York 1999
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The basic principle of closed circle anaesthesia is to reduce the anaesthetic gas and volatile agent consumption in line with the patient's own uptake while sustaining an adequate anaesthetic depth. This ensures a minimum release of surplus gases into the environment. The classical approach is to reduce the fresh gas flow to that of the patient's uptake. As a consequence the reaction time in the system is delayed dramatically. What in reality is needed is in fact a contradiction to the classical approach - a high gas flow will optimise the wash-in and wash-out characteristics due to the rapid reaction time of the system.

The evolution of a closed circuit anaesthesia system started with the Spirometer, used to measure oxygen uptake. The first step started was to modify a rolling seal respirometer so that it's bellow was driven by a time cycled external ventilator. The oxygen concentration was controlled using a feedback computer system set to a pre-determined value by an electronic dosage valve. The carrier gas, N2O or air, was used to balance the system volume values. The anaesthetic agents were administered manually by syringe injection in quantities based on the recommendations of Low & Ernst. The respirometer's circulation system, the Narcocon, created a high gas flow thus producing optimal conditions for maximal optimisation of wash-in and wash-out characteristics.

The second major step in the development process was the inclusion of an integrated flow-through chamber ventilator. The "Rotterdam" ventilator adapts to the patient lung volume by engaging or disengaging extra chambers without having any effect on the circulating gas flow. Ventilation is computer controlled by a feedback system that measures the volume displacements, corrected according to BTPS conditions, and adjusted to pre-set values.

The third step was the automatic computer controlled syringe injection of the selected anaesthetic agent, to pre-set end-expiratory or inspiratory values, into the high circulation gas flow. The gases are continuously analysed by the infra-red gas analyser.

The fourth step was the integration of this revolutionary new concept, named the PhysioFlex, into the modern clinical anaesthesia routine. This final and most important step took several years of clinical evaluation and technical adjustments before it was accepted.

The realisation of the high flow closed circuit anaesthesia machine the PhysioFlex was only possible due to the dedication of the multi-disciplinary team of physicians and technicians who shared a dream 17 years ago.

Paediatric anaesthesia commonly involves the use of an open or semi-closed anaesthesia system with a relatively high gas flow. By closing such a system the advantages of the high flow together with the safety of the anaesthetic depth control are lost.

The PhysioFlex combines a closed system with high gas flow enabling optimal wash-in and wash-out of anaesthetic gases, therefore anaesthetic depth control is no longer a problem. Anaesthetic gases and agents are computer controlled and pre-set anaesthetic gas concentrations are maintained using feedback control, either via agent injection or adsorption by the charcoal filter.

The system volume, relatively high compared to the small lung volume of a child, was another challenge to be overcome during the development of the new paediatric function in the PhysioFlex. The exact system volume and the system compliance, including patient tubing, bacterial filters etc., are estimated for each intervention enabling the systems computer to compensate for the gas compression effect. The inspiratory flow has to be accurately controlled to avoid causing any damage to the child's fragile bronchial system.

To avoid the always-present peak pressure during IPPV, a selection was added to enable the anaesthetist to choose between volume controlled ventilation and Pressure Controlled Ventilation with smooth flow control. Feedback controlled dynamic PEEP was also introduced to compensate for the excessive PEEP fluctuations during surgical procedures.

A basic problem that is often neglected in paediatric ventilation is FRC maintenance. This can only be achieved in a system with a system volume control. This is unique to the PhysioFlex, which meticulously compensates for system volume loss due to uptake and/or leakage, for example due to an un-cuffed tube.

The computer program, linked to PCV, that manages all the requirements detailed above is called Automatic Lung Inflation Control Effect.

The use of to-and-fro circuits was described in 1936 by Ralph Waters (1). The original apparatus consisted of a solid steel container for soda-lime which was inserted between the fresh gas flow and rebreathing bag of what is now described as a Mapleson C circuit. This was used as an anaesthetic technique in the middle part of this century, but over the years has fallen out of common use. There were several reasons for this; it was not possible to measure the anaesthetic concentration; it was not possible to determine when the soda-lime was exhausted; it was heavy and cumbersome. Recently with the introduction of a new soda-lime absorber by Intersurgical (Wokingham, Berkshire, UK) there has been the opportunity to re-examine the use of a to-and-fro circuits in anaesthesia.

