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Summary Aim As a result of healthcare changes, interhospital transfer has become common in the care even of patients with severely deteriorated cardiopulmonary function. This study describes experience with the use of a specially downsized, lightweight extracorporeal circulation system (Emergency-MECC) which enables percutaneous cardiopulmonary bypass support in resistant cases of severe cardiac and cardiopulmonary failure. Methods Between March 2006 and June 2007, the Emergency-MECC system, consisting of a centrifugal pump and a membrane oxygenator, was used to facilitate interhospital transfer of five adults. The technique included percutaneous cannulation, femoro-femoral venoarterial (n = 4) and femoro-jugular venovenous (n = 1) life support by extracorporeal membrane oxygenation. Results Bedside cannulation was uneventful and the extracorporeal circulation support achieved adequate systemic blood flow and oxygen delivery in all cases. Vasopressor support could be immediately reduced and hypoxaemia was treated effectively. During interhospital transfer (air ambulance in three and ground ambulance in two cases), no technical complication occurred. Hospital survival rate was 80%. Conclusions The Emergency-MECC system is safe, rapid and highly effective in restoring blood flow and oxygen delivery. Interhospital transfer on cardiopulmonary bypass was made possible without extended technical or personnel support.

Background. Occupational exposure to volatile anaesthetics cannot be completely avoided even in modern operating theatres. In 1997, the staff exposure dureing balanced anaesthesia in our hospital was low (sevoflurane 0.49 ppm; N 2 O 11.5 ppm. In 1999, N 2 O was completely omitted at our hospital, therefore, exposure to volatile anaesthetics, namely sevoflurane, might have increased. Methods. Environmental exposure was measured by photoacoustic infrared spectrometry. To determine the personal exposure and to compare it with environmental exposure, 14 anaesthetists wore diffusion samplers near their breathing zones for 1 week. Results. The median environmental concentration of sevoflurane was between 0.09 and 0.21 ppm in central operating the atres and between 0 and 24,8 ppm in intervention rooms. The median personal conCondusion. The occupational exposure to volatile anaesthetics is not higher using sevoflurane along compared to the combination of sevoflurane and N 2 O. In addition, the data acquired from environmentaland personal measurements showed similar results.

Background Autoregressive modeling with exogenous input of middle latency auditory evoked potentials (A-Line autoregressive index [AAI]) has been proposed for monitoring depth of anesthesia in adults. The aim of this study was to evaluate the performance of the AAI during induction of anesthesia with sevoflurane and remifentanil in pediatric patients. Methods Twenty preschool children were anesthetized with sevoflurane and remifentanil. AAI, heart rate, and mean arterial pressure were compared for their ability to distinguish between different hypnotic states before inhalation induction and during sevoflurane anesthesia with and without remifentanil infusion. The prediction probability was calculated for discrimination between the predefined case milestones Awake, Spontaneous Eye Closure, and insertion of a laryngeal mask airway during general anesthesia (Laryngeal Mask Insertion). Results The AAI (mean +/- SD) in Awake children was 79 +/- 10, declining to 59 +/- 22 at Spontaneous Eye Closure and 34 +/- 13 when anesthetized. AAI values significantly overlapped between anesthetic states. For the AAI, the prediction probabilities regarding the ability to discriminate the hypnotic state at the case milestones Awake versus Spontaneous Eye Closure and Awake versus Laryngeal Mask Insertion were 0.77 and 0.99, respectively. In terms of prediction probability values, heart rate and mean arterial pressure were not indicative for anesthetic states. Remifentanil did not influence the AAI. Conclusion During induction of pediatric patients with sevoflurane, the AAI is of higher value in predicting anesthetic states than hemodynamic variables and reliably differentiates between the awake and anesthetized states. However, individual AAI values demonstrate significant variability and overlap between different clinical conditions.

UNLABELLED Sevoflurane and desflurane modulate autonomic nervous activity by different mechanisms. We tested the hypothesis that these anesthetics also exhibit different effects on short-term baroreflex regulation of arterial blood pressure. Forty ASA physical status I patients, aged 20 to 42 yr, were randomly assigned to receive either 1.0 minimum alveolar anesthetic concentration of sevoflurane or desflurane for the maintenance of anesthesia. Patients were studied during awake conditions and 20 min after the anesthesia induction using sinusoidal neck suction at 0.2 Hz (baroreflex response mediated mainly by vagal activity) and 0.1 Hz (baroreflex response mediated by vagal and sympathetic activity), whereas respiratory frequency was fixed at 0.25 Hz. RR interval and arterial blood pressure responses were evaluated by power spectral analysis and complex transfer function analysis. Sevoflurane and desflurane did not disturb the linear relationship between baroreceptor stimulation and effector response, expressed as squared coherence of signals, i.e., the equivalent of the correlation coefficient of power spectra. Sevoflurane and desflurane depressed the response of the heart rate to neck suction in a similar way without affecting the time delay between baroreceptor stimulation and vagal-mediated cardiac response. The gain of the transfer function between neck suction and oscillation in arterial blood pressure at 0.1 Hz decreased with sevoflurane and desflurane to comparable values. Both anesthetics increased the delay of systolic blood pressure response to baroreceptor stimulation from approximately 3.5 to 4.3 s. Baroreflex-mediated short-term control of arterial blood pressure is similar between desflurane and sevoflurane during steady-state conditions. IMPLICATIONS Despite exhibiting different effects on autonomic activity, sevoflurane and desflurane depress the baroreflex-mediated short-term control of heart rate and blood pressure in a similar manner.

Background This investigation prospectively evaluated the effect of oral premedication of two different doses of ketamine with midazolam and midazolam alone on the recovery of children after sevoflurane anaesthesia. Methods In a randomized, double-blind study, 79 children (aged 1-8 years, ASA physical status I or II) were assigned to receive one of three premedications in a volume of 0.5 ml x kg(-1): group 1 received midazolam 0.5 mg x kg(-1) (MD); group 2 received midazolam 0.5 mg x kg(-1) with ketamine 1.8 mg x kg(-1) (MK-1); and group 3 received midazolam 0.5 mg x kg(-1) with ketamine 3 mg x kg(-1) (MK-2). The reactions of the children during administration were noted. Anaesthesia was induced by facemask with incremental sevoflurane administration. All children received alfentanil (15 micro g x kg(-1)). Tracheal intubation was facilitated by mivacurium (0.2 mg x kg(-1)). Anaesthesia was maintained with sevoflurane and an additional dose of alfentanil, if necessary. During recovery, the time interval between discontinuation of anaesthesia and arousal (spontaneous ventilation, extubation) were recorded. Results Emergence (spontaneous ventilation, extubation) and recovery times (discharge, Aldrete score=9) did not differ significantly between groups (P=0.24, P=0.59 and P=0.145, respectively). Conclusions The combination of midazolam and ketamine as oral preanaesthetic medication did not significantly affect the recovery time of children after sevoflurane anaesthesia.

