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H Stoeckel

Publications and source records attributed to H Stoeckel.

At least 73 records · Page 4Linked to original sources
PubMed1985

[Animal experiment studies on the hemodynamic effect of adrenaline following intravenous and endobronchial administration].

The objective of this study was to find a dosage of endobronchially administered epinephrine with haemodynamic effects comparable to those after intravenous injection and therefore useful in cardiopulmonary resuscitation without an intravenous line. We found that 100 micrograms/kg epinephrine given endobronchially was almost as effective as an intravenous dose of 10 micrograms/kg concerning onset (10 seconds after intravenous injection, 15 seconds after endobronchial instillation) and maximum drug effect but with a remarkable prolongation of drug action. The instillation of 250 micrograms/kg epinephrine produced no significant increase in haemodynamic response. It was concluded, that the endobronchial instillation of epinephrine--in adequate dosage--is very useful in CPR without an intravenous line.

Animals↗
PubMed1985

Quantitation of the EEG and pharmacodynamic modelling of hypnotic drugs: etomidate as an example.

Six volunteers were subjected to an infusion of etomidate designed to generate linearly increasing plasma concentrations with a slope of 0.05 microgram ml-1 min-1. Cessation of infusion was determined by the occurrence of burst suppression patterns on the EEG. Infusion was restarted when the volunteers recovered personal and temporal orientation. This cycle was repeated twice. The drug input function, the pharmacokinetic parameters of etomidate as derived from a 'least squares' fit, and the median EEG frequency were used to establish a pharmacological model of etomidate. Two modelling procedures, the pharmacokinetic-pharmacodynamic, and the input-output modelling procedure, are compared. These procedures yield different results with respect to the kinetic data. As one possible explanation, a different pharmacokinetic behaviour of etomidate in the venous blood and at the site of drug action is discussed.

Adult↗
PubMed1985

Infusion strategies to investigate the pharmacokinetics and pharmacodynamics of hypnotic drugs: etomidate as an example.

Etomidate was administered to six healthy volunteers by microprocessor controlled infusions, to generate three cycles of linearly increasing plasma levels, with an anticipated slope of 0.05 microgram ml-1 min-1. The infusions were stopped when a deep hypnotic state was obtained, as indicated by burst suppressions in the EEG. The infusions were restarted when the volunteers were fully orientated to person, place and time. The mean (+/-SD) doses of etomidate delivered by the first, second and third infusion were 165 +/- 30, 137 +/- 25 and 157 +/- 26 mg, respectively. Certain clinical signs were observed and related to the plasma concentrations of etomidate. Pharmacokinetic analysis was undertaken using an open two-compartment model. The therapeutic window was in a range of plasma concentrations between 0.3 and 1.0 microgram ml-1 of etomidate. Pharmacokinetic analysis gave a volume for the central compartment of 50 +/- 11 litre, an apparent volume of distribution of 252 +/- 51 litre and a total clearance of 1693 +/- 504 ml min-1. Microprocessor controlled infusions can serve as a powerful tool for research in clinical pharmacology. The achievement of linearly increasing plasma levels of etomidate allowed further pharmacokinetic and pharmacodynamic modelling concepts to be realized.

Adult↗
PubMed1984

[Electrostimulation anesthesia in comparison with enflurane-nitrous-oxide inhalation anesthesia during gynecologic operations. 2. Hormonal reactions in the pre-, intra- and postoperative course].

This study describes the secretion of cortisol, growth hormone, prolactin and catecholamines before, under, and following gynaecological surgery in electrostimulation anaesthesia combined with nitrous oxide (ESA). The hormonal stress reactions of ESA were compared to inhalation anaesthesia with enflurane-nitrous oxide ( EFL ). Twenty-two patients undergoing laparotomy were allocated evenly to one of these procedures. In both groups serum levels for cortisol, growth hormone, and prolactin increased during surgery. Growth hormone showed a considerably higher increase during ESA at the end of the operation, whereas prolactin was higher at all periods of surgery during EFL . Cortisol, however, was identical for both groups. Renal excretion rates of adrenaline and noradrenaline were not significantly different. During surgery more metanephrine and normetanephrine were excreted in the urine under ESA than under EFL . There is no advantage with ESA intra- or postoperatively as compared to other routine procedures of anaesthesia for abdominal gynaecological surgery with regard to the so-called stress hormones or sympathetic activity.

Anesthesia, Inhalation↗
PubMed1983

[Biochemical findings in gestosis patients with pulmonary complications].

