L. Mielke

EEG-Veränderungen unter Sedierung mit γ-Hydroxybuttersäure (GHB)

ZusammenfassungGamma-Hydroxybuttersäure (GHB) als zentraler Neurotransmitter wird zur Sedierung in der Intensivmedizin eingesetzt. Trotz insgesamt sehr günstigen pharmakologischen Profils wurde seine Eignung in Frage gestellt, da es beim Tier in sehr hoher Dosierung Krampfpotentiale auslösen kann und in dieser Absicht sogar als Modellsubstanz für die Absenzen-typische Attacke dient. Nach eigenen positiven Erfahrungen mit GHB im klinischen Einsatz wurde bei 31 postoperativen Patienten, die zur Beatmung mit GHB sediert wurden, während der Induktionsphase mit 50 mg/kg KG kontinuierlich ein Multikanal-EEG abgeleitet. Als Ausdruck der Sedierung fand sich, verglichen mit der Referenzphase, einheitlich eine Verlangsamung des EEG-Grundrhythmus mit Ausbildung eines δ/θ- bzw. reinen δ-Rhythmus. Die EEG-Veränderungen korrelierten zeitlich gut mit dem klinischen Vigilanzzustand. Weder in der rechnergestützten Auswertung noch in der klassischen visuellen Auswertung der Original-EEG waren Hinweise auf die Ausbildung von Krampfpotentialen aufzufinden, insbesondere auch keine 3/s-Rhythmen, wie sie bei Absenzen-typischen Attacken beschrieben werden. Die Unterdrückung auch des Theta-Rhythmus bei einem Teil der Patienten darf als Hinweis auf eine relative Überdosierung gewertet werden und zeigt, daß– wie bei allen Anästhetika – auch bei GHB die Dosierung am klinischen Effekt zu orientieren ist.AbstractGamma-hydroxybutyric acid (GHB) is a naturally occurring transmitter in the mammalian brain, related to sleep regulation and possibly to energy balance in diving or hibernating animals. It has been used for almost 35 years as an intravenous agent for induction of anaesthesia and for long-term sedation. Its convincing pharmacological properties, without serious adresse effects on circulation or respiration, are compromised by its unpredictable duration of action. This is not a major problem with long-term sedation during ICU treatment. GHB has been used with good results for sedation of patients with severe brain injury, where it compares favourably with barbiturates. In animal studies, it seems to possess a protective action against hypoxia on a cellular and whole organ level. However, in some experimental animals GHB has been shown to produce seizure-like activities, and the compound is being used to produce absence-like seizures. GHB has been used in our ICU for years to provide adequate sedation for patients under controlled ventilation or for patients figthing the respirator during spontaneous respiration. No serious side effects were observed in these patients, while in some patients under haemodialysis hypernatraemia and metabolic alkalosis developed; both were reversible after discontinuation of GHB and restriction of additional sodium input (Somsanit, the commercially available GHB preparation in Germany, contains 9.2 mmol sodium/g; the daily dose averages 20–40 g GHB, i.e. 180–370 mmol sodium). Patients and methods. In 31 patients after major abdominal surgery, sedation was established with GHB 50 mg/kg BW injected via perfusion pump over a 20-min period. No centrally acting medication had been given for at least 2 h. A computer-based multichannel EEG system (CATEEM, MediSyst, Linden) was used, allowing for fast Fourier transformation, spectral analysis and topographical brain mapping. EEG during induction of sedation was followed after a baseline EEG (10 min) had been recorded. Patients receiving long-term sedation were studied daily for an additional 15-min period. Corresponding well to the clinical findings, EEG pattern changed to a slow delta-theta or delta-only rhythm within 10 min of the start of injection. Alpha and beta power decreased, while delta activity exhibited an increase. All changes were most obvious in frontal and central areas of the brain. In about one out of three patients, a burst – suppression pattern developed. Since automatic processing of EEG may fail to detect special patterns like the looked-for 3/s spikes and waves, the raw EEG was analysed visually by an expert neurologist. Both processed and conventionally analysed EEG were free of any seizure-like electrical activity. Conclusion. We conclude that animal data may not apply to the use of GHB in humans, provided the dose is limited to the clinical needs. GHB is used in clinical practice in doses twice as high, or even higher, than the one we use for induction, without obvious side effects. However, the suppression of theta rhythm we observed in about half of the patients studied may indicate that even less than 50 mg/kg BW might be sufficient for adequate sedation.