OBJECTIVE: The systemic renin-angiotensin system is highly activated during septic shock. This has focused interest in regulation of the adrenal angiotensin II type 2 receptor (AT2) as the target thought to mediate angiotensin II-induced adrenal catecholamine release during experimental sepsis in vivo. In addition, the influence of typical endogenous mediators of sepsis, such as proinflammatory cytokines and nitric oxide, on AT2 receptor expression should be investigated in vitro. DESIGN: Prospective animal trial followed by a controlled cell culture study. SETTING: Laboratory of the Department of Anesthesiology. SUBJECTS: Male Sprague-Dawley rats weighing 200-250 g, PC12 cell line. INTERVENTIONS: Rats were injected with lipopolysaccharide to stimulate Gram-negative sepsis or lipoteichoic acid to stimulate Gram-positive sepsis. AT2 receptor expression, abundance of the proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma), and nitric oxide synthase II expression have been determined in the adrenal gland. Rat adrenal pheochromocytoma cells were incubated with these cytokines or with the nitric oxide donors sodium nitroprusside or S-nitroso-N-acetylpenicillamine to investigate the regulation of AT2 receptors during severe inflammation on a cellular level. MEASUREMENTS AND MAIN RESULTS: In the adrenal gland, AT2 receptor expression was down-regulated in both models of sepsis, whereas tissue cytokine concentrations were elevated and nitric oxide synthase II expression was induced. Incubation of PC12 cells with proinflammatory cytokines resulted in a dose-dependent diminished expression of AT2 receptors, which was mimicked by incubation with nitric oxide donors. Blocking of cytokine-induced nitric oxide synthesis by co-incubation of PC12 cells with NG-nitro-l-arginine methyl ester prevented down-regulation of AT2 receptors. CONCLUSIONS: These findings show that in our model of sepsis, the expression of AT2 receptors in the adrenal gland is down-regulated in a nitric oxide-dependent manner. Because AT2 receptors are thought to be involved in adrenal catecholamine secretion in a stimulatory fashion, the diminished expression of AT2 receptors could play an important role in the pathogenesis of septic shock via impaired angiotensin II-induced adrenal catecholamine release, despite a strong activation of the systemic renin-angiotensin system.

Objective: Although no dose-response relationship exists for the health risks associated with the occupational exposure to inhaled anaesthetics, public health authorities recommend threshold values. The aim of the present study was to assess whether and to what extent these threshold values are exceeded in surgeons and circulating nurses of an Eastern European university hospital, before and after measures had been taken to reduce occupational exposure. Methods: At nine workplaces, occupational exposure to nitrous oxide and the volatile anaesthetic used (halothane or isoflurane) was measured within the breathing zones of surgeons and circulating nurses by means of photoacoustic infrared spectrometry. The measurements were carried out in 1996 and were repeated in 1997 after the installation of active scavenging devices at five workplaces, and an air-conditioning system at one workplace. Results: Occupational exposure to nitrous oxide and halothane or isoflurane was lower in 1997 compared with that of 1996. In 1996, 89% of the nitrous oxide values were above the European threshold value of 100 ppm, whereas in 1997 approximately 50% were above this limit. In 1996 the majority of the measurements for the volatile anaesthetics were already below 5 ppm halothane and 10 ppm isoflurane and the number of measurements exceeding these limits was further reduced in 1997. Conclusion: The measures taken were effective in reducing waste gas exposure. Nevertheless, further efforts are necessary, especially for nitrous oxide, to reach Western European standards and to minimise possible health risks. These efforts comprise the installation of (active) scavenging devices, air-conditioning systems and new anaesthesia machines at all workplaces, the use of low-flow anaesthesia, the replacement of inhaled anaesthetics by intravenous anaesthetics and an appropriate working technique.

We have investigated inspiratory and end-tidal gas composition during sevoflurane anaesthesia in a closed circle system with continuous gas flow (70 litre min-1, Physioflex) to determine possible accumulation of sevoflurane degradation products. During five abdominal operations in adults lasting more than 2 h, anaesthesia was maintained with an end-tidal concentration of 2% sevoflurane in 40% oxygen-air. The circle included an absorbing canister filled with 1 litre of fresh soda lime. Samples were obtained at the end of an expiration from the tracheal tube and from the inspiratory limb before, and at selected times after, addition of sevoflurane. The temperature of soda lime was 24.7 +/- 0.7 degrees C at the beginning and reached a maximum of 31.2 +/- 1.0 degrees C after 20-30 min, followed by a plateau. Inspiratory compound A (CH2F-O-C(= CF2)(CF3)) 3-8 ppm was detected after 10 min, but did not accumulate in the circle over 2 h without flushing. Expired concentrations were consistently lower with 1.5-3 ppm signalling absorption by patients. Calculated total amounts absorbed over 2 h varied between 2.0 and 7.2 ppm h. Other degradation products such as compound B or methanol were not detected. In summary, we did not detect sevoflurane metabolites with soda lime in significant amounts during closed circle anaesthesia with the Physioflex. The observed concentrations of compound A were below the threshold of nephrotoxicity in rats by a factor of more than 20.

There are a number of assays available to study genetic toxicity of inhalation anaesthetics. Those discussed in this review are the Ames Salmonella mutagenesis test and assays for structural chromosome aberrations, micronuclei (MN) and sister chromatid exchanges (SCEs). None of these assays showed abnormalities induced by volatile inhalation anaesthetics. Only Compound A induced a slight increase in the number of SCEs. However, the implications of this in vitro study are unclear. Results of studies focussing on the effects of long-term occupational exposure to inhalation anaesthetics are controversial. Neither harmfulness nor safety of chronic exposure to low concentrations of inhalation anaesthetics have been proven. Although there is no clear evidence of harmfulness, there is general agreement that occupational exposure should be minimized for precautionary reasons. This particularly applies to N2O. Therefore, occupational exposure standards have been established in many countries, though not yet for sevoflurane and desflurane. In Germany, occupational exposure can be kept below the threshold values, when working in operation theatres with a standard air conditioning system, a high-flow scavenging system, low leakage anaesthesia machines and preventative maintenance of equipment. Under these conditions occupational exposure is low even when using laryngeal mask airways and uncuffed tracheal tubes. Sevoflurane is a halocarbon, but is only partially halogenated and the only halogen it contains is fluorine. Sevoflurane, therefore, appears to have an insignificant effect on ozone depletion and its contribution to the greenhouse effect is negligible.

