat.
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  • 3
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Totale intravenöse Anästhesie: Propofol ; Fentanyl ; Sufentanil ; Hämodynamik ; Katecholamine ; Laparotomien ; Key words Total intravenous anaesthesia: propofol ; fentanyl ; sufentanil ; Haemodynamics ; Catecholamines ; Abdominal surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Major abdominal surgery often leads to a marked sympathoadrenal stress response with high concentrations of plasma catecholamines, hypertension, and tachycardia. We compared the effects of sufentanil-propofol with fentanyl-propofol anaesthesia in a controlled, randomised, double-blind study of 18 ASA I–II patients aged 23–64 years undergoing major abdominal surgery. Study parameters were haemodynamics (heart rate [HR], arterial [ABP], central venous, and pulmonary arterial pressures, cardiac index [CI]), arterial catecholamine concentrations, and the median frequency of the electroencephalogram (EEG) power spectrum. Methods. After premedication with flunitrazepam 1–2 mg, promethazine 25–50 mg, and piritramide 7.5–15 mg, a five-lead electrocardiograph and a Lifescan brain activity monitor were attached and indwelling cannulae were inserted into the radial artery and two forearm veins. A thermodilution catheter was placed in the pulmonary artery via the right internal jugular vein. Anaesthesia was induced with either fentanyl 7 μg/kg followed by 5 μg/kg·h or sufentanil 1 μg/kg followed by 0.7 μg/kg·h up to the end of surgery. Additional boli of the opioids were given according to set criteria, resulting in an average consumption of 9.03 μg/kg·h fentanyl or 1.22 μg/kg·h sufentanil. Propofol 2 mg/kg was given followed by 6 μg/kg·h up to the end of surgery. Relaxation was obtained with pancuronium 0.025–0.05 mg/kg before intubation and every 60–120 min. Measurements were performed before and after induction, after tracheal intubation, before and after skin incision, after opening of the peritoneum, and at the end of surgery. Results. No significant differences were observed between the two groups with regard to the study parameters. The duration of surgery and blood loss were similar in both groups, as were patient characteristics. After induction 2 patients in each group developed thoracic rigidity, which was reversible after muscle relaxation. HR, ABP, and CI decreased significantly before skin incision; after surgical stimulation the baseline values were again reached, but not exceeded. No patient developed tachycardia (〉100/min) or hypertension (〉15% higher than baseline pressure) for longer than 10 min during the study period until the end of surgery. The plasma concentrations of epinephrine and norepinephrine decreased significantly during anaesthesia, and under maximum surgical stimulation did not increase higher than the physiological baseline concentrations. The EEG median frequencies decreased after induction, and during the entire anaesthetic period the main activity was in the delta and theta frequency bands. Conclusions. With both regimens, the sympathoadrenal stress response to major abdominal surgery was nearly completely suppressed, resulting in stable haemodynamics during the operations. Sufentanil and fentanyl were equally well suited as analgesic components of total IV anaesthesia with propofol.
    Notes: Zusammenfassung Die totale intravenöse Anästhesie (TIVA) mit Sufentanil-Propofol wurde in einer kontrollierten, randomisierten Doppelblindstudie erstmals im Vergleich zu Fentanyl-Propofol bei ASA I-II-Patienten untersucht, die sich großen, elektiven, abdominalchirurgischen Eingriffen unterziehen mußten. Zielparameter waren Hämodynamik (Herzfrequenz, arterielle, zentralvenöse und pulmonalarterielle Drücke, Herzindex), arterielle Katecholaminkonzentrationen sowie der Median der Amplitudenfrequenzspektren des EEG. Zwischen den beiden TIVA-Verfahren wurden keine signifikanten Unterschiede beobachtet. Nach Narkoseeinleitung fielen Herzfrequenz, arterieller Druck und Herzindex ab; erst nach Eröffnung des Peritoneums wurden die Ausgangswerte wieder erreicht, aber nicht überschritten. Die Plasmakonzentrationen von Adrenalin und Noradrenalin fielen bis zur analytischen Nachweisgrenze ab und stiegen im Mittel nie auf Werte oberhalb des physiologischen Konzentrationsbereichs. Die Hauptaktivität im EEG zeigte sich während der gesamten Narkose im Delta- und Thetabereich. Die TIVA mit Sufentanil-Propofol oder Fentanyl-Propofol zeichnete sich durch eine nahezu vollständige Unterdrückung der sympathoadrenalen Streßantwort und der daraus folgenden Hypertensionen und Tachykardien aus.
