OBJECTIVE To evaluate the effects of preoperative intentional hemodilution with 4% albumin solution on the extravasation rate of intravascular albumin and fluid in surgical patients. DESIGN A prospective, randomized, clinical study. SETTING University teaching hospital. PATIENTS Two groups (control group [group 1] and hemodiluted group [group 2]) of 13 healthy patients were studied during a long-term (>4 hrs) surgical procedure. INTERVENTIONS Autologous technetium-99m (99mTc)-labeled red blood cells and indium-oxine ((111)In)-labeled human serum albumin were injected intravenously during anesthesia at T = 0 min in the two groups for the determination of total blood volume and albumin diffusion space, respectively. In addition, body tetrapolar electrical impedance was used to assess extracellular fluid volume. In the hemodiluted group (group 2), 15 mL/kg of blood was withdrawn over 30 mins (T = 20 mins to T = 50 mins) and simultaneously replaced by an equal volume of 4% albumin solution (0.6 g/kg). MEASUREMENTS AND MAIN RESULTS The albumin diffusion space, the colloid oncotic pressure, the plasma albumin concentration and the electrical impedance were measured before (T = 10 mins) and after (T = 60, 120, and 240 mins) hemodilution. Urine was collected from T = 10 mins to T = 240 mins. The total blood volume was calculated at T = 10 mins. No differences in the initial values were found between the two groups. In group 2, hemodilution (hematocrit 30 +/- 3%) resulted in a steeper increase in the albumin diffusion space (p <.05) and a progressive decrease in the body electrical impedance (p <.05). The extravasation rate of albumin was 0.052 +/- 0.007 mL/kg/min in group 2 vs. 0.038 +/- 0.020 mL/kg/min in group 1 (p <.05). The value of calculated plasma volume at T = 0 min did not shown any difference between the two groups. This value was then lower than expected in group 2, corresponding to a loss of plasma volume of >3 mL/kg. Urine output was significantly lower in group 2 than in group 1 (0.7 +/- 0.4 vs. 1.4 +/- 1.0 mL/min, respectively; p <.05). A comparable decrease in colloid oncotic pressure and in plasma albumin concentration was observed in both groups. CONCLUSIONS These results suggest that preoperative hemodilution using 4% albumin on a 1:1 volume basis for blood substitution during a prolonged surgical procedure with reduced blood losses enhances the extravasation rate of albumin and fluid to the interstitial tissues, impeding the maintenance of isovolemia. These findings support the use of a volume of infused colloid solution higher than that of withdrawn blood during preoperative hemodilution.

BACKGROUND: Phosphorus magnetic resonance spectroscopy (31P-MRS) in vivo has been suggested recently as a possible noninvasive diagnostic test in malignant hyperthermia (MH) susceptibility. However, differences between protocols and also within subjects may have led to inconsistent MRS abnormalities reported during and after exercise. The aim of the current study was to detect discriminant abnormalities in the leg muscles using in vivo 31P-MRS during the rest period. METHODS: Fourteen patients shown to be MH-susceptible and 22 patients MH-negative on the basis of in vitro caffeine/halothane contracture tests according to the European MH group protocol were compared to 36 control subjects using in vivo 31P-MRS during the rest period. A score of MRS combined abnormalities was calculated from a stepwise discriminant function analysis. RESULTS: The MH-susceptible group had a significantly (P < 0.01) higher inorganic phosphate (Pi) to phosphocreatine (PCr)(Pi/PCr) value (0.134 +/- 0.022) than either the MH-negative (0.097 +/- 0.016) or the control (0.101 +/- 0.017) group. The MH-susceptible group also exhibited a significantly (P < 0.01) higher phosphodiesters (PDE) to PCr (PDE/PCr) value (0.093 +/- 0.056) than either the MH-negative (0.034 +/- 0.021) or the control (0.029 +/- 0.019) group. Combining both MRS parameters, 13 of the 14 MH-susceptible patients demonstrated abnormal MRS test results (score value < 1.65). Conversely, 21 of the 22 MH-negative patients had normal MRS results (score value > or = 1.65). The sensitivity and specificity of this threshold value were 93 and 95%, respectively. CONCLUSIONS: This study confirms that 31P-MRS could be useful for distinguishing noninvasively between MH-susceptible and MH-negative patients if several MRS parameter are combined. Moreover, the present MRS approach appears to be more reliable and easier than that used during exercise.

