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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusion All plasma substitutes in clinical use caused analphylactoid reactions in man and dog, but histamine release into the plasma or whole blood was related to them only in the case of Haemaccel. Thus a rational treatment or prophylaxis of this clinical hazard by H1- and H2-receptor antagonists can be attempted only in the case of Haemaccel [5].
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several preparations of Cremophor El®, several of other non-ionic detergents and several components of Cremophor El were tested for their histamine-releasing capacity in dogs. Lutensol AP 10 and a derivative of 1,2-propylenglycol were ineffective, but showed excellent properties as detergents. Thus the histamine-releasing capacity was not necessarily combined with the tenside effect of the surfactants. Oleic acid found in Tween 80 as well as in Cremophor El seems to be the most effective constituent, but the alcohol seems also to be important for the histamine-releasing capacity. The development of a non-toxic solubilizer for lipophilic drugs seems of considerable clinical interest.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anaphylactoid reactions in man following administration of drugs solubilized with cremophor El® (polyethylenglycolglycerol riconoleate) are a considerable clinical problem. Since these reactions occur in dogs on first exposure and in pigs on second exposure, the ‘dog model’ was used in this communication to analyse components and chemical modifications of cremophor El and its components for their clinical effects, their hypotensive actions and their histamine-releasing capacity. Two series of experiments in 1978 and 1980 were performed in 144 adult mongrel dogs of both sexes. In these studies histamine release wasnot related to the effect of the solubilizing agents as tensides and was elicited by rather low doses (about 10–100 mg/kg i.v.). The effect of these substances on blood pressure and on blood histamine levels was connected with distinct chemical features: the most potent compounds were oxethylated and additionally esterified unsaturated or hydroxylated fatty acids. Several phases in hypotensive reactions were observed, including an immediate response, a delayed blood pressure response and a late response about 15–20 min after injection. Only the delayed response was associated with histamine release. The combination of cardiovascular effects and histamine release was fatal on some occasions indicating that histamine release can be dangerous. Compared to cremophor El, the tenside effect was equal, but the toxicity was reduced in oxethylated 12-hydroxystearic acid. It is recommended that this solubilizer should be used in further extended studies in animals and — if these are successful—in clinical trials.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Der Anaesthesist 45 (1996), S. 1024-1029 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Stereoisomerie ; Muskelrelaxanzien ; Cisatracurium ; kardiovaskuläre Effekte ; Key words Stereoisomerie ; Muscle relaxant ; Cisatracurium ; Cardiovascular effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Cisatracurium – one of the ten stereoisomers of atracurium – is an intermediate long-acting non-depolarizing neuromuscular blocking agent. Cardiovascular reactions have been described after administration of cisatracurium or vecuronium in surgical patients. Methods. After approval by our institutional review board, 62 patients (ASA I–II) were randomly assigned to three groups to either receive 3×ED95 or 5×ED95 of cisatracurium or 3×ED90 of vecuronium prior to intubation as a bolus. After oral premedication with 2 mg lormetazepam anaesthesia was induced with thiopental (4–12 mg/kg) and maintained with O2/N2O and isoflurane (1.5%–2%). Six minutes after administration of thiopental, patients received the muscle relaxant. Six minutes later 0.1–0.2 mg fentanyl was given and the trachea was intubated. Heart rate (HR) and blood pressure (BP) were monitored every minute. Changes of heart rate or blood pressure 〉20% compared to baseline were defined as clinically significant. Results. After application of the study drug, median values of blood pressure and heart rate were stable. For each muscle relaxant, there were several patients who had statistically significant cardiovascular changes. After 3×ED95 cisatracurium, 3 of 21 patients exhibited haemodynamic changes 〉20% (2 exhibited hypotension and 1 tachycardia), while in the high-dose cisatracurium group 2 of 21 patients demonstrated a tachycardia that was predetermined to be statistically but not clinically significant. In the vecuronium group, 2 of 20 patients sustained statistically significant hypotension and 1 patient had statistically significant tachycardia. The frequency of all individual cardiovascular changes after the application of the muscle relaxant was not dose-dependent. Conclusion. After the administration of cisatracurium in two different doses (3×ED95 and 5×ED95) or vecuronium (3×ED90) only minor cardiovascular changes were observed. Both drugs proved to be safe for use during induction of anaesthesia in patients ASA I–II. With regard to its cardiovascular effects, cisatracurium shares with vecuronium the requirements of an ideal muscle relaxant.