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  • 4
    ISSN: 1432-055X
    Keywords: Schlüsselwörter SIRS ; Sepsis ; MODS ; Hämodynamik ; Interleukin-2 ; Interferon-α ; Key words SIRS ; Sepsis ; MODS ; Haemodynamics ; Interleukin-2 ; Interferon-alpha
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Human recombinant interleukin 2 (IL-2), alone or in combination with other cytokines, is currently under investigation for the immunotherapy of metastatic tumours. Objective responses of 20%–35% have been reported in patients with disseminated melanoma and renal cell carcinoma who received high-dose intravenous IL-2 in combination with interferon-α (IFNα). However, treatment with IL-2 is complicated by a syndrome of life-threatening adverse reactions such as disseminated vascular leakage, fluid retention, severe hypotension, and (reversible) multiple organ dysfunction (MODS). A systemic inflammatory reaction (SIRS)/sepsis sepsis-like haemodynamic pattern has been described in patients after IL-2 bolus application alone. Our purpose was to study the haemodynamic changes in patients treated with high-dose IL-2 administered as a constant infusion and in combination with IFNα. Patients and Methods. Haemodynamic variables were obtained during therapy courses of 11 patients (aged 48 to 71 years, median 61) with metastatic renal cell carcinoma receiving immunotherapy with IL-2/IFNα. Therapy consisted in (Fig. 1): IFNα 10·1010 IU/m2 body surface area (BSA) once daily on days 1–5 i.m. on a regular ward, followed by IL-2 as a constant infusion of 18·106 IU/m2 BSA on days 6–11 in an intensive care unit (ICU). Haemodynamics were first measured after 5 days of IFNα application and transfer to the ICU on day 6, a further 24 h after the beginning of IL-2 infusion (day 7), and at the end of the therapy course (days 10 and 11). Mean arterial pressure (MAP) was measured noninvasively using an oscillometric device (Dinamap®, Critikon). Mixed-venous oxygen saturation (sv¯¯ O2) was measured using an CO-oxymeter (OSM 3®, Radiometer) and peripheral arterial oxygen saturation (psaO2) was recorded continuously with a pulse oximeter (Oxyshuttle®, Critikon). In case of haemodynamic instability, stabilisation had priority over invasive haemodynamic measurements, so that nadir values of blood pressure (BP) did not influence mean MAP and are reported separately. Lactate values and criteria for SIRS were obtained before and during IL-2 infusion. Lactate measurements were performed using an enzymatic essay (Abbot FLx®). The mean effect size of the haemodynamic values, SIRS criteria, and lactate concentrations during IL-2 infusion (days 6–11) were calculated, and 95% confidence intervals for the effect sizes are indicated in Table 1. Results. After their daily i.m. injections of IFNα, patients had short episodes of fever and tachycardia without significant drops in BP. A few hours after transfer to the ICU and continuous infusion of IL-2, they developed a syndrome of fever, tachycardia and tachypnoea. The haemodynamic values after 5 days of IFNα therapy remained in the normal range, whereas those during IL-2 infusion strongly resembled SIRS and sepsis, with a decrease in MAP (98 to 82 mm Hg) and systemic vascular resistance (SVR, 1477 to 805 dyn·s·cm−5) and an increase in cardiac output (cardiac index 2.8 to 4.3 l·min−1·m−2) (Fig. 2, Table 1). MAP often had to be stabilised with colloids during the last 48 h of therapy; 5 patients had nadir values below 60 mm Hg, or 30% below basic values in hypertensive patients. Catecholamine therapy became mandatory in 1 patient and therapy had to be discontinued. Surprisingly, some patients already had elevated plasma lactate concentrations after IFNα therapy. During IL-2 infusion mean plasma lactate levels increased from 2.3 to 3.2 mmol·l−1 and all patients had lactate concentrations above 2.0 mmol·l−1 at the end of therapy (Fig. 3, Table 1). During the last 48 to 72 h of IL-2 infusion, patients suffered from MODS with altered mental state (7 patients), oligoanuria (all patients), cardiac dysrhythmias (4 patients), congestive heart failure (1 patient, which led to a second case of therapy interruption), elevated bilirubin (4 patients), and pulmonary dysfunction. In 9 patients supplementary oxygen was necessary when psaO2 fell below 92%. Chest X-rays showed signs of pulmonary interstitial oedema. All patients developed significant generalised oedema due to a vascular leak syndrome, with fluid retention and weight gains of 6.3% during IL-2 infusion (Tables 1 and 2). Leukocyte counts dropped to 3670 μl−1 after 5 days of IFNα injection and rose to 9970 μl−1 at the and of IL-2 infusion. After discontinuation of IL-2 (day 11) the body temperature, heart rate, BP, and criteria of impaired organ function rapidly returned to the normal range, but leukocyte counts rose to 15360-μl−1 on day 12 (Table 1). Conclusion. High-dose IL-2 administered as a constant infusion and in combination with IFNα results in similar haemodynamic changes to those seen during high-dose IL-2 bolus application alone. The observed haemodynamic pattern strongly resembles SIRS and sepsis. MODS, fluid retention, and increases in plasma lactate indicate microcircular disorders. Elevated levels of sepsis mediators such as tumor necrosis factor and interleukin-1, activation of the complement cascade, activated neutrophil granulocytes and endothelial cells have been reported in patients receiving high-dose IL-2 bolus treatment. Our results and data of other investigators lead us to conclude that not only the (macro)haemodynamic pattern of IL-2/IFNα therapy, but also its pathogenetic pathways parallel SIRS and sepsis. IL-2/IFNα immunotherapy may therefore be used as a clinical “model” for sepsis research.