Background: Currently, there are no data available concerning the occupational exposure to desflurane during general anaesthesia. This prospective, randomized study reports on occupational exposure to desflurane, compared to isoflurane, in a modern operation theatre (OT). Methods: The study was performed in an OT equipped with a modern air-conditioning system and with a low-leakage anaesthesia machine connected to a central scavenging system. Trace concentrations of the anaesthetics were measured continuously by means of a photoacoustic infrared spectrometer during general anaesthesia in 30 patients undergoing eye surgery. Values were obtained within the breathing zone of the anaesthetist, the surgeon, the auxiliary nurse and at the mouth of the patient. Results: Desflurane and isoflurane were administered with median (range) endtidal concentrations of 4.7 (3.8–10.3) vol% and 0.9 (0.6–1.4) vol%, respectively. The personnel-related median values of the average trace concentrations of desflurane and isoflurane were 0.5 (0.01–7.5) ppm and 0.2 (0.01–1.6) ppm, respectively. Conclusions: Occupational exposure to desflurane is low in the environment of a modern OT, even though it has to be administered in approximately 5-fold higher concentrations compared to isoflurane.

Background Nitrous oxide has been shown inconsistently to impair the oxidative function of neutrophils. The choice of the stimulus, receptor agonists, or stimuli acting independent of receptors seems to determine whether nitrous oxide impairs the oxidative functions, suggesting an interference with the cytosolic signaling of neutrophils. Methods Production of hydrogen peroxide by neutrophils was assessed using flow cytometric analysis. N-formyl-methionyl-leucyl-phenylalanine (FMLP), C5a, dioctanylglycerol, and phorbol-12-myristate-13-acetate were used as stimuli. In addition, the expression of receptors for FMLP and the cytosolic-free calcium response of cells were measured. Results Nitrous oxide depresses C5a- or FMLP-induced generation of reactive oxygen derivatives in a concentration-dependent manner. However, the response with direct activation of protein kinase C was unaffected. Further, the number of FMLP receptors and the cytosolic calcium response were unaffected. Inhibition of the oxidative response was not reversible within the observation period of 4 h. Conclusions Nitrous oxide inhibited the intracellular signaling of the investigated G-protein-coupled receptors for chemotactic peptides. No interference of nitrous oxide with reduced nicotinamide adenine dinucleotide phosphate oxidase, the oxidative enzyme system of neutrophils, nor with its activation through protein kinase C was detected.

The purpose of this study was to analyse the clinical agreement between cardiac output measurements, obtained using a newly available continuous thermodilution technique, and the conventional intermittent bolus technique. Twenty-four cardiac surgical patients were intra-operatively monitored using both techniques. Additionally, two different averaging modes for the continuous thermodilution technique, either the previous 6 min (group 1) or 3 min (group 2) were compared. The mean difference between the continuous thermodilution technique and the intermittent bolus technique (bias), were calculated at eight selected time points. These ranged from -0.09 to 0.42 litres min-1 in group 1 and from -0.02 to 0.18 litres min-1 in group 2. There were significant differences at any time point between the groups. The relative error between continuous thermodilution and intermittent bolus techniques was15% for the majority of measurements and was significantly higher in group 1 compared with group 2 just prior to cardiopulmonary bypass. Thus, the continuous thermodilution technique produced a clinically acceptable level of accuracy compared with the intermittent bolus technique measurements, especially when using an averaging mode for the previous 3 min.

Low flow and closed system anaesthesia have considerable advantages in economy, limited atmospheric pollution, and maintenance of humidification and temperature. To benefit from these techniques leakage from the breathing system should be as low as possible. The sealing of the airway is crucial to ensure this. Therefore, we have investigated in 30 children, aged 2-6 yr, the effectiveness of the laryngeal mask airway (LMA) and the uncuffed tracheal tube (TT) for closed system paediatric anaesthesia, during positive pressure ventilation, in a prospective, randomized study. Ventilation was adequate in all cases with both devices. Loss of gas from the breathing system was less than 100 ml min-1 in 13 (87%) patients in the LMA and in 12 (80%) patients in the TT group, with a maximum of approximately 700 ml min-1 in the TT and approximately 350 ml min-1 in the LMA group. We conclude that the airway sealing with both devices was tight enough to perform low flow or closed system anaesthesia in paediatric patients aged 2-6 yr.

Object: To quantify the exposure of operating room personnel to sevoflurane and nitrous oxide. Design: Prospective study at a university hospital. Methods: In 25 patients undergoing elective surgical procedures, anaesthesia was induced with thiopentone/etomidate, vecuronium and fentanyl and maintained with fentanyl, sevoflurane in 35% oxygen and 65% nitrous oxide (N2O). Occupational exposure to sevoflurane and N2O was measured in the breathing zone of one representative of each of three personnel groups (anaesthetist, surgeon, auxiliary nurse) by means of a direct reading instrument using photoacoustic infrared spectrometry. Results: The mean trace concentrations of sevoflurane for the single anaesthetic procedures exceeded the 0.5 ppm level in more than 50% of the measurements. The 2 ppm level was not exceeded in the case of the anaesthetist and the surgeon, but was exceeded in 16% of the measurements for the auxiliary nurse. The level of 25 ppm N2O were exceeded in 28% of the measurements for the anaesthetist and in 16% of these for the surgeon and for the auxiliary nurse. Conclusions: To keep exposure low, sevoflurane and N2O were used in a modern working environment: a low-leakage anaesthesia machine, high room ventilation rates, scavenging system, no intermittent mask ventilation, low to medium concentrations of sevoflurane, and strict control of the cuff pressure. Nevertheless, exposure could not be kept under NIOSH threshold values in all cases.

