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Influence of H1- and H2-receptor antagonists on the circulatory system and on the endogenous plasma histamine concentrations in dogs.

The effects of the H1-receptor antagonist dimethpyrindene and the H2-receptor antagonist burimamide on circulatory and respiratory parameters and on plasma histamine levels were tested in 21 mongrel dogs. Both drugs released histamine. The incidence for this effect was 10/11 in the case of dimethpyrindene and 5/10 in the case of burimamide. Following dimethpyrindene all animals showed arterial hypotension, pulmonal hypertension, decrease in peripheral resistance and hyperventilation. The portal venous pressure was increased in dogs reacting by a histamine release. Following burimamide both an initial arterial hypertension and a subsequent hypotension were observed the latter being more pronounced in the group with histamine release. In this group the portal venous pressure raised considerably. In the non-reacting animals cardiac output was elevated, probably due to a release of catecholamines. It seemed remarkable that the effect of exogenous histamine on portal venous pressure was completely blocked by dimethpyrindene, but not the action of histamine released by the drug itself. It is concluded that the effects of anti-histaminic drugs on possibly histamine-induced physiological and pathophysiological processes should be interpreted very carefully as far as their specificity is concerned.

Animals↗

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 patients received placebo. Anaesthesia and invasive haemodynamic monitoring were standardised in all patients. Haemodynamic parameters, plasma histamine concentrations and clinical symptoms were determined 1 min after skin incision, as well as 5 and 20 min after mesenteric traction. Statistical analyses were performed using the Student's t-test, Chi2-test for incidences and Mann-Whitney-U-test for continuous data. RESULTS: The incidence of histamine release was 55.5% (5/9) in the placebo group vs. 37.5% (3/8) in the antihistamine group (p > 0.05, Chi2-test). Plasma histamine levels (mean +/- SD) were higher in the placebo group than in the antihistamine group at 5 and 20 min after mesenteric traction but the difference did not reach statistical significance. Arrhythmias were significantly more frequent in the placebo group (6 times) than in the antihistamine group (none) (p = 0.005 Chi2-test). Systolic blood pressure was not statistically different between groups (e.g. 5 min after mesenteric traction, mean +/- SD; placebo 111 +/- 20 mm Hg vs. antihistamines 119 +/- 35 mm Hg). However, in the placebo group the haemodynamics only stabilised 5 min after mesenteric traction when anaesthetic gas concentration was repeatedly reduced and vasopressor/volume administration was increased (placebo-group = 20 times/antihistamine-group = 8 times, p = 0.001, t-test). CONCLUSION: Prophylactic administration of antihistamines reduced the incidence of histamine release as well as the incidence of arrhythmias and the amount of stabilising measures during mesenteric traction. Prophylaxis with H1 and H2 antihistamines may be of perioperative benefit and should therefore be considered in AAA-surgery.

Aortic Aneurysm, Abdominal↗

Premedication with H1 and H2 blocking agents reduces the incidence of postoperative nausea and vomiting.

OBJECTIVE: Patients undergoing anaesthesia and surgery frequently complain about postoperative nausea and vomiting (PONV). Whether pretreatment with H1 and H2 blocking agents reduces the incidence of PONV remains controversial. To answer this question, we performed a randomised, prospective, placebo-controlled clinical study to evaluate the efficacy of a premedication with H1 and H2 receptor antagonists. MATERIAL AND SUBJECTS: 1149 patients (both sexes) undergoing surgery were randomly assigned to three treatment groups and one control group. Patients in the treatment groups were premedicated with the following H1 + H2 receptor antagonists:Group 1 (n = 335): 5 mg/kg cimetidine i.v. + 0.1 mg/kg dimetindene i.v. 20 min before induction of anaesthesiaGroup 2 (n = 337): 1.25 mg/kg ranitidine i.v. + 0.1 mg/kg dimetindene i.v. 20 min before induction of anaesthesiaGroup 3 (n = 316): 300 mg ranitidine p.o. + 0.1 mg/kg dimetindene i.v. 1 to 2 h before induction of anaesthesiaGroup 4 (n = 161): 20 ml saline solution i.v. 20 min before induction of anaesthesiaPatients from the treatment groups 1, 2 and 3 received regional or general anaesthesia depending on the clinical decision. All control patients received general anaesthesia consisting of fentanyl, a thiobarbiturate, enflurane, nitrous oxide, oxygen, and vecuronium. RESULTS: The incidence of nausea and vomiting was 8.5%, 6.8% and 5.4% in patients from the treatment groups (1, 2 and 3) who underwent general anaesthesia (n = 545), with no statistically significant differences between groups. The incidence of nausea and vomiting in the control group (n = 161) was 28.3% (nausea) and 27.5% (vomiting), respectively. In patients who underwent regional anaesthesia (n = 443), the incidence of nausea and vomiting was 2.5% and 1.1%, respectively. CONCLUSIONS: Premedication with H1 and H2 blocking agents significantly reduces the incidence of postoperative nausea and vomiting.

