Arterial and mixed venous xenon blood concentrations in pigs during wash-in of inhalational anaesthesia{dagger}

M. Nalos1,2, U. Wachter*,1, A. Pittner1, M. Georgieff1, P. Radermacher1 and G. Froeba1

1Universitätsklinik für Anästhesiologie, Universität Ulm, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Parkstrasse 11, D-89073 Ulm, Germany 2Present address: Anesteziologicko resuscitaèni klinika, Karlova Univerzita, CZ-30460 Plzen, Czech Republic*Corresponding author

Accepted for publication: March 26, 2001


    Abstract
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
There are no data available on the kinetics of blood concentrations of xenon during the wash-in phase of an inhalation anaesthesia aiming at 1 MAC end-expiratory concentration. Therefore, we anaesthetized eight pigs with continuous propofol and fentanyl and measured arterial, mixed venous and end-expiratory xenon concentrations by gas chromatography–mass spectrometry 1, 2, 3, 4, 5, 7, 10, 15, 20, 30, 60 and 120 min after starting the anaesthetic gas mixture [67% xenon/33% oxygen; 3 litre min–1 during the first 10 min, thereafter minimal flow with 0.48 (SD 0.03) litre min–1]. End-expiratory xenon concentrations plateaued (defined as <5% change from the preceding value) at 64 (6) vol% after 7 min, and arterial and mixed venous xenon concentrations after 5 and 15 min respectively. The highest arterio-venous concentration difference occurred after 3 min. Using the Fick principle, we calculated a mean xenon uptake of 3708 (829) and 9977 (3607) ml after 30 and 120 min respectively.

Br J Anaesth 2001; 87: 497–8

Keywords: anaesthestic techniques, inhalation; anaesthetics, gases, xenon; pharmacokinetics, xenon; pig


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
The inert gas xenon is under investigation as an alternative to nitrous oxide as an inhalational anaesthetic. Being an almost ideal anaesthetic, xenon offers several potential advantages over classical inhalational agents.1 The low blood/gas partition coefficient (0.11)2 leads to rapid wash-in and induction and emergence from anaesthesia.3 4 In order to define precisely the kinetics of the wash-in phase of inhalational anaesthesia with xenon and to estimate its expenditure during 2 h of anaesthesia with a standard semi-closed anaesthesia circuit, we measured end-expiratory gas, arterial and mixed venous blood concentrations by gas chromatography–mass spectrometry.


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
As part of another protocol approved by the institutional animal care committee (Regierungspräsidium, Tübingen, Germany) and performed in accordance with the legal regulations for the use of laboratory animals, which investigated the effects of different anaesthesia techniques during experimental bowel obstruction, eight pigs aged 12–16 weeks and weighing 37.5–46 (SD 3.2) kg were premedicated with azaperon 4 mg kg–1 i.m. and atropine 2.5 mg i.m. Anaesthesia was induced with i.v. ketamine 2 mg kg–1 and pentobarbitone 8–10 mg kg–1. The trachea was intubated and ventilation was performed with 30% oxygen in nitrogen using a standard semi-closed ventilator (Cicero; Draegerwerk, Lübeck, Germany). Ventilatory settings throughout the experiment were tidal volume (VT) 10–14 ml kg–1 (adjusted to achieve a PaCO2 of 37–43 mm Hg), ventilator frequency (f) 12 min–1, and a positive end-expiratory pressure of 5 cm H2O. Muscle paralysis was obtained with alcuronium dichloride (0.25 mg kg–1) followed by an infusion (14 mg h–1). Anaesthesia was maintained with a continuous i.v. infusion of propofol (5–10 mg kg–1 h–1) and fentanyl (5–10 µg kg–1 min–1). Depth of anaesthesia was assessed by continuous EEG monitoring (Neurotrac; Interspec, Cronshocken, PA, USA); the 95% spectral edge frequency was always below 15 Hz during the experiment. Ringer’s solution (7 ml kg–1 h–1) was administered continuously as a maintenance fluid. A thermodilution pulmonary artery catheter was placed via the right internal jugular vein, and both femoral arteries were exposed to insert a catheter for blood sampling and continuous recording of arterial pressure. A 3 Fr thermistor-tipped fibre-optic catheter was used for measurement of cardiac output by thermal dye double indicator (indo-cyanine green) dilution and for the determination of intrathoracic blood volume (FT-Pulsiocath PV 2023, Cold Z021; Pulsion, München, Germany). A minimum of 2 h was allowed for recovery after the surgical procedure. For the measurement of minute volume, a rotating vane flowmeter was used as an independent volumeter because of the inaccuracy of the built-in volumeter of the anaesthesia machine resulting from the higher density of xenon.5 Thereafter, the inspired gas mixture was changed from 2 litre min–1 of air and 1 litre min–1 of oxygen to 2 litre min–1 of xenon and 1 litre min–1 of oxygen for 10 min, as described previously,3 6 in order to achieve an end-expiratory xenon concentration close to 1 MAC (minimum alveolar concentration) without causing hypoxaemia as a result of the expected nitrogen wash-out. For economy, the fresh gas flow was then reduced to 0.175 (SD 0.03) litre min–1 of xenon and 0.306 (0.02) litre min–1 of oxygen for the rest of the study period. End-expiratory gas, arterial and mixed-venous blood were sampled 1, 2, 3, 4, 5, 7, 10, 15, 20, 30, 60 and 120 min after starting xenon inhalation and the respective xenon concentrations were measured by gas chromatography–mass spectrometry. Whole-blood xenon calibration curves for each animal were constructed on the day of the study. The end-expiratory xenon concentration reached a plateau at 64 (6) vol% (defined as <5% change from the preceding value) after 7 min. The xenon concentrations in the arterial and mixed venous blood reached a plateau at 5 min [70 (9) µl ml–1 blood] and 15 min [52 (4) µl ml–1 blood] respectively (Fig. 1). The mixed venous xenon concentration continued to rise slowly until the end of the observation period at 120 min of xenon inhalation [63 (3) µl ml–1 blood]. The arterial–mixed venous (A–V) xenon concentration difference peaked at 3 min at a mean value of 34 (22) µl ml–1 blood, which did not significantly differ from the values at 2, 4 and 5 min. Thereafter the A–V content difference declined progressively. The mean xenon uptake, calculated according to the Fick principle, was 3708 (829) ml after 30 min and 9977 (3607) ml after 120 min of xenon anaesthesia. There were no significant changes in heart rate, arterial and central venous blood pressure, intrathoracic blood volume and cardiac output during the study period.



