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

As a consequence of the performance of a randomized controlled clinical trial on perioperative histamine release and cardiovascular and respiratory disturbances, several types of increases in plasma histamine had to be distinguished instead of only two which existed at the beginning of the study: drug-induced allergic and pseudoallergic reactions. First of all, the new classification by aetiology (clinical epidemiology) was derived from a meta-analysis (secondary analysis) of the most recent literature. According to that histamine release in the perioperative period has several, different causes and is involved in several, different disease manifestations. A clear distinction (classificatio…

Verminderung kardiovaskulärer Störungen durch perioperative Antihistaminikaprophylaxe in der Allgemeinchirurgie: Sind die Medikamente austauschbar?

Klinische Forschung hat das Ziel, die Effektivitat von diagnostischen und therapeutischen Verfahren am Patienten unter Verwendung des Goldstandards der randomisierten, kontrollierten klinischen Studie zu zeigen [1, 4]. Trotzdem kommt es immer wieder zu Fehlern (Versagen von Studien) oder sogar zu Katastrophen (Todesfalle) in Patientenstudien (z. B. in Sepsisstudien [2, 6]), obwohl die zugrunde liegenden Studien der Grundlagenforschung sehr erfolgreich und vielversprechend waren [7]. Dies verdeutlicht die Notwendigkeit, in solchen Studien mehr Komplexitat zu modellieren, bevor neue Medikamente in der realen klinischen Situation eingesetzt werden [3]. Wir schlagen deshalb als neues Konzept di…

Elevated plasma histamine concentration as a sensitive real-time parameter for distinct phases of surgical trauma: a tool for technology assessment.

High technology plays an important role in surgery, either to expand surgical procedures or to reduce tissue trauma, which is a main goal of minimum invasive surgery. Due to the tremendous increase of costs the problem of technology assessment will not only be solved by statistical methods, but also by biomedical considerations and laboratory tests. Histamine release could be an indication for tissue trauma, which is caused directly by tissue damage or indirectly by infection or hypoxia. Therefore histamine release was investigated during different phases of operation in two clinically very important and complex situations: resection of liver metastases of colorectal carcinoma and resection…

Clinic modelling randomised trials (CMRT's) in animals as a new intermediate between biological experiments and randomised clinical trials: application to antihistamine prophylaxis in anaesthesia and surgery.

Einflußfaktoren perioperativer Histaminfreisetzung in der Posteinleitungsphase: Maligne Grunderkrankung als Risiko

Die erste Auswertung der Mainz-Marburg Studie zeigte einen extrem hohe Inzidenz (72%) von Histaminfreisetzungsereignissen in der Narkoseeinleitung und Operations- vorbereitung bei 240 allgemeinchirurgischen Patienten [2]. Der naheliegende Schlus, das es sich hierbei um stresinduzierte Schwankungen der Plasmahistaminspiegel han-delte, wurde aber durch mehrere Begleitstudien an Patienten auf einer Normalstation bzw. vor und wahrend der gastrointestinalen Endoskopie widerlegt [2]. Besonders fiel aber auf, das in der Posteinleitungsphase (hamodynamische Stabilisierung nach Einleitung der Narkose mit gleichzeitiger Infusion eines Plasmasubstitutes) die Haufigkeit von Histaminfreisetzung mit 30% …

Causality-based diagnosis of histamine-related cardiorespiratory disturbances in surgical patients

Can clinically relevant histamine release be accurately diagnosed in anaesthetised patients without plasma histamine measurements? Randomised study with nested sampling aimed to change paradigms

Model building strategies for risk analysis of perioperative histamine-related cardiorespiratory disturbances.

Wiederholte Histaminfreisetzung im perioperativen Zeitraum: Spezifische Reaktion auf ärztliche Maßnahmen oder allgemeine Streßreaktion?

Die hohe Incidenz und klinische Relevanz perioperativer Histaminfreisetzung anzuerkennen, stost auch heute noch, nach zahllosen Studien [4], bei vielen Klinikern auf eine starke Resistenz. Der allgemeine Widerwille gegen die Kenntnisnahme dieses Problems grundet sich auf viele Ursachen [3], nicht zuletzt aber auch auf das Unbehagen, uber iatrogene Komplikationen, welchen Ausmases auch immer, zu diskutieren [1]. Das die tatsachliche Incidenz der Histaminfreisetzung im perioperativen Zeitraum deutlich hoher liegt als selbst von den Protagonisten dieses Prinzips angenommen wurde [3], zeigt der bisherige Verlauf an 160 Patienten einer multizentrischen kontrollierten klinischen Studie zur periop…

Problem solving strategies with biomedical and clinimetric components: The case of perioperative H1-+H2-prophylaxis

A formal (objective) problem solving strategy was developed for the question whether a perioperative histamine H1-+H2-prophylaxis should be applied to patients at risk for a histamine release reaction or for a special severity of such a reaction even in the case of a minor histamine release.

Evaluation of early and late histamine release by three standard volume substitutes

Following meta-analysis [1], the use of colloidal solutions in intensive care medicine is under discussion. Although polygeline [2] and human albumin are known to cause histamine release, other substances eg hydroxyethyl starch were thought to be without effect. Histamine release depends on the clinical scenario, concomitant drugs, infusion speed, duration and amount of infusion. However, there is no information about their effect regarding time periods longer than immediate reactions. This study investigated the histamine releasing effects of three plasma substitutes administered and observed over a longer period of time, simulating many of the clinical scenarios.