    Notes: Zusammenfassung Die Zytokine Interleukin-2 (IL-2) und Interferon-α (IFNα) werden zur Immuntherapie metastasierender Malignome eingesetzt. In der vorliegenden Studie wurde bei 11 Patienten mit Nierenzellkarzinom die Hämodynamik während einer fünftägigen, hochdosierten, kontinuierlichen IL-2 Infusion in Kombination mit der i.m.-Applikation von IFNα mit einem Pulmonalarterienkatheter invasiv überwacht. Die Patienten entwickelten wenige Stunden nach Beginn der kontinuierlichen IL-2 Infusion ein Syndrom aus Fieber, Tachykardie, Tachypnoe und im weiteren Verlauf Leukozytose (SIRS). Die Hämodynamik ähnelte den hyperdynamen Kreislaufverhältnissen bei SIRS und Sepsis. Hinweise auf eine Mikrozirkulationsstörung ergaben sich aus einem Anstieg der Plasma-Laktatkonzentrationen, muliplen Organfunktionsstörungen und einer erheblichen interstitiellen Flüssigkeitsretention aufgrund eines „vascular leak“-Syndroms. Hieraus und aus der von anderen Autoren beschriebenen Aktivierung von Sepsis-typischen Mediatoren unter IL-2-Applikation schließen wir auf eine weitgehende Parallelität in der Pathogenese von hochdosierter IL-2-/IFNα Therapie und SIRS bzw. Sepsis. Die IL-2-/IFNα Therapie bietet sich daher als klinisches Modell der Sepsis an.
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  • 5
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Ketamin ; Ketamin-Isomere ; S-(+)-Ketamin ; Sympatho-adrenerge Reaktion ; Hämodynamik ; Key words Ketamine ; Ketamine-isomers ; S-(+)-ketamine ; Sympathoadrenergic reaction ; Hemodynamic reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung General cardiovascular properties of ketamine:”In vitro”, ketamine has moderate negative inotropic effects. ”In vivo”, a significant central sympathomimetic action with consecutive hemodynamic effects is dominant. The sympathomimetic potency of ketamine is one of the most significant pharmacological features of the substance with direct clinical implications. Monoanaesthesia with S-(+)-ketamine: After application of racemic ketamine or S(+)-ketamine as well, identic and significant increases in plasma catecholamines, arterial pressure and heart rate are observed. This outstanding sympathomimetic action is beneficial in induction of patients with shock or asthmatic state. TIVA and analgosedation with S-(+)-ketamine and midazolam: The sympathomimetic effect of S(+)-ketamine, and racemic ketamine as well, is mitigated by midazolam. Nevertheless, significant increases in heart rate and arteriel pressure might be observed. Clinical use of the combination is common in short procedures like reposition maneuvers. Of greater importance is the use for analgosedation in patients with cardiovascular instability, particularly in patients with exogenous catecholamine demand. TIVA and analgosedation with S-(+)-ketamine and propofol: When S(+)-ketamine is combined with propofol, the sympatholytic effects of propofol are counteracted by S(+)-ketamine, and stable hemodynamic conditions are presented. This combination seems useful for TIVA in patients with hypotonic dysregulation or endocrine deficits like hypothyreosis and adrenal insufficiency. Furthermore, analgosedation with S(+)-ketamine and propofol is advantageous, when rapid recovery is necessary and negative circulatory effects should be avoided. Conclusion: Sympathoadrenergic and hemodynamic effects of S(+)-ketamine and racemic ketamine are generally identical. The distinctest action is observed, when S(+)-ketamine is used as a monoanaesthetic. In combination with midazolam, a significant reduction is achieved. In combination with propofol, the sympatholytic effects of this hypnotic agent are compensated by S(+)-ketamine. With respect to sympathoadrenergic and hemodynamic reactions, the clinical position of S(+)-ketamine is unchanged. Nevertheless, a significant clinical progress can be expected due to improved recovery and reduced substance load, when racemic ketamine is replaced by S(+)-ketamine.
