Biomedical subjects

R Hoernecke

Publications and source records attributed to R Hoernecke.

16 recordsLinked to original sources

PubMed2004

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↗

PubMed1999

Solvent for etomidate may cause pain and adverse effects.

We tested the hypothesis that the solvent for etomidate was a factor in the incidence of pain and other side effects after injection, and that these were associated with histamine release. Nine of 10 volunteers who received etomidate in a propylene glycol formulation reported moderate to severe pain on injection; only one of 10 subjects who received a lipid emulsion formulation reported mild pain (P < 0.05). The incidence of venous sequelae in the injected vein over the next 8 days was 50% in the propylene glycol group and 0% in the lipid emulsion group (P < 0.05). In one volunteer in the propylene group, there was a 13-fold increase in histamine concentrations and in one subject a four-fold increase. In the lipid emulsion group, no volunteer had an increase in histamine concentrations > 1 ng ml-1. We conclude that etomidate formulated in propylene glycol may cause direct injury to vascular endothelium resulting in pain and venous sequelae, whereas etomidate in lipid emulsion does not. There was no relationship between pain or venous sequelae and histamine release.

Adult↗

PubMed1998

Onset time, endotracheal intubating conditions, and plasma histamine after cisatracurium and vecuronium administration.

UNLABELLED: Cisatracurium is a nondepolarizing muscle relaxant with a slow onset. We performed a prospective, randomized, double-blind clinical trial in 60 patients (ASA physical status I or II) to assess whether cisatracurium (0.15 or 0.25 mg/kg) or vecuronium (0.15 mg/kg), administered as a bolus immediately after induction of anesthesia with fentanyl and thiopental, would provide a faster onset time and better tracheal intubating conditions than previously reported. We sought to determine whether patients given muscle relaxants in this commonly used induction sequence would exhibit cutaneous, systemic, or chemical evidence of histamine release. Onset time of the relaxants was determined by using mechanomyography. Intubating conditions were scored on a defined interval scale by an anesthesiologist blinded to the relaxant administered. Heart rate and arterial blood pressure were measured noninvasively every minute from 10 min before to 5 min after the application of the muscle relaxant. Mean (+/- SD) onset times for 0.25 mg/kg cisatracurium (68.3 +/- 19.5 s) and for 0.15 mg/kg vecuronium (69.5 +/- 29.2 s) were significantly different from those in the 0.15 mg/kg cisatracurium group (105 +/- 41.2 s). The intubating conditions were better with the larger dose of cisatracurium or vecuronium (P < 0.03). Although plasma histamine levels were not statistically different among groups, levels >1 ng/mL were observed in 5 of 40 patients who received cisatracurium but in none of the 20 patients who received vecuronium. There were no significant hemodynamic differences among the groups. In a dose of 0.25 mg/kg, cisatracurium has as rapid an onset time as vecuronium 0.15 mg/kg, but the former shows evidence of histamine release. IMPLICATIONS: Cisatracurium has been considered a drug with a relatively slow onset but that has the significant benefit of being devoid of chemically mediated histamine release. In this study, we describe an onset time faster than previously reported when cisatracurium was given immediately after thiopental. We also note that several patients had abnormal histamine levels after cisatracurium administration.

Adult↗

PubMed1997

Administration of H1 and H2 antagonists for chemoprophylaxis: a double-blind, placebo-controlled study in healthy volunteers.

A double-blind, placebo-controlled trial was performed to establish the duration of action of antihistamines and their ability to attenuate the adverse affects associated with histamine release. Thirty volunteers were assigned randomly to receive either placebo or a combination of the H1 blocker dimetindene maleate (0.1 mg/kg) and the H2 blocker cimetidine (5 mg/kg). A bolus dose of histamine (450 ng/kg) was given 15 minutes after antihistamine or placebo treatment and repeated after 2, 4, and 6 hours. Cardiovascular variables, plasma histamine levels, cutaneous manifestations, and objective and subjective signs and symptoms associated with histamine release were determined before and after each histamine injection. Although many of the signs of histamine release, including erythema and metallic taste, could be attenuated effectively for 6 hours with antihistamine treatment, the protection against histamine-induced flush and headache diminished after 2 hours. Statistically significant protection against histamine-mediated tachycardia persisted for only 2 hours. Antihistamine treatment significantly reduced the increase in plasma histamine levels after the first histamine injection but did not alter the levels after subsequent histamine injections. The currently recommended administration regimen for prophylaxis with antihistamines is insufficient to prevent histamine-mediated side effects, and additional doses may be required after 4 hours to achieve appropriate chemoprophylaxis.