Lysosomal proteases from the granula of polymorphonuclear leucocytes play an important part in the development of the shock lung syndrome and its preliminary stages. If there is a local imbalance between the neutral proteinases (e.g. elastase) and its inhibitors, the interstitium consisting of collagenous fibres and glycosaminoglycanes is damaged. In 4 patients with gestosis and pulmonary complications it became evident that the plasma levels of the elastase-alpha 1-proteinase inhibitor complex correlate well with the clinical status and the x-ray findings. Significantly increased values are seen already prepartally; maximum values represent a severe interstitial oedema, and the drop of the values occurs parallel with the improvement of the clinical pattern. The increased consumption of inhibitors is expressed by the absence of the reactive increase of alpha 1-antitrypsin. By determining the elastase-alpha 1-PI complex it becomes possible to recognize the possible risk of development of an interstitial pulmonary oedema well in time, and the success of therapeutic measures is easily ascertained and controlled.

Adult↗
PubMed1983

[Enteral-parenteral feeding with high protein content in++ severe cranio-cerebral injuries].

Brain injured patients (BIP) usually have hugh losses of nitrogen in the early posttraumatic period. Investigations on protein catabolism in 10 young male BIP, not being moribund, were performed to answer the question whether N-loss can be minimized by an enteral-parenteral nutrition with high protein content (greater than 2 g protein/kg body weight). N-balance, 24-h urinary excretion of creatinin and 3-methylhistidine were measured for 8 days after the accident. The alimentary regime, being adapted to body weight, included for an adult 70-kg patient the intake of 470 g carbohydrates, 170 g aminoacids/proteins and 45 g fats per day (3040 kcal/day = 12700 kJ/day with 112 kcal/g N = 468 kJ/g N). Laboratory data indicated a stimulated muscle turnover rate and a considerable protein catabolism. The waste of endogenous sources could therefore not be prevented by the presented combined nutritional regime.

Adolescent↗
PubMed1982

Kinetics of high-dose i.v. diazepam.

The pharmacokinetics of high-dose i.v. diazepam were studied in two patients in an intensive care unit. The first patient received up to 240 mg of diazepam daily for 21 days while the second received 60 mg daily for 30 days. Plasma concentrations of diazepam and its major metabolite, desmethyldiazepam, were very large but, despite severe underlying disease and simultaneous administration of several other drugs, the half-lives of diazepam and desmethyldiazepam washout were consistent with those found in healthy persons. Washout half-lives in the first patient were, if anything, shorter than expected, possibly caused by simultaneous administration of phenobarbitone. Thus the kinetics of diazepam are apparently not altered by administration of large doses.

Adult↗
PubMed1982

[Clinical pharmacokinetics of alfentanyl (author's transl)].

In 7 patients (ASA class I and II) the pharmacokinetic behaviour after bolus injection of alfentanyl was investigated. The plasma decay curves in each patient could be described in terms of an open two-compartment model. The plasma half-life of alfentanyl in the alpha-phase was about 4 min, the elimination half-life was 70 min. The total volume of distribution was calculated to 33 1. The total plasma clearance amounted to 336 ml/min. Plasma protein binding of alfentanyl was about 92%; binding to human erythrocytes showed values less than 0.1%. The renal excretion of unchanged alfentanyl amounted to only 0.4% of the total dose in a time period of 24h. Clinical observations showed a minor effect on cardiovascular system; apnoea was seen in all patients. Chest wall rigidity was the main unwanted effect in 5 of 7 cases. The onset of action could be observed during the injection of 5 mg alfentanyl. The recovery period was extremely short. Therefore, alfentanyl seems to be of advantage for short surgical interventions; for longer lasting anaesthesia the development of an infusion model may be helpful.

Adult↗
PubMed1982

[Principles of clinical pharmacokinetics in anaesthesiology (author's transl)].

The principles of clinical pharmacokinetics of intravenous and inhalation anaesthesia and the correlation with pharmacodynamics are reviewed with special reference to the commonly used anaesthetic agents. Pharmacokinetics is regarded mainly as an aid towards optimization of dosage. Dosage rules based on pharmacokinetic principles, for repeated administration and infusion are outlined for the induction, maintenance and termination of anaesthesia. Interindividual variations and biological disposition are not taken into account. The kinetic processes common to intravenous and inhalation anaesthesia are presented in the form of a multiexponential function for constant concentrations.

Anesthesia, Inhalation↗
PubMed1982

[A microprocessor controlled infusion scheme for midazolam to achieve constant plasma levels (author's transl)].

In seven healthy volunteers a microprocessor controlled Infusion scheme for midazolam was established on the basis of pharmacokinetic analysis. The dosage regimen is composed of three different parts (BET-infusion): 1. a bolus initially injected for filling the central compartment 2. the elimination rate compensating the drug loss by elimination and 3. the transfer rate exponentially declining and balancing midazolam transfer to the peripheral compartment. --Thus, the amount of drug necessary for well-defined plasma levels can be minimized compared with other optimized dosage regimens like repetitive boluses or combinations of different infusion rates. By using this BET-infusion technique we were able to attain nearly constant therapeutic plasma levels from the beginning on (without initial overshoot). Unwanted cardiovascular and respiratory side effects could be prevented. The median of EEG-power spectra was used for monitoring EEG-background activity and for the correlation of plasma levels and pharmacological effect. The minimal plasma level producing a deep hypnotic effect with an EEG-median of less than 5 s-1 was about 0.5 microgram/ml. On the basis of these findings several modes of dosage are presented obtaining at least therapeutic midazolam concentrations of 0.6 microgram/ml for a secure hypnotic effect.