Bei HNO-arztlichen Eingriffen unter Allgemeinanasthesie findet eine Kontamination der Operationssaalraumluft durch Narkosegase in subanasthetischen Konzentrationsbereichen (ml/m 3 =ppm) statt. Eine daraus resultierende chronische Exposition kann moglicherweise zu Gesundheitsschaden fuhren. Ziel dieser Studie war es, die Belastung des Operationspersonals zu quantifizieren. Mittels eines hochempfindlichen, direktanzeigenden Mesgerats wurde die Kontamination an der Leckagequelle „Mundoffnung des Patienten“ und die daraus fur Operateur und Anasthesist resultierende Belastung durch Isofluran und Stickoxydul in 2-min-Intervallen bestimmt. Die Messungen erfolgten unter modernen Arbeitsplatzbedingungen wahrend 20 HNO-arztlichen Eingriffen unter Allgemeinanasthesie. Trotz hoher Konzentrationen an der Mundoffnung der Patienten blieben die mittleren Belastungen fur das operative Personal bezuglich Isofluran unter der Grenzwertempfehlung von 10 ppm. Der Stickoxydulgrenzwert von 100 ppm wurde bei 20% der Eingriffe uberschritten. Der fur Beschaftigungsverbote fur schwangere Frauen masgebliche Schwellenwert von 25 ppm Stickoxydul wurde fur die Personengruppe „Operateur“ bei nahezu allen Eingriffen (93%) uberschritten. Leckagen am Beatmungstubus fuhren zu einer unerwunscht hohen Belastung des operativen Personals mit Stickoxydul. Eine Grenzwertuberschreitung findet wegen moderner Arbeitsbedingungen (Klimatechnik, Cuffdruckkontrolle) in den meisten Fallen nicht statt, sind aber dennoch zu hoch, um eine Tatigkeit gefahrdeter Personen (z.B. Schwangere) im Operationssaal (OP) zu gestatten. Die Belastung durch Isofluran ist dagegen als gering einzustufen.

Doppler cardiac output (CO) determination is discussed as a non-invasive alternative to CO estimation by thermodilution. This study was designed to compare the accuracy of a new transoesophageal Doppler device with the thermodilution technique. In 24 patients undergoing coronary artery bypass surgery, CO was determined simultaneously by the oesophageal Doppler (OD) and thermodilution (TD) method in triplicate for three sample episodes: after induction of anaesthesia during clinical steady-state conditions (A), after start of surgery (B), and after sternotomy (C). The agreement between ODCO and TDCO estimations was assessed by analysing the mean difference, indicating the systematic error, and analysing the distribution of differences between the two methods. The bias between ODCO and TDCO estimations was 0.38 (-0.06 to +0.81) L min-1 (mean and 95% confidence interval) for sample episode A, 0.48 (-0.11 to +1.1) L min-1 for sample episode B, and 0.69 (+0.08 to +1.3) L min-1 (P < 0.05 vs. zero) for sample episode C. Bias analysis of the log-transformed data revealed that 95% of the ODCO values differed from TDCO values by 43% below to 50% above for sample episode A, by 39% below to 95% above for sample episode B, and by 32% below to 96% above for sample episode C. Analysis of the changes in CO from sample episode A to B and from sample episode B to C, expressed as percentage values, showed a non-significant bias between the methods, but the 2 SD limits were +/-44% and +/-36% respectively. Our findings suggest that CO estimation by OD cannot replace estimation by the TD method.

In einer offenen, randomisierten, prospektiven und vergleichenden Studie zwischen Sevofluran und Enfluran wurden bei 30 nierengesunden Patienten die Serumfluoridkonzentrationen und die exokrine Nierenfunktion bis zum 3. postoperativen Tag untersucht. Die applizierte Dosis betrug in beiden Gruppen ca. 1,65 MAC-Stunden. Die maximale Serumfluoridkonzentration war mit 34,5 μmol/l nach Sevofluran fast doppelt so hoch wie nach Enfluran (19,4 μmol/l). 24 h nach Anasthesieende war die Serumfluoridkonzentration in der Sevoflurangruppe auf ca. 25% des Maximalwerts abgefallen, in der Enflurangruppe auf ca. 40% des Maximalwerts. Ab diesem Zeitpunkt war kein Unterschied mehr zwischen den beiden Gruppen nachweisbar. Die Fluoridbelastung (Area under the curve, AUC) war nach Sevofluran (688 μmol/l·h) etwas groser als nach Enfluran (591 μmol/l·h). Die Korrelation von MAC-Stunden (applizierte Dosis) und AUC war in beiden Gruppen besser als die von MAC-Stunden und maximaler Serumfluoridkonzentration. Veranderungen von Laborvariablen (Natrium, Osmolalitat, Kreatinin, Harnstoff und Harnsaure i.S., spez. Gewicht, Osmolalitat und pH-Wert i.U.), die auf eine Nierenschadigung hinweisen wurden, wurden nicht nachgewiesen.

Bei Kindern, dem wesentlichen Patientenkollektiv fur inhalative Narkoseeinleitungen, liegen nur geringe Erfahrungen mit dem vermutlich besonders geeigneten Sevofluran vor. In einer offenen, randomisierten Studie haben wir daher Einschlaf- und Aufwachzeiten, Atemwegsreflexe und Kreislaufwirkungen von Sevofluran (S) mit denen von Halothan (H) bei Kindern (Alter 1–10 Jahre) wahrend mindestens einstundigen Eingriffen verglichen. Mit Zustimmung der Ethikkommission wurden 40 Kinder der Risikogruppen ASA I und II nach schriftlicher Einwilligung der Eltern rekrutiert. Die Narkosen wurden ohne Pramedikation mit ansteigenden Konzentrationen von S oder H in N2O/O2 (65:35) induziert. Der Frischgasflow (FGF) betrug 6 l/min. Nach Relaxation und Intubation wurden die Narkosen mit S (Fi 2–2,4 Vol.-%) oder H (1,1–1,4 Vol-%) in N2O/O2 (65:35, 3 l/min) weitergefuhrt. Zur Ausleitung wurde der FGF auf 6 l/min erhoht. Fluoridspiegel wurden bei Einleitung, am Narkoseende sowie 70 min nach Narkose bestimmt. Die Gruppen waren biometrisch vergleichbar. Blutdruck und Herzfrequenz waren in beiden Gruppen stabil. Die Einschlafzeit betrug 183±32 (H) bzw. 129±34 s (S) (p