Adult↗

PubMed1997

[Cisatracurium--is the stereoisomer an "ideal" relaxant? Histamine liberation and tryptase determination after bolus administration of cistracurium: a comparison with vecuronium].

UNLABELLED: Cisatracurium (51W89, Nimbex, Glaxo-Wellcome), an intermediate-acting non-depolarizing neuromuscular blocking agent, is a stereoisomer of atracurium. Histamine releasing propensities and serum tryptase level have been investigated after administration of cisatracurium (3 x ED95, 5 x ED95) or vecuronium (3 x ED90) in surgical patients. METHODS: After approval by our institutional review board, 62 patients (ASA I-II) were randomly assigned to three groups to receive either 3 x ED95 or 5 x ED95 cisatracurium, or 3 x ED90 vecuronium as a rapid bolus. A prick test was done the day before by scarification of the skin in the forearm. After premedication with 2 mg lormetazepam, anaesthesia was induced with thiopentone (4-12 mg/kg) and maintained with O2/N2O and isoflurane (1.5-2 vol.%). Six minutes after thiopentone, the patients received the relaxant and after further 6 min 0.1-0.2 mg fentanyl was given and the trachea was intubated. Heart rate (HR) and blood pressure (BP) were monitored every minute. Blood samples for histamine were withdrawn 5 min prior 3 and 5 min after each drug administration (thiopentone, relaxants). Plasma histamine was measured by radioimmunoassay (RIA) with a sensitivity of approximately 10 pg/ml. Additionally, serum tryptase was measured by RIA at baseline (-10 and -1 min) and 15 and 60 min after the relaxant administration. Levels for histamine > 1000 pg/ml and for tryptase > 2 micrograms/ml were considered significant. Cutaneous signs of histamine release were documented. RESULTS: Ten patients showed a positive prick-test reaction. Only after thiopentone some cutaneous signs (4 flush, 1 erythema) of histamine release were observed. There were no cutaneous signs of histamine release correlating with cardiovascular changes. Analysis of the blood samples demonstrated no significant increase in the histamine level in all three groups. Only in 1 patient was a significant higher histamine level (1133 pg/ml) measured 5 min after 5 x ED95 cisatracurium. All measurements of serum tryptase were within the physiological limits. DISCUSSION: In this study, with the particular time course of drug administration, neither cisatracurium nor vecuronium increased plasma histamine levels. Only after 5 x ED95 cisatracurium was 1 elevated histamine level documented after 5 min. In several studies increased histamine levels have been described, but without clinical manifestations. It is known that cutaneous signs can occur without increased plasma histamine levels due to the structural heterogeneity of mast cells. The cutaneous reactions in this study were caused by thiopentone. The tryptase values were within normal limits even in the patient with histamine release. No relationship between the positive results in the prick test and the incidence of cutaneous reactions and/or histamine release for drugs used in the induction of anaesthesia was observed. Whether cisatracurium has a potential for immunologic release is unknown.

Anesthesia, Intravenous↗

PubMed1997

Haemolysis after etomidate: comparison of propylene glycol and lipid formulations.

We sought to determine if the solvent in the formulation of etomidate is responsible for haemolysis in patients. In a randomized, prospective, double-blind study of 49 patients undergoing otolaryngological surgery, patients received etomidate dissolved in propylene glycol or in lipid emulsion. Concentrations of free haemoglobin and haptoglobin were measured before and for up to 360 min after injection of etomidate. Free haemoglobin concentrations increased by 216.8 mg litre-1 in patients who received the propylene glycol formulation and by 11.8 mg litre-1 in the lipid emulsion group (P < or = 0.0004). Correspondingly, reductions in haptoglobin concentrations were significantly greater in the propylene glycol group (P < or = 0.002). We conclude that with respect to haemolysis, lipid emulsion is superior to propylene glycol as a solvent for etomidate.

Anesthetics, Intravenous↗

PubMed1997

The lack of histamine release with cisatracurium: a double-blind comparison with vecuronium.

