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A Doenicke

Publications and source records attributed to A Doenicke.

At least 55 records · Page 3Linked to original sources
PubMed1991

Controlled clinical trials and cross-sectional studies with plasma histamine measurements and histamine receptor antagonists: solving the problem of preoperative H1- + H2-prophylaxis by asking new questions?

The problem of a preoperative histamine H1- + H2 - prophylaxis was tackled by a group of new studies including randomized controlled clinical trials and cross-sectional studies with plasma histamine measurements and administration of H1- + H2 - antagonists to a control group. The first study demonstrated serial histamine release in the induction of anaesthesia up to 4 times in a single patient. Basal plasma histamine levels in resting subjects fell below 100 pg/ml during the time necessary for preparation of the surgical patient. Hence, spikes of elevated plasma histamine concentrations corresponded to histamine release. Although this histamine release very often was less than 1 ng/ml plasma histamine, it created systemic reactions after atracurium. The cut-off point of 1 ng/ml for such anaphylactoid reactions does no longer exist, also lower plasma levels are of patho-physiological significance. The clinical signs of histamine release in the induction of anaesthesia vary from drug to drug. Sometimes tachycardia and hypertension produce the highest likelihood ratio, sometimes tachy- and bradycardia, but no changes in blood pressure as in the case of atracurium. It is concluded that the reasons why histamine release in anaesthesia and surgery is so much underreported and under-estimated include the present paradigms about plasma histamine levels and the "classical picture" of histamine release. Both are no longer valid and need a re-assessment.

Adolescent↗
PubMed1991

[The neuromuscular blocking effects of ORG 9426].

ORG 9426 is a new non-depolarizing steroidal muscle relaxant with a short onset time and intermediate duration of action. Its ED90 ist estimated to be between 0.25 and 0.36 mg/kg. The present study investigated the onset time, duration of action and time to spontaneous recovery after 0.3 and 0.9 mg/kg ORG 9426, respectively (i.e. about single or triple ED90). METHODS. Following the consent of the ethics committee and informed patient consent, two groups of 18 patients (ASA I or II) were formed, each scheduled for general or ORL surgery. After premedication with lormetazepam, anesthesia was induced with midazolam (0.07 mg/kg) and etomidate (0.3 mg/kg) and maintained with N2O/O2 at a 65:35 ratio, enflurane (0.8-1.5%) and supplements of fentanyl as needed. The ulnar nerve was stimulated with supramaximal 2 Hz Train-of-four (TOF) every 20 s. Neuromuscular twitch response was registered with EMG. Muscle relaxation was achieved by administration of ORG 9426 0.3 (group 1) and 0.9 mg/kg (group 2), respectively. The following parameters were measured: onset time (time interval from injection to maximal or total block), T125/75 (time for T1 to reach 25% or 75% of control), TOF70 (time for TOF ratio to reach 70% of control), heart rate and blood pressure. RESULTS. (mean +/- SD). At a dosage of 0.3 mg/kg, the onset time was 3.1 +/- 0.8 min and the maximum blockade was 87 +/- 9%. A dosage of 0.9 mg/kg led to complete paralysis (100%) in all patients within 1.2 +/- 0.3 min. The time for recovery of T1 to 25 and 75% of baseline was 18 +/- 7 and 26 +/- 8 min in group 1, in group 2 46 +/- 11 and 53 +/- 17 min, respectively. TOF70 (i.e., time to adequate spontaneous recovery of neuromuscular function) was achieved after 30 +/- 10 and 63 +/- 14 min, respectively. CONCLUSIONS. At a dosage of 0.3 mg/kg, ORG 9426 has an onset time of about 3 min and a duration of activity of nearly half an hour. Its neuromuscular effects are similar to a single ED90 dose of vecuronium. In contrast to a previous study, we observed a much shorter onset time of 70 s following the administration of 0.9 mg/kg. The clinical duration of action and spontaneous recovery of neuromuscular function, however, were significantly prolonged to more than 1 h. The hemodynamic parameters showed only slight alterations.

Adult↗
PubMed1991

[The pharmacokinetics of lormetazepam following cimetidine].

