First commissioning results with the Grenoble test electron cyclotron resonance ion source at iThemba LABS.

iThemba Laboratory for Accelerator Based Science (iThemba LABS) is a multi-disciplinary accelerator facility. One of its main activities is the operation of a separated-sector cyclotron with a K-value of 200, which provides beams of various ion species. These beams are used for fundamental nuclear physics research in the intermediate energy region, radioisotope production, and medical physics applications. Due to the requirements of nuclear physics for new ion species and higher energies, the decision was made to install a copy of the so-called Grenoble test source (GTS) at iThemba LABS. In this paper, we will report on the experimental setup and the first results obtained with the GTS2 at iThemba LABS.

[Simulator training in anesthesia. Applications and value]. / Simulatortraining in der Anästhesie. Möglichkeiten und Stellenwert.

Simulation has gained an important role in medical education and continuing education in the field of anaesthesia and emergency medicine. This article gives background information on how full-scale simulators are applied in medical education as well as in continuing education for advanced anesthesia and scientific applications. Acceptance of training seems enhanced by inclusion of the human factor aspect, since this has proven to be a major source for the development of critical situations in our specialty. Furthermore, drawbacks of the simulators available and the current training availability in Germany is described.

[Experienced anesthetists show better reaction to central gas supply dropout--an anesthesia simulator study]. / Erfahrene Anästhesisten reagieren gezielter bei Ausfall der Zentralen Gasversorgung--Eine Studie am Anästhesiesimulator.

The loss of pipeline pressure in a central gas supply system is a rare but potentially hazardous complication in anaesthesia and critical care. In an anaesthesia simulator study, reactions of 20 anaesthetists to this simulated critical incident were monitored and evaluated. A comparison between novice (n = 10) and experienced anaesthesia residents/consultants (n = 10) determined a significantly quicker and more on-target reaction by the experienced anaesthetists. Unlike older cycle system anaesthesia machines, update anaesthesia ventilators (CICERO EM, Dräger, Lübeck) do not permit manual ventilation of a patient in a "closed-system" once pipeline pressure drops to zero. In this highly hazardous event, the patient has to be ventilated by reservoir bag until a sufficient back-up system delivering high inspiratory oxygen concentrations can be installed, because he is otherwise prone to diffusion hypoxia. Installation of mandatory (anaesthesia-machine integrated) back-up systems for respirators without cycle systems would therefore increase patient safety. A general algorithm for loss of pipeline pressure can be described only after a back-up system has been installed.

Potential risks of high-dose epinephrine for resuscitation from ventricular fibrillation in a porcine model.

The arterial plasma concentrations and hemodynamic effects of epinephrine, 10 micrograms/kg, IV (group A, N = 8) and 50 micrograms/kg, IV (group B, N = 8) were compared in a porcine resuscitation model after 3 minutes of circulatory arrest induced by ventricular fibrillation. All animals in group A were successfully resuscitated after 4.9 +/- 2.8 minutes and 2.8 +/- 1.6 defibrillations. In group B, only 6 of 8 animals were successfully resuscitated after 6.3 +/- 1.1 minutes and 4.0 +/- 2.7 defibrillations (mean +/- SD). During CPR, cardiac output (CO), left ventricular systolic pressure (LVSP), and mean arterial pressure (MAP) were nearly identical in the groups. The hemodynamic situation during the first hour after restitution of spontaneous circulation in group B was characterized by a significantly higher heart rate, combined with significantly lower values for cardiac inotropy, CO, LVSP, and MAP compared to group A. Mean arterial peak epinephrine concentrations (group A 197 +/- 133 ng/mL, group B 1173 +/- 298 ng/mL) were approximately fivefold higher in group B. After resuscitation, plasma concentrations returned to baseline levels within 7 minutes in group A and 15 minutes in group B. Later hemodynamic differences between the groups are thereby attributed to a detrimental impact of high-dose epinephrine on the heart during resuscitation.

[New standards for catecholamine therapy in cardiopulmonary resuscitation? Results of a modified application in a resuscitation model]. / Neue Standards zur Katecholamintherapie bei der kardiopulmonalen Reanimation? Ergebnisse einer differenzierten Anwendung im Reanimationsmodell.

Using a standardized porcine CPR-model (3 min of cardiac arrest induced by ventricular fibrillation) the effects of epinephrine (10 micrograms/kg iv, 50 micrograms/kg iv, 100 micrograms/kg endobronchially, eb) and norepinephrine (10 micrograms/kg iv, 100 micrograms/kg eb) on resuscitability and early post-resuscitation haemodynamics were compared. Success rate was 100% after epinephrine 10 micrograms/kg iv and 100 micrograms/kg eb, 75% after epinephrine 50 micrograms/kg iv, 80% after norepinephrine iv and 60% after norepinephrine eb. In an unmedicated control group 50% of all animals were successfully resuscitated. Early post-resuscitation haemodynamics in the high dose epinephrine group were characterized by tachycardia and progredient myocardial failure, while in the norepinephrine groups a low cardiac output was accompanied by small cardiac stroke volumes and an increased vascular resistance. It is concluded that iv or eb epinephrine given in standard doses has still to be considered as the drug therapy of choice after short term cardiac arrest or in the presence of ventricular fibrillation. Before different drugs or dosing strategies can be recommended, further experimental and clinical validation is required.

[The pulmonary first pass effect of noradrenaline following intravenous and endobronchial administration for resuscitation]. / Untersuchungen zum pulmonalen first-pass-Effekt von Noradrenalin nach intravenöser und endobronchialer Gabe zur Reanimation.