A prospective, randomized, double-blind study was performed in 62 patients (ASA Classes I and II) treated with either 0.15 or 0.25 mg/kg cisatracurium or 0.15 mg/kg vecuronium administered as a rapid bolus. We wished to determine whether the muscle relaxants caused cutaneous, systemic, or chemical evidence of histamine release. Six minutes after induction of anesthesia with thiopental, patients received one of the muscle relaxants over 5 s. Plasma histamine levels were measured by radioimmunoassay after thiopental administration and 3 and 5 min after the administration of the relaxant. Additionally, plasma was assayed for tryptase, a marker of mast cell release. Cutaneous manifestations to both thiopental and the muscle relaxant were graded by an independent observer. Arterial blood pressure and heart rate were measured every minute. Although systolic and diastolic blood pressure decreased and heart rate increased significantly after thiopental administration (P < 0.0001), there were no further hemodynamic changes after either cisatracurium or vecuronium. One patient who received 0.25 mg/kg cisatracurium exhibited a slight elevation in plasma histamine level 5 min after hemodynamic changes. Cutaneous signs of histamine release were noted in five patients after thiopental administration (flush in four, erythema in one), but no further cutaneous reactions were observed after administration of either cisatracurium or vecuronium. We conclude that cisatracurium and vecuronium do not cause systemic or cutaneous histamine release. Tryptase levels showed no evidence of mast cell degranulation.

Atracurium↗

PubMed1996

[Cardiovascular effects after bolus administration of cisatracurium. A comparison with vecuronium].

UNLABELLED: Cisatracurium-one of the ten stereoisomers of atracurium-is an intermediate long-acting non-depolarizing neuromuscular blocking agent. Cardiovascular reactions have been described after administration of cisatracurium or vecuronium in surgical patients. METHODS: After approval by our institutional review board, 62 patients (ASA I-II) were randomly assigned to three groups to either receive 3xED95 or 5xED95 of cisatracurium or 3xED90 of vecuronium prior to intubation as a bolus. After oral premedication with 2 mg lormetazepam anaesthesia was induced with thiopental (4-12 mg/kg) and maintained with O2/N2O and isoflurane (1.5%-2%). Six minutes after administration of thiopental, patients received the muscle relaxant. Six minutes later 0.1-0.2 mg fentanyl was given and the trachea was intubated. Heart rate (HR) and blood pressure (BP) were monitored every minute. Changes of heart rate or blood pressure > 20% compared to baseline were defined as clinically significant. RESULTS: After application of the study drug, median values of blood pressure and heart rate were stable. For each muscle relaxant, there were several patients who had statistically significant cardiovascular changes. After 3xED95 cisatracurium, 3 of 21 patients exhibited haemodynamic changes > 20% (2 exhibited hypotension and 1 tachycardia), while in the high-dose cisatracurium group 2 of 21 patients demonstrated a tachycardia that was predetermined to be statistically but not clinically significant. In the vecuronium group, 2 of 20 patients sustained statistically significant hypotension and 1 patient had statistically significant tachycardia. The frequency of all individual cardiovascular changes after the application of the muscle relaxant was not dose-dependent. CONCLUSION: After the administration of cisatracurium in two different doses (3xED95 and 5xED95) or vecuronium (3xED90) only minor cardiovascular changes were observed. Both drugs proved to be safe for use during induction of anaesthesia in patients ASA I-II. With regard to its cardiovascular effects, cisatracurium shares with vecuronium the requirements of an ideal muscle relaxant.

Adolescent↗

PubMed1995

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

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.

Adolescent↗

PubMed1994

Are hypotension and rash after atracurium really caused by histamine release?