Da Gesundheitsschaden des Personals durch Spurenkonzentrationen von Lachgas nicht grundsatzlich auszuschliesen sind, existiert seit Ende 1993 in der Bundesrepublik Deutschland eine gesetzlich verbindliche Maximale Arbeitsplatzkonzentration (MAK) fur Lachgas von 100 ppm. Systematische Untersuchungen zur Lachgasbelastung in Aufwachraumen liegen derzeit nur stichprobenhaft vor. Ziel dieser Untersuchung war es, unter den Bedingungen einer modernen Klimatechnik an 5 Tagen uber jeweils 12 h die Exposition des Personals im Aufwachraum kontinuierlich zu bestimmen. Mittels eines direktanzeigenden, hochsensitiven Spurengasmonitors wurde die Schadstoffbelastung an 6 Arbeitsplatzen simultan und kontinuierlich analysiert. Insgesamt lag die durchschnittliche Belastung deutlich unter den MAK-Werten von 100 ppm. Selbst die amerikanischen Empfehlungen von 25 ppm wurden unterboten. Kurzzeitige Spitzenkonzentrationen von bis zu 25 ppm waren zeitlich mit einer Vollbelegung des Aufwachraums korreliert. Die gemessenen niedrigen Konzentrationen konnen auf mehrere Faktoren zugefuhrt werden: 1. Die Effektivitat der Klimatechnik mit 10,7 Wechseln pro Stunde ohne Rezirkulation, 2. die Raumgrose, 3. eine Transportzeit von ca. 15 min, wahrend der die Patienten Restkonzentrationen an Lachgas abatmen und 4. eine lange Verweildauer der Patienten im Aufwachraum und damit ein hoherer Anteil Patienten mit niedrigen Lachgaskonzentrationen in der Ausatemluft. Unter den genannten Bedingungen ware eine Beschaftigung schwangerer Mitarbeiterinnen im Aufwachraum der Tatigkeit im OP vorzuziehen. In Aufwachraumen mit anderen baulichen Voraussetzungen sollten systematische Messungen uber mehrere Tage durchgefuhrt werden, um eine Aussage bezuglich des Belastungsprofils treffen zu konnen.

BACKGROUND AND OBJECTIVE The present study investigated whether positioning of the heart during off-pump coronary artery bypass grafting leads to changes in regional cerebral oxygen saturation measured by near infrared spectroscopy. METHODS In 35 consecutive patients undergoing elective off-pump coronary artery bypass grafting, cerebral oxygen saturation was measured by near infrared spectroscopy. A 20% decrease from baseline values was considered to be cerebral hypoperfusion. Mean arterial pressure, cardiac index, arterial carbon dioxide partial pressure, central venous pressure, haemoglobin concentration, and body temperature were determined simultaneously. Each value was recorded at the following time points: at baseline; after positioning the heart for distal anastomoses of the left anterior descending artery, the circumflex, and the right coronary artery; after repositioning the heart; and after chest closure. Significant changes in each parameter from baseline were detected using repeated-measures analysis of variance. Determinants of cerebral oxygen saturation during surgery were analysed by means of generalized estimation equations. RESULTS Cerebral oxygen saturation remained constant during grafting of the left anterior descending artery and decreased significantly during grafting of the circumflex (P = 0.001) and the right coronary artery (P < 0.001). Cerebral hypoperfusion was found in seven (20%) patients. Changes in haemoglobin concentration (P = 0.014), arterial CO2 partial pressure (P = 0.001), cardiac output (P < 0.001), and central venous pressure (P = 0.014) determined alterations in cerebral oxygen saturation. CONCLUSION Positioning of the heart during off-pump coronary artery bypass grafting leads to a decrease in regional cerebral oxygen saturation. This decrease is associated with changes in cardiac output, haemoglobin concentration, arterial CO2 partial pressure, and central venous pressure.

Background: Although no dose–response relationship for the health risks associated with the occupational exposure to inhaled anaesthetics exists, public health authorities recommend threshold values. The aim of the present study was to assess if and to what extent these threshold values are exceeded in an eastern European university hospital before and after measures had been taken to reduce occupational exposure. Methods: At nine workplaces occupational exposure of anaesthetists to nitrous oxide and halothane or isoflurane was measured by means of photoacoustic infrared spectrometry. The measurements were carried out in 1996 and were repeated in 1997 after the installation of active scavenging devices at five workplaces and an air-conditioning system at one workplace. Results: Occupational exposure to nitrous oxide and halothane or isoflurane was lower in 1997 compared to 1996. In 1997 most of the nitrous oxide values still exceeded the threshold value of 100 ppm, whereas most of the halothane and isoflurane values were already below the threshold values of 5 ppm and 10 ppm in 1996. Conclusion: The measures taken were effective in reducing waste gas exposure. Nevertheless, further efforts are necessary, especially for nitrous oxide, to reach western European standards. These efforts comprise structural measures such as active scavenging devices and air-conditioning systems at all workplaces, the use of total intravenous anaesthesia, low-flow anaesthesia and an appropriate working technique.

Our study aimed to determine the role of cyclooxygenase-2 in the release of prostaglandin-(PG)-I2 following mesenteric traction during abdominal surgery. In a prospective double-blind, randomized, placebo-controlled study, 40 patients electively scheduled for non-laparoscopic abdominal surgery, were pretreated with the cyclooxygenase-2 inhibitor parecoxib (n=20) or placebo (n=20). Heart rate, arterial blood pressure, oxygenation ratio and plasma concentrations of the stable PGI2-metabolite 6-keto-PGF1alpha were compared between groups before injection of parecoxib (-40 min), immediately before mesenteric traction (0 min), and 5, 10, and 30 min thereafter. In addition, plasma concentrations of valdecoxib, the active metabolite of the prodrug parecoxib, were determined. Plasma concentrations of 6-keto-PGF1alpha and heart rate increased in both groups after mesenteric traction. There were no significant differences between groups at individual times in heart rate, arterial blood pressure and plasma concentrations of 6-keto-PGF1alpha. Oxygenation ratio decreased after 10 and 30 min following mesenteric traction in the parecoxib group with a significant difference between treatment groups at 10 and 30 min. Plasma concentrations of valdecoxib revealed therapeutic values. Our data indicate that PGI2 release following mesenteric traction is mediated by cyclooxygenase-1.

We have compared occupational exposure to isoflurane and desflurane during cardiopulmonary bypass, with and without a scavenging system at the membrane oxygenator outlet. Trace concentrations of volatile anaesthetics were measured by a direct reading instrument in 40 elective heart surgery procedures. Measurements were obtained in the breathing zones of the anaesthetist and perfusionist. When a scavenging system was used, median desflurane values were less than 0.3 ppm and isoflurane values less than 0.2 ppm. Without a scavenging system values were, in general, three- (isoflurane) to five- (desflurane) fold higher. We conclude that the use of a scavenging system at the membrane oxygenator outlet can reduce occupational exposure to volatile anaesthetics. We therefore recommend routine use of scavenging devices during cardiopulmonary bypass.

