UNLABELLED:The minimum alveolar concentration (MAC) of a volatile anesthetic defines anesthetic potency in terms of a suppressed motor response to a noxious stimulus. Therefore, the MAC of an anesthetic might in part reflect depression of motor neuron excitability. In the present study we evaluated the effect of isoflurane (ISO) on neurons in the substantia gelatinosa driven synaptically by putative nociceptive inputs in an in vitro spinal cord preparation of the rat. Whole-cell patch-clamp recordings were performed in neurons with their soma in the substantia gelatinosa of transverse rat spinal cord slices. We investigated the effect of ISO on excitatory postsynaptic currents (EPSC) evoked by dorsal root stimulation (eEPSC), spontaneous (sEPSC), and miniature (mEPSC) EPSC. ISO reversibly reduced the amplitude of eEPSC to 39% +/- 22% versus control. ISO decreased the frequency of sEPSC and mEPSC to 39% +/- 26% and 63% +/- 7%. Neither the amplitudes nor the kinetics of mEPSC and sEPSC were altered by ISO. We conclude that ISO depresses glutamatergic synaptic transmission of putative nociceptive primary-afferent inputs, presumably by reducing the release of the excitatory transmitter. This effect may contribute to an antinociceptive action of volatile anesthetics at the spinal cord level. IMPLICATIONS:The present electrophysiological in vitro experiments provide evidence that the volatile anesthetic isoflurane reduces excitatory transmitter release at the first site of synaptic integration of nociceptive inputs, the spinal cord superficial dorsal horn. This effect may contribute to the anesthetic action of volatile anesthetics at the spinal cord level.

Isoflurane (ISO) increased the agonist-induced chloride flux through the gamma-aminobutyric acid A receptor (GABA(A)R). This may reflect an anesthetic-induced increase in the apparent agonist affinity. A dual effect of anesthetics was postulated for both the nicotinic acetylcholine receptor (nAChR) and the GABA(A)R. We tested the hypothesis that, in addition to a blocking effect, ISO increases gamma-aminobutyric acid (GABA)-gated currents through recombinant GABA(A)R channels. HEK293 cells were transfected with rat cDNA for alpha(1),beta(2),gamma(2L) subunits. Currents elicited by 1 mM or 0. 01 mM GABA, respectively, alone, or with increasing concentrations of ISO, were recorded by using standard patch clamp techniques. ISO reduced the peak current elicited by 1 mM GABA. Currents induced by 0.01 mM GABA were potentiated by small ISO (twofold at 0.5 mM ISO) and inhibited by larger concentrations. Withdrawal of ISO and GABA induced rebound currents, suggesting an open-channel block by ISO. These currents increased with increasing concentrations of ISO. At large concentrations of ISO, the inhibitory effect predominated and was caused by, at least partly, an open-channel block. At small concentrations of ISO, potentiation of the GABA-gated currents was more prominent. This dual action of ISO indicates different binding sites at the GABA(A)R. The balance between potentiation and block depends on the concentrations of both ISO and GABA.

Acid aspiration syndrome still contributes to the few anaesthesia-related deaths in caesarean section. Although none of the numerous measures intended to prevent such fatalities is based on clear evidence, many different regimens are being used. As obstetric acid aspiration syndrome occurs mainly in general anaesthesia, using regional techniques wherever possible may be the most effective prophylactic measure.

Haptelmeier, G.; Haseneder, R; Scheller, M; Neumahr, S; Schneck, H.; Kochs, E. Author Information

Hapfelmeier, G.; Haseneder, R.; Scheller, M.; Neumahr, S.; Kochs, E. Author Information

Institut für Anaesthesiologie der Technischen Universltät München, Ismaninger Str. 22, D-81675 Munich, Germany