Adult↗

[Systemic mastocytosis. Classification, symptoms, therapy].

BACKGROUND: Systemic mastocytoses are a group of diseases, which are characterized by accumulation and unusual growth of mast cells infiltrating two different organs or types of tissue. Two case reports are introduced. CLASSIFICATION: According to the new WHO classification of 2000, mastocytoses are separated into cutaneous and systemic mastocytoses. Systemic mastocytosis is subdivided into an indolent course with good prognosis and four subgroups with poor prognosis (systemic mastocytosis with associated clonal hematologic non-mast-cell disease, aggressive systemic mastocytosis, mast cell leukemia, and mast cell sarcoma). GENETICS: Systemic mastocytoses are clonal disorders of mast cells and their progenitor cells, which may show point mutations of the protooncogene c-kit. This gene codes for the stem cell receptor (CD117). THERAPY: Therapy of systemic mastocytosis depends on patient's symptoms. There is no known cure of the disease. Besides diet and avoidance of skin irritations, symptoms are treated with H(1)- or H(2)-blockers, steroids, leukotriene receptor antagonists, and PUVA therapy. If patients suffer from systemic reactions such as hypotension or syncope, epinephrine solution should be prescribed for emergency use.

Adult↗

Incidence and clinical importance of perioperative histamine release: randomised study of volume loading and antihistamines after induction of anaesthesia. Trial Group Mainz/Marburg.

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 relevant, or life-threatening from observers' records of the anaesthesia and the actions taken by the anaesthetists. Disturbances that were accompanied by significant rises in plasma histamine were further designated histamine-related, and those that were not were designated histamine-unrelated. Anaesthetists, observers, and designators were blinded to whether or not the patients had received antihistamines and to which solution was used for circulatory volume loading. Clinically relevant or life-threatening histamine-related disturbances occurred in 8% of the patients who after induction of anaesthesia received Ringer without antihistamines, in 26% of those who received Haemaccel without antihistamines, and in 2% or less of those who received antihistamines (p < or = 0.0001). There were 4 life-threatening histamine-related disturbances, all in patients who received Haemaccel without antihistamines (p < 0.01). Histamine-unrelated disturbances occurred in 16% overall, with no obvious effect of Haemaccel or antihistamines. The histamine-related disturbances under anaesthesia were remarkable for their severity (even with small rises in histamine concentrations), for the prevalence of bradycardia, and for the absence of skin signs. Their likelihood and severity were increased in patients with tumours. The results of the trial make a case for routine prophylaxis with antihistamines as part of anaesthetic management.

Adolescent↗

Resolution improvement by use of carboxymethyl-beta-cyclodextrin as chiral additive for the enantiomeric separation of basic drugs by capillary electrophoresis.

Three beta-cyclodextrin derivatives--carboxymethyl-, dimethyl- and hydroxypropyl-beta-cyclodextrin--were tested as chiral selectors for the enantioseparation of seven basic drugs in free solution capillary electrophoresis, using buffers made of 100 mM phosphoric acid adjusted to pH 3.0 with triethanolamine in fused silica capillaries thermostatted at 15 degrees C. The best results with respect to chiral resolution were obtained with carboxymethyl-beta-cyclodextrin (CMCD): the enantiomers of all compounds examined were completely resolved with this beta-cyclodextrin derivative. The influence of the CMCD concentration on the migration times, the apparent electrophoretic mobility difference and the resolution of the drug enantiomers was investigated thoroughly. Particularly impressive resolution values, up to 23.7, were obtained for several compounds in these capillary electrophoretic systems, using CMCD in the 5-15 mM concentration range.

Anesthetics, Local↗

Pruritic urticarial papules and plaques of pregnancy (PUPPP)--a case report.

Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a rare dermatosis of unknown etiology that is most frequently seen in primiparas and twin/multiple pregnancies. The prognosis is favorable. We report a case of PUPPP in a primipara and review the clinical signs, differential diagnosis, possible etiologic factors, diagnosis, and therapy.

Administration, Topical↗

[Premedication with H1- and H2-receptor antagonists for intravenous urography using contrast media].

Intravenous urography using Telebrix was performed on 500 patients. Two hundred patients (group I) received no pre-medication; 300 patients (group II) were premedicated with H1 and H2 receptor antagonists. All patients were examined for signs of contrast reactions, blood pressure, pulse rate and plasma histamine levels. These were measured before and three minutes after the administration of the antihistamine substances and/or the contrast medium, and also at the end of the examination. Following the administration of H1 and H2 receptor antagonists, a slight, transient and insignificant rise in plasma histamine could be demonstrated. Both groups showed a significant rise in plasma histamine levels after the injection of the contrast medium. Although the pre-medicated group contained a higher percentage of high risk patients, there were significantly fewer patients with contrast reactions. Pre-medication with H1 and H2 receptor antagonists in high risk patients is therefore advisable.

Adult↗