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Prophylaxis of anaphylactoid reactions to a polypeptidal plasma substitute by H1- plus H2-receptor antagonists: Synopsis of three randomized controlled trials

Prophylaxe von anaphylaktoiden Reaktionen durch ein Plasmasubstitut auf Polypeptidbasis mit Hilfe von H1- plus H2-Rezeptorantagonisten: Synopse von drei randomisierten kontrollierten Studien

  • 6. Prophylaxis And Treatment Of Adverse Reactions And Histamine Release In Anaesthesia And Surgery — H1- And H2-Receptor Antagonists
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Summary

To demonstrate the efficacy of a premedication with H1- +H2-receptor antagonists against histamine-release responses in anaesthesia and surgery 3 randomized controlled trials were conducted in patients, volunteers and experimental animals (dogs). Cutaneous anaphylactoid reactions following infusion of polygeline (Haemaccel®) in orthopedic patients were successfully abolished by premedication with 0.1 mg/kg dimethpyrindene (Fenistil) and 5 mg/kg cimetidine (Tagamet). Chlorpheniramine (Piriton) was also useful, but dimethpyrindene was more effective in the doses recommended and used. Side-effects of the premedication were not observed when the 2 drugs were slowly administered (2 min each).

Systemic anaphylactoid reactions following infusion of polygeline were completely prevented in volunteers by the same premedication (0.1 mg/kg dimethpyrindene and 10 mg/kg cimetidine). Life-threatening reactions could not be tested in human subjects, but were elicited in experimental animals (dogs). In this species which resembles man in its sensitivity against histamine, in plasma histamine levels and in response to polygeline life-threatening reactions were prevented or in especially severe cases diminished to such an extent by the premedication with H1- +H2-blockers that this premedication was finally judged to be very effective against histamine-release responses of any grade of severity.

To confirm this clinically very important hypothesis more clinical trials in patients at risk for anaphylactoid reactions to drugs are urgently needed.

Zusammenfassung

Um die Wirksamkeit einer Prämedikation mit H1- +H2-Rezeptorantagonisten gegen Histaminfreisetzungsreaktionen während Narkose und Operation nachzuweisen, wurden drei randomisierte kontrollierte Studien bei Patienten, Probanden und Versuchstieren (Hunden) durchgeführt. Cutane anaphylaktoide Reaktionen nach Infusion von Polygeline (Haemaccel) wurden bei orthopädischen Patienten durch Prämedikation mit 0.1 mg/kg Dimethpyrinden (Fenistil) und 5 mg/kg Cimetidin (Tagamet) nahezu vollständig verhindert. Der H1-Blocker Chlorpheniramin (Piriton) war ebenfalls wirksam, aber es war dem Dimethpyrinden in der empfohlenen Dosis an Wirksamkeit unterlegen. Nebenwirkungen der Prämediaktion wurden bei langsamer Applikation (2 min) nicht beobachtet.

Systemische anaphylaktoide Reaktionen nach Infusion von Polygeline wurden bei Versuchspersonen durch dieselbe Prämedikation (0.1 mg/kg Dimethpyrinden und 10 mg/kg Cimetidin) vollständig verhindert. Lebensbedrohliche Reaktionen konnten am Menschen nicht geprüft werden, wohl aber beim Hund. Dieselbe Prämediaktion wie in den beiden vorangehenden Studien (1 mg/kg Dimethpyrinden und 5 mg/kg Cimetidin) war außerordentlich erfolgreich und verhinderte in jedem Falle eine lebensbedrohliche Situation. Im Mittel wurden die klinischen Symptome der Histaminfreisetzungsreaktion sogar vollständig unterdrückt.

Es wird geschlossen, daß eine Prämedikation mit H1-plus H2-Rezeptorantagonisten wirksam genug ist, um auch beim Patienten Histaminfreisetzungsreaktionen aller Schweregrade zu verhindern oder soweit zu verringern, daß sie für den Patienten keine Gefährdung mehr darstellen. Zur Erhärtung dieser Schlußfolgerung sind weitere klinische Studien an Risikopatienten erforderlich.

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Authors and Affiliations

  1. Department of Anaesthesia, Orthopedic Clinic, University of Heidelberg Schlierbacher Landstr. 200a, D-6900, Heidelberg, Federal Republic of Germany

    B. Schöning

  2. Department of Theoretical Surgery, Centre of Operative Medicine I, University of Marburg (Lahn), Federal Republic of Germany

    W. Lorenz

  3. Department of Anaesthesia, Surgical OPC Clinic, University of Munich, Federal Republic of Germany

    A. Doenicke

Authors
  1. B. Schöning
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  2. W. Lorenz
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  3. A. Doenicke
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Supported by Grant of Deutsche Forschungsgemeinschaft (Lo 199/10 and Lo 199/13-6)

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Schöning, B., Lorenz, W. & Doenicke, A. Prophylaxis of anaphylactoid reactions to a polypeptidal plasma substitute by H1- plus H2-receptor antagonists: Synopsis of three randomized controlled trials. Klin Wochenschr 60, 1048–1055 (1982). https://doi.org/10.1007/BF01716970

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