Histamine release in mesenteric traction syndrome during abdominal aortic aneurysm surgery: prophylaxis with H1 and H2 antihistamines

Objective and design: Mesenteric traction syndrome is described as sudden tachycardia, hypotension and flush. Among other etiological factors eventeration or mesenteric traction of the small intestine may cause histamine release from mesenteric mast cells. We hypothesized that mesenteric traction syndrome may be positively influenced by prophylactic antihistamine administration.¶Methods: Male patients (n = 17, ASA groups III-IV, 48–78 years old) were investigated in a randomised double blind study during elective abdominal aortic aneurysm (AAA) repair. Eight patients had pre-anaesthetic prophylaxis with dimetindene (H1-receptor antagonist) plus cimetidine (H2-receptor antagonist), 9 patient…

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

Although histamine release is recognised as a common event during anaesthesia and surgery, few clinicians judge the resultant cardiorespiratory disturbances serious enough to warrant prophylaxis with antihistamines. We have assessed the incidence and importance of histamine release in a randomised 2 x 2 factorial study. 240 patients representing a routine throughput of major general surgery were studied during a standardised induction of anaesthesia and preoperative loading of the circulation with either Ringer solution or Haemaccel-35, with or without antihistamine prophylaxis with dimetindene (H1) plus cimetidine (H2). Cardiorespiratory disturbances were graded as detectable, clinically r…

Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings.

Objective: The perioperative use of colloidal plasma substitutes is still under discussion. We therefore conducted a prospective randomised study with three commonly used plasma substitutes to examine their histamine releasing effects in 21 volunteers. Material or subjects: 21 male volunteers were enrolled in this prospective, randomised, controlled clinical study. Endpoints were the incidence of early and late histamine release and the time course of the release kinetics. Normovolemic hemodilution technique was used with hydroxyethyl starch (n = 6), human albumin (n = 6) and polygeline (n = 9). Measurement and observation period was 240 min after the start of the plasma substitute infusion…

Models with clinically-relevant and life-threatening histamine-related cardiovascular disturbances: Evaluation of the clinical effectiveness of H1/H2-histamine receptor antagonists in perioperative histamine release

Einfluß relevanter hämodynamischer Störungen in der Posteinleitungsphase auf die postoperative Wiederherstellung in der Allgemeinchirurgie

Pra- und intraoperative kardiovaskulare Storungen sind haufige Ereignisse des klinischen Alltages. In der Auswertung und Publikation des ersten Teiles der hier vorgestellten Studie konnte nachgewiesen werden, das deren Inzidenz unmittelbar nach Einleitung der Anasthesie und vor Beginn der Operation deutlich hoher liegt, als dieses bisher allgemein angenommen wurde. Dabei sind diese Storungen uberwiegend histaminabhangig, erfullen aber nicht die klassischen Paradigmen der Histaminfreisetzungsreaktion und sind somit im klinischen Alltag schwer als solche zu identifizieren [1]. Obwohl des in der Literatur deutliche Hinweise zumindest fur den Zusammenhang schwerer postoperativer kardialer Probl…

Histamine release during induction of anaesthesia and preparation for operation in patients undergoing general surgery: Incidence and clinically severe cases

Histamine release events were shown in a prospective randomized controlled trial in patients undergoing elective general surgery with an extraordinarily high incidence: 73 per cent. This high incidence was explained by several factors: — the sample size which was much greater than in previous studies — the improved plasma histamine assay — the precise definition of histamine release in clinical conditions and its measurement at the top of Bateman functions — the standardized induction of anaesthesia and preparation of the surgical patient — and finally the considerable number of cancer patients since more than 60% of the reactions >5 ng/ml occurred in this group which comprised only 20% of …

Cardiorespiratory disturbances following antibiotic prophylaxis in general surgery: Reasons for a complex reappraisal of a common problem

Klinische Studien in der Notfallmedizin

Bei klinischen Studien wird in erster Linie an kontrollierte randomisierte Studien, an retrospektive Serienberichte und an Einzelfallberichte gedacht. Diese Klassifikation ist aber viel zu eng und ubersieht die vielen Moglichkeiten und Notwendigkeiten von andersartigen Studienplanen und -durchfuhrungen. Prospektive kontrollierte randomisierte Studien sind experimentelle Studien an Patienten mit dem hochsten Anspruch an Wissenschaftlichkeit (Goldstandard), aber nur unter strengsten ethischen Pramissen: therapeutische Vertretbarkeit im Hinblick auf den jeweiligen Patienten und deshalb vergleichbare Ungewisheit fur die Uberlegenheit eines Verfahrens am einzelnen Patienten. Daneben gibt es sech…

Gastric histamine methyltransferase: Different methylation rates for enantiomers of side-chain methylated histamine analogues using a highly purified enzyme preparation

The inhibitor/activator and substrate properties of enantiomers of two methylated histamines (MH) were investigated using a histamine methyltransferase preparation which was purified 1207-fold from pig fundic mucosa by ultracentrifugation, ion-exchange chromatography on DEAE-cellulose and preparative electrofocusing. In 1-100 microM concentrations, S-alpha-MH and R-alpha-MH were acceptor substrates as good as histamine itself. When substrate concentrations were increased to 1 mM these substances were methylated to an even greater extent than histamine, since they did not exert substrate inhibition on HMT. Introduction of a further methyl-group into the N alpha-position reduced acceptor subs…