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Fig 1 End-expiratory (vol%) and arterial and mixed venous blood (µl ml–1) concentrations of xenon. Data are mean ±SD.

 

    Comment
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
In a pig model, we measured the xenon concentration in blood during the wash-in phase of inhalational anaesthesia. Arterial and mixed venous blood xenon concentration increased rapidly, with a time lag of 10 min, indicating the prompt establishment of equilibrium in the vascular compartment and, hence, the main target of anaesthesia, the brain. When compared with a previous study,4 the time needed to reach an arterial equilibrium was relatively long, probably because of the lower initial fresh gas flows used in the present investigation. Gas accumulation in the gut and adipose tissue may cause the mixed venous xenon concentration to slowly rise until the end of the experiment.7 The calculated mean xenon uptake of approximately 4 litres after 30 min and 10 litres after 120 min of inhalational anaesthesia with xenon at end-expiratory gas concentrations close to 1 MAC in 45-kg animals confirms the prediction reported by Luttropp and co-workers for an average adult during the first 2 h of xenon administration using a minimal flow technique.8


    Acknowledgements
 
We thank Mrs R. Engelhardt and Mr W. Siegler for skilful technical assistance.


    References
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
1 Dingley J, Ivanova-Stoilova TM, Grundler S, Wall T. Xenon: recent developments. Anaesthesia 1999; 54: 335–46[ISI][Medline]

2 Goto T, Suwa K, Uezono S, Ichinose F, Uchiyama M, Morita S. The blood–gas partition coefficient of xenon may be lower than generally accepted. Br J Anaesth 1998; 80: 255–6[ISI][Medline]

3 Froeba G, Baeder S, Calzia E, Georgieff M, Marx T. Xenon washin and washout time during controlled mechanical ventilation in an animal model. Appl Cardiopulm Pathophysiol 1998; 7: 157–60

4 Nakata Y, Goto T, Morita S. Comparison of inhalation inductions with xenon and sevoflurane. Acta Anaesthesiol Scand 1997; 41: 1157–61[ISI][Medline]

5 Goto T, Saito H, Nakata Y, et al. Effects of xenon on the performance of various respiratory flowmeters. Anesthesiology 1999; 90: 555–63[ISI][Medline]

6 Marx T, Froeba G, Wagner S, Baeder S, Goertz A, Georgieff M. Effects on haemodynamics and catecholamine release of xenon anaesthesia compared with total i.v. anaesthesia in the pig. Br J Anaesth 1997; 78: 326–7[Abstract/Free Full Text]

7 Marx T, Kozerke J, Musati S, et al. Time constants of xenon elimination after anaesthesia. Appl Cardiopulm Pathophysiol 2000; 9: 91–6

8 Luttropp HH, Thomasson R, Dahm S, Persson J, Werner O. Clinical experience with minimal flow xenon anaesthesia. Acta Anaesthesiol Scand 1994; 38: 121–5[ISI][Medline]