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 the study population.

Two cases of life-threatening anaphylactoid reactions occurred in this trial corresponding to an incidence of 1 per cent. This was — again — very high compared to previous epidemiological studies. Both cases were again cancer patients and occurred in the placebo group — information given by the external study advisory group for further treatment of the individual patient.

The data on the high incidence of histamine release including the high incidence of life-threatening reactions favourrationally a preoperative H₁ ⁻+H₂-prophylaxis with the drugs used in this study: dimetindene and cimetidine. The question of the incidence was one of the unsettled problems which led to this trial. Analysis of the first 180 patients already answered this question more than we had ever expected.

     

PCR for Detection and Identification of Abiotrophia spp.

Members of the genus Abiotrophia, formerly known as nutritionally variant streptococci, are important pathogens causing septicemia and endocarditis. Cultivation and biochemical differentiation of Abiotrophia spp. are often difficult. Based on 16S rRNA sequences, two PCR assays for detection and identification of Abiotrophia spp. were developed. The first PCR assay was positive for all Abiotrophia spp. Subsequently performed restriction fragment length polymorphism analysis allowed the verification of the PCR amplicons and the differentiation of the three species. The second PCR assay was positive only for A. elegans, the most fastidious species of Abiotrophia. Both PCR assays were shown to be specific and sensitive and should facilitate the identification of Abiotrophia spp.     

The clinical and biological signs of histamine release during induction of anaesthesia and preparation of the surgical patient: A farewell party for the classical manifestations of anaphylaxis

The clinical manifestations of histamine release and their clinical relevance are still matter of considerable debate among anaesthesiologists whereas surgeons have no opinion at all. In a series of six clinical-experimental trials a gold standard for histamine release was established, the term “histamine release reaction” was determined, and a combination of clinical predictors was created for assessing the effectiveness of a prophylaxis with histamine H₁+H₂-antagonists.

After the construction of the gold standard “elevated plasma histamine”, in the first three trials the experimental validation, the selection of standard variables for a clinical test and the validation with authentic histamine was accomplished. In three further trials this test was applied to several histamine releasers which have been commonly used for induction of anaesthesia and preparation of a surgical patient, namely, the hypnotic propanidid, the muscle relaxant atracurium, and the plasma substitute Haemaccel. In these trials, H₁+H₂-sensitive variables were also selected for a diagnostic classification of histamine release reactions.

Trial 1 demonstrated that elevated plasma histamine levels indicated histamine release with a high accuracy. Selection of variables after authentic histamine with and without H₁+H₂-antagonists chose the following clinical signs: cutaneous signs, tachycardia, and hypertension (trial 2). This test including the three variables, after injection of authentic histamine, showed a high accuracy (trial 3). However, when for each histamine releaser and H₁+H₂-sensitive combination of variables was assessed in trial 4–6, the results were very different in all the performance criteria (Table 6). Propanidid showed very bad results in accuracy which differed not at all from those of the prevalence (incidence) of adverse reactions (flipping a coin, no gain by diagnostic information). Atracurium was in-between, not very convincing with its gains, but Haemaccel was the best-however not for the classical signs of anaphylaxis. It is concluded-that the standard variables of histamine release, in combination with a broader spectrum of signs, can be used for diagnosing (classifying) the endpoint of a histamine release reaction. This definition is urgently needed for analysing the data of an extended randomized trial which used H₁+H₂-receptor antagonists for preventing adverse reactions in anaesthesia due to histamine release.

     

Differential effects of upper gastrointestinal fill on milk ingestion and nipple attachment in the suckling rat

Milk intake and nipple attachment behaviors were studied in the natural suckling situation after gastrointestinal preloading. Rat pups, deprived of their dam for 9 hr at 1, 10, or 20 days of age, were preloaded by gavage with volumes ranging from 2 to 16% of their body weight and returned to suckle. Preloads of artificial bitch's milk decreased the intake of mother's milk in a volume-related manner at all ages. At 1 and 10 days 4% preloads decreased milk intake without affecting attachment behaviors; larger prelods of 8 and 16% decreased intake and reduced the incidence of attachment. At 20 days of age small and large preloads decreased both incidence of attachment and milk intake. Preloads up to 8% of body weight had no effect on latency to attach at any age. Complete subdiaphragmatic bilateral vagotomy increased milk intake of 7–9–day-old pups fed automatically through an anterior mouth cannula in a nonsuckling situation. Vagotomy combined with spinal cordotomy (T2-T3) resulted in a synergistic hyperphagia and massive distension of the upper GI tract. The results indicate that suckling rats can control their intake of mother's milk while remaining attached to a nipple as early as 1 day of age. The suppression of ingestion in response to GI filling appears to be mediated by visceral afferent activity. Conversely, attachment behaviors are less affected by GI fill. This suggests that ingestive behaviors and attachment behaviors have different controls during the 1st 10 days of postnatal development.     