    Notes: Zusammenfassung Ketamin verfügt „in vitro”über schwach negativ-inotrope Eigenschaften, die „in vivo” von einer ausgeprägten zentralen Sympathikusstimulation mit insgesamt positiv-inotroper Wirkung und entsprechenden Kreislaufeffekten überlagert werden. Die sympathomimetische Potenz ist das herausragende pharmakologische Charakteristikum von Ketamin und bestimmt wesentlich den klinischen Stellenwert der Substanz. Die Monoanästhesie mit S-(+)-Ketamin führt zu einer ausgeprägten sympatho-adrenergen Reaktion mit deutlichen Anstiegen von Blutdruck und Herzfrequenz, die den Veränderungen nach Zufuhr von Ketamin-Razemat vergleichbar sind. Klinisch ist die Monoanästhesie mit S-(+)-Ketamin insbesondere zur Einleitung von Patienten im Schock oder mit Status asthmaticus geeignet. Die sympatho-adrenergen und Kreislaufeffekte von S-(+)-Ketamin können, ebenso wie die von Ketamin-Razemat, durch Kombination mit Midazolam deutlich abgeschwächt werden; sie werden allerdings nicht vollständig unterdrückt. Die klinische Anwendung dieser deutlich sympathomimetischen TIVA-Variante konzentriert sich neben kürzeren Eingriffen wie Repositionsmanövern usw. insbesondere auf die Analgosedierung hämodynamisch instabiler Patienten. Die Kombination von S-(+)-Ketamin mit Propofol, einem ausgeprägt sympatholytischen Hypnotikum, führt zu einem insgesamt stabilen hämodynamischen Verhalten. Indikationen für diese Form der TIVA stellen u.a. Patienten mit Hypotonie oder endokrinen Defiziten wie Hypothyreose oder Nebennierenrinden-Insuffizienz dar. Darüber hinaus erscheint die Kombination von S-(+)-Ketamin und Propofol wegen ihrer hervorragenden „horizontalen Steuerbarkeit” besonders vorteilhaft zur Analgosedierung mit „diagnostischem Fenster” bei gleichzeitiger hämodynamischer Stabilität geeignet. Hinsichtlich der sympatho-adrenergen Reaktion und des Kreislaufverhaltens bleibt der klinische Stellenwert von S-(+)-Ketamin damit gegenüber dem des Razemat unverändert, der erwartbare klinische Fortschritt konzentriert sich auf das verbesserte Aufwachverhalten sowie die halbierte Substanzbelastung.
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  • 6
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Hemihepatektomie ; Hämodynamik ; Oxygenierung ; Lebervenenkatheter ; Key words Hemihepatectomy ; Hemodynamic ; Oxygenation ; Liver venous catheter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Objective: The aim of this study was to compare low dose dopamine and dopexamine with respect to of liver-venous oxygen saturation, oxygen delivery and – demand, liver function tests and cardiocirculatory effects in the reperfusion period during a hemihepatectomy operation with occlusion of the liver hilus. Methods: Twenty patients were studied in a randomised, doubleblind setting. They either received 2 µg/kg per min dopamine or 0.5 µg/kg per min dopexamine perioperatively. For monitoring purposes a pulmonary artery and a liver venous catheter were placed. At four different time points hemodynamic parameter were assessed and blood samples were drawn. Results: Significant changes between groups were found 5 min after opening the liver hilus for the cardiac index and the systemic oxygen delivery, as well as at the end of the operation for pulmonary shunt volume, which had increased more in the dopexamine group. No significant difference between liver venous oxygen saturation and liver function tests was found. Conclusion: Until more detailed studies concerning the influence of dopamine on the hepatic-splanchnic region during liver surgery are performed, dopexamine can not be considered superior to dopamine during these operations.
    Notes: Zusammenfassung Fragestellung: Gibt es einen Unterschied bezüglich der leber-venösen Sauerstoffsättigung, des Sauerstoffangebots und -verbrauchs, der Leberfunktion sowie der kardiozirkulatorischen Effekte während der Reperfusion zwischen niedrig dosiertem Dopamin und Dopexamin bei Leberteilresektionen mit Leberhilusokklusion? Methodik: 20 Patienten wurden randomisiert, doppelblind in zwei Gruppen eingeteilt und erhielten entweder 2 µg/kg/min Dopamin oder 0,5 µg/kg/min Dopexamin. Für das perioperative Monitoring wurden ein pulmonalarterieller- und ein Lebervenenkatheter gelegt. Zu vier Meßzeitpunkten wurden Parameter der Hämodynamik erhoben und Blut abgenommen. Ergebnisse: Ein signifikanter Unterschied zwischen den Gruppen bestand 5 min nach Eröffnung des Leberhilus in einem stärker angestiegenen Cardiacindex und systemischen Sauerstoffangebot sowie am OP-En-de in einem stärker angestiegenen pulmonalen Shuntvolumen in der Dopexamingruppe. Es gab keinen Unterschied bezüglich der leber-venösen Sauerstoffsättigung und der Leberfunktionsparameter. Schlußfolgerung: Bis weiterführende Untersuchungen mit differenzierter Betrachtung der Wirkung von Dopexamin bei leber-chirurgischen Eingriffen vorliegen, ist Dopexamin bei diesen Operationen gegenüber Dopamin nicht als überlegen zu betrachten.