The blocking effect of electropharmaceutical anesthesia (EPA) and neuroleptanalgesia (NLA) on adrenergic and hormonal reactions to abdominal surgery were compared in 17 ASA class I to III randomized patients. This study was intended to define the indications for each of these techniques in patients with heart diseases. Each individual received the same anesthetic premedication and induction and was submitted to iterative identical measurements and biological dosages. Before and during surgery, both groups were catheterized with a Swan-Ganz and a radial catheter. Blood sampling for catecholamines, cortisol, glycemia, blood gases dosages were regularly drawn. Electrical stimulation was performed in the EPA group, and fentanyl injections were repeated in the NLA group patients only. The same doses of pancuronium and droperidol were given to every patient. A circulatory hyperkinesia and hyperadrenergia were observed during surgery in all of the subjects but, during EPA, the tachycardia, the cardiac index and the rate-pressure product were higher than during NLA. The body temperature increased towards normal in EPA, not in NLA. Adrenergic and hormonal levels were equal in both groups. The slow variations of all the important parameters demonstrate that the measured phenomenons have a long time-course what legitimates this kind of prolonged on-the-spot observation. The role of droperidol, pancuronium and fentanyl in the observed variations is discussed. The characteristic high hyperkinesia in EPA may be due partly to an inefficacious analgesia because of the fentanyl suppression after induction, partly to the preserved thermogenesis partly to a direct effect of the electrical stimulation on cerebral tissues.

Sixty-two suspected crises of anaesthetic malignant hyperthermia (MH) were collected between 1969 and 1988 by a retrospective inquiry which lasted four years. 33 patients (53%) died whilst 29 survived. 20 cases were confirmed to be MH, either directly or indirectly by way of muscle biopsy and halothane and caffeine contracture tests carried out according to the European MH group protocol by two laboratories. This group included 11 of the deaths, one family member of whom, at least, is sensitive (MHS), 7 MHS survivors and 2 survivors too young to undergo muscle biopsy but belonging to MHS families. 21 cases were highly suspect of MH: 15 of the deaths which occurred in a typical way, and 6 patients of three different families who have suffered from anaesthetic deaths which, clinically, suggested MH. Another 15 were possible MH cases, all survivors, including one case of Steinert's disease and a brother of a case of central core disease. 2 cases were still being debated, because they had equivocal results for the caffeine test (MHEc); the last 4 had negative muscle biopsies and were excluded. 33 close relatives of the MH patients were diagnosed as MHS. 44 others were found to be free from the genetic predisposition. It was strongly recommended to yet 11 others that they carry the MHS card because they were MHEc. The clinical, surgical and anesthetic pictures were always as described in the literature. The anaesthetic protocols included inhalational agents in 90% of cases; these were combined with suxamethonium in 55% of cases. Dantrolene was only used in 32% of cases, and then at inadequate doses and very often too late; this probably explains the large number of treatment failures. The number of severe forms of MH was also very high in this series (70%). The need to increase the means of prevention and screening for MH in France is stressed.

Death from malignant hyperthermia (MH) still occurs in France. However, anaesthesia of the MH susceptible (MhS) patient is quite possible without any more risk than for patients who are not MhS. Guidelines have been worked out:"trigger" drugs such as volatile anaesthetics (halothane, enflurane, isoflurane) and depolarizing muscle relaxants must be imperatively avoided;"non-trigger" drugs should be used, such as nitrous oxide, barbiturates, benzodiazepines, propofol, opiates, non-depolarizing muscle relaxants, amide or ester local anaesthetics at the usual doses without adrenaline. Moreover, dantrolene should be available in all hospitals, 12 bottles being a minimum at hand, or, better, 30 (about 10 mg.kg-1). In some cases, such as emergencies, an unprepared operating theatre, or an unprepared ventilator, the patient should be premedicated with 2.5 mg.kg-1 dantrolene intravenously. The ventilator, the circuit and the operating theatre should not contain any trace of halogenated vapour. The usual parameters, as well as temperature and expired CO2 concentration, should be closely monitored. MhS patients must also be given counselling. This includes explanations about MH, its genetic features, the main laboratory tests used to detect susceptibility, as well as advice about lifestyle, the use of drugs other than general and local anaesthetics, and a discussion concerning the association of MH with other diseases. This counselling is not always easy to provide, because many answers are not, as yet, definitive.

