In current practice propofol total intravenous (i.v.) anaesthesia is frequently administered because of its pharmacological properties and fast recovery after anaesthesia. A total i.v. anaesthetic with propofol/fentanyl improved early postoperative patient well-being compared with inhalation anaesthesia using sevoflurane/fentanyl .
Xenon, first used as an anaesthetic in 1951 , may become a future alternative to the currently used inhaled anaesthetics. Xenon anaesthesia is associated with a remarkable cardiovascular stability, does not affect myocardial contractility [3-6] and has proven its clinically safety [5,7]. In vitro and in vivo models have shown neuroprotective effects as xenon inhibits the glutaminergic N-methyl-D-aspartate (NMDA) receptor . Xenon, as a noble gas, has no negative environmental effects. Moreover, induction and recovery with xenon anaesthesia are rapid because of its blood/gas coefficient of 0.115, the lowest of all known anaesthetics .
Fung and Cohen pointed out, that patients' satisfaction is a rising factor of evaluating anaesthesia. The use of patients' satisfaction has been approved as a unique clinical end-point and as an indicator of the quality of healthcare provided . However, to our knowledge there have been no investigations about patients' self-evaluation after xenon anaesthesia.
We hypothesized, that xenon/remifentanil anaesthesia resulted in similar subjective postoperative patients' evaluation as a total i.v. anaesthesia with propofol/remifentanil.
The study was designed as a randomized-controlled trial and the study protocol was approved by the local Ethics Committee. Haemodynamic data were taken as primary outcome measures and patients' self-evaluations were recorded as secondary outcome measures . All patients gave their informed, written consent before participation in this clinical trial. Information of the patients were assigned to two experienced anaesthetists. After the interview, the patients were assigned randomly to receive total i.v. anaesthesia with propofol or inhalation anaesthesia with xenon by a computer-generated randomization system. Allocation concealment was ensured by enclosing assignments in sealed, sequentially numbered envelopes. For each patient, the corresponding envelope was attached to the premedication notes and was opened the next day in the operating room before induction of anaesthesia. Blinding to the anaesthetist was not possible owing to the different administration methods of the anaesthetics (total i.v. anaesthesia via infusion pump or inhaled anaesthesia). The premedication anaesthetists, study personnel (telephone poll investigator) and patients were blinded to group assignment during study period.
A total of 160 adults were included. To participate in this study, all of the following inclusion criteria had to be met: age 18-60 yr; ASA I-II; Mallampati classification I-II; elective surgery; planned duration of anaesthesia of at least 60 min and German speaking.
Premedication was performed with midazolam 7.5 mg orally, 45 min prior to induction. Monitoring included electrocardiography, pulse oximetry, non-invasive blood pressure (BP), temperature, end-tidal carbon dioxide, oxygen and xenon concentration and neuromuscular monitoring (TOF-Watch SX®; Organon Teknika GmbH, Eppelheim, Germany). Non-invasive BP and heart rate (HR) were measured at 5-min intervals with an AS/3 monitor (Datex-Ohmeda, Helsinki, Finland). Bispectral index was monitored (BIS; Model A-2000®, software version 2.21; Aspect Medical Systems Inc., Newton, MA, USA) as a surrogate parameter to have some extra information about depth of anaesthesia knowing that it is not validated for use in xenon anaesthesia. BIS values of <50 was used because the depth of hypnosis for surgical intervention is reported to lie between 40 and 60 . Application of the BIS electrodes® (Aspect Medical Systems) was performed after the skin of the forehead and temple were cleaned and dried. BIS monitoring value was recorded every 5 min.
Anaesthesia was induced i.v. with a single dose of propofol 2 mg kg−1 and remifentanil with 0.5 μg kg−1 in an infusion pump over 60 s in both groups. Xenon administration was started via a face mask (xenon group) with 60% xenon in O2 or propofol was administered via an infusion pump and ventilation was performed with oxygen/air (propofol group). Tracheal intubation was facilitated by one of the following non-depolarizing neuromuscular blocking drugs: mivacurium (0.16 mg kg−1), cisatracurium (0.1 mg kg−1), rocuronium (0.6 mg kg−1) or vecuronium (0.1 mg kg−1).