    Notes: Zusammenfassung In einer randomisierten, doppelblinden Studie wurden bei insgesamt 62 Patienten (ASA I–II) die Veränderungen von Blutdruck und Herzfrequenz nach Bolusapplikation von Cisatracurium (0,15 mg/kg oder 0,25 mg/kg) im Vergleich zu Vecuronium (0,15 mg/kg) untersucht. Die Narkoseinduktion erfolgte mit Thiopental (4–12 mg/kg) und wurde mit N 2 O/O 2 sowie Isofluran (1,5–2,5 Vol.-%) aufrechterhalten. Sechs Minuten nach Thiopental erhielten die Patienten binnen 5–10 s das jeweilige Relaxans. Blutdruck und Herzfrequenz wurden minütlich registriert und Abweichungen 〉20% des Ruhewerts als individuell bedeutsam gewertet. Nach Applikation der jeweiligen Prüfsubstanz zeigte sich in allen drei Patientengruppen eine Stabilität von Blutdruck und Herzfrequenz. Die maximalen individuellen Veränderungen der hämodynamischen Parameter (auch 〈/ 〉20%) blieben stets im physiologischen Bereich. Eine statistische Signifikanz oder Dosisabhängigkeit der hämodynamischen Veränderungen nach der jeweiligen Prüfsubstanz konnte nicht nachgewiesen werden. Hinsichtlich der hämodynamischen Stabilität zeigte Cisatracurium vergleichbare Eigenschaften wie Vecuronium.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Der Anaesthesist 45 (1996), S. 1082-1084 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Etomidat ; Propofol ; Lipidemulsion ; Narkoseeinleitung ; Key words Anaesthetics ; Induction agents ; Etomidate ; Propofol ; Lipid emulsion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Etomidate has become an important induction agent in high-risk patients because of its cardiovascular stability. Its unwanted side-effects such as pain on injection and thrombophlebitis could be significantly reduced by a new (medium chain triglyceride and soya bean) emulsion formulation. Propofol is solved in a mixture of long chain triglyceride and soya bean emulsion. In this double-blind, randomized study we compared the haemodynamic effects, the patients' sensations, signs of thrombophlebitis and postoperative nausea and vomiting (PONV) following injection of both drugs. Methods. Following premedication with 2 mg Lormetazepam p.o. in 50 patients per group, anaesthesia was induced with either 0.51 mg etomidate in lipid emulsion or 3.04 mg propofol per kg bw. No opioid or benzdiazepine was given i.v. before induction. After injection of the tested drug, the cannula was removed. Changes in blood pressure and heart rate were recorded as well as signs of discomfort during and after injection (pain, burning, tension, cold). Venous sequelae were assessed for 5 days after injection to register signs of thrombophlebitis. Results. Demographic data showed no difference between the two groups. After propofol more often a fall in blood pressure was seen. Pain (25 vs 1 pt), burning 19 vs 1), tension 15 vs 3), cold (35 vs 17) after injection was registered significantly more often in the propofol group, whereas myocloni predominated in the etomidate group (13 vs 6) P〈0.05, chi-squared-test). No difference was seen in PONV in either groups. Conclusion. Etomidate formulated in a medium chain lipid emulsion causes significant less discomfort for the patients than propofol, which is solved in a long chain formulation. Myocloni, however, occur significantly more frequently after etomidate than after propofol.