Preoperative acute hypervolemic hemodilution with hydroxyethylstarch: an alternative to acute normovolemic hemodilution?

Acute normovolemic hemodilution (ANH) may help to reduce demand for homologous blood but requires extra time and apparatus.A more simple procedure is acute hypervolemic hemodilution (HHD), where hydroxyethylstarch is administered preoperatively without removal of blood. In a prospectively randomized study we compared ANH (preoperatively 15 mL/kg autologous blood removal and replacement with 15 mL/kg of hydroxyethylstarch with HHD (15 mL/kg of hydroxyethylstarch administered preoperatively) in 49 patients undergoing hip arthroplasty. To avoid excessive intravascular volume, we used the vasodilating effect of isoflurane. No significant differences were found between groups (ANH, n = 23; HHD, n = 26) for intraoperative blood loss (ANH versus HHD, median [minimum-maximum]); 545 [295-785] mL versus 520 [315-825] mL) and postoperative blood loss (730 [525-945] mL versus 780 [495-895] mL), postoperative hemoglobin, hematocrit, platelet count or coagulation variables, and transfusion requirements (ANH 43% versus HHD 35% of patients received homologous blood) (P > 0.05). Heart rate did not change significantly in either group. In the ANH group mean arterial blood pressure (MAP) decreased after hemodilution (P < 0.05) while in the HHD group MAP did not change over time. Mean time required to perform ANH was 58 (46-62) min versus HHD 16 (12-19) min (P < 0.05). Costs for ANH were

Plasma catecholamine levels following tracheal and intravenous epinephrine administration in swine

63.60 USD and for HHD

A lower solubility recommends the use of desflurane more than isoflurane, halothane, and enflurane under low-flow conditions.

32.75 USD (labor costs not included). In orthopedic patients undergoing hip replacement with a predicted blood loss of about 1000 mL, HHD seems to be a simple as well as time- and cost-saving alternative for ANH. (Anesth Analg 1997;84:26-30)

Plasma epinephrine levels after epinephrine administration using different tracheal administration techniques in an adult CPR porcine model

We compared plasma epinephrine levels after three different tracheal epinephrine application techniques and intravenous injection in male and female anesthetized and paralyzed domestic pigs. Epinephrine was administered intravenously (10 microg/kg) (group i.v.) or tracheally (100 microg/kg) either by direct injection into the upper end of the tracheal tube (group Tube), via a suction tube placed into the bronchial system (group Catheter) or using an EDGAR tube (group EDGAR), each group: n = 8. Arterial plasma samples were drawn before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7 and 10 min after epinephrine administration. Plasma concentrations of epinephrine were measured with high pressure liquid chromatography using electrochemical detection. Analysis was performed by regression analysis for correlated data. Total plasma epinephrine concentrations showed a significant increase within 0.5 min in all groups. However, peak plasma epinephrine levels in group i.v. were significantly higher than in tracheal groups, while no differences between tracheal groups over the time were found. We conclude that in swine with spontaneous circulation tracheal instillation techniques using special devices such as suction tubes or EDGAR tubes result in onset and peak plasma epinephrine levels equivalent to those after direct injection into the upper end of the tracheal tube.

Intravenous clonidine decreases minimum end-tidal isoflurane for induction of electroencephalographic burst suppression.