The reduced pressure response to vasopressin during acute sepsis has directed our interest to the regulation of vasopressin V1Areceptors. Rats were injected with lipopolysaccharide for induction of experimental gram-negative sepsis. V1Areceptor gene expression was downregulated in the liver, lung, kidney, and heart during endotoxemia. Inasmuch as the concentrations of proinflammatory cytokines such as interleukin-1β, tumor necrosis factor-α, and interferon-γ were highly increased during sepsis, the influence of these cytokines on V1Areceptor expression was investigated in primary cultures of hepatocytes and in the aortic vascular smooth muscle cell line A7r5. V1Areceptor expression was downregulated by the cytokines in a nitric oxide-independent manner. Blood pressure dose-response studies after injection of endotoxin showed a diminished responsiveness to the selective V1receptor agonist Phe2,Ile3,Orn8-vasopressin. Our data show that sepsis causes a downregulation of V1Areceptors and suggest that this effect is likely mediated by proinflammatory cytokines. We propose that this downregulation of V1Areceptors contributes to the attenuated responsiveness of blood pressure in response to vasopressin and, therefore, contributes to the circulatory failure in septic shock.

Our study aimed to characterize the mechanisms underlying the attenuated cardiovascular responsiveness toward the renin-angiotensin system during sepsis. For this purpose, we determined the effects of experimental Gram-negative and Gram-positive sepsis in rats. We found that sepsis led to a ubiquitous upregulation of NO synthase isoform II expression and to pronounced hypotension. Despite increased plasma renin activity and plasma angiotensin (Ang) II levels, plasma aldosterone concentrations were normal, and the blood pressure response to exogenous Ang II was markedly diminished in septic rats. Mimicking the fall of blood pressure during sepsis by short-term infusion of the NO donor sodium nitroprusside in normal rats did not alter their blood pressure response to exogenous Ang II. Therefore, we considered the possibility of an altered expression of Ang II receptors during sepsis. It turned out that Ang II type 1 receptor expression was markedly downregulated in all organs of septic rats. Further in vitro studies with rat renal mesangial cells showed that NO and a combination of proinflammatory cytokines (interleukin-1β, tumor necrosis factor-α, and interferon-γ) downregulated Ang II type 1 receptor expression in a synergistic fashion. In summary, our data suggest that sepsis causes a systemic downregulation of Ang II type 1 receptors that is likely mediated by proinflammatory cytokines and NO. We suggest that this downregulation of Ang II type 1 receptors is the main reason for the attenuated responsiveness of blood pressure and of aldosterone formation to Ang II and, therefore, contributes to the characteristic septic shock.

We have analysed the clinical agreement between two methods of continuous cardiac output measurement pulse contour analysis (PCCO) and a continuous thermodilution technique (CCO), were both compared with the intermittent bolus thermodilution technique (BCO). Measurements were performed in 26 cardiac surgical patients (groups 1 and 2, 13 patients each, with an ejection fraction > 45% and < 45%, respectively) at 12 selected times. During operation, mean differences (bias) between PCCO-BCO and CCO-BCO did not differ in either group. However, phenylephrine-induced increases in systemic vascular resistance (SVR) by approximately 60% resulted in significant differences. Significantly higher absolute bias values of PCCO-BCO compared with CCO-BCO were also found early after operation in the ICU. Thus PCCO and CCO provided comparable measurements during coronary bypass surgery. After marked changes in SVR, further calibration of the PCCO device is necessary.

Background Airway irritation was hypothesized to trigger the transient cardiovascular stimulation associated with desflurane. The authors administered desflurane during cardiopulmonary bypass (CPB), thus avoiding airway contact, and compared the effects of rapid increases of desflurane to 1.5 MAC on systemic vascular resistance index (SVRI) and catecholamine response to those of 1.5 MAC sevoflurane. Methods Forty-eight patients, undergoing elective coronary bypass surgery, were randomly allocated to receive either desflurane or sevoflurane during hypothermic (32-33 degrees C) nonpulsatile CPB at exhaust gas concentrations of 1.5 MAC for 15 min. SVRI was calculated at baseline, 1, 2, 3, 4, 5, 7, 9, 12, and 15 min after starting volatile anesthetics' delivery. Plasma catecholamine concentrations were determined in 12 desflurane-treated patients and 12 sevoflurane-treated patients at baseline, 5, and 15 min. Results The time-course of deltaSVRI, (changes in SVRI from baseline), from baseline to 5 min was significantly different between desflurane- and sevoflurane-treated patients, whereas there was no difference from 7 to 15 min. In the desflurane group, SVRI from 1 to 7 min remained unchanged to baseline level, thereafter declining to significantly lower values at 9, 12, and 15 min compared with values from 0 to 5 min, whereas sevoflurane produced an immediate and significant reduction in SVRI. With desflurane, catecholamine concentrations remained unchanged to baseline level at 5 and 15 min; with sevoflurane, they decreased with time. Conclusions The authors' results indicate that desflurane is associated with a different hemodynamic and catecholamine response compared with sevoflurane when administered into the oxygenator's gas supply line during CPB.

We report the findings of a study on exposure of operating room staff to sevoflurane, halothane and nitrous oxide during induction and maintenance of anaesthesia in children. Concentrations of anaesthetic agents in the operating theatre were measured directly by highly sensitive, photoacoustic infrared spectrometer during 20 anaesthetics. Samples were taken from the breathing zones of the anaesthetist and the circulating nurse. The operating theatre was of modern design with an air conditioning system providing 20 changes of air each hour. The threshold values of 100 ppm N2O, 50 ppm isoflurane and 10 ppm halothane recommended by the United Kingdom Committee for Occupational Safety and Health (COSH) were exceeded in several cases for a short time during mask induction. After tracheal intubation, trace concentrations of sevoflurane, halothane and N2O were mostly under the recommended levels and comparable to levels measured during adult anaesthesia.

Objective: The objective of this study was to evaluate whether chronic severe mitral regurgitation leads to an artifactual elevation of mixed venous oxygen saturation. Design: Prospective study. Setting: University hospital setting. Participants: Thirty patients with chronic severe mitral regurgitation undergoing surgery on the mitral valve and 25 patients without mitral regurgitation scheduled for elective coronary artery surgery. Interventions: Blood samples were simultaneously withdrawn from the distal port and the paceport of a pulmonary artery catheter. Measurements and Main Results: During steady-state anesthesia, oxygen saturation and hemoglobin concentration were measured. There was no difference between mean oxygen saturation in blood from the pulmonary artery and the right ventricle in patients with mitral regurgitation, no matter whether large v waves were present, and in patients without mitral regurgitation. The distribution of individual differences between mixed venous and right ventricular oxygen saturation did not differ between groups. Conclusions: Because mixed venous oxygen saturation is not affected by chronic severe mitral regurgitation, it can be used in patients with mitral regurgitation just as in patients without mitral regurgitation.

