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UNLABELLED The anaesthetic potency of the (S)-ketamine isomer is approximately double that of racemic ketamine. The aim of this study was to compare the recovery of cerebral function after a bolus of 1.3 mg/kg racemic ketamine or 0.65 mg/kg (S)-ketamine followed by continuous application of 4 or 2 mg/kg x h over 15 minutes. METHODS With their informed consent and approval of the local ethics committee 12 healthy volunteers were enrolled in a double-blind, cross-over study. All drugs were dissolved in identical volumes. On three dates with an interval of one week at least ketamine/NaCl, (S)-ketamine/physostigmine or (S)-ketamine/NaCl was administered (table 1). The sequence was randomized. In addition, the unspecific antagonistic potential of the centrally acting, cholinergic agonist physostigmine (0.012 mg/kg) after (S)-ketamine was tested against saline-placebo. Neuropsychological tests (tests 3-5 of the syndrome-short-test [Erzigkeit, see references]) were used to quantify cerebral function before and at 45, 75, 105, 135, 165 and 195 min after anaesthesia. All data are mean values and standard deviation. Comparisons over time and between drugs were carried out using two-dimensional analysis of variance (ANOVA). Wilcoxon-tests were used post-hoc. p < 0.05 was considered significant. RESULTS After (S)-ketamine the subjects were able to carry out the tasks more rapidly than after racemic ketamine (p < 0.05). Mean time to reach preoperative test performance +10% was 117.5 min for (S)-ketamine/physostigmine, 121.3 min for (S)-ketamine/NaCl and 141.6 min for racemic ketamine (p < 0.05 between (S)-ketamine and racemic ketamine). No differences were found between physostigmine and placebo. The incidence of side effects (mainly nausea, vomiting) was not different. DISCUSSION (S)-ketamine offers a shorter recovery time after short anaesthesia compared to racemic ketamine. The investigated dose of physostigmine was probably too low to produce antagonism of (S)-ketamine. An increased dosage of physostigmine has yet to be studied, but is likely to cause a higher rate of side effects such as nausea, vomiting, bradycardia and possibly even tonic-clonic seizures.

Ketamin ist ein Razemat, dessen Isomere S-(+)- und R-(−)-Ketamin ein Aquipotenzverhaltnis von etwa 4:1 aufweisen. Fruher wurde spekuliert, das S-(+)-Ketamin die erwunschten anasthetischen und R-(−)-Ketamin die unerwunschten psychomimetischen Wirkungen hervorruft. Daher wurde S-(+)-Ketamin in einigen randomisierten Untersuchungen an Probanden und an Patienten mit razemischem Ketamin verglichen. In dieser Ubersicht wird die Bedeutung von S-(+)-Ketamin fur die Dauer der Aufwachphase, die Inzidenz von Traumerlebnissen, deren Inhalt und fur sonstige Nebenwirkungen dargestellt. Das Dosisverhaltnis von S-(+)-Ketamin zu Ketamin-Razemat war 1:2. Mit einer Ausnahme war die Aufwachphase in allen Untersuchungen nach S-(+)-Ketamin deutlich kurzer als nach Razemat. Dies gilt unabhangig davon, ob die Substanz als intravenoser Einzelbolus, als Bolus mit anschliesender kontinuierlicher Infusion oder als intramuskulare Injektion verabreicht wurde. Demgegenuber war die Inzidenz der psychomimetischen Reaktionen nur in einer Studie nach S-(+)-Ketamin niedriger als nach Ketamin-Razemat. Daher sollte auch S-(+)-Ketamin in der klinischen Anasthesie mit einem Hypnotikum oder Sedativum kombiniert werden.

The anaesthetic potency of the (S)-ketamine isomer is approximately double that of racemic ketamine. The aim of this study was to compare the recovery of cerebral function after a bolus of 1.3 mg/kg racemic ketamine or 0.65 mg/kg (S)-ketamine followed by continuous application of 4 or 2 mg/kg x h over 15 minutes.With their informed consent and approval of the local ethics committee 12 healthy volunteers were enrolled in a double-blind, cross-over study. All drugs were dissolved in identical volumes. On three dates with an interval of one week at least ketamine/NaCl, (S)-ketamine/physostigmine or (S)-ketamine/NaCl was administered (table 1). The sequence was randomized. In addition, the unspecific antagonistic potential of the centrally acting, cholinergic agonist physostigmine (0.012 mg/kg) after (S)-ketamine was tested against saline-placebo. Neuropsychological tests (tests 3-5 of the syndrome-short-test [Erzigkeit, see references]) were used to quantify cerebral function before and at 45, 75, 105, 135, 165 and 195 min after anaesthesia. All data are mean values and standard deviation. Comparisons over time and between drugs were carried out using two-dimensional analysis of variance (ANOVA). Wilcoxon-tests were used post-hoc. p0.05 was considered significant.After (S)-ketamine the subjects were able to carry out the tasks more rapidly than after racemic ketamine (p0.05). Mean time to reach preoperative test performance +10% was 117.5 min for (S)-ketamine/physostigmine, 121.3 min for (S)-ketamine/NaCl and 141.6 min for racemic ketamine (p0.05 between (S)-ketamine and racemic ketamine). No differences were found between physostigmine and placebo. The incidence of side effects (mainly nausea, vomiting) was not different.(S)-ketamine offers a shorter recovery time after short anaesthesia compared to racemic ketamine. The investigated dose of physostigmine was probably too low to produce antagonism of (S)-ketamine. An increased dosage of physostigmine has yet to be studied, but is likely to cause a higher rate of side effects such as nausea, vomiting, bradycardia and possibly even tonic-clonic seizures.