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  • 7
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Akzeleromyographie ; Cisatracurium ; Intubationsbedingungen ; Hämodynamik ; Niereninsuffizienz ; Pharmakodynamik ; Key words Acceleromyography ; Cisatracurium ; Intubating conditions ; Pharmacodynamics ; Renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Objectives: The choice of cisatracurium, especially for patients with organ dysfunction, seems to be beneficial, because of organ-independent Hofmann-elimination and less histamine release propensity. This study was designed to investigate pharmacodynamics and intubating conditions after bolus administration of 0.15 mg/kg cisatracurium (3 x ED95) in patients with renal failure and maintained with isoflurane/N2O in oxygen. Methods: 20 patients with renal failure and 19 patients with normal renal function were studied. Anaesthesia was induced with fentanyl (2–3 µg/kg) and thiophentone (4–7 mg/ kg). After rapid bolus administration of 0.15 mg/kg cisatracurium (3 x ED95), onset time and intubating conditions were assessed. Clinical duration (DUR 25%), recovery index and duration 90% were investigated by acceleromyography. Changes of mean arterial blood pressure and/or heart rate ≥ 20% were defined as clinically significant. Results: The onset time (3.1 ± 0.8 min) was shorter in patients without renal failure (Cis-1) than in patients with normal renal function (3.6 ± 0.8 min), but without statistical significance. Intubating conditions, scored according to a 3-step scale, were slightly better in patients with normal renal function. Other pharmacodynamic parameters did not differ significantly. However, a small tendency to a prolonged recovery with a wide inter-individual variety was characteristic for patients with renal failure. Regarding the hemodynamic actions, only minor individual cardiovascular changes occured. No clinical evidence of histamine release was observed in any patient. Conclusions: The results of this clinical study suggest, that cisatracurium is a suitable choice for patients with renal failure. The necessity for an intraoperative neuromuscular monitoring is given by the marked heterogeneity in the recovery parameters in patients with renal failure.
    Notes: Zusammenfassung Ziel dieser Untersuchung war es, Veränderungen der Pharmakodynamik von Cisatracurium (3 x ED95) bei Patienten mit terminaler Niereninsuffizienz (Cis-2) im Vergleich zu Patienten ohne Nierenfunktionsstörung (Cis-1) zu erfassen. Des weiteren sollten die Intubationsbedingungen sowie der Einfluß dieser Substanz auf den Blutdruck und die Herzfrequenz und Isofluran-Lachgas-Anästhesie untersucht werden. Methodik: 39 Patienten (ASA-Klassifikation I–III) wurden entsprechend ihrer Nierenfunktion den jeweiligen Gruppen zugeordnet (Cis-1: normale Nierenfunktion n = 19; Cis-2: Niereninsuffizienz n = 20). Die Narkoseeinleitung erfolgte mit Fentanyl (2–3 µg/kg) und Thiopental (4–7 mg/kg). Nach Bolusapplikation von 0,15 mg/kg (3 x ED95) Cisatracurium wurden Anschlagzeit und Intubationsbedingungen ermittelt. Weiterhin wurden mittels Akzeleromyographie die klinische Wirkdauer (DUR 25%), der Erholungsindex (DUR 25%–DUR 75%) und die Spontanerholung auf 90% (DUR 90%) sowie die TOF-Ratio (T4:T1 〉 0,7) bestimmt. Veränderungen des mittleren arteriellen Blutdrucks und der Herzfrequenz von 〈 20% zum Ausgangswert wurden als klinisch signifikant angesehen. Ergebnisse: Insgesamt 95% der Patienten konnten nach 120 s unter guten bis sehr guten Bedingungen intubiert werden. Die Anschlagzeit von 3,1 ± 0,8 min war bei den nierengesunden Patienten kürzer, unterschied sich aber statistisch nicht signifikant von 3,6 ± 0,8 min bei den niereninsuffizienten Patienten. Alle anderen pharmakodynamischen Parameter unterschieden sich ebenfalls nicht signifikant zwischen beiden Gruppen. Eine ausgeprägte individuelle Schwankungsbreite der Spontanerholung war charakteristisch, besonders für die Patienten mit terminaler Niereninsuffizienz. 8 Patienten zeigten eine Abnahme des mittleren arteriellen Blutdruckes von 〉 20% des Ruheausgangswertes nach Cisatracurium. Die Herzfrequenz veränderte sich bei keinem der 39 Patienten. Schlußfolgerung: Cisatracurium in der 3fachen ED95 ist für die Anwendung bei Patienten mit terminaler Niereninsuffizienz geeignet. Aufgrund der großen individuellen Schwankungsbreite der neuromuskulären Spontanerholung ist bei dieser Substanz, wie auch bei allen anderen bisher verwendeten Muskelrelaxanzien, ein intraoperatives Monitoring der neuromuskulären Blockade bei Patienten mit eingeschränkter Nierenfunktion zu empfehlen.