Study Objective: To compare the clinical efficacy and safety of sevoflurane and isoflurane when used for the maintenance of anesthesia in adult ASA I, II, and III inpatients undergoing surgical procedures of at least 1 hour's duration. Design: Phase III, randomized, open-label clinical trial. Setting: 12 international surgical units. Patients: 555 consenting inpatients undergoing surgeries of intermediate duration. Interventions: Subjects received either sevoflurane (n = 272) or isoflurane (n = 283) as their primary anesthetic drug, each administered in nitrous oxide (N 2 O) (up to 70%) and oxygen (O 2 ) after an intravenous induction using thiopental and low-dose fentanyl. The concentration of volatile drug was kept relatively constant but some titration in response to clinical variables was permitted. Comparison of efficacy was based on observations made of the rapidity and ease of recovery from anesthesia and the frequency of untoward effects for the duration of anesthesia to the return of orientation. Safety was evaluated by monitoring adverse experiences, hematologic and non-laboratory testing, and physical assessments. In 25% of patients (all patients in both treatment groups at selected investigational sites), plasma inorganic fluoride concentrations were determined preoperatively, every 2 hours during maintenance, at the end of anesthesia, and at 1, 2, 4, 8, 12, 24, 48, and 72 hours postoperatively. Measurements and Main Results: Emergence, response to commands, orientation, and the first request for postoperative analgesia were all more rapid following discontinuation of sevoflurane than following discontinuation of isoflurane (sevoflurane, 11.0 ± 0.6, 12.8 ±0.7, 17.2 ± 0.9, 46.1 ± 3.0 minutes, respectively, versus isoflurane, 16.4 ± 0.6, 18.4 ± 0.7, 24.7 ± 0.9, 55.4 ± 3.2 minutes). The incidence of adverse experiences was similar for sevoflurane and isoflurane patients. Forty-eight percent of patients in the sevoflurane group had no untoward effects versus 39% in the isoflurane group. Three patients who received sevoflurane had serum inorganic fluoride levels 50 μM/L or greater though standard tests indicated no evidence of associated renal dysfunction. Conclusion: Sevoflurane anesthesia, as compared with isoflurane, may be advantageous in providing a smoother clinical course with a more rapid recovery.

We have examined the dose-related effects of sevoflurane and isoflurane on systemic vascular resistance (SVR) during cardiopulmonary bypass (CPB) in patients undergoing elective coronary artery surgery. Fifty-two patients were allocated randomly to one of six groups to receive 1.0, 2.0 or 3.0 vol% (inspiratory) sevoflurane or 0.6, 1.2 or 1.8 vol% isoflurane, or to a control group. During hypothermic (32-33 degrees C) non-pulsatile CPB, systemic vascular resistance index (SVRI) was recorded before administration of volatile anaesthetics and every 5 min for 20 min. Sevoflurane and isoflurane concentrations were measured next to the gas inlet port and at the gas outlet port of the oxygenator. Wash-in of sevoflurane occurred more rapidly than that of isoflurane, reaching a relatively steady state for both agents from the 10th to the 20th min. There was no significant change in SVRI in patients receiving 1.0 and 2.0 vol% sevoflurane, and 0.6 and 1.2 vol% isoflurane, compared with baseline values. However, 3 vol% sevoflurane decreased SVRI at 10, 15 and 20 min, and 1.8 vol% isoflurane decreased SVRI significantly at 15 and 20 min, whereas SVRI increased at 15 and 20 min in the control group. Thus during CPB, sevoflurane had similar vasodilator effects on SVRI as isoflurane.

Polarographic oxygen sensitive electrodes can be used to measure tissue oxygen pressures on the surface of the beating heart. The purpose of the study was to clarify the significance of these PO2 determinations.Changes in left ventricular surface oxygen pressures, subendocardial or subepicardial wall functions (ultrasonic dimension technique), and blood flow (radioactive microsphere technique) were correlated during different degrees of acute coronary artery stenoses in pigs.19 anaesthetised open chest pigs, 28-40 kg body weight, were studied during different degrees of constriction of the left anterior descending artery which did not influence overall left ventricular function or irreversibly damage the myocardium.Highly significant (p less than 0.001) correlations (each % delta) were obtained for surface tissue oxygen pressures (y) with subepicardial (y = 0.002 e 0.10x; r = 0.89) and subendocardial (y = 1.44 e 0.04x; r = 0.98) blood flow values, as well as with subendocardial function (y = 82.4 + 0.22x; r = 0.89); a significant correlation was also obtained for subendocardial function (y) with subendocardial blood flow (y = 66.0 + 0.28x; r = 0.69). However, no significant correlation was obtained for polarographic tissue PO2 with subepicardial segment function, indicating that regional function was maintained when tissue PO2 recordings were not much above 0 kPa and when blood flow was reduced by 25 to 30%.Oxygen pressures of the superficial layers of the left ventricle are relatively high at normal values of oxygen consumption but decrease rapidly if blood supply is reduced. Regional wall function is preserved at low oxygen pressures. Polarographic surface PO2 electrodes hence can be used to study influences of experimental interventions on oxygenation of the normally perfused and of the moderately ischaemic myocardium.

To investigate whether local (LA) or general anesthesia (GA) provides more perioperative stability in cardiac autonomic tone, we analyzed heart rate variability (HRV) by means of spectral analysis, intraoperatively and up to 3 h postoperatively, in otherwise healthy patients scheduled for cataract surgery. Fourteen patients received GA (premedication : clorazepate ; anesthetic induction: propofol, alfentanil, atracurium ; anesthetic maintainance : isoflurane, alfentanil ; airway management: laryngeal mask airway), and 14 patients received LA (retrobulbar block with bupivacaine/mepivacaine). In the GA group, total power, as an indicator of cardiac autonomic activity, was significantly reduced intraoperatively and increased slowly during the postoperative period. The ratio of low frequency/high frequency (LF/HF) power, indicating cardiac sympathovagal balance, did not change significantly intraoperatively and remained stable in the postoperative period. The LA group showed no significant changes in total power intraoperatively. Postoperatively, heart rate and the LF/HF power ratio were significantly increased in the LA group compared to the GA group. GA as described above was associated with intra- or postoperative stability of the cardiac sympathovagal balance. Thus GA had no disadvantageous effects on the perioperative cardiac autonomic tone during ophthalmic surgical procedures compared to LA in otherwise healthy patients.