Cimetidine delays the elimination from plasma of those benzodiazepines that are subject to oxidative drug metabolism. An open-label cross-over study was conducted to discover whether cimetidine also changes the plasma level profile of lormetazepam. METHODS. Ten volunteers (5 female, 5 male) took part in the study. After oral administration of 1 mg lormetazepam alone followed by a 6-day washout phase, the subjects received five 200-mg cimetidine tablets at intervals of 6 h (Table 1). The subjects took another 1-mg dose of lormetazepam p.o. together with the last tablet of cimetidine. Blood was sampled at specified intervals after both lormetazepam administrations, and the concentration of the drug in the plasma was determined by means of a specific radioimmunoassay. RESULTS. Cimetidine had no influence on the plasma levels of lormetazepam (Fig. 1). The drug concentrations increased quickly after both treatments regardless of sex and reached their highest values 1-2 h after oral ingestion. half-lives of 30-40 min were determined for the beta-phase and 8-10 h for the terminal elimination phase (Table 2). DISCUSSION. Lormetazepam, over 90% of which is excreted in humans as lormetazepam glucuronide, like oxazepam and lorazepam, does not obviously interact with cimetidine. All other benzodiazepines, which have to undergo oxidation before excretion, interact with drugs that inhibit the microsomal (cytochrome-P-450-dependent) enzyme system. CONCLUSION. In this study, no influence of simultaneous administration of cimetidine--a well-known inhibitor of P-450 dependent drug metabolism--on the pharmacokinetics of lormetazepam in either men or women was observed. This is in agreement with theoretical considerations: due to a 3-hydroxy group, lormetazepam does not require oxidation (hydroxylation) before it is metabolized into a water-soluble form capable of being excreted from the body. Cimetidine is therefore unlikely to potentiate the sedative effect of lormetazepam.

Anti-Anxiety Agents↗
PubMed1990

[Beta activation following the intravenous administration of benzodiazepines and the specific antagonist flumazenil (Ro 15-1788)].

In a prospective randomized study involving 32 male subjects aged 18 to 38, the effects of flunitrazepam (0.25 to 2 mg/70 kg), lormetazepam (0.5 to 4 mg/70 kg), midazolam (1.5 to 12 mg/70 kg) and diazepam (4 to 32 mg/70 kg) on the beta-activity (13 to 20/s) were investigated. Each subject received four benzodiazepine injections of increasing dosage. The doses were selected so that the lowest had only a slight effect on the test person's condition, while the highest resulted in deep sedation. The increase in beta-activity started off with a latency of 30 to 60 s; it was proportional to the dosage and reached its maximum between the 2. and 3. minutes. The subsequent decrease in beta-activity could be represented by an exponential function. The effect could be cancelled temporarily by administering repeated doses of the specific antagonist, flumazenil (0.1, 0.3 and 0.9 mg/70 kg). The method is suited for describing pharmacodynamic processes, determining equipotential doses of benzodiazepines and detecting the interaction between benzodiazepines and specific antagonists.

Adult↗
PubMed1990

[The effect of propofol-ketamine anesthesia on hemodynamics and analgesia in comparison with propofol-fentanyl].

Propofol (Diprivan), a modern intravenous hypnotic, produces a reduction in both cardiac index (CI) and mean arterial pressure (MAP). Ketamine (Ketanest), a potent analgesic, in contrast, causes an increase in MAP and CI. The aim of the present study was to investigate whether the combination of propofol and ketamine can give better hemodynamic stability during the induction and maintenance of general anesthesia than propofol used with fentanyl, whose cardiodepressant actions may cumulate. METHODS. For induction of general anesthesia 10 patients (ASA I and II) each received 3-5 boluses of propofol (0.5 mg.kg-1 during 35 s until predetermined level of anesthesia was reached (stage D2/E0 according to [20]) followed by a continuous propofol infusion (0.120 mg.kg-1.min). Fentanyl 0.1 mg was administered to each patient in group A for induction of anesthesia and again if evident pain was present. In group B ketamine was given following a pharmacokinetic model based on computer-simulated calculation. After an initial bolus of 38 mg injected within 2 min further doses of 42 mg, 35 mg, 32 mg and 28 mg ketamine were administered over 30 min at a time. Signs of evident pain were treated by means of supplementary doses of 0.5 mg.kg-1. RESULTS. In both groups a moderate drop of MAP was observed after the induction of general anesthesia. Two patients in each group showed a distinct decrease in MAP (-32%). The heart rate dropped slightly (-9%) in group A, but did not change in group B. Following intubation the MAP rose by less in group A (+8%) than in group B (+21%). After the beginning of the operation the group treated with propofol/fentanyl showed major hemodynamic changes; in particular, bradycardia with less than 40 bpm was observed in more patients than in the propofol/ketamine group. Postoperatively, fewer patients in group B required rescue doses of analgesics (1 of 10) than these in group A (7 of 10), though vigilance was better in group B. DISCUSSION. The dose of ketamine administered during the induction of general anesthesia may have been not high enough to neutralize the cardiodepressant effect of propofol. But during the maintenance of anesthesia there was in fact better hemodynamic stability in group B than in group A as a result of the neutralization of opposing actions. Fentanyl even intensified the fall in MAP after propofol. Patients in group B showed better vigilance as well as better pain relief postoperatively. The population of the fentanyl group was obviously more deeply sedated and analgesia was still inadequate. In our study general intravenous anesthesia with propofol and ketamine offered the advantages of better analgesia, a higher state of vigilance and the absence of respiratory depression during the postoperative phase compared with the combination of propofol and fentanyl.