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  • 8
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Propanidid ; Liposomen ; Propofol ; Hämodynamik ; Histamin ; Katecholamine ; Key words Propanidid ; Liposomes ; Propofol ; Haemodynamics ; Histamine ; Catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. Propanidid was widely used as a short-acting i.v. anaesthetic until it was withdrawn due to severe haemodynamic side effects. It was presumed that anaphylactoid reactions with massive histamine release were caused by the solvent cremophor rather than by propanidid itself. A new liposomal preparation of propanidid was examined in this animal study and compared with propanidid in cremophor solution and with propofol. Methods. Eighteen pigs were randomly assigned to one of the following groups: Group 1 (n=6): Propanidid in liposomal preparation (PropaLip; Braun Melsungen, Germany). Anaesthesia was induced with 60 mg/kg, followed by continuous infusion of 400 mg/kg·h. Group 2 (n=6): Propanidid in cremophor solution (PropaCrem; Sombrevin, Gedeon Richter, Budapest) 15 mg/kg, 100 mg/kg·h. Group 3 (n=6): Propofol (Disoprivan, Zeneca, Plankstadt, Germany) 5 mg/kg, 20 mg/kg·h. After induction and tracheal intubation, the animals were ventilated with 50% oxygen in air. Basic monitoring included noninvasive blood pressure measurements, electrocardiographic monitoring, and capnography. In a short surgical procedure, arterial and pulmonary artery catheters were placed via the right carotid artery and right internal jugular vein, respectively. As soon as the animals responded to a pain stimulus a second anaesthetic induction was performed, followed by a 60-min continuous infusion of the agent studied with invasive haemodynamic monitoring including arterial and pulmonary arterial pressures and cardiac output. Blood samples were taken for the measurement of serum levels of adrenaline, noradrenaline, cortisol, aldosterone, adrenocorticotropic hormone, and histamine. Results. Intubation conditions and quality of anaesthesia were best in propofol animals, followed by PropaCrem animals. In spite of the large dose of 410 mg/kg·h, resulting in a volume load of as much as 16.4 ml/kg·h, the PropaLip animals showed evidence of poor anaesthetic quality. In group 1 we recorded the highest increases in heart rate (91 vs. 115/min), cardiac output (5.4 vs. 7.7 l/min), plasma catecholamine levels, and histamine concentrations (124–268 ng/ml). Conclusions. In our animal study, propanidid in liposomal preparation failed to show promise as a new anaesthetic agent. Our results are discussed in view of a drug targeting the cells of the reticuloendothelial system, especially the liver, where liposomes are eliminated from the blood. This may result in the transport of propanidid to one of its major places of inactivation.
    Notes: Zusammenfassung In einer tierexperimentellen Studie wurden 18 Läuferschweine untersucht, von denen je 6 Tiere (1) Propanidid in Liposomendispersion (abgekürzt PropaLip), (2) Propanidid in Cremophor (abgekürzt PropaCrem) und (3) Propofol erhielten. Nach Narkoseeinleitung mit 60 mg/kg PropaLip, 15 mg/kg PropaCrem bzw. 5 mg/kg Propofol wurden die Tiere intubiert, für die weiteren Messungen instrumentiert und in einer anschließenden 60minütigen Narkose untersucht. Der Anästhetikaverbrauch betrug 16 mg/kg·h Propofol, 120 mg/kg·h PropaCrem und 410 mg/kg·h PropaLip. Trotz dieser hohen Dosierung und der damit verbundenen Volumenbelastung von 16,4 ml/kg·h war die Anästhesiequalität in der PropaLip-Gruppe unbefriedigend. Bei diesen Tieren traten die ausgeprägtesten Anstiege von Herzfrequenz, HZV, Katecholamin- und Histaminspiegeln auf, weitgehend konstant blieben die genannten Parameter bei der Propofolgruppe, während die PropaCrem-Tiere eine Mittelstellung einnahmen. Offenbar ist die Verfügbarkeit von Propanidid in der Liposomenpräparation schlechter als in der Cremophorlösung. Ein Zusammenhang der geringen Wirksamkeit mit der gezielten Aufnahme von Liposomen in die Zellen des RES, z.B. der Leber, wo Propanidid inaktiviert wird, wird diskutiert.