The basic concept was to develop a circuit which could be used in the theatre environment to provide general anaesthesia. To ensure that it was used as a closed circuit, it was decided to use a hydraulic piston ventilation technique (2), which would obviate the necessity to add further fresh gas to the circuit. A Penlon Nuffield ventilator was used with 20 metres of elephant tubing between it and the soda-lime absorber. Between the soda-lime absorber and the patient were ports for the input of a volatile anaesthetic and fresh gas, outlets for gas sampling and temperature monitoring, and a breathing filter.

I decided not to include a rebreathing bag in the circuit, as this was an unnecessary relic of prior circuits. In the final design there was no provision to return the sample gases to the circuit. This was part of the original design, and worked very well, until the para-magnetic oxygen analyser of the Datex Capnomac was repaired. This had an adverse effect on the circuit, and as a result the sampled gas was not returned. This is presumed to be a function of the gas analyser, and the circuit may perform differently with other analysers.

The circuit works well in practice, and has been used to give several anaesthetics of up to four hours duration. There are aspects of this circuit which are still being investigated, but it seems that, even with the sampled gas not returned to the circuit, it is a simple and cheap means of providing general anaesthesia for patients who are ventilated.

1. Waters RM. Carbon dioxide absorption technic in anesthesia. Annals of Surgery (1936) 103:38-45
2. Walker TJ, Chakrabarti, MK, Lockwood GG. Uptake of Desflurane during anaesthesia. Anaesthesia (1996) 51:33-36

Introduction. During sevoflurane anesthesia compound A can be generated upon contact with alkaline CO2 absorbents. Its formation is dependent upon multiple factors such as fresh gas flow rate: the lesser the flow, the more compound A is formed. Limited data exist on compound A production using true closed-circuit conditions, performed with modern computer controlled liquid injection and automatic volume and concentration control, as implemented in the PhysioFlexâ (Dräger)1. Such data suggest that only minor compound A concentrations are present in the circuit. In order to substantiate this hypothesis a reproducible method for sampling and quantitative analysis of compound A is indispensable.
Experimental. A protocol was developed allowing in-vitro testing of multiple operational variables on compound A formation. Basically, a PhysioFlexâ apparatus was connected to a testlung, wherein CO2 was introduced. Gas concentrations were measured using a Datex Ultima. Ventilation rate was 10/min. Prior to each experiment, canisters were filled with fresh CO2-absorbent and new charcoal. After baseline analysis, a set of sevoflurane concentration (ET) was dialed on the apparatus for a duration of 120 min, whereafter administration was halted. At baseline and at 5, 15, 30, 45, 60, 75, 90, 105, 120 min as well as at 5, 10 min after suspension of sevoflurane several measurements were made including compound Ainsp and compound Aexp. To that end, 2 ml gas samples were withdrawn, in duplo, at the inspiratory and expiratory limb using 2.5 ml gastight syringes, attached to the anesthesia circuit by means of 3-way valves and luer-lock connections. Applying an overdraw and compress technique, samples were then immediately transferred into sealed glass headspace vials. Samples were then ready for analysis and stored at room temperature for only a brief period of time. Compound A determination was performed by gas chromatography combined with mass-spectrometric detection (HP 6890-7359MSD). Taken into account the large number of gaseous samples (analysis duration of a complete experiment: 24h), their limited stability and the fairly short analysis time for a single sample (20 min), injection had to be fully automated from a practical point of view. We therefore chose to apply a technique similar to head-space extraction, using a computer controlled autosampler in conjunction with a tray accommodating for 60 head-space vials to inject 1 ml of the gas phase. This technique offered not only full automation of the method but also guarantied completely gastight and reproducible injections. The use of a thick film capillary column (CP-select 624 with 6% cyanopropylphenyldimethylsilicone) allowed for excellent separation, thus selectivity. Mass-spectrometric detection provided high sensitivity and added to the selectivity. The assay for determination of compound A furthermore is fully quantitative: prior to each analysis a standard curve consisting of 8 points was prepared and injected. Standards of compound A in the gas phase were prepared departing from liquid volumetric dilutions of stock solutions of compound A and sevoflurane in ethyl acetate.
Conclusion. This report describes uncomplicated and swift sampling procedures as well as a sensitive and fully validated assay for the quantitative determination of compound A in the gas phase. Currently these methods are applied in investigating compound A formation under various simulated closed circuit conditions. Additionally, in-vivo experiments will be conducted in the near future, using the same basic protocol.

