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Definition and classification of the histamine-release response to drugs in anaesthesia and surgery: Studies in the conscious human subject

Definition und Klassifikation von Histaminfreisetzung nach Gabe von Arzneimitteln in Anästhesie und Chirurgie: Studien am wachen Menschen

  • 1. Adverse Reactions And Histamine Release In Anaesthesia And Surgery
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Summary

In 2 clinical studies in 40 conscious human volunteers and 164 orthopedic patients histamine-release responses were diagnosed, defined and classified. Polygeline (Haemaccel) in its now outdated formulation [40] was chosen as a clinical histamine releaser. The main interest was not concentrated on the extreme, the “classical” anaphylactic response, but on theaverage histamine-release response found in clinical experiments with so many drugs in the last 10 years.

In human volunteers 600 ng/kg histamine was i. v. injected. Indicants for a systemic anaphylactoid reaction with the highest incidence ratio were tachycardia, plasma histamine levels >1 ng/ml, “metallic taste”, flush, congestion of head, “wet eyes” and tears, hypertension and headache. Following polygeline none of these subjects developed a life-threatening reaction, but 12 showed a systemic response, 11 a cutaneous reaction and 17 were non-responders. Indicants for a systemic anaphylactoid reaction with the highest incidence ratio were plasma histamine levels >1 ng/ml, tachycardia, wheals, sensation of heat, narrowness of throat, hypertension, headache and wet eyes or tears.

In a prolective, cohort study in the orthopedic patients 3 subjects with life-threatening reactions, 27 with systemic response, 96 with cutaneous reaction and 38 non-responders were included. Indicants with the highest incidence ratio were tachycardia, plasma histamine levels >1 ng/ml, erythema and wheals, cough, flush, stuffy nose and facial oedema. With this trial the indicants for diagnosing a systemic histamine release response in volunteers were validated in patients to a large extent.

Thus the average histamine-release response was defined by clinical signs such as tachycardia and mild hypertension, scattered hives such as spots of erythema and wheals, respiratory symptoms in the laryngeal and nasal region, such as cough, narrowness in the throat, stuffy nose and sneezingand by pathological plasma histamine levels (>1 ng/ml). In addition histamine-release responses were differentiated as cutaneous responses, systemic responses and life-threatening responses by clinical and operational criteria and by plasma histamine levels. Using clinical trials and medical decision making procedures the incidence of systemic histamine-release responses in patients higher by two orders of magnitude than in other studies reported hitherto.

Zusammenfassung

In 2 klinischen Studien bei 40 wachen Freiwilligen und 164 orthopädischen Patienten wurde versucht, Histaminfreisetzungsreaktionen zu diagnostizieren, zu definieren und zu klassifizieren. Haemaccel in einer heute klinisch nicht mehr verwendeten Zubereitung [40] wurde als klinischer Histaminfreisetzer verwendet. Das Hauptinteresse galt nicht der extremen, der klassischen anaphylaktischen Reaktion, sondern einer durchschnittlichen Histaminfreisetzung, die in klinischen Untersuchungen der letzten 10 Jahre mit so vielen Arzneimitteln gefunden wurde.

Bei den Freiwilligen wurden 600 ng/kg Histamin intravenös verabreicht. Indikatoren für eine systemische anaphylaktoide Reaktion mit der höchsten Inzidenzrate waren Tachykardie, Plasmahistaminspiegel über 1 ng/ml, metallischer Geschmack, Flush, Kopfdruck, feuchte Augen oder Tränen, Hypertension und Kopfschmerzen. Nach Haemaccel-Infusion zeigte keiner der Probanden eine lebensbedrohliche Reaktion, aber 12 eine systemische und 11 eine Hautreaktion, während bei 17 keine Symptome gefunden werden konnten. Indikatoren mit der höchsten Inzidenzrate waren wiederum Plasmahistaminspiegel über 1 ng/ml, Tachykardie, Quaddeln, Hitzegefühl, Enge im Hals, Hypertension, Kopfschmerzen und Tränen.

In einer prolektiven Cohortstudie wurden aus 600 orthopädischen Patienten 164 ausgewählt: 3 hatten eine lebensbedrohliche Reaktion, 27 eine systemische und 96 eine Hautreaktion, 38 Patienten zeigten keine Symptome. Indikatoren mit der höchsten Inzidenzrate waren wiederum Tachykardie, Plasmahistaminspiegel über 1 ng/ml, Erytheme und Quaddeln, Husten, Flush, verstopfte Nase und Gesichtsödem. Damit wurden durch die Patientenstudie die Indikatoren für eine systemische Histaminfreisetzungsreaktion in Probanden zu einem großen Teil validiert. So läßt sich eine durchschnittliche Histaminfreisetzungsreaktion als eine systemische anaphylaktoide Reaktion charakterisieren, mit klinischen Symptomen wie Tachykardie und leichte Hypertension, verstreuten Effloreszenzen, respiratorischen Symptomen im Bereich des Kehlkopfs und der Nasenschleimhautund durch pathologische Plasmahistaminspiegel (>1 ng/ml). Außerdem wurden die Histaminfreisetzungsreaktionen in kutane, systemische und lebensbedrohliche Reaktionen eingeteilt, wobei klinische und operationale Kriterien sowie Plasmahistaminspiegel für die Klassifikation verwendet wurden.

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Authors and Affiliations

  1. Division of Theoretical Surgery, Department of Operative Medicine I, University of Marburg, Robert-Koch-Str. 8, D-3550, Marburg, Federal Republic of Germany

    W. Lorenz, Ch. Ohmann & E. Neugebauer

  2. Division of Anaesthesia, Surgical OPC Clinic, University of Munich, D-8000, Munich, Federal Republic of Germany

    A. Doenicke & B. Grote

  3. Division of Anaesthesia, Orthopedic Clinic, University of Heidelberg, D-6900, Heidelberg, Federal Republic of Germany

    B. Schöning

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  1. W. Lorenz
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  2. A. Doenicke
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Dedicated to Professor Otto Lindenschmidt

Supported by grant of Deutsche Forschungsgemeinschaft (Lo 199/10 and Lo 199/13-6)

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Lorenz, W., Doenicke, A., Schöning, B. et al. Definition and classification of the histamine-release response to drugs in anaesthesia and surgery: Studies in the conscious human subject. Klin Wochenschr 60, 896–913 (1982). https://doi.org/10.1007/BF01716946

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