In a porcine CPR-model, we investigated the pharmacokinetics and pharmacodynamics of norepinephrine (NE) after intravenous (10 g/kg, n = 10, group A) and endobronchial (e.b., 100 micrograms/kg, n = 10, group B) administration. After 3 min of cardiac arrest induced by electroshock, restitution of spontaneous circulation (ROSC) was achieved in 8 animals in group A after 3.3 +/- 1.6 min, and in group B in 6 animals after 2.5 +/- 0.6 min. Haemodynamics during CPR were not significantly different, but during the first hour after ROSC e.b. NE showed a depot effect. Maximum venous (642 +/- 182 ng/ml after 3.5 +/- 0.3 min) and arterial (147 +/- 21 ng/ml after 4.2 +/- 0.4 min) NE concentrations in group A were significantly higher compared with values in group B (77 +/- 18 ng/ml after 5.5 +/- 0.5 min venous, 46 +/- 11 ng/ml after 6.0 +/- 0.7 min arterial). The area under the curve (AUC) in group A was calculated to be 55 +/- 12 ng/ml min (venous) and 35 +/- 7 ng/ml min (arterial) representing a pulmonary first-pass effect of 40%. In group B, the dose-adjusted AUC (39 +/- 13 ng/ml min venous, 30 +/- 10 ng/ml min arterial) represented a pulmonary first-pass effect of only 25%. Despite this lower pulmonary first pass, however, it is concluded that after e.b. administration of NE absorption is too much delayed and peak concentrations are too low. Therefore, NE should not be given via this route during CPR.

[The blood level and a pharmacokinetic model of prilocaine during a continuous brachial plexus blockade]. / Blutspiegel und pharmakokinetisches Modell von Prilocain bei der kontinuierlichen Plexus-Brachialis-Blockade.

Continuous brachial plexus blockade achieved by repeated injections through an axillary catheter is used increasingly often for microsurgical procedures and for postoperative pain relief. Repetitive administration, especially of long-acting agents, can cause problems with local anesthetic toxicity. Based upon a pharmacokinetic analysis of prilocaine serum concentrations after single-dose axillary plexus blockade in 14 patients, a pharmacokinetic model was established from which to predict serum concentrations after successive doses. METHODS. Each of 14 patients (ASA I-II, age 42 +/- 20 years, height 171 +/- 10 cm, body weight 72 +/- 9 kg) undergoing minor hand surgery received a single dose of 600 mg (40 ml 1.5%) prilocaine for axillary plexus blockade. Serial samples were taken from the contralateral antecubital vein and serum local anesthetic concentrations were measured by gas chromatography. Least square, non-linear regression analysis was performed to fit a triexponential curve; standard formulas were applied to develop the corresponding open two-compartment model. Computer simulation was carried out to predict the accumulation of mean local anesthetic concentrations after repetitive dosages. The kinetic model was verified with another set of 5 patients receiving a repetitive dose of prilocaine. The initial dose was 400 mg (40 ml 1%), followed by insertion of a catheter which allowed repetition at 2 and 4 h. The repetition dose was 300 mg (20 ml 1.5%). RESULTS. Maximal prilocaine serum levels of 2.32 +/- 0.80 micrograms/ml were found after 34 +/- 13 min. Mean pharmacokinetic data of the open two-compartment model with first order absorption from extravascular sites were: t alpha 1/2 = 10 min; t beta 1/2 = 139 min; V1 = 661; V dss = 254 1; Cltot = 2310 ml/min; tabs 1/2 = 35 min. The comparison of predicted and observed serum concentrations after continuous anesthesia was excellent. DISCUSSION. Pharmacokinetic data after axillary plexus blockade are comparable to those found after i.v. injection. Low serum levels were found throughout the 8 h of investigation and accumulation in serum was minimal following repetitive doses. There was no loss of action on repetition. Predicted values after pharmacokinetic modeling showed good agreement with actual measured values. Prilocaine may be a reasonable choice for repetitive use, as is appears to be toxicologically safe. Methemoglobinemia resulting from metabolites of prilocaine did not lead to complications in our study. It may, however, be a problem with repetitive dosages. Further investigations concerning this question would be useful.

[An infusion model for intraoperative peridural anesthesia by catheter using mepivacaine]. / Ein Infusionsmodell zur intraoperativen Katheterperiduralanästhesie mit Mepivacain.

With the introduction of repetitive or continuous catheter techniques in regional anaesthesia, potential systemic intoxication hazards have increased. Especially high dose techniques such as peridural anaesthesia or plexus brachialis blockade consecutively generate high blood levels. In this study, blood levels collected from 20 patients (36 +/- 19 y, 173 +/- 9 cm, 73 +/- 15 kg) after lumbar epidural anaesthesia with mepivacaine led to the development of a linear open one-compartment-model (VD,ss: 109 l, Cltot: 594 ml/min, t1/2abs: 13 min, t1/2 beta: 149 min). With that model, dosage strategies could be studied via computer simulation. A mepivacaine dosage regimen for lumbar epidural anaesthesia, consisting of 250 mg as an initial bolus dose and an infusion rate of 150 mg/h after 15 min, cumulated to maximum concentrations of 2.5-3.5 micrograms/ml after 150 min. Such an infusion regimen may lead to concentrations of more than 4 micrograms/ml if applied for longer than 4 h. The pharmacokinetic computer simulation proved to be precise and could be compared to the measured blood levels of mepivacaine.