We have been analyzing the pattern of anesthetic gas washin to the circle C02 absorption system, washin similar to what one would do prior to inhalation induction. Our goal is to be able to recommend an efficient method which results in a gas concentration throughout the circle equivalent to the delivered concentration. This would be the ideal situation for single breath induction and continuation with low flow anesthesia.
When washin is attempted by occluding the y-piece port while gas fills the cannister and reservoir bag, no agent enters the delivery hose portion of the circle regardless of how many times the bag is emptied at the relief valve and refilled.
METHOD: In this project, using the approach to filling the system just described, we delivered 8% sevoflurane to the circuit until the % sevoflurane in the reservoir bag was >7%. At this time no sevoflurane was detected at the y-piece. We then measured how much gas had to be aspirated at the y-piece (as a patient would have to do during induction) before the % sevoflurane was nearly equal at the y-piece and reservoir bag. We compared volumes when using 2 and 5 liter reservoir bags and when the delivery hoses were fully compressed and fully expanded.
RESULTS AND CONCLUSIONS: With the hoses compressed, 600 ml, and with them expanded, 1200 ml of gas had to be withdrawn for y-piece and reservoir % sevoflurane to be nearly equal. As expected, the volumes required were similar with the 2 and 5 liter bags. The advantage of the 5 liter bag is that sufficient gas remains in the bag for a vital capacity breath to allow a single breath induction without additional gas from the machine. During and after the first breaths of sevoflurane, management of stable anesthesia should be possible with low flows when the large reservoir is used. With the approach described here, the expiratory limb of the delivery system still was not filled with sevoflurane.

Power Spectral Analysis of blood Pressure Fluctuation and Heart Rate Variability in Low Flow Anesthesia with Isoflurane, Sevoflurane or Desflurane
Minwen Yang, MD, Chung-Yuan Lin, MD
Department of Anesthesia, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; Department of Anesthesia and Critical Care, the University of Chicago Hospitals, Chicago, USA
The aim of this study is to evaluate the stability of the hemodynamic responses in low flow anesthesia with three different inhalation anesthetics- isoflurane, sevoflurane or desflurane, using the power spectral analysis of blood pressure fluctuations and heart rate variabilities. Methods: The study was approved by our institutional research review board, and informed consent was obtained from all patients. Sixty ASA physical status I or II adults of both sexes were enrolled. Patients were randomly as signed to one of three groups: isoflurane group (n=20), sevoflurane group (n=20) and desflurane group (n=20). Premedication consisted of atropine 0.5 mg, and fentanyl 1.5 mcg/kg. Anesthesia was induced with sodium pentothal 2-3 mg/kg. Endotracheal intubation was facilitated by vecuronium 0.12 mg/kg. After the endotrachel intubation, we set the two stages of total fresh gas flow (FGF): the first stage for the filling out the anesthetic circuits and the FRC with the FGF at O2 6000 ml/min for 4.5 min (about 3 time-constant), then the second stage for the closing the circuit with the FGF at O2 500 ml/min for isoflurane group and desflurane group or with the FGF at O2 1000 ml/min for sevoflurane group. The end-tidal concentration of inhalation anesthetics was setting as isoflurane 1.6%, desflurane 6.8% or sevoflurane 2.0%, respectively. We also calculated the effective blood concentration of three different inhalation anesthetics according to the Lin's method. Data processing and spectral analysis: Arterial blood pressure (SAP) and ECG signals were monitored by Hewlett Packard 78354 monitor, digitized by using analog-to-digital converter (PCL-812, Advantech) connected to the computer. The SAP and ECG signals were digitized at 128 Hz, and were transferred by the process of direct memory access to a 64-kB memory segment in the random access memory defined as the circular buffer. For each time (64s, 2048 data points), our algorithm first estimated the power density of the spectral components based on fast Fourier transform. We were interested in the low frequency components of SAP and ECG spectra. These included the very low frequency (VLF, 0.016-0.080 Hz), low frequency (LF, 0.08-0.15 Hz), high frequency (HF, 0.15-0.25 Hz) components. The former three components purported reflect the influence of vasomotor activity, baroreceptor activity and respiration on SAP and ECG. Results: At an anesthetic depth, arterial blood pressure, indices of sympathetic activity derived from spectral analysis, decreased with three different anesthetics.
Conclusion: Low flow anesthesia might provide a stable hemodynamic response throughout operation procedure.