We measured transthoracic electrical impedance in 17 anesthetized and mechanically ventilated dogs with a four-electrode system. A current (5 KHZ, 50 mu A) is injected and detected at axillary levels. Transthoracic impedance was 67 +/- 14 ohms (S.D.) with insignificant shifts in control animals. Pulmonary edemas were induced by saline and dextrose overloads with large but opposite variations in impedance. Fifty to hundred per cent increases in total lung water content (determined at autopsy) were induced by intravenous injection of alloxan or instillation of endotracheal saline. Significant but small decreases in impedance followed. Validity of experimental pulmonary edemas with or without blood resistivity and pulmonary blood volume changes is discussed.

Background and Objectives  Several pathogen inactivation methods currently applied to therapeutic plasma may result in products with different hemostatic properties. This study aims at evaluating and comparing the hemostatic potential of different therapeutic plasma preparations currently available in France. Materials and methods  We studied three types of pathogen-reduced plasma for transfusion (MB/light, Amotosalen/UVA, industrial S/D plasma). Quarantine, non-pathogen-reduced plasma, was used as a control. This study compared more specifically the content in FVIII, fibrinogen (clottable and antigen assays) and ADAMTS-13 and evaluated the intrinsic hemostatic properties using a thrombin generation test [Calibrated Automated Thrombogram (CAT)] at high and low concentrations of tissue factor to assess the maximum quantity of thrombin generated or the contribution of FVIII and FIX in the amplification phase of thrombin generation, respectively. Results  The median FVIII concentration was >70 IU/dl for each preparation. Endogenous thrombin potential values were significantly different among the methods of plasma preparation (P < 0·001) but were all in the range of the values measured in donors' plasma. Control by the thrombomodulin-activated protein C system was preserved in all preparations (>50% inhibition of endogenous thrombin potential). Fibrinogen concentrations were all within normal range but fibrinogen levels were lower in the plasmas treated with photochemical methods. ADAMTS-13 levels were preserved. Conclusion  The hemostatic potential appears well preserved in all therapeutic plasmas tested but there are some differences between preparations, the clinical relevance of which remains to be elucidated.

INTRODUCTION: Patients with moderate traumatic brain injury (TBI)(Glasgow Coma Scale, GCS, 9-13) or minor TBI (GCS 14-15) are at risk for subsequent neurological deterioration. Serum protein S-100 is believed to reflect brain damage following TBI. In patients with normal or minor CT scan abnormalities on admission, we tested whether the determination of serum protein S-100 beta could predict secondary neurological deterioration. METHODS: Sixty-seven patients with moderate or minor TBI were prospectively studied. Serum samples were collected on admission within 12 hours postinjury to measure serum protein S-100 levels. Neurological outcome was assessed up to seven days after trauma. Secondary neurological deterioration was defined as two points or more decrease from the initial GCS, or any treatment for neurological deterioration. RESULTS: Nine patients had a secondary neurological deterioration after trauma. No differences in serum levels of protein S-100 were found between these patients and those without neurological aggravation (n=58 patients): 0.93 microg/l (0.14-4.85) vs 0.39 microg/l (0.04-6.40), respectively. The proportion of patients with abnormal levels of serum protein S-100 at admission according to two admitted cut-off levels (>0.1 and >0.5 microg/l) was comparable between the two groups of patients. Elevated serum levels of protein S-100 were found in patients with Injury Severity Score (ISS) of more than 16 (n=23 patients): 1.26 microg/l (0.14-6.40) vs 0.22 microg/l (0.04-6.20) in patients with ISS less than 16 (n=44 patients). DISCUSSION: The dosage of serum protein S-100 on admission failed to predict patients at risk for neurological deterioration after minor or moderate TBI. Extracranial injuries can increase serum protein S-100 levels, then limiting the usefulness of this dosage in this clinical setting.