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  • 9
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    Der Anaesthesist 45 (1996), S. 37-46 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Desfluran ; Isofluran ; Aufwachverhalten ; Hämodynamik ; Key words Desflurane ; Isoflurane ; Emergence times ; Haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Objectives. The new volatile anaesthetic desflurane is characterized by very low blood-gas and tissue-blood partition coefficients, so that rapid induction of anaesthesia and shorter recovery times can be expected. The aim of this investigation was to compare the effects of desflurane and isoflurane on haemodynamics and recovery time when used as part of a balanced anaesthesia technique for elective surgery. Methods. Fifty patients (18 years and older, ASA status I-III) scheduled for elective surgery (no laparoscopies) of at least 60 min duration were included in this open, randomised, phase-III clinical trial. After oral premedication with midazolam 7.5 mg 45 min before transfer to theatre, anaesthesia was induced with fentanyl 0.1 mg and thiopental 5 mg/kg; succinylcholine or vecuronium facilitated intubation. Desflurane and isoflurane, respectively, were used for maintenance of anaesthesia, both in 50% N2O, with the inspired concentration adapted to the degree of stimulation. All patients were ventilated in a semi-closed system; muscle relaxation was achieved with vecuronium. The electrocardiogram, heart rate (HR), and direct arterial blood pressure (BP) were recorded continuously and anaesthetic gas detection was performed by an infrared absorption technique. With termination of surgery the volatile anaesthetic was discontinued and the following emergence times recorded: spontaneous ventilation (VT〉300 ml), extubation, eye opening, correctly answering the date of birth, arrival in and possible discharge from the post-anaesthesia care unit (PACU). Results. In all, 49 patients were studied at random (desflurane n=24, isoflurane n=25). Data of demographics and anaesthetic technique were comparable in both groups (Tables 2 and 3). Anaesthetic elimination (expressed as FA/FAO) was significantly more rapid in the desflurane group 3 min after termination of anaesthesia (Fig. 1). Comparing the emergence times, there was no significant difference between desflurane and isoflurane: in both groups patients opened their eyes 12 min (median time) after termination of the operation (Table 4). Haemodynamics (HR, systolic and diastolic BP) were comparable at intubation, skin incision, end of surgery, extubation, and in the PACU (Fig. 2a, b). In 2 patients a rapid increase in the inspired concentration of desflurane during induction of anaesthesia produced a profound sympathoadrenergic reaction with an excessive increase in BP and HR. Similar reactions in other patients did not occur when the inspired concentration of desflurance was slowly increased. Conclusions. Despite the physicochemical properties of the new agent, emergence times were similar for desflurane and isoflurane in our study. These results, which are in contrast to those of some other authors, are most probably due to the study design, which included the use of premedicants (midazolam) and a low dose of fentanyl. The reported sympatho-adrenergic reactions after rapid changes in the inspired concentration of desflurane during induction of anaesthesia have been observed by others as well. It seems that this initial cardiovascular stimulation can be avoided by slow increases in desflurane concentration. In summary, desflurane compares to isoflurane in balanced anaesthesia for general surgical procedures with regard to haemodynamics, while the time to awakening is not necessarely reduced.
    Notes: Zusammenfassung Das neue Inhalationsanästhetikum Desfluran besitzt sehr niedrige Blut-Gas- und Gewebe-Blut-Verteilungskoeffizienten und läßt so raschere Ein- und Ausleitungszeiten erwarten. In der vorliegenden Phase-III-Studie wurden Aufwachverhalten und Hämodynamik unter Desfluran und Isofluran prospektiv randomisiert verglichen. Untersucht wurden 49 chirurgische Patienten (Desfluran n=24, Isofluran n=25) in balancierter Anästhesietechnik: orale Prämedikation mit 7,5 mg Midazolam; Einleitung mit 0,1 mg Fentanyl und 5 mg/kg Thiopental; Narkosebeatmung mit Desfluran 0,5–18 bzw. Isofluran 0,2–3,0 Vol%, jeweils in 50% N 2 O. Bei den hämodynamischen Parametern ergaben sich keine wesentlichen Unterschiede. Zwei Patienten reagierten nach rascher Erhöhung der Desfluran-Vapor-Einstellung mit Blutdruck- und Herzfrequenzanstieg. Diese Reaktion ließ sich bei allen weiteren Patienten durch langsame Dosissteigerung vermeiden. Nach Anästhesie-Ende flutete Desfluran signifikant schneller ab als Isofluran (F A /F A0 ). Trotzdem zeigten die Aufwachzeiten keinen signifikanten Unterschied (Augenöffnen jeweils nach 12 min), vermutlich bedingt durch die angewandte balancierte Anästhesietechnik, die durch gleichzeitigen Einsatz mehrerer Anästhetika zum Profilverlust der Einzelsubstanz führen kann. Zusammengefaßt ergibt sich, daß Desfluran als Hauptkomponente einer balancierten Anästhesie unter den Gesichtspunkten Steuerbarkeit und hämodynamische Stabilität für chirurgische Eingriffe ebenso geeignet erscheint wie Isofluran. Mit einem rascheren Erwachen ist aber bei der balancierten Anästhesietechnik nicht zwangsläufig zu rechnen.
