Biomedical subjects

A E Nebauer

Publications and source records attributed to A E Nebauer.

7 recordsLinked to original sources

PubMed1996

[Propofol and etomidate-Lipuro for induction of general anesthesia. Hemodynamics, vascular compatibility, subjective findings and postoperative nausea].

UNLABELLED: Etomidate has become an important induction agent in high-risk patients because of its cardiovascular stability. Its unwanted side-effects such as pain on injection and thrombophlebitis could be significantly reduced by a new (medium chain triglyceride and soya bean) emulsion formulation. Propofol is solved in a mixture of long chain triglyceride and soya bean emulsion. In this double-blind, randomized study we compared the haemodynamic effects, the patients' sensations, signs of thrombophlebitis and postoperative nausea and vomiting (PONV) following injection of both drugs. METHODS: Following premedication with 2 mg Lormetazepam p.o. in 50 patients per group, anaesthesia was induced with either 0.51 mg etomidate in lipid emulsion or 3.04 mg propofol per kg bw. No opioid or benzdiazepine was given i.v. before induction. After injection of the tested drug, the cannula was removed. Changes in blood pressure and heart rate were recorded as well as signs of discomfort during and after injection (pain, burning, tension, cold). Venous sequelae were assessed for 5 days after injection to register signs of thrombophlebitis. RESULTS: Demographic data showed no difference between the two groups. After propofol more often a fall in blood pressure was seen. Pain (25 vs 1 pt), burning 19 vs 1), tension 15 vs 3), cold (35 vs 17) after injection was registered significantly more often in the propofol group, whereas myocloni predominated in the etomidate group (13 vs 6) P < 0.05, chi-squared-test). No difference was seen in PONV in either groups. CONCLUSION: Etomidate formulated in a medium chain lipid emulsion causes significant less discomfort for the patients than propofol, which is solved in a long chain formulation. Myocloni, however, occur significantly more frequently after etomidate than after propofol.

Anesthetics, Intravenous↗

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

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

[Pharmacodynamics and clinical adverse effects of mivacurium. The effect of oral premedication with H1/H2 antagonists].

Duration of neuromuscular block may be prolonged by H1/H2 antagonists. This study was designed to determine the influence of H1/H2 antagonist treatment on onset, duration and recovery after mivacurium chloride (MIV), a new nondepolarizing neuromuscular blocking agent with a relatively short duration of action, which is metabolized by human plasma cholinesterase (PChE). METHODS. After approval from the hospital ethical committee and written informed consent, 48 ASA I-II patients of either sex (ages 18-65 years, weight 45-100 kg) were included in this double blind study and randomly allocated to four groups of 12 each: group A, 0.105 mg/kg MIV (1.5 x ED95) and H1/H2 antagonist; group B, 0.105 mg/kg MIV and placebo; group C, 0.21 mg/kg MIV (3 x ED95) and H1/H2 antagonist; Group D 0.21 mg/kg MIV and placebo. Premedication consisted of 2 mg lormetazepam p.o., 300 mg ranitidine and 0.1 mg/kg dimetindene, or placebo p.o. Anaesthesia was induced with thiopentone (5-7 mg/kg) and maintained with N2O/O2 at a 65/35 ratio, enflurane (0.8-1.5%) and supplements of fentanyl. The ulnar nerve was stimulated with supramaximal 2 Hz train-of-four (TOF) every 10 s. Neuromuscular twitch response was recorded with EMG. Onset time (time from end of injection to maximal or total block), maximal block (%), T125 (time from end of injection to 25% recovery) were recorded after each dose, and recovery index (T1 from 25% to 75% recovery) and TOF70 (time from end of injection to TOF ratio of 70%), after the last dose. RESULTS. The four groups did not differ with respect to age, weight or height. There was no difference in the pharmacodynamics of mivacurium between the groups receiving H1/H2 antagonists and those receiving placebo. Following 1.5 x ED95 the onset was at 3.7 +/- 1.2 (H1/H2) and 3.8 +/- 0.9 min (placebo), respectively. Clinical duration (T125) was 13.1 +/- 3.4 and 12.8 +/- 3.4 min. 3 x ED95 led to a significant faster onset and longer duration (P < or = 0.05). Onset was at 1.9 +/- 0.7 (H1/H2) and 2.1 +/- 0.5 min (placebo), respectively, and clinical duration 19.1 +/- 6.1 and 19.3 +/- 3.8 min. Duration of repetitive doses (10.1 +/- 5.3 min), recovery index (6.8 +/- 2.9 min) and interval from last dose to spontaneous recovery (22.4 +/- 7.0 min) did not differ between groups. Three patients in group D (placebo and 0.21 mg/kg MIV) had haemodynamic changes of over 20% from baseline. Flush and erythema were significantly less pronounced after H1/H2 premedication than after placebo (4 vs 12 pts). CONCLUSIONS. Our results suggest that time of onset and clinical duration of effects of MIV are not altered by dimetindene and ranitidine. The duration depends more heavily on the dose of MIV. The recovery of neuromuscular function, once it has begun, is prolonged neither by MIV nor by H1/H2 antagonists. As MIV is mainly broken down by PChE, it is evident that its duration of action is more prolonged by atypical PChE activity than by interaction with other drugs. Oral H1/H2 premedication may diminish haemodynamic side-effects and clinical signs of histamine release.

Administration, Oral↗

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↗

PubMed1992

[The action of S-(+)-ketamine on serum catecholamine and cortisol. A comparison with ketamine racemate].

The S(+)-isomer of ketamine has about twice the anaesthetic potency of the commercially available racemic mixture of ketamine. It is assumed that the known side-effects of ketamine are significantly reduced when administering half the usual dose with the same pharmacodynamic effect [17, 25]. The aim of the present study was to determine the haemodynamic effects, the catecholamine and cortisol plasma levels after administration of equally potent doses of S-(+)-Ketamine and racemic mixture of ketamine. In addition, the effect of premedication with i.v. midazolam was assessed. METHOD. After approval by the ethics committee and written informed consent, 30 healthy male volunteers were randomly allocated to three groups (n = 10). Group 1 received 2 mg/kg ketamine racemate, group 2 1 mg/kg S-(+)-Ketamine, and group 3 1 mg/kg S-(+)-Ketamine 5 min after i.v.-premedication with 0.1 mg/kg midazolam. Non-invasive blood pressure (BP) and heart rate (HR) were continuously recorded. Blood samples were drawn 7 min before, and 2, 4, 8, 16, 32, 64 and 128 min after drug administration. Plasma epinephrine and norepinephrine (NE) levels were determined by HPLC and cortisol plasma levels by RIA. Data were analysed with the Kruskal-Wallis test (P < or = 0.05) for differences between groups. RESULTS. HR and BP showed a significant rise after injection of racemate and isomer, without any significant differences between groups. This was also seen for norepinephrine and cortical plasma levels. Epinephrine levels, however, differed between groups, showing a significant rise after racemate compared to isomer. Premedication with midazolam, in contrast, blunted major haemodynamic and hormonal changes. DISCUSSION. The haemodynamic changes did not differ between the racemate and isomer group despite a reduced isomer dose. HR and BP rise were similar, although epinephrine levels were significantly lower after isomer than racemate. Hence we assume that the increase in the haemodynamic parameters were mainly caused by NE. Midazolam apparently prevented the centrally mediated sympathetic stimulation caused by ketamine and its isomers. Therefore, i.v. premedication with midazolam should be applied when racemate or isomer is used, especially in high-risk cardiac patients.

Adult↗