BACKGROUND Studies of offspring of mothers exposed to anesthetic gases have shown associations with congenital anomalies reported by the mothers, but rarely in studies with objectively ascertained outcomes. We conducted a retrospective cohort study to examine associations between registry-ascertained congenital anomalies in offspring and anesthetic gas exposure of mothers employed as nurses. METHODS A cohort of registered nurses in British Columbia, Canada, was linked to records of births and congenital anomalies from 1990 to 2000. Exposures were assessed via a survey of anesthetic gas use in all hospitals in the province and records of nurses' jobs, departments, and hospitals. RESULTS Departments most frequently reporting anesthetic gas use were operating rooms, post-anesthetic recovery rooms, and maternity units. In the cohort of 15,317 live-borne children of 9,433 mothers, 1,079 had congenital anomalies. Anomalies were associated with ever and probable maternal exposure to halogenated gases (ORs: 1.49, 95% CI: 1.04-2.13; and 2.61, 95% CI: 1.31-5.18, respectively) and to nitrous oxide (ORs: 1.42, 95% CI: 1.05-1.94; and 1.82, 95% CI: 1.11-2.99). Anomalies most frequently associated with exposure were those of the heart (OR, halogenated gases: 2.31, 95% CI: 1.07-4.97) and integument (OR, halogenated gases: 3.56, 95% CI: 1.53-8.32; OR, nitrous oxide: 3.02, 95% CI: 1.37-6.64). Gases most frequently associated with anomalies were halothane (predominantly used early in the study period), isoflurane, and sevoflurane (predominantly used later in the period). CONCLUSIONS In this study, where both exposures and outcomes were assessed objectively, certain congenital anomalies were associated with estimated anesthetic gas exposure.

Communication is a key skill for anaesthetic practice. The 'non-informational' aspects of communication, such as non-verbal elements and the degree to which the style of communication reflects the implied relationship between the sender and the recipient, are relevant to interactions both between anaesthetists and patients and to interactions with other members of staff in the team. Communication and interaction between members of the anaesthesia team in isolation has received less attention than communication in the operating theatre during surgery. Most aspects of such communication are informally learned and developed with experience. Studies of communication at induction of anaesthesia have used qualitative methods to identify a range of styles of talk. This is nominally directed at the patient but also serves to unite and co-ordinate the team to ensure the patient's smooth, safe progress into anaesthesia. In particular, the use of positive words and phrases seems to benefit patient comfort and safety. On emergence, a more limited range of communication styles is found. Handover of the recently anaesthetized patient to recovery room staff is often brief and distracted by concurrent patient-related activities. Both information about the patient, and responsibility for the patient's continuing care, have to be transferred. The handover event also serves as an opportunity to review the care the patient has received and plan for further progress. Anaesthetists and nurses use unspoken and implicit negotiation strategies to achieve the aims of handover without compromising future collaborative work. This is in contrast to the more formalized handover approaches in other safety-critical settings.

Modern anaesthesia is still mostly administered by the inhalational route and there is increasing concern over its potential for pollution. One of the first gaseous anaesthetic agents was nitrous oxide and this is still widely used today despite being associated with adverse effects caused by depression of vitamin B(12) function and diminished reproductive health. The use of halothane is associated with hepatitis but the adverse effects of newer halogenated hydrocarbons are less well recognised. Chronic exposure may cause reduction in antioxidant activity in plasma and erythrocytes, inhibition of neutrophil apoptosis, depression of central neuro-respiratory activity, increased DNA breaks, effects on cerebral blood circulation and altered renal function. Inhalational anaesthetics also have adverse environmental effects, including ozone damage and greenhouse gas effects. Levels of inhalational anaesthetics in the ambient air of operating theatres and recovery rooms often exceed those stated in national guidelines. Anaesthetic procedures can be modified and air-conditioning and air scavenging systems should be used to minimise the risks from occupational exposure and threats to the environment. Such contamination could be avoided with the use of total intravenous anaesthesia.