E. Kochs Institut für Anaesthesiologie der Technischen Universität München, Ismaninger Str 22, D-81675 Munich, Germany

UNLABELLED:We surveyed routine anesthetic practice and measures to prevent acid aspiration syndrome (AAS) in patients undergoing cesarean section (CS) throughout Germany. Of 1061 questionnaires, 81.9% were returned. For scheduled CS, general anesthesia was used in 63% of cases, and for urgent CS, it was used in 82% of cases. Regional anesthesia was used less often for both scheduled and urgent CS in smaller (< or =500 deliveries/yr; 28% and 16%, respectively) than in medium-sized (500-1000 deliveries/yr; 42% and 19%, respectively) or major obstetric departments (>1000 deliveries/yr; 45% and 21%, respectively). Among the regional techniques, epidural anesthesia (59%) was preferred more than spinal anesthesia (40%) in scheduled CS. In urgent CS, spinal anesthesia predominated (56% vs 42%). Pharmacological AAS prophylaxis is routinely used in 69% (68%) of departments before elective (urgent) CS under general anesthesia and in 52% under regional anesthesia. H2-blocking drugs are preferred for AAS prophylaxis over H2-blocker plus sodium citrate and sodium citrate alone. Both the incidence of and the mortality from AAS at CS are very low in Germany (<1 fatality per year). Nevertheless, AAS prophylaxis deserves more widespread use in obstetric anesthesia and in other patients at risk (e.g., children, outpatients). IMPLICATIONS:According to a countrywide survey, the use of regional anesthesia for cesarean section and pharmacological prophylaxis of acid aspiration syndrome is considerably less common in Germany than in the United States, United Kingdom, or other European countries.

A survey of all German hospitals providing obstetric anesthesia was performed in 1997 (n = 1061, recovery rate 82%; comprising about 700,000 deliveries and 115,000 cesareans, resp.) concerning the routine prophylactic measures for acid aspiration syndrome (AAS) in pregnant patients and before obstetric procedures (i.e., prevention of aspiration by positioning, Sellick's manoeuvre, reduction of intragastric volume, or reduction of gastric content acidity). In pregnant patients, any prophylaxis of AAS is performed in 36%. Of the patients expecting delivery in the labour ward, only 7% receive pharmacological AAS treatment. Before scheduled (urgent, non-emergency) cesarean section in general anesthesia, 93% (94%) of patients receive prophylactic treatment, either pharmacological or non-pharmacological. Before regional anesthesia, the corresponding numbers are 52% for both scheduled or urgent CS.

A survey of all German hospitals providing obstetric anesthesia was performed in 1997 (n=1061, recovery rate 82%; comprising about 700 000 deliveries and 115 000 cesareans, resp.) concerning the routine prophylactic measures for acid aspiration syndrome (AAS) in pregnant patients and before obstetric procedures (i. e., prevention of aspiration by positioning, Sellick's manoeuvre, reduction of intragastric volume, or reduction of gastric content acidity). In pregnant patients, any prophylaxis of ABS is performed in 36%. Of the patients expecting delivery in the labour ward, only 7% receive pharmacological AAS treatment. Before scheduled (urgent, non-emergency) cesarean section in general anesthesia, 93 % (94%) of patients receive prophylactic treatment, either pharmacological or non-pharmacological. Before regional anesthesia, the corresponding numbers are 52% for both scheduled or urgent CS.

P-1 Introduction: The GABAA receptor complex is the major inhibitory ligand-gated receptor in the mammalian CNS. This receptor is sensitive to many anaesthetics. A pentamere is formed from five out of 15 different subunits known so far (α1-6, β1-3, γ1-3 and ρ1-2). The most common wildtype of the receptor is α1β2γ2. The respective composition causes differences in sensitivity to various drugs. Methods: To prepare a well defined GABAA receptor for electrophysiological experiments, plasmides of heterologous DNA are introduced into eukaryotic mammalian cells by means of 'transfection'. Human embryonic kidney (HEK) cells or HeLa cells (carcinoma of the cervix) are most appropriate. Common techniques of transfection are: calcium phosphate, lipofectine, and electroporation. In the latter case, plasmides enter the cell through small holes created by short current pulses of about 300 V. Along the pattern defined by the plasmide DNA, the cell expresses receptor proteins, which are subsequently incorporated into the membrane. This allows for direct investigation of a well defined receptor within a natural membrane surrounding. Comparison of different pentamere compositions could further elucidate the importance of each single subunit for the effects of a given drug. Results: Transfection is successful in about 30% of the cells. The cells are easily studied with standard patch-clamp methods in the whole cell configuration. The small size of the cells complies well with the use of sophisticated techniques for rapid exchange of solutions. Thus, the effects of anaesthetics can be studied with a very high resolution over time, and the kinetics of the receptor can be characterized in detail. Conclusion: Our first results point to a considerable increase of transmembrane current under the influence of isoflurane. This effect would favourably comply with the effect expected with anaesthetic drugs.