Xenon (medical quality) was provided by Messer-Griesheim GmbH (Business Unit, Messer Medical, Krefeld, Germany) in steel cylinders. Each cylinder contained 1000 L. Xenon was applied using a closed circuit anaesthesia machine (Physioflex®; Draeger, Lübeck, Germany) with modified software to reduce xenon consumption under minimal flow conditions. Inspiratory xenon concentration was determined using the thermo-conductivity measuring device incorporated in the Physioflex anaesthesia machine (accuracy: ±3 vol%), which was calibrated automatically when starting the anaesthesia machine.
Maintenance of anaesthesia was achieved either by xenon (60% xenon in O2) or propofol (0.1-0.12 mg kg−1 min−1). If the xenon concentration fell below 55% during the inhalation period, the Physioflex system was flushed to displace any accumulated nitrogen previously dissolved in blood and emerging into the closed circuit of the anaesthesia system due to the pressure gradient. Flushing was continued until 60% xenon was reached. Remifentanil was administered via infusion pump at a base rate of 0.15 μg kg−1 min−1 and then titrated to clinical needs regarding the patient's haemodynamic, autonomic and somatic signs. BIS values were kept <50 in both groups. Haemodynamic signs were defined as a change in systolic arterial pressure or HR more than 20% from baseline in the absence of hypovolaemia. Autonomic signs were defined as sweating, salivation, flushing and somatic signs as movement and swallowing. In this case the remifentanil concentration was increased by 0.05 μg kg−1 min−1. Antihypertensive, anticholinergic or inotropic agents could be given during surgery if the HR or BP indicated their use despite adequate anaesthesia. The clinic's standard treatment of blood fluid loss and fluid replacement strategy were used if necessary.
Ventilation was adjusted to maintain an end-expiratory carbon dioxide partial pressure at 36-45 mmHg. Normothermia (35.5-37.0°C) was achieved by using warming blankets. Anaesthesia was discontinued when all surgical interventions, including the bandaging of the surgical fields, were completed and total recovery of neuromuscular block was reached. None of the patients required reversal of neuromuscular block. From this time point, adequate spontaneous ventilation, with an end-expiratory carbon dioxide partial pressure ranging between 40 and 50 mmHg, had to be ensured. After the patient had opened eyes on command, extubation was performed. Postoperative analgesia was ensured with pirinitramide (piritramide) 0.05 mg kg−1 20 min before the end of anaesthesia and metamizole 15 mg kg−1 in a short infusion during anaesthesia. In case of continued pain (visual analogue score > 3) in the postoperative care unit piritramide 0.05 mg kg−1 was administered until pain relief was adequate. Aldrete scores were recorded in the postoperative care unit at 5, 15, 30, 45, 60 and 120 min. Recovery time was defined as the time period until a specialist discharged the patient from the postanaesthesia care unit.
The investigator for the telephone poll called the patients at between 4 and 12 weeks after anaesthesia. The telephone calls were repeated weekly until response or were stopped after the cut off time of 12 weeks. All patients received the same introduction and explanation of the poll. The questions were presented in a clear and timed flow in the German language. The patients were requested to report postoperative feelings spontaneously. The early spatial orientation was tested by the first location the patient could recall postoperatively. The patients could choose between operation theatre, transport to recovery unit, being in the recovery unit, ward or cannot remember. Patients' self-evaluation of the anaesthesia procedure was presented in numbers from six to one (excellent-unsatisfactory). Further the patients were asked if they would choose the same anaesthesia if necessary for further operations. Finally recall of uncomfortable feelings after anaesthesia were asked. They included pain, fear, sleepiness, appetite/thirst, nausea and vomiting, cold/shivering. Multiple responses were possible.
Patient characteristics data were analysed for homogeneity using the two-tailed Wilcoxon's rank sum test for age, height and body weight of the patient and the two-tailed Fisher's exact test for gender, ASA and Mallampati classification. The data of age, height and bodyweight are presented as mean and standard deviation. Gender, ASA and Mallampati are presented in frequencies and percentages. BIS monitoring, remifentanil consumption and duration in the post anaesthetic care unit were tested with the two-tailed Wilcoxon's test and shown as mean and standard deviation. Orientation after anaesthesia, patients' self-evaluation after anaesthesia, repetition of anaesthesia and recall of uncomfortable feelings following anaesthesia were tested with the two-tailed Fisher's exact test and are shown in frequencies and percentages. Statistical analysis was performed using SAS software version 8.0® (SAS Institute Inc., Cary, NC, USA).