Ketamine is a racemic mixture containing equal parts of S-(+)-ketamine and R-(-)-ketamine. Their potency relation is approximately 4:1. In early human studies S-(+)-ketamine was presumed to produce the desired anaesthetic effects and R-(-)-ketamine the undesired psychic emergence reactions. Therefore, ketamine was compared in a number of randomised studies in volunteers and patients with racemic ketamine. This review addresses the impact of S-(+)-ketamine on recovery from anaesthesia, incidence and content of vivid dreams, and other side effects. The dose relation applied in the studies was 1:2. With only one exception, the recovery phase was clearly shorter after S-(+)-ketamine compared to racemic ketamine irrespective of its application as a single bolus, a bolus followed by continuous infusion, or an intramuscular injection. However, the incidence of psychic emergence reactions was lower after S-(+)-ketamine in only a single study. In conclusion, S-(+)-ketamine should be always combined with a hypnotic or sedative drug in clinical anaesthesia.

The potency of S-(+)-ketamine is approximately double that of the racemic ketamine. This study was carried out to investigate the recovery of cerebral electrical function after a bolus of 1.3 mg/kg ketamine or 0.65 mg/kg S-(+)-ketamine and subsequent continuous application of 4 mg/kg h ketamine per h or 2 mg/kg S-(+)-ketamine, per h for 15 min. Furthermore, the centrally acting, cholinergic agonist physostigmine has been reported to antagonize ketamine and to shorten the recovery period. Therefore, after S-(+)-ketamine 0.012 mg/kg physostigmine was tested against saline placebo. METHODS. With their own informed consent and the approval of the ethics committee 12 healthy volunteers were enrolled in a double-blind cross-over study. All drugs were dissolved in identical volumes. On three dates with intervals of at least 1 week between, ketamine/NaCl, S-(+)-ketamine/physostigmine or S-(+)-ketamine/NaCl was administered (Table 1). The sequence was randomized. The EEG was recorded from 20 sites according to the 10/20 system and after Fast-Fourier transformation computed into amplitudes within the delta, theta, alpha, and beta bands and within the total spectrum. The median, the spectral edge frequency and the dominant frequency (dF) were also determined. Mean values of all electrodes before and at 10, 15, 30, 45 and 195 min after the bolus injection were compared using two-dimensional analysis of variance (ANOVA, significance level P0.05). RESULTS. The characteristic increase in theta-amplitude and decrease of alpha-amplitude were observed after ketamine and S-(+)-ketamine. Median and dF dropped from the alpha to the theta frequency range. Ketamine led to a greater increase in total, delta, theta and beta amplitude during anaesthesia. 3 hours after ketamine/S-(+)-ketamine anaesthesia a significant decrease in the median and dominant frequency and in total, delta, theta, alpha and beta amplitudes confirmed residual impairment of cerebral function after all study drugs. No differences were found between physostigmine and placebo. DISCUSSION. The EEG changes during ketamine/S-(+)-ketamine administration suggest a slightly deeper anaesthetic level after ketamine. The course of recovery was not different after ketamine and after S-(+)-ketamine. The spectral edge frequency did not differ between measurement points, and is therefore not suitable for assessment of the depth of anaesthesia reached with ketamine/S-(+)-ketamine. The dose of physostigmine tested was probably too low to produce antagonism of S-(+)-ketamine. An increased dosage of physostigmine has yet to be studied, but is likely to cause a higher rate of side effects, such as nausea, vomiting and bradycardia, and possibly even tonic-clonic seizures.