STUDY OBJECTIVE To determine whether the lower solubility of desflurane, over that of isoflurane, enflurane, and halothane, favors its use in low-flow anesthesia. DESIGN Prospective clinical study. SETTING Technical University of Munich. PATIENTS 40 elderly (> or = 65 yrs), ASA physical status II and III surgical patients. INTERVENTIONS All patients were anesthetized and received delivered concentrations (FD) of 4% desflurane, 1.5% isoflurane, 1.8% enflurane, or 0.9% halothane (n = 10 patients for each anesthetic) in a fresh gas inflow of 3 L/min (high-flow), until end-tidal target concentrations (FA) of 2% desflurane, 0.5% isoflurane, 0.6% enflurane, and 0.3% halothane were obtained. After 30 minutes, the inflow was decreased to 1 L/min (low-flow), and the FD and the inspired concentration (FI) were adjusted to maintain the target concentration. MEASUREMENTS AND MAIN RESULTS The concentrations of the halogenated anesthetics, as well as nitrous oxide, oxygen (O2), and carbon dioxide, were measured in delivered gas at the common gas outlet and at the endotracheal tube connector. Transcutaneous O2 saturation, noninvasive blood pressure, and heart rate were also measured. During the first 30 minutes of high-flow administration, the target concentration was attained sooner with desflurane than with isoflurane, enflurane, or halothane (median levels: 4 min vs. 6 min, 8 min, or 10 min; p < 0.01). After the reduction of inflow to 1 L/min, FD had to be materially increased to maintain F1 and FA for the more soluble anesthetics, but not for desflurane. CONCLUSIONS At low flows, FD provides a reasonable surrogate of F1 and FA for desflurane, but not for isoflurane, enflurane, or halothane. The rapid and predictable titrability of desflurane favors its safe use in low-flow technique.

Ein alternatives Konzept für den Blutersatz bei der Massivtransfusion

The aim of the study was to compare arterial plasma epinephrine levels after tracheal epinephrine application using three different tracheal instillation techniques at different tracheal levels in a porcine adult cardiopulmonary resuscitation model. In the prospective, randomized study, electrically-induced cardiopulmonary arrest was applied to 32 anaesthetized and paralyzed domestic pigs. After 3 min of cardiopulmonary arrest and 2 min of external chest compressions using a pneumatic compression device and mechanical ventilation, epinephrine was administered intravenously (20 microg/kg) or tracheally (50 microg/kg): using either direct injection into the upper end of the tracheal tube, via a catheter placed into the bronchial system and using a special tracheal application tube. In each group, there were eight pigs. Arterial blood samples were taken before and up to 10 min after epinephrine administration. Regression analysis was performed of the correlated data. The values of mean arterial blood pressure and end-tidal CO(2) during the time of observation did not differ between groups. Total plasma epinephrine concentrations showed a significant increase in all groups, but with no difference between the tracheal groups. However, peak epinephrine levels in the intravenous group were significantly higher than in tracheal groups. We conclude that administration using three different tracheal instillation levels result in similar onset and peak plasma epinephrine levels in this setting and therefore the preferred method of tracheal epinephrine application for cardiopulmonary resuscitation may be selected by other criteria.

The time required to perform different methods for endotracheal drug administration during CPR

The aim of this study was to determine the individual end-tidal isoflurane (ET ISO) threshold concentration for the induction of electroencephalographic (EEG) burst suppression with and without intravenous (IV) clonidine and to evaluate the EEG and cardiovascular response to skin incision during isoflurane/N2 O anesthesia. Thirty-nine patients (ASA physical status I or II, 20-68 yr of age) undergoing orthopedic surgery were randomly assigned to receive IV saline (n = 20) or IV clonidine (3 micro g/kg, n = 19). After detection of isoflurane-induced burst suppression, ET ISO was decreased in 0.1% ET steps until burst suppression diminished. Median minimum ET ISO for induction of burst suppression was 1.4% in the saline group and 0.9% in the clonidine group (P < 0.05). Before skin incision, EEG alpha 2 activity was significantly higher in the clonidine group compared with saline group. Fourteen patients (70%) in the saline group and 12 patients (63%) in the clonidine group showed a cardiovascular response to skin incision. After skin incision, EEG alpha 2 power was significantly decreased in both groups. A significant increase of delta activity was only found in the saline group. We conclude that the known minimum alveolar anesthetic concentration reduction of clonidine seems to be due to a direct cerebral action. (Anesth Analg 1997;85:193-8)

Die „Hypervolämische Hämodilution“ (HHD): Eine einfache Alternative zur isovolämischen Variante

