Anaphylaxis

Observations in 205 patients with cardiovascular manifestations of anaphylactic shock confirmed the belief that adrenaline is the drug of first choice in management and that colloid solutions are preferable to crystalloid solutions in volume replacement. Arrhythmias and elevated filling pressures are more common in patients with cardiac disease but the sympathetic response appears to override the cardiac effects of histamine in healthy patients.

Clinical observations on the pathophysiology and treatment of anaphylactic cardiovascular collapse.

Anaphylactic reactions to anaesthetic and associated agents used during the perioperative period have been reported with increasing frequency in most developed countries. Any drug administered in the perioperative period can potentially produce life-threatening immune-mediated anaphylaxis. Most published reports on the incidence of anaphylaxis come from France, Australia, the UK and New Zealand. These reflect an active policy of systematic clinical and/or laboratory investigation of suspected immune-mediated reactions. The estimated incidence of anaphylaxis ranges from 1:10,000 to 1:20,000. Muscle relaxants (69.1%) and latex (12.1%) were the most frequently involved drugs according to the most recent French epidemiological survey. Clinical symptoms do not afford an easy distinction between immune-mediated anaphylactic reactions and anaphylactoid reactions resulting from direct non-specific histamine release. Moreover, when restricted to a single clinical symptom, anaphylaxis can easily be misdiagnosed. Pre- and postoperative investigation must be performed to confirm the nature of the reaction, the responsibility of the suspected drugs and to provide precise recommendations for future anaesthetic procedures. These include plasma histamine, tryptase and specific IgE concentration determination at the time of the reaction and at skin tests 6 weeks later. In addition, since no specific treatment has been shown reliably to prevent the occurrence of anaphylaxis, allergy assessment must be performed in all high-risk patients. Treatment of anaphylaxis is aimed at interrupting contact with the responsible antigen, inhibiting mediator production and release, and modulating the effects of released mediators. It must be initiated as quickly as possible and relies on widely accepted principles. Finally, the need for proper epidemiological studies and the relative complexity of allergy investigation should be underscored. They represent an incentive for further development of allergo-anaesthesiology clinical networks to provide expert advice for anaesthetists and allergologists.

Allergic reactions occurring during anaesthesia

Modification of the cardiac rhythm by histamine has been appreciated almost since the compound's isolation from ergot by Barger and Dale in 1910. The major arrhythmogenic actions of histamine are an Hi-receptor-mediated slowing of atriovenrricular (AV) conduction and H2-receptor-mediated increases in sinus rate and ventricular automaticity. These actions were elucidated by observing the salutary effects of histamine antagonists on the arrhythmias of anaphylaxis, and by administering exogenous histamine to various cardiac preparations in the presence and absence of histamine antagonists. The ability to record transmembrane action potenrial(s) (TAP) from single cells has permitted the study of electrophysiological mechanisms underlying histamine-induced arrhythmias.

Histamine and cardiac arrhythmias.

Incidence and clinical importance of perioperative histamine release: randomised study of volume loading and antihistamines after induction of anaesthesia

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.

/pdf/definition-and-classification-of-the-histamine-release-5dyv2reifp.pdf

Definition and Classification of the Histamine-Release Response to Drugs in Anaesthesia and Surgery: Studies in the Conscious Human Subject* **

https://epub.uni-regensburg.de/21901/1/lorenz73.pdf

Blood and blood substitutes

1.

In 5 randomisierten kontrollierten Studien wurde die Verhinderung und Abschwachung von unerwunschten Reaktionen auf Arzneimittel mit hist-aminfreisetzender Wirkung durch eine Pramedikation mit Histamin H1- und H2-Rezeptor-Antagonisten untersucht.




2.

In der 1. Studie an Patienten erwies sich die Pramedikation als auserordentlich wirksam in der Verhinderung von Hautreaktionen (cutanen anaphylaktoiden Reaktionen).




3.

In der 2. und 3. Studie an Probanden wurde auch die systemische anaphylaktoide Reaktion nach klassischem Haemaccel vollstandig verhindert, nach Propanidid wurde die Mischung von anaphylaktoiden und sonstigen unerwunschten Reaktionen deutlich abgeschwacht.




4.

Lebensbedrohliche anaphylaktoide Reaktionen konnten in den kontrollierten Studien nur am Versuchstier untersucht werden. Hierfur wurden Hunde ausgewahlt, da sie in dieser Hinsicht dem Menschen am ahnlichsten sind. Sowohl die lebensbedrohliche Reaktion durch klassisches Haemaccel als auch durch Compound 48/80, gelost in Ringerlosung wurde durch die Pramedikation wirksam unterdruckt bzw. vermindert. Nur extrem starke Histaminfreisetzungsreaktionen konnten nicht vollstandig geblockt werden, aber der Schweregrad der Reaktionen wurde auf ein Mas reduziert, das fur den Organismus ertraglich war.




5.

Unter den Bedingungen, die an Patienten, Probanden und Hunden getestet wurden, war die Pramedikation mit Histamin H1- und H2-Rezeptor-Antagonisten wirksam gegen Histaminfreisetzungsreaktionen von jedem Schweregrad.

B. Grote

Papers

Definition and Classification of the Histamine-Release Response to Drugs in Anaesthesia and Surgery: Studies in the Conscious Human Subject* **

Blood and blood substitutes

Prospektive Studien mit Histamin-H1- und H2 -Rezeptor-Antagonisten