Development of Na+-dependent hexose transport in a cultured line of porcine kidney cells

LLC-PK1 cells in culture do not concentrate alpha-methylglucoside (alpha-meG) during their early growth phase but develop the capacity to concentrate this hexose as the growth rate decreases in confluent cultures. The concentrating ability is dependent on the Na+ electrochemical gradient and is inhibited by phlorizin with KI,0.5 approximately 0.2 microM. The development of the concentrative capacity can be accelerated by the Friend cell inducer hexamethylene bisacetamide (HMBA) and by the phosphodiesterase inhibitors dibutyryl cAMP, theophylline, and 1-methyl-3-isobutylxanthine (MIX). In cultures treated with any of these differentiation-accelerating chemicals, the development of alpha-meG concentrating capacity is severely inhibited by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) but not by inactive (in tumor promotion) analogs of TPA. In all cases, an early event in the development of alpha-meG accumulating capacity is an elevated intracellular cAMP concentration; however the results suggest that this increase in cAMP may be necessary but not sufficient to induce the differentiated hexose-accumulating capacity.     

Induced histidine decarboxylase in endotoxic shock: Identification of the enzyme in rat liver and influence of its inhibitors on survival parameters

The hypothesis of a causal relationship between a progressive and unrestrained increase of tissue histamine formation by activation of an inducible histidine decarboxylase (HDC) and lethality in endotoxic shock (Schayer's induced histamine concept) was tested in a standardized rat endotoxic shock model.Initial enzyme identification studies in the rat shock liver (8 hrs after endotoxin challenge) clearly demonstrate that the induced histidine decarboxylase is an acid (specific) HDC. The succeeding randomized, controlled study with appropriate inhibitors of the enzyme, -methyl-histidine (competitive inhibitor) and -fluoromethyl-histidine (irreversible inhibitor) using doses of 2, 20 or 100 mg/kg showedno significant effect on the survival rate of rats in endotoxin shock. The survival rate of the non-treated endotoxin control group (NaCl) was 25%; all methylprednisolone treated rats (50 mg/kg) survived.Thus, the induced histamine isnot a predominant factor (necessary or sufficient determinant) for the lethal outcome in rat endotoxic shock. The protective effect of MP isnot predominantly due to the inhibition of the induced histidine decarboxylase. The use of HDC-inhibitors as the appropriate instruments for evaluation of the significance of this mechanism is discussed.Clinic of General Surgery, City Hospital Sieburg.     

Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier

Bone substitute materials can induce bone formation in combination with mesenchymal stem cells (MSC). The aim of the current study was to examine ectopic in vivo bone formation with and without MSC on a new resorbable ceramic, called calcium deficient hydroxyapatite (CDHA). Ceramic blocks characterized by a large surface (48 m2/g) were compared with beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA) ceramics (both ca. 0.5 m2/g surface) and demineralized bone matrix (DBM). Before implantation in the back of SCID mice carriers were freshly loaded with 2x10(5) expanded human MSC or loaded with cells and kept under osteogenic conditions for two weeks in vitro. Culture conditions were kept free of xenogenic supplements. Deposits of osteoid at the margins of ceramic pores occurred independent of osteogenic pre-induction, contained human cells, and appeared in 416 MSC/CDHA composites compared to 216 MSC/beta-TCP composites. ALP activity was significantly higher in samples with MSC versus empty controls (p<0.001). Furthermore, ALP was significantly (p<0.05) higher for all ceramics when compared to the DBM matrix. Compared to previous studies, overall bone formation appeared to be reduced possibly due to the strict human protocol. Ectopic bone formation in the novel biomaterial CDHA varied considerably with the cell pool and was at least equal to beta-TCP blocks.     

