Detrimental effects on the reproductive, haematological and nervous system are inherent to nitrous oxide [1,2]. Although long-term consequences are not definitely known, US and European health authorities recommend limits from 25-100 ppm as a time-weighted average for nitrous oxide. In contrast, xenon exerts no deleterious effect on any organ system and as a naturally occurring constituent of the environment it has no detrimental ecological effect . In several clinical trials xenon has proven its efficacy, safety and haemodynamic stability when used as an anaesthetic [4-6]. Though xenon will not replace nitrous oxide, it was selected as a comparative group, since its pharmacokinetic properties are similar to those of xenon. In particular, blood solubility, an important factor influencing gas diffusion, is low for both xenon and nitrous oxide. The aim of this study was to measure waste gas concentrations in the direct environment of patients receiving either xenon or nitrous oxide anaesthesia.
After approval by the local Ethics Committee the study was performed in the University Hospital Aachen. The study subjects were randomly divided into a xenon or nitrous oxide anaesthesia group. In all, 64 patients aged from 18 to 59 yr, with ASA physical status I-II, undergoing elective surgery were enrolled in this study. The following inclusion criteria had to be met: planned endotracheal intubation and anaesthesia in the supine position. Patients meeting general exclusion criteria for the use of xenon or nitrous oxide were not eligible.
The Xenotec 2000 (Leybold Vakuum GmbH, Cologne, Germany) was used to measure waste gas concentrations. It is a fully automatic quadrupole mass spectrometer, which consists mainly of a mass filter unit and a high-vacuum pump system with a gas inlet section. The mass spectrometer ionizes gas molecules, separates them according to their mass-to-charge ratio and collects the ions that are to be detected. To analyse the data from the Xenotec 2000, the Masterquad-Software v. 3.0 A1 (Leybold Vakuum GmbH, Cologne, Germany) was used. The Xenotec 2000 was started and calibrated 45 min prior to the first measurement. Note, prior to each assessment the Xenotec 2000 has been calibrated implementing a two-point calibration for each xenon and nitrous oxide, respectively.
The following time-points for the gas concentration measurement were 5, 15 and 30 min after endotracheal intubation. A final measurement was obtained after extubation of the patient. At each time-point the probe was sequentially located as follows:
- Approximately 5 cm from the patient's head, at the buccal level;
- Approximately 5 cm from the patient's thorax, at the intersection between midaxillary and mamillary lines;
- At a height of 180 cm from the floor level, above the patient's head;
- At the floor level, below the patient's head.
In both groups anaesthesia was induced intravenously with a single dose of 2 mg kg−1 propofol and remifentanil with 0.5 μg kg−1 in an infusion pump over a period of 60 s. Xenon or nitrous oxide administration was started via a face mask until 60% xenon in oxygen or 60% nitrous oxide in oxygen was reached. Xenon and nitrous oxide were applied using a closed-circuit anaesthesia machine (Physioflex®; Draeger, Lübeck, Germany). Gas flows in the Physioflex® anaesthesia machine are software-controlled to reduce gas consumption. Experiments were performed with the same Physioflex® anaesthesia machine, which was tested to have similar leak conditions. To ensure comparability between the two groups, the administration via face mask was utilized in the mask mode of the Physioflex® in both groups. Patients were intubated and ventilated via a Hi-Contour®-Tube (MallinckrodtTM; Hazelwood, MT, USA). The cuff pressure was kept between 20 and 40 cm H2O as controlled with a Control Inflator (Klinika Medical GmbH, Usingen, Germany). During the disconnection from the patient, the circuit was manually blocked and the disconnecting time was reduced to a minimum. As soon as the circuit was connected to the tube, the mode was changed to the intubation mode in both groups. Ventilator parameters were recorded from the Physioflex® anaesthesia machine over a 5-min interval. Maintenance of anaesthesia was achieved either by xenon (60% xenon in oxygen) or by nitrous oxide (60% nitrous oxide in oxygen). If required, supplemental propofol infusion (0.02-0.08 mg kg−1 min−1) was applied, due to the high mean alveolar concentration (MAC) value (104%) of nitrous oxide. Remifentanil was administered via an infusion pump at a base rate of 0.15 μg kg−1 min−1 and then titrated to clinical needs. Ventilation was adjusted to maintain an end-expiratory carbon dioxide partial pressure between 36 and 45 mmHg.
Parametric variables were compared using a one-way ANOVA. Categorical data were compared with the two-tailed Fisher's exact test. All data are presented as mean values and standard error of the means. Statistical analysis was performed using the SPSS software v. 14.0 (SPSS Inc., Chicago, IL, USA).
A total of 64 study subjects were assessed either in the xenon (n = 32) or nitrous oxide (n = 32) group. The study subjects were comparable regarding age, height, weight and gender. The anaesthesia gas concentration in the xenon group (58.8 ± 0.6%) and in the nitrous oxide group (58.3 ± 0.8%) was similar. Ventilator parameters were comparable in both groups except for the maximum airway pressure, which was higher in the xenon group (28.3 ± 1.2 mmHg) compared with the nitrous oxide group (22.0 ± 0.6 mmHg).