Introduction: The recent interest in earlier tracheal extubation after coronary artery bypass grafting (CABG) surgery has focused our attention on inhalation anaesthesia instead of traditional fentanyl anaesthesia. The present study was designed to investigate the comparison between isoflurane (IBA) and fentanyl based anaesthesia (FBA) in CABG surgery in terms of extubation time and intensive-care-unit (ICU) staying time.
Methods: Our study included 123 patients (34 with poor ventricular function) undergoing CABG surgery to receive either an IBA (n=72) or FBA (n = 51) anesthetic. Induction of anaesthesia consisted of fentanyl 15 mg/kg and midazolam 0.05 mg/kg intravenously in the FBA group. The group received an additional bolus of fentanyl 5 mg/kg prior to sternotomy and fentanyl 10 mg/kg with pancuronium 0.1 mg/kg at the commencement of cardiopulmonary bypass (CPB). In the IBA group, anaesthesia was induced with 2% isoflurane in 2 L/min O2 via mask for about 25 minutes and intubation was assisted with pancuronium. And then the fresh gas flow was reduced to 300 ml O2/min with increased vaporizer setting of isoflurane up to 4-5% (about 12-15 ml/min of isoflurane vapor supply) for the maintenance of anaesthesia.
Results: Patients in the IBA group were extubated earlier (8.7 ± 10.7 h vs. 30+/-20 h, p < 0.001), and demonstrated shorter ICU stay (2.3 ± 1.3 days vs. 3.9 ± 2 days, p < 0.001) than in the FBA group. Both groups had acceptable hemodynamic changes throughout anaesthesia, but the inotropic requirements for better hemodynamic maintenace were more in the FBA group than in the IBA group (dopamine: 4 ± 2.6 vs. 0.7 ± 1.5, p < 0.001; dobutamine: 3.7 ± 3.3 vs. 0.0.5 ± 1.9; p< 0.001).
Discussion: The results of the IBA method in CABG surgery demonstrated that isoflurane with minimal low flow technique is an alternative anesthesia technique for CABG surgery, even for patients with limited cardiac reserve. Additionally, the IBA method can facilitate the fast track cardiac surgery.

Introduction: The body uptake of isoflurane was determined using the difference (between inspired isoflurane (FI iso) and end-expired isoflurane (FE iso) multiplied by alveolar ventilation or that (between arterial isoflurane (A iso) and pulmonary arterial mixed venous isoflurane (PA iso), multiplied by cardiac output. There are few studies to look into measuring A iso and PA iso simultaneously from the beginning of isoflurane in humans. The study was designed to investigate the simultaneous measurements of FE iso, A iso, PA iso when FI iso kept at 2% in patients undergoing coronary artery bypass graft (CABG) surgery.
Methods: Following IRB approval, 10 patients, aged 50-78 years old, selectively scheduled to undergo CABG surgery, were included in the study. A 20-gauged arterial cannula and a Swan-Ganz catheter under local anaesthesia were inserted into a radial and a pulmonary artery, respectively. The breathing circuit was prewashed with 2% isoflurane in 6-L oxygen for 3 minutes before mask induction with 2% isoflurane in 2-liter oxygen for 25 minutes. Intubation was facilitated with 8 mg pancuronium. Inspired concentration of isoflurane was maintained about 2% in 300 ml oxygen during next 95-minute anaesthesia. Anesthetic gas concentrations were monitored with a multiage analyzer. FI iso, FE iso, end-tidal CO2 and vital sign of each patient were recorded every 10 seconds. Cardiac output was measured intermittently. Two 2-ml blood each time, from arterial and pulmonary arterial accesses, respectively, for isoflurane measurement in the following time intervals: 1, 2, 5, 10, 20, 30, 60, 90, 120 minutes. Isoflurane concentrations in arterial and pulmonary arterial blood were determined using head-space gas chromatography with flame-ionization detector.
Results: The FE iso increased rapidly within 5 minutes and then became gradually slowly increasing throughout the remaining 115 minutes. FE iso was kept much higher than A iso throughout the study and its difference was almost same except the initial 5 minutes. The differences between FI iso and FE iso as well as between A iso and PA iso against time were almost the same within 120 minutes, but it was less between A iso and PA iso than between FI iso and FE iso.
Discussions: Our results show that the uptake of isoflurane, according to the differences between FA iso and FE iso or between A iso and PA iso, kept near constant amount during 120-minute period. The membrane factor is a limited step in diffusion between pulmonary alveolar and capillary since the difference between FE iso and A iso exists during the whole study. No clinically significant change in blood pressure and heart rate was noted within 120-minute isoflurane anaesthesia. It indicates that we are able to practice minimal-low-flow anesthesia safely and easily once we fill the functional residual capacity with anesthetic at high flow initially.