ZusammenfassungGfundlagenAdäquater Blutersatz gehört insbesondere bei großen chirurgischen Eingriffen zu den vordringlichsten Aufgaben des Anästhesisten. Je nach Geschwindigkeit und Umfang des auftretenden Blutverlustes stehen hierfür unterschiedliche Therapiekonzepte im Vordergrund. Bei protrahiert auftretenden, intraoperativen Blutverlusten haben sich etablierte Infusions- und Transfusionsschemata mit dem primären Einsatz von kristallinen und kolloidalen Volumenersatzlösungen bewährt. Die zunehmende Anzahl von Operationen, bei denen von vornherein mit großen Blutverlusten gerechnet werden muß, erfordert die Entwicklung neuer Konzepte des Vorgehens, um bei solchermaßen “geplanten” Massivtransfusionen die auftretenden Komplikationen im Vorfeld zu minimieren bzw. zu verhindern.MethodikUm einer dilutionsbedingten Koagulopathie und Thrombozytopenie mit daraus resultierender verstärkter Blutungsneigung zu begegnen, wird auf kolloidale Plasmaexpander verzichtet und ein entstehender Volumenverlust von Beginn an mit Fresh-frozen-Plasma ausgeglichen. Entsprechend einer patientenadaptierten Interventionsgrenze erfolgt die Substitution von Erythrozyten und Thrombozyten. Dabei ist vor allem der zeitgerechte Ersatz entscheidend. Grundsätzlich können spezielle Geräte zur Massentransfusion verwendet werden, diese sind aber kostenintensiv und erfordern speziell geschultes Personal. Um diese Nachteile zu egalisieren, wurde ein einfacheres und kostengünstigeres Konzept, bestehend aus einem dreilumigen 12F-Katheter (Fa. Arrow) jeweils einem 51, fassenden Infusionsbeutel (MTSM®, Fa. MTK) für die Erythrozytenkonzentrate und die Fresh-frozen-Plasmen, zwei Infusionspumpen (Intramat®, Fa. MSB, maximale Infusionsgeschwindigkeit je 165 ml/min) mit jeweils einem Blutwärmer (H250 INT. Fa. Level 1® Technologies Inc.), entwickelt. An den Erythrozytenkonzentratbeuteln ist zusätzlich ein Autotransfusionsgerät angeschlossen, um gegebenenfalls intraoperativ gewonnene autologe Erythrozyten zurückführen zu können.ErgebnisseDie Kosten für die Grundausstattung belaufen sich auf etwa 100.000 ATS, die Einmalprodukte für je eine Einheit etwa 1750,-ATS.SchlußfolgerungenDas vorgestellte Transfusionskonzept sowie die apparative Ausstattung wurde bei “geplanten” massivtransfusionen während ausgedehnter chirurgischer Eingriffe mit Erfolg eingesetzt.

Wertigkeit der endexspiratorischen CO2-Messung bei der Reanimation

We compared the times necessary to perform different endotracheal drug application techniques during CPR. In a simulated CPR situation with a mannequin 28 paramedics and seven emergency physicians performed different drug instillation techniques in a randomized manner: direct injection into the upper end of the endotracheal tube (group tube), via a suction catheter placed into the bronchial system (group suction catheter), via a flexible venous catheter placed into the bronchial system (group venous catheter), using an EDGAR tube (an endotracheal tube with an injection channel within the wall of the tube (group EDGAR). We measured the time necessary to prepare the drug solution and compared the time necessary to prepare and perform each instillation method and the time the ventilation was interrupted. Comparison between groups was performed by the Kruskal-Wallis test. It took significantly longer to perform the more complicated techniques using suction catheters (26; 18 54 s) and venous catheters (30; 22-50 s) compared to the other two groups (median; min-max) (p < 0.05). No differences concerning the application time were found between the group tube (7; 5 14 s) and group EDGAR (8; 5-13 s). The time of interruption of chest compressions and ventilation: group suction tube (11; 5-19 s) and group catheter (12; 6-18 s) was significant longer than in group tube (5; 2-9 s) (p < 0.05). In group EDGAR the connection ventilator-tube remained intact due to its concept of drug application. The use of special devices such as suction catheters or venous catheters for endotracheal instillation during CPR results in significantly longer preparation and instillation times with a longer interruption of the oxygen supply and chest compressions.