Adult↗
PubMed1981

[Clinical pharmacokinetics of midazolam, flunitrazepam and diazepam (author's transl)].

Diazepam, flunitrazepam and midazolam have different pharmacokinetic properties, their biological halflives for instance, being 24 to 48 hours, 4,5 hours and 2,5 hours respectively. Moreover, the total plasma clearances calculated for these drugs resulted in 30 ml/min for diazepam, 250 ml/min for flunitrazepam and 450 ml/min for midazolam. On the other hand, all three drugs were found to have nearly the same volumes of distribution (V1: 25 l, VdSS: 80-100 l). A tissue binding of over 90% of the drugs applied can further be computed from their high plasmaprotein binding action and their volumes of distribution. Of the 3 benzodiazepines investigated, diazepam reveals extremely complex pharmacokinetic effects which vary the duration of pharmacological responses very widely; besides drug interaction, enzyme induction and -inhibition it gives rise to the active metabolite N-desmethyl-diazepam (biological halflife 50 to 120 hours). In this respect however, the metabolic products of flunitrazepam and midazolam seem to be of minor clinical importance only. The pharmacokinetics of flunitrazepam will be presented as an example to discuss several modes of dosage.

Anti-Anxiety Agents↗
PubMed1981

[Pharmacokinetics of midazolam in man (author's transl)].

Plasma concentrations of midazolam (Ro 21-3981/001) were studied in six gynaecological patients following a 12.5 mg intravenous bolus injection of the drug for induction of anaesthesia. The plasma decay curves were found to be biphasic. Therefore the data were interpreted according to an open two compartment model. The fast distribution phase (alpha-phase) lasted about 30 to 45 min with a mean halflife of about 8-9 min. The half-life of the slow redistribution and elimination phase (beta-phase) amounted to a mean of about 150 min. The apparent volume of distribution of the cental compartment (V1) was calculated as 24.11 and the volume of distribution at steady state as 84.21 (Vd, ss). The volume of distribution in the beta-phase (Vd beta) ranged from 71.5 to 129.51 with a mean of 104.21. The total plasma clearance varied from 380 to 527 ml/min with a mean of 472 ml/min. It is suggested that the pharmacokinetic behavior is due to water-solubility and plasma protein binding of this new benzodiazepine.

Adult↗
PubMed1981

[Prevention of fentanyl rebound by administration of cimetidine (author's transl)].

Pre- and intraoperatively 8 orthopaedic patients were given cimetidine in order to raise the pH of gastric juice. Following an 0.5 mg i.v. bolus injection of fentanyl at the beginning of anaesthesia, the pH of the gastric juice and plasma concentrations of fentanyl were measured. After oral medication with cimetidine 400 mg on the evening prior to anaesthesia and an i.v. administration of 200 mg/h during the course of an enflurane-N2O-anaesthesia no secondary peak of plasma fentanyl concentration was observed. Thus it would seem possible to prevent fentanyl sequestration into the stomach and consecutively gastro-entero-systemic recirculation by administration of cimetidine. While duration and half-life of the alpha-phase are prolonged, the half-life of the beta-phase (150 min) remains almost unchanged. This pharmacokinetic effect is explained by an altered biodisposition.

Adult↗
PubMed1981

[Comparison of various empirical dosage suggestions for etomidate infusions on the basis of pharmacokinetic data (author's transl)].

The superposition principle of linear pharmacokinetics allows in a simple way simulation of blood levels and amounts of drug in other compartments for arbitrary dosage schemes provided the pharmacokinetic data are known. Assuming a 2-compartment model we compare for etomidate different dosage schemes as described in the literature with respect to the resulting course of blood levels or amounts of drug in different compartments. In conjunction with the reported clinical observations one can estimate minimal therapeutic blood levels and identify the compartment to which the site of action may be associated.

Anesthesia, Intravenous↗
PubMed1980

Infusion model for fentanyl based on pharmacokinetic analysis.

The calculation of pharmacokinetic parameters after a bolus injection of fentanyl allowed an i.v. infusion scheme which guarantees analgesia for the entire duration of surgery, with the advantage of steady plasma concentration and body content. In the initial phase after bolus injection, the serum concentration decreased rapidly for about 10 min, indicating extensive transfer to the peripheral compartment. This was followed by a slower elimination phase with a half-life of about 2 h. The total volume of distribution of 80 litre exceeded the body weight only slightly. The total plasma clearance was 500ml min-1. In developing a model for total i.v. anaesthesia we considered two different consecutive infusion rates. The pharmacokinetic model proved to be valid for all patients. The plasma concentrations duration anaesthesia coincided well with the predicted steady state plasma concentrations and provided continuous analgesia during operation.

Adult↗