    Notes: Zusammenfassung Venenverträglichkeit, subjektives Empfinden, Kreislaufverhalten und postoperative Übelkeit/Erbrechen wurden nach Etomidat in einer neuen galenischen Zubereitung (Etomidat- ® Lipuro) und nach Propofol (Diprivan ® ) bei 100 Patienten miteinander verglichen. In einer randomisierten Doppelblindstudie erhielten je 50 Patienten ohne vorherige Gabe eines Opioids oder Benzodiazepins im Mittel 0,51 mg Etomidat oder 3,03 mg Propofol pro kg KG zur Narkoseeinleitung. Die Narkose wurde nach Vecuronium zur Relaxation mit O 2 /N 2 O (35:65) und Isofluran aufrechterhalten. Kreislaufverhalten und subjektive Mißempfindungen der Patienten (Brennen, Kälte, Druck, Ziehen) während der Einleitung wurden registriert. Postoperativ wurde die Injektionsvene über 5 Tage auf Zeichen einer Thrombophlebitis untersucht. Es zeigte sich nach Propofol häufiger ein Blutdruckabfall als nach Etomidat. Schmerzen, Kältegefühl, Brennen und Ziehen wurden signifikant häufiger nach Propofol geäußert, während Myokloni öfter nach Etomidat- ® Lipuro registriert wurden. Postoperativ zeigten sich nur geringgradig Verhärtung, Schwellung oder Rötung der Venen, ein Unterschied zwischen den Substanzen fand sich nicht. Postoperative Übelkeit und Erbrechen (PONV) waren mit 24% nach Propofol und 26% nach Etomidat- ® Lipuro nicht signifikant verschieden.
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  • 8
    ISSN: 1432-055X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Cisatracurium ; Muskelrelaxanzien ; Stereoisomer ; Histaminfreisetzung ; Tryptasebestimmung ; Key words Cisatracurium ; Muscle relaxants ; Histamine release ; Serumtryptase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Cisatracurium (51W89, Nimbex, Glaxo-Wellcome), an intermediate-acting non-depolarizing neuromuscular blocking agent, is a stereoisomer of atracurium. Histamine releasing propensities and serum tryptase level have been investigated after administration of cisatracurium (3×ED95, 5×ED95) or vecuronium (3×ED90) in surgical patients. Methods: After approval by our institutional review board, 62 patients (ASA I–II) were randomly assigned to three groups to receive either 3×ED95 or 5×ED95 cisatracurium, or 3×ED90 vecuronium as a rapid bolus. A prick test was done the day before by scarification of the skin in the forearm. After premedication with 2 mg lormetazepam, anaesthesia was induced with thiopentone (4–12 mg/kg) and maintained with O2/N2O and isoflurane (1.5–2 vol.%). Six minutes after thiopentone, the patients received the relaxant, and after further 6 min 0.1–0.2 mg fentanyl was given and the trachea was intubated. Heart rate (HR) and blood pressure (BP) were monitored every minute. Blood samples for histamine were withdrawn 5 min prior 3 and 5 min after each drug administration (thiopentone, relaxants). Plasma histamine was measured by radioimmunoassay (RIA) with a sensitivity of approximately 10 pg/ml. Additionally, serum tryptase was measured by RIA at baseline (−10 and −1 min) and 15 and 60 min after the relaxant administration. Levels for histamine 〉1000 pg/ml and for tryptase 〉2 µg/ml were considered significant. Cutaneous signs of histamine release were documented. Results: Ten patients showed a positive prick-test reaction. Only after thiopentone some cutaneous signs (4 flush, 1 erythema) of histamine release were observed. There were no cutaneous signs of histamine release correlating with cardiovascular changes. Analysis of the blood samples demonstrated no significant increase in the histamine level in all three groups. Only in 1 patient was a significant higher histamine level (1133 pg/ml) measured 5 min after 5×ED95 cisatracurium. All measurements of serum tryptase were within the physiological limits. Discussion: In this study, with the particular time course of drug administration, neither cisatracurium nor vecuronium increased plasma histamine levels. Only after 5×ED95 cisatracurium was 1 elevated histamine level documented after 5 min. In several studies increased histamine levels have been described, but without clinical manifestations. It is known that cutaneous signs can occur without increased plasma histamine levels due to the structural heterogeneity of mast cells. The cutaneous reactions in this study were caused by thiopentone. The tryptase values were within normal limits even in the patient with histamine release. No relationship between the positive results in the prick test and the incidence of cutaneous reactions and/or histamine release for drugs used in the induction of anaesthesia was observed. Whether cisatracurium has a potential for immunologic release is unknown.