Severe pulmonary hypertension after protamine neutralization of heparin is an infrequent but life-threatening event following cardiopulmonary bypass. The effect of left ventricular infusion of protamine on pulmonary hypertension as well as a possible role of platelet-activating factor (PAF) or histamine in the heparin-protamine reaction was investigated in 30 pigs in four different groups during general anesthesia. Group 1 animals received 250 IU/kg heparin, followed by 100 mg protamine intravenously after 15 min. In group 2 protamine was infused into the left ventricle. Group 3 animals received the histamine H1- and H2-antagonists clemastine and ranitidine 5 min before protamine infusion. In group 4 the PAF receptor blocker WEB 2086 was given 5 min before protamine. Platelet-activating factor was measured by a bioassay in serum samples of group 1 and group 4 animals. In all four groups protamine caused severe pulmonary hypertension, thromboxane A2 release, and a transient decrease in leukocyte counts. No PAF release was detected after protamine infusion. Neither left ventricular infusion of protamine nor histamine or PAF antagonists prevented or attenuated the reactions after protamine infusion. The authors conclude that left ventricular infusion of protamine provides no protection from pulmonary hypertension, and that histamine and PAF are not involved in the acute pulmonary vasoconstriction after protamine neutralization of heparin.

The effects of a pyridoxalated polyhemoglobin solution (SFH-PLP)n-solution) on cardiovascular hemodynamics and oxygen transport were investigated in a model of partial and total blood exchange in seven dogs. Cardiac output, mean arterial pressure and heart rate were essentially unchanged, even after total blood exchange, due to the long plasma half-disappearance time of (SFH-PLP)n (36 h) and due to the addition of albumin to the solution. The oxygen-binding capacity of (SFH-PLP)n was 1.1 to 1.2 ml O2/g hb. Oxygen availability was reduced to about 50%, resulting from the low hemoglobin concentration and the decreased oxygen-binding capacity of (SFH-PLP)n. Since cardiac output did not increase, O2-consumption was maintained by an increase in O2-extraction from 21 to about 50%. However the decrease in mixed venous PO2 to values not below 30 mmHg (4.00 kPa) proves the sufficient unloading capacity of (SFH-PLP)n. The adequate tissue oxygenation of (SFH-PLP)n could be demonstrated by the lack of a metabolic acidosis, the essentially unchanged PO2-histograms of the skeletal muscle and the only moderate decrease in mixed venous PO2. Four dogs survived for more than 3 days; three of them were long-term survivors. This suggests that oxygen supply was maintained by (SFH-PLP)n until red blood cells were restored.

The hemodynamic effectiveness and the oxygen characteristics of stroma-free hemoglobin (SFH) solutions were studied in 11 dogs. the animals were bled two-thirds of the estimated blood volume or until cardiac arrest. The shed blood was immediately replaced by equivalent amounts of either SFH or polyhemoglobin (SFH-PLP). Sixty min later, Ringer's lactate was given iv for 180 min to maintain right atrial pressure at the initial value. In a second set of experiments, the intravascular persistence of SFH-PLP was investigated in 5 dogs by withdrawal of blood (7 ml/kg bw) and immediate replacement with 131I-labeled SFH-PLP. Hemodynamic disorders after severe blood loss could be reversed by infusion of hemoglobin solutions. Due to the short intravascular persistence, cardiac output did not increase as one would expect from the degree of hemodilution. Pyridoxalation of the hemoglobin molecule reduced oxygen affinity and improved oxygen unloading at the tissue level. The short intravascular half-time of this compound could be overcome by crosslinking of the pyridoxalated hemoglobin molecules. Further studies must prove whether this polyhemoglobin can be used as a long-term oxygen-carrying blood substitute.

Blood flow to and oxygen consumption of the splanchnic organs were determined together with hepatic surface oxygen tensions in 18 mongrel dogs anesthetized with the long-acting narcotic piritramid. Twelve animals also received 0.7 Vol% and 1.4 Vol% isoflurane; six time-related controls received piritramid only. Surgical preparation consisted of a left thoracotomy for inserting a catheter into the left atrium for microsphere injections and for gaining access to the hepatic surface through an incision in the diaphragm. Parameters in the animals receiving isoflurane were recorded at three stages: stage 1--piritramid anesthesia after surgical preparation; stage 2-60 min after addition of 0.7 Vol% (end-expiratory) isoflurane; stage 3-60 min after addition of 1.4 Vol% (end-expiratory) isoflurane. Hepatic surface oxygen tension was determined at each stage using an eight-channel oxygen sensitive electrode. Mean arterial pressure and cardiac output decreased during both stages with isoflurane; hepatic arterial inflow remained constant. Portal blood flow and, hence, total hepatic inflow decreased significantly. An unchanged splanchnic O2 consumption induced lower hepatic venous pO2 values: 40 +/- 1 mmHg at control, 35 +/- 2 mmHg, and 31 +/- 2 mmHg (mean +/- SEM; both P less than 0.05) during isoflurane. A concomitant decrease of hepatic surface pO2 values indicated an altered tissue oxygenation. The percentage of hepatic surface pO2 values in the lowest pO2 range (0-5 mmHg) increased significantly from 8.4 to 20.3% during 1.4 Vol% isoflurane; the percentage of values of 0 mmHg increased from 2.4 to 9.8% during 1.4 Vol.%. No changes of these parameters were detected in the control animals during the 3-h observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary The oxidative burst response of neutrophils to bacteria is crucial for effective host defence. It has been shown that inhalation anaesthetics interfere with neutrophil function and the object of this study was to characterize the mechanisms of interaction of volatile anaesthetics with the oxidative response of neutrophils. H2O2 production by neutrophils after stimulation with the bacterial peptide, N-formyl-L-methionyl-L-leucyl-phenylalanine (FMLP) and phorbol-12-myristate-13-acetate (PMA) was measured by oxidation of the indicator dye dihydrorhodamine using flow cytometry. FMLP binds to a specific surface receptor on neutrophils and initiates via receptor specific signal transduction respiratory burst as an all-ornone event, whereas PMA is an artificial activator of protein kinase C, which bypasses receptormediated signal transduction. In the presence of halothane, enflurane and sevoflurane, there was an increase in activation threshold on FMLP stimulation. Overall, this correlated with reduced H2O2 production. Isoflurane had no effect. In the presence of desflurane, however, H2O2 production of neutrophils increased two-fold, followed by transient suppression of neutrophil function. PMAinduced H2O2 generation was unchanged in the presence of volatile anaesthetics. We conclude that volatile anaesthetics modulated FMLP receptordependent signal transduction upstream of protein kinase C activation, leading to a reduced response in the presence of halothane, enflurane and sevoflurane and to an increased response in the presence of desflurane. (Br. J. Anaesth. 1997; 78: 718–723). Immune response. Blood, leucocytes. Blood, neutrophils. Anaesthetics volatile, desflurane. Anaesthetics volatile, enflurane. Anaesthetics volatile, halothane. Anaesthetics volatile, isoflurane. Anaesthetics volatile, sevoflurane.