Patients receiving intravenous morphine at doses of 0.3 and 1.0 mg/kg for general anesthesia have been reported to show significant elevations in plasma histamine that are associated with hemodynamic changes. We undertook a prospective, randomized, double-blind trial in which 0.15 mg/kg morphine or 0.3 mg/kg nalbuphine was administered intravenously to normal volunteers. Thirteen of 15 subjects receiving morphine and 10 of 14 subjects receiving nalbuphine had elevations in plasma histamine levels and symptoms of histamine release within 5 minutes of drug administration. Six subjects in the morphine group and five in the nalbuphine group exhibited levels of plasma histamine > 2.0 ng/ml, but these levels were not associated with hemodynamic changes and occurred 10 to 15 minutes after drug administration. Our study suggests that the opiate-induced elevation of plasma histamine derives from cutaneous mast cells.

Intravenous morphine and nalbuphine increase histamine and catecholamine release without accompanying hemodynamic changes.

Hemodynamic and Adrenergic Responses to Anesthesia and Operation for Myocardial Revascularization

Risk adjustment and stratification play an important role in quality assurance and in clinical research. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a patient risk prediction model based on 12 patient characteristics and 6 characteristics of the surgery performed. However, because the POSSUM was developed for quality assessment in general surgical units, its performance within specific subgroups still requires evaluation. The aim of the present study was to assess the accuracy of POSSUM in predicting mortality and morbidity in patients with gastric cancer undergoing D2-gastrectomy. 137 patients with gastric cancer undergoing gastrectomy were included in this study. Detailed, standardized risk assessments and thorough documentation of the post-operative courses were performed prospectively, and the POSSUM scores were then calculated. The 30- and 90- day mortality rates were 3.6% (n = 5) and 5.8% (n = 8), respectively. 65.7% (n = 90) of patients had normal postoperative courses without major complications, 14.6% (n = 20) had moderate and 13.9% (n = 19) had severe complications. The number of mortalities predicted by the POSSUM-Mortality Risk Score (R1) was double the actual number of mortalities occurring in the median and high-risk groups, and was more than eight times the actual number of mortalities occurring in the low-risk group (R1 < 20%). However, the calculated R1 predicted rather well in terms of severe morbidity or post-operative death in each risk group: in predicted low risk patients the actual occurrence rate (AR) of severe morbidity or post-operative death was 14%, for predicted medium risk patients the AR was 23%, and for predicted high risk patients the AR was 50% (p < 0.05). The POSSUM-Morbidity Risk Score (R2) overestimated the risk of morbidity. The POSSUM Score may be beneficial and can be used for assessment of the peri- and post-operative courses of patients with gastric carcinoma undergoing D2-gastrectomy. However, none of the scores examined here are useful for preoperative prediction of postoperative course.

https://link.springer.com/content/pdf/10.1186%2F1471-2482-5-8.pdf

Evaluation of POSSUM scoring system in patients with gastric cancer undergoing D2-gastrectomy

Toxic effect of MDMA on brain serotonin neurons

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. Heart rate, blood pressure, SaO2, clinical symptoms/signs and plasma histamine were measured during the observation period. Results: The incidence of histamine release over the whole observation period in all three groups was 100%. Histamine release occurred frequently in all three groups until 30 min (50%–78%) and up to 240 min (late release reaction: 67%–83%) after the start of infusion. Surprisingly even hydroxyethyl starch, which is regarded as a generally safe and effective plasma substitute, caused high incidences of late histamine release (67%). Histamine release is a well known side effect of polygeline and – to a lesser extent – also of albumin, but was a novel finding for hydroxyethyl starch. Conclusions: We demonstrated for the first time histamine releasing effects of hydroxyethyl starch over a long period of time after administration. This perioperatively and for intensive care possibly relevant finding should make clinicians aware of late side effects not yet connected with the clinical use of these colloidal plasma substitutes.

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

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 (classification), 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. Histamine release by neuro-endocrine and neuro-inflammatory mechanisms, cytotoxic histamine release and local, cytokine induced histamine release have been distinguished from pseudoallergic histamine release, but its functions are not yet clear. It has been analysed in prospective trials which used special clinical situations as models: patients on a normal ward or before and during upper GI endoscopy without premedication, but also in specific phases of laparoscopic cholecystectomy (trocar phase and dissection phase). Their existence in the clinical reality is now very likely, but new trials must investigate the pathophysiological effects such as in metabolism, coagulation, pulmonary haemodynamics (shunt volume) and gastric acid secretion. Histamine release by pseudoallergic mechanisms, however, was identified in the very vulnerable post-induction phase of anaesthesia up to skin incision. Its incidence was much higher than ever expected and its clinical relevance was demonstrated by the severity of reactions and the intervention strategies of the anaesthetists who were blinded concerning the type of the plasma substitute given and the prophylaxis with antihistamines. Pseudoallergic histamine release was clearly unwanted (adverse). Its occurrence in the other phases of anaesthesia has to be further evaluated in the tedious procedure of data analysis of the Mainz-Marburg-trial. The overall incidence of histamine release in the trial was so incredible high (72% of all patients, some of them with up to 4 episodes of histamine release) that a distinction between pseudoallergic (unwanted) and other types of histamine release (possibly less unwanted or even beneficial) is urgently needed. In the phase of steady state (maintenance) of anaesthesia the H1-(+)H2-prophylaxis was highly effective. Further analysis must show whether this is also the case during the phases of induction of anesthesia.(ABSTRACT TRUNCATED AT 400 WORDS)

https://epub.uni-regensburg.de/21757/1/lornez29.pdf

Perioperative nonspecific histamine release: a new classification by aetiological mechanisms and evaluation of their clinical relevance Liberation periop6ratoire non specifique d'histamine causes anesthesiques et non anesthesiques

Operative risks should be assessed before surgical intervention not only by heuristic means, but in addition also by quantitative methods. ASA-classification and Recovery Index (McPeek) are offered for a critical routine assessment of global perioperative risk.

Analysis of risk in the perioperative period

Bei der Einfuhrung von Risikoforschung in die Chirurgie wurde fruher von einfachen Modellen (relatives Risiko, Risikofaktoren) ausgegangen, aber die perioperative Periode wird heute als ein komplexes System betrachtet. Dabei werden Risikofaktoren mit multivariaten Methoden analysiert (z.B. logistische Regression), die Pathogenese unerwunschter Verlaufe mit Markovprozessen und das Endergebnis (Outcome) mit einem Konstrukt aus mechanistischen und hermeneutisehen Endpunkten (Beispiel: McPeek Index). In einem solchen komplexen System werden infolge verschiedener interagierender Prophylaxen sowohl Risikoabnahmen wie auch -zunahmen beobachtet. Beispiel: Volumen-, Antibiotika- und Antihistaminikaprophylaxe. Bei Antibiotikagabe traten Herz-Kreislaufreaktionen auf, die sich auch im Tierversuch am isolierten Gefas (Aorta) demonstrieren liesen. Daraus folgt, das Prophylaxen im perioperativen Zeitraum mit breiter Outcome-Analyse und mit relevanten Zeitperioden verbunden werden mussen.

W. Dick

Papers

Perioperative nonspecific histamine release: a new classification by aetiological mechanisms and evaluation of their clinical relevance Liberation periop6ratoire non specifique d'histamine causes anesthesiques et non anesthesiques

Analysis of risk in the perioperative period

Das Problem der Interaktionen von perioperativen Prophylaxen: Risikominderung oder Risikomehrung?