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

Abstract

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 Polygeline (Haemaccel) in its now outdated formulation [40] was chosen as a clinical histamine releaser.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 the average 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 > t 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. Indieants 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, stuff), nose and sneezing and 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 * Dedicated to Professor Otto Lindenschmidtt ** Supported by grant of Deutsche Forschungsgemeinschafl (Lo 199/10 and Lo 199/13-6) Offprint requests to: Professor Dr. W. Lorenz (address see above) decision making procedures the incidence of systemic histamine-release responses in patients higher by two orders of magnitude than in other studies reported hitherto.

Plasma histamine levels in patients in the course of several standard operations: Influence of anaesthesia, surgical trauma and blood transfusion

“…A pathological plasma histamine level was defined as one exceeding 1 ng/mt according to Lorenz et al (1982). Individual increases or decreases in plasma histamine concentrations had to be greater than the 3 S.D.…”

Anti H1- and anti H2-premedication

“…They only consisted of wheals of 2-3 mm diameter and caused, if nothing else was detectable, itching and burning which was usually neglected by the patients expecting surgery. The incidence of this banal histamine-release response to polygeline was less than in studies with ~ classical ~ Haemaccel [7], but still 18% ! However, by premedicating with H1-and H2-receptor antagonists, it was drastically reduced, not only in the overall number of reactions (table III), but also in the ~ severity >~ of those remaining.…”

“…In the test group receiving the H Iand HE-blockade, seven volunteers released histamine to greater levels than in the control group, including two subjects with plasma histamine concentrations of 5 ng • m1-1, at the top of the Bateman curve. Since in all previous studies (see especially [5,7]), increasing plasma histamine levels to this order of magnitude always caused anaphylactoid reactions of a considerable severity, the complete prevention of any clinical signs and cardiovascular reactions in these subjects was very remarkable. The result of this trial justified the definition of histamine release as predominant in the adverse reaction to polygeline [2].…”

Perioperative nonspecific histamine release : a new classification by aetiological mechanisms and evaluation of their clinical relevance

“…It will be demonstrated by elevated plasma histamine levels which will show pharmacokinetics and clinical symptoms resembling those after i.v. histamine injection [66], and not those of histamine release from mast cells in the tissues after histamine-releasing drugs or allergic reactions in which the amine invades the plasma compartment more slowly, but for a longer time period.…”

“…The criteria which had to be fulfilled were described in detail by LORENZ et al [64,66,68], DUDA et al [13] and STTrER et al [99].…”