Introduction: The goal of isoflurane in clinical practice should be safely and conveniently reach adequate partial pressure in the brain to anesthetize patients. Although brain isoflurane partial pressure cannot be measured directly in patients, it could be represented by isoflurane concentration in the internal jugular bulb blood (JB iso). Furthermore, brain uptake of isoflurane can be estimated using the concentration difference between arterial blood (A iso) and JB iso when we assume cerebral blood flow remains constant. The study was looked into brain isoflurane uptake in patients under isoflurane anaesthesia.
Methods: Following IRB approval, 7 ASA I-II patients underwent elective colorectal surgery under isoflurane anaesthesia. A 20-gauged catheter and a single-lumen central venous catheter were inserted into a radial artery and a internal jugular bulb under local anaesthesia, respectively. The breathing circuit was prewashed with 2% isoflurane in 6 L oxygen for 3 minutes. Anaesthesia was induced with fentanyl 100 mg, and thiopentone 5-6 mg/kg and intubation was facilitated with pretreated pancuronium (0.015 mg/kg) and succinylcholine (1.25 mg/kg). For maintenance of anaesthesia, inspired concentration of 2% isoflurane in 2 L oxygen was given for 30 minutes and then 300 ml oxygen applied with adjusting vaporizer setting to keep the inspired concentration of isoflurane at 2%. Anaesthetic gas concentrations were monitored with a multiage analyzer. The inspired and end-expired isoflurane (FE iso) concentration, end-tidal CO2, blood pressure and heart rate were recorded every 10 seconds. Two 2-ml blood each time, for A iso and JB iso measurements were withdrawn in the following time intervals: 1, 2, 5, 10, 20, 30, 60, 90, 120 minutes. The A iso and JB iso were determined using head-space gaschromatography flame-ionization detector.
Results: The FE iso concentration was increased rapidly within the first five minutes and the rate of increase slowed down during next 115 minutes. The rates of increase A iso and JB iso were similar to that of FE iso but lower than FE iso. Interestingly, the concentration difference between A iso and JB iso became small at 30-minute point and no difference between A iso and JB iso from 60-minute point on was found.
Discussion: Our study demonstrates that the brain uptake of isoflurane is different from the whole body uptake of it. After 30-minute administration of isoflurane, brain is almost saturated with it. The pharmacodynamic meaning implicated by pharmacokinetic phenomenon is not clear and needs further studies.