A survey of all German hospitals providing obstetric anaesthesia in 1997 (n =1061, recovery rate 82% comprising 115 000 Caesarean sections revealed that most Caesarean sections (CS) are performed under general anaesthesia (GA). For elective CS, the average was 63 %, and 82 % for urgent (not emergency) section. Succinylcholine is the standard neuromuscular blocker for intubation. Of the regional techniques, epidural continuous anaesthesia (ED) is preferred for elective CS (59 %) over subarachnoid (SA, 10 %) and combined epidural and subarachnoid anaesthesia (CSE). In urgent CS, SA is used more often (56 %) than ED (42 %) and CSE. With increasing number of births per year, the use of regional techniques is more common.

(1) Nitric oxide (NO) synthase inhibitors (NOS-I) such as L-Name (N(G)-nitro L-arginine methyl ester) and L-NMMA (N(G)-monomethyl L-arginine) may enhance anesthesia indirectly by inhibiting the NO pathway. Moreover, NOS-I interact directly with receptor proteins. In an animal study, L-NMMA potentiated muscle relaxants. (2) The present experiments investigate the effects of L-NMMA, L-Name, and L-arginine on the nicotinic acetylcholine receptor channel (nAChR) using patch clamp techniques and a piezo-driven application system. Both NOS-I appear to directly interact with the nAChR in the open as well as in the closed conformation. L-Arginine has no effect.

Scheller, Michaela MD; Neumahr, Susanne MD; Kochs, Eberhard MD; Franke, Christian PhDAuthor Information

A survey of all German hospitals providing obstetric anaesthesia in 1997 (n = 1061, recovery rate 82% comprising 115,000 Caesarean sections revealed that most Caesarean sections (CS) are performed under general anaesthesia (GA). For elective CS, the average was 63%, and 82% for urgent (non-emergency) section. Succinylcholine is the standard neuromuscular blocker for intubation. Of the regional techniques, epidural continuous anaesthesia (ED) is preferred for elective CS (59%) over subarachnoid (SA, 10%) and combined epidural and subarachnoid anaesthesia (CSE). In urgent CS, SA is used more often (56%) than ED (42%) and CSE. With increasing number of births per year, the use of regional techniques is more common.

Background This study was performed to elucidate and compare the effects of sevoflurane and of isoflurane on the nicotinic acetylcholine receptor of mouse myotubes. The experiments were done with special reference to anesthetic concentrations considerably less than those used for clinical anesthesia. Methods The patch-clamp technique was used to record acetylcholine-activated currents from the embryonic type of the nicotinic acetylcholine receptor in the outside-out mode. A piezo-driven liquid filament switch was used for the ultrafast application of acetylcholine alone or in combination with isoflurane or sevoflurane. In addition, the patches were preexposed to either anesthetic, preceding the activation with acetylcholine. Results The current elicited by acetylcholine was reduced reversibly and in a concentration-dependent manner by both anesthetics, which were equally effective. Preexposure of the patches to isoflurane or sevoflurane showed an additional inhibition that was present at micromolar concentrations. The time courses of current decay could be fitted by single exponentials for isoflurane. At higher concentrations of sevoflurane, the current decay became biexponential. In contrast to isoflurane, sevoflurane increased the time constants of desensitization when applied in low concentrations. Conclusions At the nicotinic acetylcholine receptor, isoflurane and sevoflurane act primarily through the same mechanisms: Both affect the open and the closed state of the channels in concentrations equal to and less than those encountered clinically. The kinetics of desensitization, however, are altered in a different manner. Thus there may be several different sites of interaction.