Glasgow Meeting - May 2003

# Universitaetsklinik für Anaesthesiologie, Ulm, Germany. * Freie Universitaet Berlin, Department of Pharmacy, Berlin, Germany

Hyperpolarized Xenon129 (Hp Xe) dissolved in a lipid emulsion is used intravenously to enhance magnetic resonance imaging [1]. In a recent compartimental model the predicted tissue concentration of Hp Xe in the brain was proven to be comparable using respiration or injection technique [2]. Xenon131 (Xe) is a known NMDA receptor antagonist, with anaesthetic, analgesic and neuroprotective properties [3]. We therefore dissolved Xe131 in lipid emulsions for parenteral use, and compared the Xe blood concentrations, as well as the anaesthetic and analgesic properties of intravenous versus inhalative application. With the approval of the institutional animal care committee we anaesthetised 9 pigs with Sevoflurane and measured arterial, mixed- and sagittal sinus-venous blood concentrations of Xe by gas chromatography-mass spectrometry [4] 1, 2, 3, 4, 5, 7, 10, 15, 20 and 30 minutes after starting intravenous application of a bolus of Xe dissolved in a lipid emulsion, followed by a continuos infusion of this Xe-emulsion (n=4, Group I) or administration of a gas mixture of 70% Xe in oxygen (n=5, Group II). In order to minimise the loss of Xe by ventilation during the initial bolus application, we carried out a phase of apnea (2 min) [5]. Prior to Xe-administration, we determined the individual MAC for Sevoflurane in every animal by clamping the dew claw [6]. During Xe-application, we used this standardized stimulus, to determine the individual reduction of Sevoflurane requirement, by Xe intravenously or inhalative. Furthermore, we determined catecholamine plasma levels at the MAClevel and when a reaction to our stimulus occurred. All values are presented as Mean (±SEM).

In group I Xe blood concentrations in the different vascular beds were rather low when compared to Group II. Arterial, mixed- and sagittal- venous Xe-blood concentrations reached a peak concentration at 1 min (3 ± 0.3 ml ml-1 blood) 2 min (1,7 ± 0.1 ml ml-1 blood) and 2 min (1.7 ± 0.2 ml ml-1 blood), respectively, followed by a rapid decrease of Xe concentrations in all vascular beds. But the amount of additional Sevoflurane could be reduced from 2.5 (±0.3) Vol% to 1.0 (±0.3) Vol% (p=0.051), during the first 5 minutes of intravenous application. Contrary to gaseous Xe application, the response to the stimulus was not followed by an increase of the catecholamine concentrations. In Group II arterial, mixed- and sagittal- venous Xe-blood concentrations reached a plateau at 7 (68 ± 4 ml ml-1 blood) 20 (52 ± 2 ml ml-1 blood) and 15 min (65 ± 2 ml ml-1 blood), respectively. The administration of Xe at an end-expiratory concentration of 65% resulted in a significant reduction of sevoflurane from 1.7 (±0.04) Vol% to 0.9 (±0.09) Vol% (p<0.001). At this endtidal sevoflurane concentration the response to the stimulation was accompanied by a slight increase in the catecholamine levels.

Our results show that intravenous Xenon is associated with a significant anaesthetic and analgesic effect. Due to respiratory losses of lipid bound Xe though, this effect is maintained only over a period of approximately 15 min.. We hope to further reduce pulmonary losses with the help of specially designed lipid carriers. The anaesthetic, analgesic and neuroprotective properties of Xe merit an evaluation during cardiopulmonary bypass surgery, where first pass of intravenous Xe pulmonary losses can be avoided.

1. Moeller HE Magnetic Res Med 1999; 41: 1058-64

2. Lavini C NMR Biomed 200; 13: 238-44

3. Ma D Brit J Anaesth 2002; 89: 739-46

4. Nalos Brit J Anaesth 2001; 87: 497-8

5. Juoppilla Acta Obstet Gynecol Scand 1979; 58: 249-53

6. Eger E II Anesth Analg 1988; 67: 1174-6