OBJECTIVES: The goal of the present study was to develop an automated method to assess by biological monitoring, the volatile-anaesthetic exposure (nitrous oxide, sevoflurane, isoflurane and halothane) in operating theatre personnel. METHODS: Post-shift urine samples were analysed by gas chromatography-mass spectrometry coupled with static headspace sampling (GC-MS/ HSS); intra-assay %-RSD (n= 10) was less than 5% for nitrous oxide and less than 7% for each halogenated vapour. The biomonitoring method was validated with air monitoring data, obtained by personal samplers and a similar GC-MS method. The sensitivity achieved by single ion monitoring (SIM) was sufficient to reveal low biological and environmental exposure averages down to 1 microg/l(urine) and 0.5 ppm for nitrous oxide and 0.1 microg/l(urine) and 50 ppb for halogenated compounds, respectively. RESULTS: In 1998 we collected and analysed 714 post-shift urine samples for the biological monitoring of volatile anaesthetics in the urine of the operating-theatre personnel of Sant'Orsola-Malpighi Hospital (Bologna, Italy). Our data showed that nitrous oxide (N20), the anaesthetic most largely used in general anaesthesia, is still the decisive factor in operating-theatre pollution. Moreover, on the basis of our results, working in close contact with anaesthetics seems to be the main determinant of risk: surgical nurses and anaesthesiologists are the most-exposed professional categories (mean post-shift urinary N2O approximately 65 microg/l(urine)) while general theatre staff, surgeons, and auxiliary personnel have significantly lower exposure. CONCLUSIONS: The biological monitoring of post-shift unmodified urinary volatile anaesthetics was confirmed to be a useful tool for evaluating individual exposure to these chemicals. The urinary concentrations of N2O and of halogenated vapours might reflect, to a certain extent, the external exposure to these compounds, and respiratory air-monitoring data support the validity of biological monitoring. Furthermore, the good relationship between air and urinary concentration of anaesthetics in people working in closer contact with these chemicals may be a good indirect means of revealing the bad air conditions of operating rooms, and may contribute to the highlighting and correction of service defects in anaesthesiology equipment and of human errors.

The efficiency of facilities available for anaesthetic gas scavenging in East Anglian hospitals has been assessed using infrared spectrophotometry. Simple scavenging systems proved to be very effective and reduced the ambient nitrous oxide levels by a factor of ten. Sources of pollution outside of the influence of a scavenging system were due to damaged breathing systems, leaking ventilators and the anaesthetic technique. High levels could be further aggravated by poor maintenance of air conditioning equipment.

A study was undertaken to assess the performance of the Komesaroff vaporizer, placed within the circuit, in ventilated patients during maintenance of closed circuit anaesthesia with halothane or isoflurane. Following intravenous induction, anaesthesia was maintained by inhalation. This was achieved using a conventional vaporizer outside the circle for the first 10 minutes to manage the fast uptake phase. The fresh gas flow was then reduced to the basal oxygen requirement with the Komesaroff vaporizer within the circle maintaining inhalational anaesthesia. Complete isolation of the circuit was achieved by returning all anaesthetic gases to the circuit following analysis and using a bag-in-bottle ventilator. The Komesaroff vaporizer dial was positioned at between the first and second division and end-tidal volatile anaesthetic agent levels were measured. This study demonstrated that at dial positions 1 or 1.5 with either agent, the end-tidal volatile concentration plateaued at clinically acceptable levels. The Komesaroff vaporizer can therefore be used safely in ventilated patients to maintain closed circuit anaesthesia provided clinical observation and monitoring are meticulous.

Here, we report the possible in vivo induction DNA damage by exposure to various waste anaesthetic gases such as halothane, nitrous oxide and isoflurane. The alkaline comet assay (single cell gel electrophoresis technique) was carried out on 66 operating room personnel (anaesthetists [doctors]; anaesthesia nurses and anaesthesia unit technicians) currently employed at the Ankara Hospital in Turkey. A significant increase in the number of lymphocytes with DNA migration was observed in operating room personnel as compared to controls. Also, the extent of damage in exposed smokers were significantly higher than exposed nonsmokers. This study supports the existence of an association between DNA damage and occupational exposure to inhalation anaesthetics.

OBJECTIVE To review anaesthesia ventilators in current use in France by categories of ventilators. DATA SOURCES References were obtained from computerized bibliographic search.(Medline), recent review articles, the library of the service and personal files. DATA SYNTHESIS Anaesthesia ventilators can be allocated into three groups, depending on whether they readminister expired gases or not or allow both modalities. Contemporary ventilators provide either constant volume ventilation, or constant pressure ventilation, with or without a pressure plateau. Ventilators readministering expired gases after CO2 absorption, or closed circuit ventilators, are either of a double- or a single-circuit design. Double-circuit ventilators, or pneumatical bag or bellows squeezers, or bag-in-bottle or bellows-in-bottle (or box) ventilators, consist of a primary, or driving circuit (bottle or box) and a secondary or patient circuit (including a bag or a bellows or membrane chambers). Bellows-in-bottle ventilators have either standing bellows ascending at expiration, or hanging bellows, descending at expiration. Ascending bellows require a positive pressure of about 2 cmH2O throughout exhalation to allow the bellows to refill. The expired gas volume is a valuable indicator for leak and disconnection. Descending bellows generate a slight negative pressure during exhalation. In case of leak or disconnection they aspirate ambient air and cannot act therefore as an indicator for integrity of the circuit and the patient connection. Closed circuit ventilators with a single-circuit (patient circuit) include a insufflating device consisting either in a bellows or a cylinder with a piston, operated by a electric or pneumatic motor. As the hanging bellows of the double circuit ventilators, they generate a slight negative pressure during exhalation and aspirate ambient air in case of leak or disconnection. Ventilators not designed for the readministration of expired gases, or open circuit ventilators, are generally stand-alone mechanical ventilators modified to allow the administration of inhalational anaesthetic agents.