Introduction
The inert gas xenon is regarded to be the ideal inhalation anesthetic. Its routine use failed because of high costs of the substance. Recycling devices and the use of closed anesthesia systems have renewed the interest in xenon anesthesia.
The organ kinetic of xenon has not been yet investigated under conditions of anesthesia. We therefore investigated the correlation between expiratory xenon concentrations and body content of xenon in different compartments..
Material and methods
7 pigs were anesthetized with an inspiratory concentration of 70% xenon in closed system anesthesia. Anesthesia time was 4 hours, washout phase was 2 hours. Inert xenon 131 was marked with radioactive xenon 133. Organ distribution was measured with a double head gamma camera. Expiratory xenon concentrations were measured by mass spectrometer. Measured activities of radioactive xenon were correlated with expiratory measured xenon concentrations. Correlation coefficients were calculated for the compartments whole body, fatty tissue, lung and bowels.
Results
After the washout phase 27.15% of the measured activity remained in the animals. Simoultaneously expiratory concentrations of only 0.22% of xenon were measured. Correlation coefficients were found for whole body: 0.87, fatty tissue 0.64, lung: 0.98, bowels: 0.54.
Discussion
Measuring expiratory xenon concentrations is a good prediction of the organ kinetic of distribution compartments with fast kinetics like the lung. Distribution spaces with slow kinetics like fatty tissue or bowels are less accurately included in the predictions. From the expiratory measured xenon concentration the amount of xenon remeining in the tissues cannot be calculated exactly. These results have to be considered in kinetic calculations of all inhalation anesthetics.

Fig.1: Xenon organ kinetics in whole body and bowels (measuring point 30 minutes) Image in preparation

Pollution of the global and the working environment can be reduced by low-flow- and minimal flow anaesthesia with the additional benefit of reduced expenditure on anaesthetic agents. Xenon is a rare and expensive anaesthetic agent and must be used in a safe and cost-effective manner.
Accumulation of nitrogen is a concern in minimal-flow and closed system anaesthesia. In closed system anaesthesia it leads to a reduction of the anaesthetic agent's concentration. Three concepts of denitrogenation have been described:
1. Denitrogenation with a high fresh gas flow (FGF) for 5 to 25 minutes in an open system followed by changing the patient onto a closed system thereafter. Using this procedure, nitrogen concentrations of 3.5% - 14% have been reported in anaesthesias lasting from 34 - 165 minutes.
2. Denitrogenation using a FGF of 4 l/min in a rebreathing system with a subsequent reduction in flow to that of closed system anaesthesia. Nitrogen accumulation was measured ranging from 12% - 16 % in 2 hours of anaesthesia.
3. Denitrogenation for 5- 10 minutes using a FGF of 4- 5 l/min and reduction to 1 l/min (low-flow anaesthesia). In low-flow-anaesthesia nitrogen accumulation is not considered a problem.

Our investigation aimed to avoid rebreathing of nitrogen during the denitrogenation phase by using a semi-open ventilator and to minimise xenon usage by using closed system anaesthesia. Nitrogen accumulation in our closed system and xenon expenditure were measured in comparison to low-flow anaesthesia.

Methods and Results
After consent of the animal care commission, 14 pigs were anaesthetised with xenon, administered in an inspiratory concentration of 70%. Anaesthesia was inducted with a bolus dose of 8 mg/kg bodyweight of pentobarbital and 0.01 mg/kg buprenorphine. Neuromuscular relaxation was provided by a single dose of 0.25 mg/kg alcuroniumchloride. Xenon 70% in oxygen was administered in a rebreathing system (Draeger Cicero, Draegerwerk Luebeck, Germany) calibrated for xenon anaesthesia by the manufacturer. In group 1, the FGF was set to 1 l/min (0.5 l/min Xenon / 0.5 l/min oxygen). To achieve denitrogenation, the flow was increased to 3 l/min during the first five minutes of anaesthesia (3). Group 2 was denitrogenated in a semi-open ventilator (Draeger Oxylog) using oxygen 100% for 20 minutes and then connected to the xenon-ventilator primed with xenon and oxygen (70:30). Xenon and oxygen flows first were set to uptake values calculated by the computer simulation program "Narkup 4.03" (White and Lockwood, Northwick Park Hospital, Harrow, Middlesex) and then held constant by the measured values. Both groups were anaesthetised for 2 hours. Mass-spectrometry was used to measure inspired and expired xenon, oxygen and nitrogen levels with the analysed sample reintroduced into the closed system to minimise wastage. In the low flow group no reintroduction into the system was available. The gas-expenditure was calculated from the fresh-gas flows in group 1 and in group 2 by weighing xenon bottles before and after anaesthesia.
For statistic analysis the Mann-Whitney-U-test was used for comparisons (p = 0.05).