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  • 10
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Eltanolon ; Thiopental ; Hämodynamik ; Anästhesieeinleitung ; Koronarpatienten ; Key words Eltanolone ; Thiopentone ; Coronary artery disease ; Haemodynamics ; Anaesthesia induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Eltanolone is a new steroid anaesthetic agent that is a 5-β reduced derivative of progesterone. In the present study we investigated the haemodynamic effects of eltanolone or thiopentone in patients scheduled for coronary artery bypass grafting. Methods. After obtaining approval of the institutional ethics committee and informed patient consent, 40 patients (age 45–70 years, ASA III and IV, ejection fraction 〉50%, cardiac index 〉2.5 l/min per m2) were randomly assigned to four groups, each containing 10 patients: After premedication with 2 mg flunitrazepam, anaesthesia was induced with 3 mg/kg thiopentone in group 1, 0.5 mg/kg eltanolone in group 2, 0.75 mg/kg eltanolone in group 3, 1.0 mg/kg eltanolone in group 4. Each patient additionally received 3 μg/kg fentanyl after induction and 0.1 mg/kg pancuronium. Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, pulmonary artery occlusion pressure and cardiac output were recorded in the awake state, 2 min after induction of anaesthesia, and 1 and 5 min after intubation. Cardiac index and systemic vascular resistance were calculated. Results. Two minutes after induction, mean arterial pressure was significantly lower than the baseline (P〈0.05) in each group. Mean arterial pressure changes were more prominent in the case of eltanolone, but intergroup tests did not reveal significant differences between the four groups. There was a fall in cardiac index in all groups, and these changes reached the level of significance only in the thiopentone patients. The most obvious difference between eltanolone and thiopentone was systemic vascular resistance. It dropped significantly 2 min after induction with eltanolone at all dosages. In contrast, there was an increase in systemic vascular resistance following induction of anaesthesia with thiopentone. Intergroup tests also showed significantly (P〈0.05) lower systemic vascular resistance 1 and 5 min after intubation with eltanolone compared to thiopentone. Discussion. Mean arterial pressure reduction induced by eltanolone is most likely the result of the combination of a decrease in cardiac contractility and peripheral vasodilatation. In contrast, mean arterial pressure reduction in the case of thiopentone seems to be exclusively related to the negative inotropic properties of the drug. Results of a dosage finding study [5] with eltanolone revealed an AD50 of 0.33 mg/kg. In our study 0.5 mg/kg eltanolone brought all the patients to sleep within 2 minutes. The haemodynamic results do not show any significant difference up to twofold dosage. Therefore, the therapeutic margin seems to be large. Because of considerable interindividual variability additional studies in larger collectives are required for definitive evaluation of the drug.
    Notes: Zusammenfassung Das Steroid Eltanolon ist ein neues kurzwirksames Hypnotikum, welches in einer Fettemulsion gelöst ist. Ziel der Studie war es, die hämodynamischen Veränderungen nach Anästhesieeinleitung mit unterschiedlichen Dosierungen von Eltanolon zu untersuchen. Thiopental diente als Vergleichsmedikament. Die Untersuchung wurde an 40 Patienten im Rahmen elektiver koronarer Bypassoperationen vorgenommen. Vor Anästhesieeinleitung wurde mittels Pulmonalarterienkatheter und arterieller Blutdruckmessung der Ausgangswert der hämodynamischen Variablen ermittelt. Die weiteren Meßzeitpunkte waren 2 min nach Anästhesieeinleitung sowie 1 und 5 min nach Intubation. Die Anästhesie wurde randomisiert entweder mit Eltanolon 0,5, 0,75 oder 1,0 mg/kg oder mit Thiopental 3 mg/kg induziert (4 Gruppen; je 10 Patienten). Danach erhielt jeder Patient 3 μg/kg Fentanyl und 0,1 mg/kg Pancuronium. Zu keinem Meßzeitpunkt ergaben sich statistisch signifikante Unterschiede zwischen den 3 Eltanolongruppen. Im Vergleich zu Thiopental war der arterielle Blutdruck zu allen Meßzeitpunkten niedriger, der systemische Gefäßwiderstandsindex signifikant (p〈0,05) niedriger. Bereits die niedrigste Dosis Eltanolon (0,5 mg/kg) führte bei allen Patienten zum Eintritt der Anästhesie. Da im untersuchten Bereich keine wesentlichen Veränderungen der hämodynamischen Parameter nach Eltanolon gefunden wurde, erscheint die Sicherheitsbreite relativ groß. Der ausgeprägtere Blutdruckabfall nach der Anästhesieeinleitung mit Eltanolon ist zumindest zum Teil durch den verminderten systemischen Gefäßwiderstandsindex bedingt.
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