In contrast to the bipyridine derivatives amrinone and milrinone, the phosphodiesterase III/IV inhibitor enoximone is an imidazolone that creates the possibility of inhibiting adrenal steroid synthesis, as has already been demonstrated for other imidazoles, e.g. ketoconazole and etomidate. To clarify this point we carried out a double-blind sequential study in seven healthy volunteers. METHODS. After obtaining the approval of the ethics committee and the written consent of the volunteers, 1.25 mg/kg enoximone or saline was infused intravenously over a period of 20 min using a randomized crossover design with an interval of at least 5 days between the two trials. Twenty minutes after administration of the drug, 250 micrograms ACTH was injected. Plasma cortisol was measured prior to stimulation of the adrenal cortex and 30, 60 and 120 min afterwards; levels of aldosterone and 11-desoxy-cortisol were determined after 60 min. Standard radioimmunoassays were used. Haemodynamic parameters were measured non-invasively. RESULTS. In contrast to the placebo, enoximone resulted in a significant (P0.01) increase in the cardiac index (from 3.2 +/- 0.7 to 3.9 +/- 0.9 l min-1 m-2) and heart rate (from 69 +/- 11 to 81 +/- 8 min-1) and a decrease in peripheral resistance (from 1120 +/- 202 to 894 +/- 183 dyn s cm-5); blood pressure fell only slightly. Following injection of ACTH there were significant increases in cortisol (from 63 +/- 29 to 274 +/- 58 micrograms/l), aldosterone (from 86 +/- 37 to 300 +/- 105 ng/l) (both P0.001) and 11-desoxycortisol (from 5.3 +/- 1.2 to 9.8 +/- 4.6 micrograms/l; P0.05). There was no difference between enoximone and placebo at any time (P0.2). CONCLUSIONS. This study confirms the inodilation caused by enoximone. The normal response to ACTH rules out a direct inhibitory effect of a loading dose of 1.25 mg enoximone on the adrenal cortex. As the concentration of the major metabolite of enoximone, the sulphoxide, has been shown to surmount that of the parent drug after 40 min, this also holds true for the metabolite. We conclude that in contrast to etomidate, which causes a substantial reversible adrenal suppression after a single dose of 0.2 mg/kg, enoximone 1.25 mg/kg did not interfere with corticosteroid synthesis or release. Taking into account the metabolism and pharmacokinetics of this inodilator, there is no reason to expect an inhibitory effect even after repeated dosage.

In 1986 the discussion on the further use of halothane broke out anew, especially after the Bristol symposium and the European Congress of Anesthesiology in Vienna. Everywhere there is great uncertainty on whether or not halothane should continue to be used. A critical analysis of the literature shows that there are two standards applied to halothane. When judged by the same stringent criteria as halothane other anesthetic techniques are also dubious, e.g. neuroleptanesthesia or epidural block. Finally, experience with isoflurane, the strongest rival of halothane, is not adequate to warrant abandoning halothane, especially as long as the question of coronary steal is still open. At present there is no solid scientific basis for vanishing halothane.

Dose-response-curves for rectal induction of anaesthesia in children with 1%- or 5%-methohexitone-solutions and dosages of 5, 10, 15, 20 and 25 mg/kg body wt. were obtained in 10 groups of 20 children. Methohexitone and hydroxy-methohexitone serum-levels were compared in another 23 children after application of 1%- or 5%-methohexitone-solutions at dosages of 15 and 20 mg/kg body wt. The sleep induction quota after 1%-methohexitone-solution in the 20 and 25 mg/kg body wt.-dosages was significantly higher, 20% and 25% respectively, and the mean sleep induction time shorter, 37% and 45% respectively compared with results after 5%. The change after 15 mg/kg body wt. was not significant. A study of dosages 5 and 10 mg/kg body wt. was discontinued due to insufficient effect. Methohexitone serum-levels ranged from 0.7-8 mg/l. All of the children after the use of 1%-methohexitone-solution, and only 60% after 5%-methohexitone had serum concentrations above the sleep inducing "borderline" concentration of 2 mg/l. The differences between mean methohexitone and hydroxy-methohexitone-serum-levels were not significant due to the small groups and the wide range of results. We conclude that individual dosages of 15 or 20 mg/kg body wt. 1%-methohexitone-solution should be applied according to clinical criteria such as physical and psychic status of the child.

Some workers state that sinus rhythm is essential for electrocardiographic placement of central venous catheters. We performed a prospective study to compare location control by ECG and by chest X-ray in 40 patients with absolute arrhythmia and atrial fibrillation. The criteria accepted as allowing the assumption of an intracardiac position of the catheter tip were: (1) Abrupt appearance of high-voltage P-waves when the right atrium (RA) was entered and their brisk disappearance when pulling the catheter back into the vena cava superior (VCS) and/or (2) a change in configuration and voltage of the QRS complex on withdrawal of the catheter from the right ventricle (RV). After establishment of an intracardiac position, the catheter was withdrawn until the ECG changed to show a trace identical to that seen before it had entered the heart. Then, in this study, the correct central venous position was confirmed by chest X-ray. The intravascular ECG revealed a correct placement of the catheter tip in the VCS in all patients but one. In this patient who had severe dysrhythmia, an intracardiac ECG could not be obtained, although the chest X-ray showed a correct position of the catheter in the VCS. While false-negative results (where an intracardiac catheter position cannot be documented although the catheter is in a central venous position) occasionally do occur, false-positive results (with ECG suggesting an intracardiac location read, though the catheter tip is actually in a peripheral vein) are virtually impossible.(ABSTRACT TRUNCATED AT 250 WORDS)

The external jugular vein can easily be identified in most patients and provides an alternative access to the superior vena cava. Unfortunately, advancement of the catheter may be hampered for anatomical reasons, e.g. the presence of valves. Use of a flexible guide-wire with curved tip (J-wire), as first proposed by Blitt et al., results in a significant increase in the rate of successful cannulations. This method necessitates tedious surgical draping, however, that may not always be practicable. Therefore, a catheter was developed that is wrapped in a protective sleeve and contains a J-wire instead of the common plastic mandrin, thus making contamination during insertion impossible.