Analgesia↗
PubMed1990

[Etomidate using a new solubilizer. Experimental clinical studies on venous tolerance and bioavailability].

Pain following intravenous injection as well as thrombophlebitis are substantial side effects of etomidate that have been reported from the first clinical study (1972-1973) onwards. Investigations of our own and by Gran et al. have pointed out that injectable etomidate with intralipid as a solvent removes side effects without impairing the good hypnotic action. The idea of using a lipid emulsion as a solvent was presented a few years later, inducing two further studies. METHOD. Both pharmacodynamic (continuous EEG registration) and pharmacokinetic [determination (HPLC) of plasma levels of the active substance] investigations were carried out on volunteers. At random 16 volunteers received etomidate in propylene glycol or etomidate in lipid emulsion for general anesthesia. A dose of 0.3 mg kg-1 was given over 60 s. In a clinical study 100 patients were divided into two independent groups of 50 each. They received either the commercially available etomidate in 35% propylene glycol (group I) or the new formulation containing 20 mg etomidate in 10 ml of a lipid-emulsion (Lipofundin MCT 20%) (group II). A dose of 0.3 mg kg-1 etomidate was given. RESULTS. There was a higher concentration of etomidate for 8 min after injection in lipid emulsion compared with etomidate in propylene glycol. The plasma concentration of etomidate (200 ng/ml) correlates with C2 corresponding to the light sleep stage after etomidate in propylene glycol, but with D0 according to the deep sleep stage after etomidate in lipid emulsion. At lower plasma concentrations, the hypnotic action of etomidate in propylene glycol is stronger than the effect of the lipid emulsion. This result means that it is possible that a part of the etomidate remains in the lipid particles. In the clinical study the anesthetic induction time was nearly identical in both groups; blood pressure and heart rate were stable. Following etomidate in propylene glycol, 36% of the patients complained of a painful injection. On the first postoperative day, 9 of 47 patients showed signs of phlebitis and three others thrombosis. On the 7th day a venous reaction was evident in 22% of these patients; 2 patients had developed phlebitis, 5 thrombosis and 4 thrombophlebitis. After etomidate in lipid emulsion, there were no signs of local irritation. The same results have been obtained in the study with volunteers. CONCLUSION. Two unpleasant side effects of etomidate, pain on injection and postoperative thrombophlebitis, were abolished by the solvent "lipid emulsion".

Adult↗
PubMed1989

Overview of initial clinical studies with intravenous and oral GR43175 in acute migraine.

The novel 5-HT 1-like receptor agonist GR43175 has been evaluated as a treatment for acute migraine in a series of open, dose-ranging and controlled clinical trials. Patients with severe attacks of migraine have attended special pain or headache clinics for treatment and assessment. Given intravenously as a bolus, GR43175 is capable of aborting all migraine symptoms within 10-30 min in over 90% of cases at a dose of 64 micrograms/kg. Characteristic transient and reversible side effects with such a regimen include feelings of heaviness, pressure and occasionally warmth or tingling which can be diminished by extending the duration of drug administration to a short infusion. Initial dose-ranging studies with a dispersible tablet formulation of GR43175 have revealed an efficacy of 70-85% within 2 h with doses of 70-280 mg. Furthermore, tolerability is excellent. These encouraging early results warrant larger-scale controlled studies of GR43175 in acute migraine.