A prospective, randomized, double-blind study was performed in 40 patients (ASA class I-III) treated with atracurium to ascertain whether histamine release caused hemodynamic or cutaneous changes. The treated group of 20 patients was premedicated with the H1 antagonist dimetindene (0.2 mg/kg) and the H2 antagonist ranitidine (1.25 mg/kg); the control group of 20 patients received saline. Six minutes after the induction of anesthesia with thiopental/fentanyl, patients received atracurium 0.5 mg/kg over 5 s. Plasma histamine levels were measured fluorometrically 5 min after administration of thiopental/fentanyl and 2 and 5 min after atracurium. Arterial blood pressure and heart rate were recorded every 2 min. Histamine levels (0.24 ng/mL) did not change significantly after thiopental/fentanyl. In the control group, 2 min after injection of atracurium, plasma histamine levels were 0.76 +/- 0.76 ng/mL, and in the antihistamine-treated group, 0.39 +/- 0.24 ng/mL (P < 0.05 control versus treated), suggesting that pretreatment with antihistamines may attenuate atracurium-induced histamine release. Systolic and diastolic blood pressure decreased significantly in both groups after thiopental (P < 0.05), but did not decrease further after the administration of atracurium. There were cutaneous manifestations in 7 of 20 patients in the control group and in none of the 20 patients treated with H1 and H2 antagonists (P < 0.0005). We conclude that atracurium caused modest histamine release in our patients but that the decrease in arterial blood pressure may have been due, in part, to thiopental. Cutaneous manifestations of histamine release did not correlate with hemodynamic events or with plasma histamine levels, but were prevented with antihistamine pretreatment.

Adolescent↗

PubMed1994

A comparison of two formulations for etomidate, 2-hydroxypropyl-beta-cyclodextrin (HPCD) and propylene glycol.

The unphysiologic osmolality of commercial preparations of etomidate dissolved in propylene glycol has limited its use as a drug to induce anesthesia. We wanted to determine whether hydroxypropyl-beta-cyclodextrin (HPCD) is a more suitable solvent than propylene glycol by comparing pharmacokinetics, pharmacodynamics, and side effects of etomidate preparations in each solvent. Twenty-four healthy, male volunteers, randomly assigned to either the male volunteers, randomly assigned to either the HPCD or the propylene glycol group received etomidate, 0.3 mg/kg, dissolved in one of the two test solvents. We recorded arterial blood pressure, heart rate, electrocardiogram, electroencephalogram, pain on injection, myoclonic movements, and venous sequelae. Systolic and diastolic blood pressure and heart rate were similar in both groups. Frequency and severity of pain on injection differed significantly between groups. In the propylene glycol group, five subjects suffered venous sequelae: in three, thrombophlebitis resolved after 5 days; in one, after 10 days; and in the other, after 12 days. In the HPCD group, only one subject suffered severe pain on injection and none had venous sequelae. We conclude that HPCD may be superior to propylene glycol as a solvent for etomidate. HPCD is associated with less pain, less thrombophlebitis, and no hemolysis without clinically important alteration of pharmacokinetics or pharmacodynamics of etomidate.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1993

[Treatment of migraine attacks: combination of dihydroergotamine tartrate and paracetamol in comparison with individual drugs and placebo].

BACKGROUND AND METHODS: In a multi-center, double-blind, placebo-controlled crossover study safety and efficacy of oral dihydroergotamine tartrate (DHE) 2 mg, paracetamol 1000 mg, and a fixed combination of these two agents was compared for the relief of migraine attacks. The effect of the four different treatments on severity and duration of migraine headache was assessed pretreatment and at one and two hours post-treatment in the patient diary (10 point numerical rating scale 0 = no pain, 9 = unbearable pain). Nausea, vomiting, photophobia, phonophobia, and adverse events were also recorded in the patient diary. RESULTS: For 288 patients (81% female, 19% male) of 474 enrolled the results of four consecutive migraine attacks could be evaluated; 186 patients were excluded from the analyses because of missing data or protocol violations. Compared with placebo, headache severity was significantly reduced after all three treatments at one and two hours and all three treatments resulted in statistically significant rapid relief of pain, proving a superior effect of the combination over the mono agents. Duration of headache was significantly shorter when the combination was taken and the number of patients having either no headache or a reduction of pain of more than 50% after one and two hours was bigger in the combination group. Eight adverse events were experienced in patients during placebo treatment, seven in patients during treatment with the fixed combination, five in patients during DHE treatment and two in patients during paracetamol treatment. All adverse events were transitory and none was serious. CONCLUSION: The oral combination of 2 mg DHE and 1000 mg paracetamol is safe and effective in the treatment of acute migraine attacks and should be first choice of therapy in patients who do not respond to mild analgesics like paracetamol alone.

Acetaminophen↗

PubMed1993

Histamine release after injection of benzodiazepines and of etomidate. A problem associated with the solvent propylene glycol.

