PERIOPERATIVE NONSPECIFIC HISTAMINE-RELEASE - A NEW CLASSIFICATION BYETIOLOGIC MECHANISMS AND EVALUATION OF THEIR CLINICAL RELEVANCE

As a consequence of the performance of a randomized controlled clinica l trial on preioperative histamine release and cardiovascular and resp iratory disturbances, several types of increases in plasma histamine h ad to be distinguished instead of only two which existed at the beginn ing of the study : drug-induced allergic and pseudoallergic reactions. First of all, the now classification by aetiology (clinical epidemiol ogy) was derived froin a metaanalysis (secondary analysis) of the most recent literature. According to that histamine release in the periope rative period has several, different causes and is involved in several , different disease manifestations. A clear distinction (classificatio n), however, is necessary if histamine release as an unwanted (adverse ) effect has to be recognized, value judged according to its clinical relevance and therefore also prevented by histamine antagonists. Hista mine release by neuro-endocrine and neuro-inflammatory mechanisms, cyt otoxic histamine release and local, cytokine induced histamine release have been distinguished from pseudoallergic histamine release, but it s functions are not yet clear. It has been analysed in prospective tri als which used special clinical situations as models : patients on a n ormal ward or before and during upper GI endoscopy without premedicati on, but also in specific phases of laparoscopic cholecystectomy (troca r phase and dissection phase). Their existence in the clinical reality is now very likely, but new trials must investigate the pathophysiolo gical effects such as in metabolism, coagulation, pulmonary haemodynam ics (shunt volume) and gastric acid secretion. Histamine release by ps eudoallergic mechanisms, however, was identified in the very vulnerabl e post-induction phase of anaesthesia up to skin incision. Its inciden ce was much higher than ever expected and its clinical relevance was d emonstrated by the severity of reactions and the intervention strategi es of the anaesthetists who were blinded concerning the type of the pl asma substitute given and the prophylaxis with antihistamines. Pseudoa llergic histamine release was clearly unwanted (adverse). Its occurenc e in the other phases of anaesthesia has to be further evaluated in th e tedious procedure of data analysis of the Mainz-Marburg-trial. The o verall incidence of histamine release in the trial was so incredibly h igh (72 % of all patients, some of them with up to 4 episodes of hista mine release) that a distinction between pseudoallergic (unwanted) and other types of histamine release (possibly less unwanted or even bene ficial) is urgently needed. In the phase of steady state (maintenance) of anaesthesia the H-1- + H-2-prophylaxis was highly effective. Furth er analysis must show whether this is also the case during the phases of induction of anaesthesia. Many of the pseudoallergic histamine rele ase reactions (72 %) occur without cutaneous signs - even with plasma histamine levels of 12 ng . ml-1, i.e. in the range of usually life-th reatening reactions. The clinical picture of these reactions has to be revised. Since in the case of haemodynamic instability alone the anae sthetist cannot distinguish between histamine-induced reactions and ca rdiovascular reactions based on other mechanisms, a considerable under reporting of the reactions is fully understandable. Plasma histamine a ssays are necessary under strict quality control to create awareness o f this considerable clinical problem. If that is understood the questi ons of antihistamines : yes or no ? to whom ? at which time ? and whic h drugs and dose ? will be asked in a different way than hitherto.