Waste gas concentrations throughout all time-points and assessment locations were at least ninefold higher in the nitrous oxide group than in the xenon group. Both groups showed a peak after intubation and extubation at all assessment locations with a maximum peak after extubation next to the patient's head. The gas concentration corresponding to the ambiance of the anaesthetist's head (height of 180 cm from floor level, above the patient's head) reached in the nitrous oxide values up to 1107 ± 38 ppm in the nitrous oxide group compared to 25 ± 8 ppm in the xenon group, as shown in Figures 1 and 2.
In the xenon and nitrous oxide groups, waste gas concentrations reached peak levels after intubation and extubation, which is not surprising. Interestingly waste gas concentrations during xenon anaesthesia were lower compared to nitrous oxide.
To ensure comparability between the groups, we chose nitrous oxide as a control with pharmacokinetic properties that are similar to xenon. The comparison of xenon and nitrous oxide is not ideal. Xenon and nitrous oxide are not likely to be used interchangeably as the indications for xenon are not defined yet.
The low waste gas levels of xenon can be explained by the difference in xenon's physical properties (molecular mass = 131.3, density ρxe = 5.366 g L−1 and viscosity ηxe = 23.2 μPa.s) compared to nitrous oxide (molecular mass 44.0, density ρxe = 1.799 g L−1 and viscosity ηxe = 15.0 μPa.s) and additionally in xenon's fivefold lower self-diffusion constant (0.048 cm2 s−1) . The low self-diffusion constant and the above-mentioned physical properties of xenon might lead to a ‘fluid-like' diffusion compared to a faster spreading ‘emission-like' diffusion of nitrous oxide, which could be one of the reasons for the low waste gas concentrations of xenon. Furthermore, xenon has a fourfold lower blood-gas partition coefficient as nitrous oxide, which reduces the transport capacity to the tissue . Combined with xenon's physical properties, this could be another reason for xenon's low waste gas concentrations .
It is worth noticing that both groups followed an identical protocol and maintenance with xenon and nitrous oxide was started before intubation via a face mask until 60% xenon or 60% nitrous oxide in oxygen was reached. This technique limits the results, since an unnecessary high concentration might have been measured early after intubation. In contrast, if xenon or nitrous oxide had been administered with a cuffed tube in place, the high concentrations during the anaesthetic procedure might have been reduced.
Although long-term consequences are not definitely known, US and European health authorities recommend limits from 25-100 ppm as a time-weighted average for nitrous oxide. In this setting, measurements exceeded these limits. However, nitrous oxide concentrations relevant for the anaesthetist (at a height of 180 cm from the floor level) decreased from 165.6 ± 31.9 to 134.1 ± 58.1 ppm measured at 15 and 30 min after induction of anaesthesia. These certainly reflect peak levels after induction. Measurements after 30 min have not been carried out in this study. Therefore these results are limited and do not allow a conclusion on possible toxicity of nitrous oxide.
The lack of side-effects from xenon anaesthesia attests to this benefit when compared with nitrous oxide. However, whether or not xenon is indeed beneficial concerning ecological effects remains to be determined. During xenon production, a substantial amount of energy has to be spent, leading to substantial pressure on the environment.
Despite our findings, the high cost of xenon (approximately $ 15 L−1) would, at the moment, not seem to justify the use of xenon based solely on its low waste gas concentrations. However, the low waste gas levels during xenon anaesthesia might be beneficial for personnel at risk.
This work was supported by Air Liquide Deutschland GmbH, Düsseldorf (donor of xenon and the Xenotec 2000 mass spectrometer). Further, this work is part of the doctoral thesis of André Zuehlsdorff at the Medical Faculty of the RWTH Aachen, Germany.
1. Baum VC. When nitrous oxide
is no laughing matter: nitrous oxide
and pediatric anesthesia. Paediatr Anaesth
2007; 17: 824-830.
2. Myles PS, Leslie K, Silbert B, Paech MJ, Peyton P. A review of the risks and benefits of nitrous oxide
in current anaesthetic practice. Anaesth Intensive Care
2004; 32: 165-172.
3. Sanders RD, Maze M. Xenon
: from stranger to guardian. Curr Opin Anaesthesiol
2005; 18: 405-411.
4. Rossaint R, Reyle-Hahn M, Schulte Am Esch J et al.
Multicenter randomized comparison of the efficacy and safety of xenon
and isoflurane in patients undergoing elective surgery. Anesthesiology
2003; 98: 6-13.
5. Coburn M, Kunitz O, Baumert JH et al.
Randomized controlled trial of the haemodynamic and recovery effects of xenon
or propofol anaesthesia. Br J Anaesth
2005; 94: 198-202.
6. Wappler F, Rossaint R, Baumert J et al.
Multicenter randomized comparison of xenon
and isoflurane on left ventricular function in patients undergoing elective surgery. Anesthesiology
2007; 106: 463-471.
7. Liede DR. CRC Handbook of Chemistry and Physics
, 87th edn. Cleveland, Ohio: Chemical Rubber Company, 2006.
8. 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: 255-256.
9. Reinelt H, Schirmer U, Marx T, Topalidis P, Schmidt M. Diffusion of xenon
and nitrous oxide
into the bowel. Anesthesiology
2001; 94: 475-477.