Administration, Oral↗
PubMed1989

Early clinical experience with subcutaneous GR43175 in acute migraine: an overview.

In six European clinics 111 migraine patients were treated in a series of open dose-ranging studies with subcutaneous injections of 1 to 4 mg GR43175, a novel 5-HT 1-like receptor agonist. Response rates after 20-30 min were dose related and rose from 33% with 1 mg to 96% with 4 mg GR43175. Side effects were minor and transient. These promising results warrant confirmation in placebo-controlled double-blind trials. Migraine, treatment, 5-HT agonist, open studies.

Adolescent↗
PubMed1989

Treatment of acute migraine with subcutaneous GR43175 in West Germany.

A subcutaneous preparation of GR43175, a novel antimigraine 5-HT 1-like agonist, was considered to represent a convenient way of administering the drug to patients during an acute migraine attack. In a series of open, uncontrolled dose-ranging studies, 82 patients with migraine were assessed serially for changes in severity of headache and associated symptoms following subcutaneous GR43175 in doses of 1-4 mg. Subcutaneous injection of 3 mg or 4 mg was found to be most effective. Within 60 min, 90% of patients had obtained complete relief of all migraine symptoms. Tolerability was good, 59% of patients reporting no adverse effects. Those reported mainly comprised transient local irritation to the injection. There were no changes attributable to GR43175 in heart rate, blood pressure, ECG readings or laboratory parameters.

Adult↗
PubMed1989

Effective improvement of symptoms in patients with acute migraine by GR43175 administered in dispersible tablets.

GR43175, a selective 5-HT 1-like agonist, was administered as oral dispersible tablets in an open, uncontrolled dose-ranging study to assess its efficacy as an agent for acute migraine. Nine patients, all with well established attacks, were assessed for changes in severity of headache and associated symptoms over 2 h. Drug absorption was compared during and between attacks in five patients. Doses of 140 mg and 280 mg resulted in complete relief of all symptoms within 2 h. Treatment was well tolerated in all patients.

Administration, Oral↗
PubMed1989

[Visual EEG analysis in controlling intravenous anesthesia using propofol].

Since the discovery of brain waves by Berger, repeated efforts have been made to use the electroencephalogram EEG for monitoring and controlling anesthesia. Owing to its susceptibility to failure and the high expenditure regarding technology and personnel, the technique has not yet been adopted in routine anesthesia, however. In the study now reported an attempt was made to apply the positive experience with the recording and interpretation of EEG in the development of new anesthetic agents in the experimental laboratory, during routine clinical operations. The anesthetic used in the study was Propofol, an induction hypnotic that has only recently been introduced, together with nitrous oxide and repeated doses of fentanyl. Propofol is distinguished by its fast onset of action and short inactivation time; it is therefore suitable for induction and maintenance of anesthesia. The aim of the study was to maintain predetermined stages of sleep during anesthesia with the aid of visual on-line analysis of the EEG and to establish the dose of Propofol required for this purpose. The operations-general and orthopedic surgery-lasted 70-190 min (average duration: 120 min). In accordance with the randomization plan, the maintenance dose of Propofol was controlled in such a way that in ten patients light sleep levels (C0 to D1) and in the other ten deep sleep levels were maintained. The EEG was recorded via five active scalp electrodes (FP2, F4, C4, P4, O2) with reference to a joint electrode (A2). The stages of sleep were classified according to Kugler.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[A new formulation of etomidate in lipid emulsion--bioavailability and venous provocation].

In a prospective, randomized study of 16 volunteers, a new galenic formulation of the induction hypnotic etomidate in lipid emulsion was compared with the commercial form in propylene glycol (Hypnomidate). After 0.3 mg/kg etomidate plasma levels (HPLC) and hypnotic effects (visual EEG analysis) of both formulations were almost identical. Onset of action occurred after 41.6 s in the propylene glycol group (group I) and 35.6 s in the lipid emulsion group (group II). The hypnotic effect (greater than or equal to D0) lasted 7 min 20 s in group I and 6 min in group II. Plasma levels in group I decreased from 630 ng/ml after 2 min to 170 after 8 min and 37 after 130 min. With group II the plasma levels decreased from 770 ng/ml after 2 min to 150 after 8 min and 42 after 130 min (Fig. 1). In the propylene glycol experiment, 4 of 8 volunteers reported pain on injection. Within 7 days 4 persons developed phlebitis or thrombophlebitis. One showed signs of an allergic reaction (urticaria). With the new formulation of etomidate in lipid emulsion, neither venous sequelae nor allergic reactions were observed in any of the 8 volunteers (Table 2).