The biological monitoring of inhalation anaesthetics. Occupational exposure to inhalation anaesthetics is an undesired consequence of the work in the operating theatre. Anaesthesia is currently practised using nitrous oxide associated with one or more potent anaesthetics (halothane, enflurane, isoflurane). In the present study we evaluated the occupational exposure to inhalation anaesthetics during anaesthesia in 190 operating theatres of 41 hospitals in Italy. Nitrous oxide, halothane, enflurane, isoflurane were detected in the urine of 1521 exposed subjects (anaesthetists, surgeons and nurses). Significant correlations were found between the anaesthetic concentrations in urine produced during the shift (Cu) and anaesthetic environmental concentrations (CI). The results show that the urinary anaesthetic concentration can be used as an appropriate biological exposure index. The biological threshold values (urinary concentration values) proposed are the following: nitrous oxide, 15, 28 and 57 micrograms/L for an environmental exposure of 25, 50 and 100 ppm respectively; halothane, 97 micrograms/L (for an environmental exposure of 50 ppm), 6.1 micrograms/L (for an environmental exposure of 2 ppm) and 3.3 micrograms/L (for an environmental exposure of 0.5 ppm); enflurane, 145 micrograms/L (for an environmental exposure of 50 ppm), 22.7 micrograms/L (for an environmental exposure of 10 ppm), 3.7 micrograms/L (for an environmental exposure of 1 ppm); isoflurane, 5.3 micrograms/L (for an environmental exposure of 2 ppm) and 1.8 micrograms/L (for an environmental exposure of 0.5 ppm). These values apply to urine samples collected at the end of 4-hours' exposure to the anaesthetics.

Anaesthetic personnel is exposed to different workload conditions. The individual impact is influenced by external factors and human stress stability. Different symptoms reported to be present in anaesthetic personnel are comparable to symptoms of the sick building syndrome, defined by the WHO in the 90's. They are caused by work-induced distress and the exposure to chemical hazards. In anaesthesia, health defects by anaesthetic vapours and gases have been deplored for many years. After the Russian anaesthesiologist Vaisman published a report in 1967, controlled studies concerning cancerogenicity and teratogenicity of volatile anaesthetics under workspace conditions were carried out. In 1989, time-weighted average exposure threshold limit values of 5 ppm were released in the Federal Republic of Germany for halothane. In 1993 thresholds for enflurane (20 ppm) and nitrous oxide (100 ppm) were released. TLV concentrations for the new anaesthetic agents desflurane and sevoflurane have not yet been defined by authorities. Factors influencing workplace concentrations of anaesthetic gases are the anaesthetic procedures, apparatus leakage, air conditioning, fresh gas flow and the function of the scavenging system. Although cancerogenicity, mutagenicity, teratogenicity and reduction of fertility are discussed as effects of chronic exposure to anaesthetic gases, several review articles doubted the results of studies, finding positive correlations of incidence of occupational disease and the exposure to the volatile and gaseous substances. Mainly coexisting factors like smoke-induced exposure to polybromated biphenyls, disturbance in circadian rhythm, stress and enclosure in narrow exposure systems, increasing teratogenicity and cancerogenicity in animal experiments, are considered to promote unreliability of the studies. All reviewers do not discuss the fact, that all of these co-factors are present in the reality of the anaesthetic workplace. Thus, the studies by Corbett, enthusiastically criticized by different reviewers, simulate the all-day reality of the anaesthetic workplace more precisely than controlled experiments conducted, for example, by Eger and co-workers. The results of animal experiments and retrospective studies therefore do not justify realization of large controlled prospective studies but require the overall revision of the anaesthesiological workplace and the reduction of occupational waste gas exposure to the lowest possible levels below all chronic exposure threshold values.