    Notes: Zusammenfassung Die Häufigkeit kutaner Reaktionen, Plasmahistamin- und Tryptasespiegel nach 0,15 mg/kg (3×ED95) oder 0,25 mg/kg (5×ED95) Cisatracurium [51W89] oder 0,15 mg/kg (3×ED90) Vecuronium wurden während der Narkoseeinleitung an 62 Patienten im Alter von 18–65 Jahren (ASA-II) untersucht. Methode: Im Rahmen der Prämedikationsvisite wurde ein standardisierter Prick-Test durchgeführt. Nach der Narkoseinduktion mit Thiopental (4–12 mg/kg) erhielten die Patienten 6 min später binnen 5–10 s das jeweilige Relaxans und 6 min später 0,1 mg–0,2 mg Fentanyl. Blutentnahmen zur Bestimmung des Plasmahistamins (Radioimmunoassay) erfolgten 10 min vor der Prüfsubstanz als Nullwert sowie 3 bzw. 5 min nach Thiopental sowie der Prüfsubstanz. 10 min und 1 min vor sowie 15 und 60 min nach der initialen Verabreichung des Relaxans sind venöse Blutproben für die Serumtryptase (RIA) entnommen worden. Die Dokumentation kutaner Reaktionen erfolgte über die gesamte Einleitungszeit. Ergebnisse: Nach Thiopental wurden 5 kutane Reaktionen (1×Erythem, 4×Flush) beobachtet. Der Histaminbasalwert aller Patienten betrug 232,3 pg/ml±120,5 pg/ml. Die Applikation der jeweiligen Prüfsubstanz führte im Mittel nicht zu einem signifikanten Histaminanstieg. Lediglich ein Patient zeigte nach der 5fachen ED95 51W89 einen Wert von 1133 pg/ml (5 min) ohne klinisches Korrelat. Eine Erhöhung der Serumtryptase trat in keinem Fall auf. Im Prick-Test fand sich trotz einer positiven Reaktion bei 10 Patienten kein Zusammenhang zu den kutanen Reaktionen und dem Histaminanstieg. Fazit: Cisatracurium kann aufgrund der uns bisher vorliegenden Ergebnisse als mittellang wirkendes nicht depolarisierendes Muskelrelaxans ohne histaminassoziierte kardiovaskuläre Veränderungen eingeschätzt werden. Weitere Untersuchungen mit einer klinisch relevanten Einleitungsphase sind erforderlich.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 47 (1969), S. 154-157 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary 1. Depressor response, stimulation of gastric secretion and increase of histamine concentration in the blood strongly support the view that Epontol® (Propanidid, dissolved in cremophor-EL) releases histamine. 2. Cremophor-EL, the dissolver of propanidid, could be excluded as histamine releasing substance in man. 3. Atropine nor inhibits the release of histamine nor the stimulation of gastric secretion. Histamine stimulates the gastric secretion directly and does not need acetylcholine as transmitter. 4. Before Epontol® injection not only atropine, but also an antihistaminie drug should be used for premedication. The rapid injection of Epontol® should be avoided.
    Notes: Zusammenfassung 1. Anhand von Blutdruckabfall, Magensaftstimulierung und Zunahme des Bluthistamingehalts wird bewiesen, daß Epontol® beim Menschen Histamin freisetzt. 2. Cremophor-EL, der Lösungsvermittler des Propanidids, konnte als Ursache der Histaminfreisetzung ausgeschlossen werden. 3. Atropin verhindert weder die Histaminfreisetzung, noch die Wirkung auf die Magensaftsekretion. Histamin stimuliert die Magensaftsekretion direkt und ohne Vermittlung durch Acetylcholin. 4. Bei Epontol®-Narkosen wird neben Atropin und bei entsprechender Disposition die Verabreichung eines Antihistaminicums empfohlen. Schußinjektion ist zu vermeiden.
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