Many drugs, especially when given in rapid sequence can cause histamine release. Ten healthy volunteers were premedicated with diazepam 10 mg.70 kg-1 i.v. and lormetazepam 1 mg.70 kg-1 i.v., respectively, 30 min prior to etomidate 0.15 mg.kg-1 i.v. in a single-blind, crossover study. The benzodiazepine lormetazepam and the hypnotic etomidate caused distinct increases in histamine plasma levels in two subjects. Maximal histamine levels after lormetazepam were 2.05 and 2.7 ng.ml-1, and after etomidate 1.85 and 3.2 ng.ml-1, respectively. Both drugs are solved in propylene glycol, a solvent that conveys very high osmolality (lormetazepam 6,750 mosm.kg-1, etomidate 4,900 mosm.kg-1). Clinical symptoms, like tachycardia, hypotension or allergic reactions, associated with similar histamine levels were not seen in either case. This limited histamine release appears to be caused by osmotic damage of tissue and blood cells.

Adult↗

PubMed1993

[Perioperative enzyme therapy. A significant supplement to postoperative pain therapy?].

METHODS: Following ethics committee approval and with written informed consent, 80 patients (61 female, 19 male) were randomly allocated in this double-blind, placebo-controlled, parallel group study to two groups of 40 patients each. The treatment group received a compound of proteolytic, glycolytic, and lipolytic enzymes and rutoside (Wobenzym), while the control-group received placebo. Efficacy and tolerance of the study medication was examined before and after day case surgery for the carpal tunnel syndrome. Medication was given 10 tabs t.i.d. for 15 days, starting 7 days before surgery. Pain intensity (visual analogue scale), intake of analgesics, and tolerance of the study medication were recorded daily and treatment differences between the two groups were statistically evaluated. RESULTS: Comparison of demographic data of all enrolled patients showed no significant difference between the two groups. In the enzyme group, pain scores were lower on the day of operation and for the following 5 days but did not differ significantly from the control group; however, patients of the enzyme group took significantly less analgesics and experienced significantly earlier pain relief than those of the control group, thus demonstrating a pain-reducing effect of the enzyme compound. Only few side effects were reported in both groups, none of them serious. CONCLUSION: Enzyme therapy is an effective and safe adjuvant treatment for the control of postoperative pain.

Adult↗

PubMed1992

Does etomidate cause haemolysis?

Etomidate is currently presented as a solution with propylene glycol as solvent. This organic solvent has an extremely high osmolality and is probably responsible for some of the side effects of this drug. In order to detect haemolysis, an indication for cell damage, we have measured serum haptoglobin concentrations in 12 healthy male volunteers after administration of etomidate 0.3 mg kg-1. Six subjects received etomidate in propylene glycol (EtoPG) with an osmolality of 4965 mosmol kg-1 and six received etomidate in lipid emulsion (EtoLip, 400 mosmol kg-1). Haptoglobin concentrations in the EtoPG group decreased by 44% and 43% from baseline values at 2 and 4 h after administration, respectively, and were significantly smaller than after administration of EtoLip. After 24 h, haptoglobin concentrations had not reached baseline values.

Adult↗

PubMed1992

Osmolalities of propylene glycol-containing drug formulations for parenteral use. Should propylene glycol be used as a solvent?

Propylene glycol (PG) is a widely used vehicle for water-insoluble drugs. Injection of drugs formulated with this solvent often results in pain, thrombosis, or thrombophlebitis that can be reduced by premedication with local anesthetics or opioids. Because osmolality and pH that are unphysiologic may cause these adverse effects, we assessed the contribution of PG to the osmolality of parenteral drug formulations. Osmolality of PG measured in distilled water showed that PG content and osmolality were directly related: 2% wt/vol PG, 264 mOsm/L; 100% PG, 15, 200 mOsm/L. The osmolalities of commercially available preparations of drugs dissolved in PG ranged from 365 mOsm/L (2% PG content) to 12,800 mOsm/L (83.46% PG), with most above 1000 mOsm/L. Replacement of PG by a solvent with lower osmolality in Germany has effectively reduced the incidence of side effects for one drug. Until PG can be replaced in drugs, we recommend diluting drugs in a large volume of saline solution; this may help to minimize the undesirable effects of this solvent.

Anesthesiology↗