A total of 160 patients, 80 in the xenon and 80 in the propofol group, were enrolled. 17 patients in the xenon group and 27 patients in the propofol group were lost to follow-up leaving 63 xenon patients and 53 propofol patients for analysis. The patient characteristics data of the two study groups were comparable with respect to age, weight, height, sex and ASA classification (Table 1). Anaesthesia was induced with propofol 2.0 mg kg−1 and remifentanil 0.5 μg kg−1 in both groups. Maintenance of anaesthesia was achieved using 59.5 ± 2.6% xenon or with 0.11 ± 0.10 mg kg−1 min−1 propofol. Throughout the duration of anaesthesia, remifentanil consumption was 0.19 ± 0.08 μg kg−1 min−1 in the xenon group and 0.17 ± 0.07 μg kg−1 min−1 in the propofol group (Table 1). No differences were found in haemodynamic stability, recovery or duration of anaesthesia between the groups.
The time points of the interviews were comparable in both groups (Table 1). First early spatial orientation (operating theatre) recalled by patients in the telephone poll appeared sooner in the xenon group than in the propofol group but this difference was not significant. In the period after the operating theatre there was no difference in recall of spatial orientation between the groups (Table 2).
Patients' self-evaluation of anaesthesia with marks ranging from six to one (excellent-unsatisfactory) was addressed in the poll. There were no significant differences, both groups demonstrating equal satisfaction with either technique (Table 3). Seventy-three percent of patients in the xenon group and 83% of patients in the propofol group would have the same anaesthetic again. Recall of uncomfortable feelings after anaesthesia concerning postoperative pain and appetite/thirst were significantly more frequent in the xenon group compared with the propofol group. There was otherwise no difference between the groups in regard to fear, sleepiness, postoperative nausea and vomiting (PONV) and cold/shivering (Table 4).
Early spatial orientation was comparable in both groups. Patients' self-evaluation of anaesthesia revealed high marks and repetition of the same anaesthesia if necessary was similar in both groups. Recalls of uncomfortable feelings such as postoperative pain and appetite/thirst were significant more frequent in the xenon group. Concerning cold/shivering, PONV, sleepiness and fear the groups appeared to be similar.
A limiting factor in this study is the absence of established psychometric tests for patients' self-evaluation after anaesthesia. We decided to include subjective questions about spatial orientation after anaesthesia, patients' self-evaluation, choice of the same anaesthesia in future operations and recall of uncomfortable feelings following anaesthesia in our telephone poll.
The telephone poll was limited to a period of 4-12 weeks post anaesthesia. First, we tried to exclude patient's judgements which may be confounded by the outcome of their surgery, their interaction with a number of healthcare personnel, and other environmental factors. Second, we wanted to ensure a long enough period for the patient to recover from the operation to avoid evaluation interference . Consequently we accepted the possible disadvantage of postoperative telephone interviews being less accurate and further a possible difference between memory and actual event.
Memory of first spatial orientation was similar in both groups. This corresponds to the rapid recovery from xenon as well as from propofol after anaesthesia [5,7]. We observed a high incidence of recalled pain after xenon anaesthesia compared to propofol, both having the same post anaesthetic pain treatment.
Interestingly, there were higher numbers of patients who complained about appetite and thirst after xenon anaesthesia. Brandner and colleagues found that patients anaesthetized with a total i.v. technique using propofol had more dreams than those anaesthetized with thiopentone induction followed by inhalation anaesthesia with nitrous oxide and isoflurane. Furthermore, patients who received propofol were happier than those in the thiopentone group . This could be an explanation for the lower incidence of recalled pain, appetite and thirst after propofol anaesthesia compared to xenon. To our knowledge there are no data for the development of drowsiness after propofol compared to xenon anaesthesia. Drowsiness also could be an explanation for the decreased incidence of pain, appetite and thirst.
In summary, patient's evaluations and recall of early spatial orientation following xenon anaesthesia are comparable to a total i.v. anaesthetic with propofol.
This work was supported by: Messer-Griesheim (donor of xenon), Fütlingsweg 34, 47805 Krefeld. Organon GmbH Deutschland, Mittelheimer Straße 62, 5784 Oberschleißheim.
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