Xenon expenditure in group 1 was calculated at 67 l over the 2 hours of anaesthesia. In group 2 we measured a xenon expenditure of 7.58 liters (Median. 25. percentile - 75. percentile: 6.42 l-9.5 l) for the same time period.
The nitrogen concentrations are shown in table 1.

Table 1
Comment
Denitrogenation in a semi-open system avoids rebreathing of nitrogen. We measured lower nitrogen concentrations in our closed system than Luttrop et al. using the same system (12%-16% vs. 0.7%-3.8%). There was no significant difference between nitrogen concentrations in our closed and low-flow system.
Xenon usage was in the same range as in the experiments of Luttrop. The use of closed-system anaesthesia resulted in a ten-fold decrease in xenon expenditure as compared to low-flow-anaesthesia. We conclude that a separate denitrogenation phase in a semi-open system improves closed system anaesthesia and can be used routineously in anaesthetic practice. This may be especially useful whilst monitoring lines and catheters are being inserted post-induction. For more convenience, the denitrogenation system could be integrated in the main ventilator. Additionally, the priming volume of the system can be reused if washout is achieved by the second ventilator system, leading to a further reduction of the xenon expenditure by a volume equivalent to the deadspace of the ventilator ( 4.5 l approximately).
In short duration procedures no period of washout is possible and recycling systems which separate xenon from nitrogen and oxygen are preferable.
Tables

Time of measurement (min)	Group 1 (low-flow) Nitrogen conc. (%) Median (25.-75. Perc.)	Group 2 (closed system) Nitrogen conc. (%) Median (25.-75. Perc.)
0	2.88 (1.9-5.9)	0.88 (0.07-5.1)
10	2.82 (1.5-5.5)	0.77 (0.07-5.1)
20	1.89 (1.39-3.56)	1.04 (0.07-5.18)
30	5.38 (0.92-5.69)	1.17 (0.07-5.15)
40	0.98 (0.74-2.23)	1.22 (0.07-5.26)
50	0.81 (0.63-1.17)	1.26 (0.08-5.44)
60	0.83 (0.74-2.59)	1.29 (0.08-5.31)
70	1.30 (0.84-3.76)	1.37 (0.08-5.35)
80	2.95 (0.91-5.55)	1.7 (0.08-5.67)
90	2.21 (0.73-4.86)	1.84 (0.08-5.59)
100	1.23 (0.75-3.62)	3.62 (0.08-6.80)
110	1.39 (0.74-1.97)	3.2 (0.08-6.27)
120	1.78 (0.82-3.37)	3.8 (0.08-7.04)

Table 1: Nitrogen concentrations in % in the ventilator circle system in group 1 (low-flow-anaesthesia) and group 2 (closed system anaesthesia). No significant differences

Fig.1: Concentrations of xenon, nitrogen and oxygen during 4 hours of anesthesia. Image in preparation

The accumulation of trace gases resulting from human metabolism is a problem of minimal flow and closed circuit anesthesia. Infrared spectrometry, Raman spectrometry or mass spectrometry are used to measure gas concentrations in closed rebreathing systems. Infrared spectrometry basically measures the absorption of infrared light by the chemical bonds of different molecules. Methane (CH4) is measured in the range of 3.6 mm and 7.7 mm where infrared light is absorbed by the C-H bond. Enflurane and isoflurane have absorption bands at 8-10 mm, halothane at 8.5 - 8.8 mm. In addition to these specific wavelengths of absorption, all non-aromatic hydrocarbons, including volatile anesthetics, absorb infrared light at 3.2-3.6 mm, as long as one or more C-H bond exists in the molecule.

More than 100 different organic substances have been identified in human breath. The most important of them are acetone, isoprene and acetonitrile. Peroxides are exhaled under ARDS conditions.