Adult↗
PubMed1988

Possible benefit of GR43175, a novel 5-HT1-like receptor agonist, for the acute treatment of severe migraine.

GR43175, a selective 5-HT1-like agonist, was given as an intravenous infusion in an open dose-ranging study to treat 46 attacks of severe migraine in 34 patients. The highest dose, 2 mg infused over 10 min in 24 severe attacks, resulted in rapid and complete relief of symptoms in 17 attacks (71%) and in improvement to a non-migrainous residual headache in 7 attacks. Treatment was well tolerated, the only adverse effects being transient feelings of heaviness and pressure, predominantly in the head. GR43175 may represent an important advance in the treatment of acute migraine.

Adult↗
PubMed1988

Human studies on the mu opiate receptor agonist fentanyl: neuroendocrine and behavioral responses.

The neuroendocrine and behavioral responses to the potent mu opiate receptor agonist Fentanyl (FE) have been systematically investigated in healthy male volunteers. These volunteers received, according to a randomized block design, different doses of FE: 0.1 mg/70 kg (n = 11), 0.2 mg/70 kg (n = 11), 0.25 mg/70 kg (n = 8), and saline (n = 11). FE induced a pronounced dose-dependent increase of plasma prolactin concentrations, which was significant at the lowest dose. In contrast, growth hormone was significantly stimulated by the highest FE dose only. Moreover, FE induced a maximum reduction of plasma cortisol concentrations at the lowest dose (0.1 mg/70 kg). In parallel, marked euphoric responses were also observed at this lowest FE dose. These results suggest a mu specific influence on all neuroendocrine and behavioral parameters investigated. Different responses of these parameters to different doses of FE, however, suggest a differential modulation of these parameters by the mu receptor agonist FE.

Adult↗
PubMed1988

[Subjective verbal methods in preoperative measurement of anxiety].

The role of preoperative anxiety in perioperative adaptation is viewed in two different ways. Janis suggested that anxiety is a drive that evokes the cognitive work of worrying. Leventhal stresses the importance of coping behavior for adaptation, while anxiety may or may not accompany this coping process. Both theories have empirical support. The aim of this study was to determine whether both theories could show empirical support because the scientists chose different methods: Janis used interviews, Leventhal and Lazarus anxiety scales. The study analyzed the pre- and postoperative emotional reactions of surgical patients with three different methods of anxiety measurement: an anxiety scale, a fear thermometer, and a psychoanalytic interview (Gottschalk-Gleser content analysis method). The different methods were compared and related to the adaptation behavior (Table 3). The data showed a clear interaction between the selected methods and respective theories about the effects of preoperative anxiety on intra- and postoperative adaptation. The anxiety scales showed no correlation with adaptation behavior (blood pressure and heart rate during surgery; postoperative pain medication) and were not related to the anxiety scores obtained from the interview (content analysis). On the other hand, the interview anxiety measurements showed a clear relationship between separation anxiety (and also shame anxiety), physiological excitement during surgery (increase in heart rate), and postoperative medication (increased analgesics and tranquilizers). The patients who worried about the risks of surgery (Verletzungsangst, see Fig. 3) had very good perioperative adjustment, so that the quality of anxiety measured in the interview was very important for the prediction of adaptation.

Adaptation, Psychological↗
PubMed1987

[Biomedical and clinimetric approaches in determining the causes of perioperative risk: developing a German ASA classification].

Perioperative risk research with biomedical (biochemical, physiological) methods must grow up as a main topic in surgical research. However, operative risk has also to be analysed with methods of clinimetrics, such as formal (objective) decision making and epidemiology. Only by this way a convincing practical dimension is added to basic scientific statements. ASA-classification of the preoperative physical status is a global index for estimating the operative risk. It contains objective findings, subjective impressions and the final clinical judgement. For this reason it is so flexible. For a multicentre trial on perioperative risk and histamine an empirical index was constructed using both the ASA-classification and the Mannheim-Munich risk check list.

Germany, West↗