Report of the symposium

Summary The past decades have seen considerable shifts of emphasis in surgical care. The recognition that pus was not laudable, was followed by a realisation that not all complications were inevitable and that prophylaxis could effectively reduce the incidence of most common problems in the post-operative period. As anaesthesia has become safer, it has been possible to embark on more intricate and prolonged procedures and for sufficient time to be available to ensure adequate intraoperative care.These two phenomena have firstly increased the complexity of management in the post-operative period, and have brought this aspect of surgical care more obviously to the limelight. However, many separate disciplines are involved in the care of the patient post-operatively, and the Symposium was organised¹ to bring the different groups together to identify the areas of recent development in the different specialities and to integrate the overall care of the individual patient.Abbreviations ARDS adult respiratory distress syndrome - DIC disseminated intravascular clotting     

Possible coumarin-like mechanism of action for cephalosporins

Summary In three patients treated with cephalosporins (one patient with latamoxef, two patients with cefazedone) vitamin K₁ was injected to investigate whether this was followed by an increase in vitamin K₁ 2,3-epoxide plasma concentrations as compared to controls. Such a rise in K₁-epoxide concentrations in the plasma can be demonstrated following treatment with coumarins. This reflects an inhibition of the vitamin K₁-epoxide reductase in the liver. Coumarins are thought to induce hypoprothrombinaemia by such a mechanism. In all three patients we found a considerable increase in the vitamin K₁-epoxide plasma concentrations following injection of 10 mg vitamin K₁, whereas in normal subjects only traces of K₁-epoxide could be detected (<0.030 µg/ml). The K₁-epoxide concentrations found in our three patients treated with cephalosporins were 0.12, 0.16 and 0.19 µg/ml, respectively. This indicates that latamoxef or cefazedone might reduce clotting factor synthesis by a coumarin-like mechanism of action in these patients. Although the effect of cephalosporins in enhancing vitamin K₁-epoxide plasma concentrations is less than that of coumarins, it might cause severe hypoprothrombinaemia in the presence of latent vitamin K deficiency.Abbreviation PT prothrombin time - TT thrombin time - PTT partial thromboplastin time - PC platelet count - ICU intensive care unit - EEG electroencephalogram - K₁-epoxide vitamin K₁ 2,3-epoxide     

Niedrig dosierte Acetylsalicylsäure (100 mg/Tag) nach aortokoronarer Bypassoperation

Summary A prospective, randomized, doubleblind, placebo-controlled trial was conducted to evaluate the efficacy of Acetylsalicylic Acid (ASS) (100 mg/d, starting 24 h after operation) on vein graft patency. Sixty of 88 patients having undergone surgery entered the study; in 24 of 31 patients in the placebo group and 22 of 29 patients in the ASS-group angiography was performed 4 months postoperatively. There were no significant differences between the groups with respect to age, number of diseased vessels or previous myocardial infarctions. Mean number of grafts per patient was 2,2 (placebo) and 1,8 (ASS) for proximal anastomoses (p<0.10) and 3.4 (placebo) and 2.6 (ASS) for distal anastomoses (p<0.05). Graft occlusion rate for proximal anastomoses was less in the ASS-group, 10% (4/40), as compared with placebo 32% (17/53) (p<0.05). Graft occlusion rate for distal anastomoses was also less in the ASS group, 19% (11/57) as compared to 35% (28/81) in the placebo group (p<0.10). All grafts were patent in 16/22 patients in the ASS group but only in 9/24 in the placebo group (p<0.05). On designation of patients without postoperative angiograms but cardiovascular events as well as those with at least one graft occluded as failures, the incidence of the latter was 9/29 in the ASS group and 20/31 in the placebo group (p<0.05). Early postoperative bleeding was similar in both groups, no side effects of ASS were observed. In this trial with initiation of low — dose ASS therapy 24 h after operation, antiplatlet therapy reduced the graft occlusion rate significantly.

Teile dieser Studie wurden auf der 49. Tagung der Deutschen Gesellschaft für Herz- und Kreislaufforschung in Mannheim im April 1983 [32] und auf der 89. Tagung der Deutschen Gesellschaft für Innere Medizin, Wiesbaden, April 1983 [18] vorgetragen. Mit Unterstützung der Deutschen Forschungsgemeinschaft