In a study carried out by Versichelen and co-workers using gas chromatography, methane concentrations up to 800 ppm were detected. The infrared spectrometer of the anesthetic circuit, calibrated for halothane and measuring at a wavelength of 3.6 mm, indicated false-postive measurements of halothane within a range of 1 % (10,000 ppm). In another investigation, anattempt was made to measure methane accumulation during closed circuit anaesthesia using a Brüel & Kjaer 1302 infrared monitor. The Brüel & Kjaer monitor is a technical variation of an infrared spectrometer. The monitor measures gas concentrations of up to 5 gases simultaneously at specific single absorption bands. Cross-interferences of known substances are compensated.
Methane concentrations up to 941 ppm were detected, the results were interpreted based on the differences in metabolism and nutrition of the patients. Although no halothane was used in the anesthetic procedures, the monitor of the ventilation apparatus "Physioflex" falsely measured halothane at a wavelength of 3.6 mm. Concentrations of up to 0.79% (7900 ppm) were detected. Statistic calculations demonstrated positive correlations between the concentrations of halothane and methane.
Our experiment was carried out to demonstrate the influences of cross-interferences of organic hydrocarbons in infrared spectrometry.

Methods
The experimental setup consisted of a partial rebreathing system. A test lung was ventilated with a fresh-gas flow of 0.5 l /min and a breathing volume of 8 l /min. An oxygen/air mixture was used as carrier gas. The rubber tubes of the system were new. The ventilator had not been in use for more than one year. A multi-gas monitor Brüel & Kjaer 1302, calibrated for isoflurane, methane, acetone, and ethanol was used to measure trace gas concentrations in the system. After establishing baseline values, 1 ml of acetone, ethanol, propanol and acetaldehyde in 100 ml of aqueous solution were atomized in the system by a medical atomizer. The substances were added after each hour of ventilation.

Results

Image in preparation

Fig.1

Acetone and ethanol concentrations were detected by the multi-gas monitor (Fig 1, C: acetone, maximum concentration 661 ppm, D: ethanol, maximum concentration 204 ppm, starting point of vaporisation of acetone at point I, ethanol at point II). Cross-interferences were compensated. Methane was initially measured at a concentration of 57 ppm, which exceeds the natural concentration of methane (1.8 ppm) (E). Addition of isopropanol (point III) increased the measured concentrations of methane from 22 ppm to 92 ppm and those of isoflurane (B) from 6 ppm to 14 ppm, although these substances were not added to the system. H2O2 did not interfere with the results (point IV). Adding acetaldehyde (V) increased the measured methane concentration from 80 ppm to 102 ppm, isoflurane from 12 ppm to 26 ppm and ethanol from 170 ppm to 204 ppm.

Discussion
For detecting accumulations of hydrocarbonic trace substances by infrared monitors, cross compensation is only possible if these gases can be measured at alternative specific wavelengths with the monitor calibrated for the substances. The vaporisation of acetaldehyde and isopropanol in our experiment clearly led to invalid measurements of trace gases because the monitor was not calibrated for these substances and interpreted the absorption maxima as methane, ethanol or even isoflurane.
The 3.2-3.6 mm and 7.7 mm absorption bands are the only suitable ones for measuring methane. Because any non-aromatic hydrocarbon will absorb infrared light at the same wavelength as methane, the increased methane concentrations in the first phase of our experiment were probably attributable to cross-interferences with organic volatiles emitted from the new rubber tubes of the system or to traces of volatile anesthetics remaining in the ventilator. Also, another cause might be enrichment of methane in compressed air. Infrared spectroscopy proves to not be feasible for interpreting these measured values.
Organic volatiles exhaled by humans are detected in the ppb (parts per billion) or ppm (parts per million) range. Because these organic volatiles possess long C-H chains, each of them absorb infrared light in the 3.6 mm area and have higher molecular weights than methane. The amount of interferences caused by the sum of more than 100 different organic compounds should not be regarded as insignificant. The results of a former study that simultaneously measured methane by gas chromatography within a range of 850 ppm and false-positive halothane concentrations within a range of 10,000 ppm give an impression of the problem's quantitative importance.
Our experiment demonstrated the fact that cross-interferences exist in infrared spectroscopy. Thus, we conclude that it is neither possible to measure exact methane concentrations by infrared spectrometry in closed-system anaesthesia nor to interprete these results based on the differences in metabolism or nutrition.
Nevertheless, the methane concentration could be used as a rough estimation of the concentration of the sum total of all organic volatiles possessing C-H bonds. To obtain the best results, either mass spectrometry or gas chromatography should be preferred.
Infrared measurement of volatile anesthetics in anaesthetic ventilators should be carried out at different wavelength than in the 3.6 mm area.

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