Anaesthesiologists need to be aware of the costs of the anaesthetics, additional drugs and disposables commonly used in clinical practice to minimize excessive costs. Because of its cost-saving potential, office-based surgery is becoming increasingly popular, recruiting young and healthy patients as outpatients . However, the majority of in-patients in anaesthesiology are older, ranked up to ASA III . In this regard, it is important to select the most appropriate general anaesthetic technique that should be associated with a low incidence of perioperative side-effects and rapid recovery, and with minimal total costs . This is fundamental when planning a safe and practical office-based general anaesthesia for older patients without compromising their clinical outcome and satisfaction. In several studies, the well-established volatile anaesthetic isoflurane was compared with the more 'modern' intravenous drug propofol and with the total intravenous anaesthesia (TIVA). Propofol is associated with faster recovery and better patient comfort, but it costs more than isoflurane . However, focussing on total costs, propofol might be more cost-effective than isoflurane owing to the reduction in personnel costs because of faster recovery . Moreover, these positive aspects of propofol may not hold true when compared with sevoflurane. Comparative analyses of these two anaesthetic agents therefore were performed in patients aged 65 yr or more, focussing on different aspects of the perioperative period. The anaesthetic side-effects, quality of recovery, patient comfort, costs of anaesthetics and total costs for the perianaesthetic period were investigated for either TIVA based on propofol or balanced anaesthesia with propofol induction followed by sevoflurane maintenance or on anaesthesia induced and maintained by sevoflurane.
Our institution approved the study and written informed consent was obtained from all patients. In-patients scheduled for elective, unilateral ophthalmic surgery were investigated in this prospective and randomized study. The inclusion criteria were 65 yr or more and ASA I-III. Patients with either obvious cardiovascular complaints (NYHA III-IV), any previous adverse reactions to one of the study drugs or those participating in another clinical study were excluded. Patients with a history of general anaesthesia during the last 3 months and those with less than 60% vision in the contralateral eye were also excluded.
Treatment groups and anaesthesia regimen
Patients were allocated to one of three groups for different induction and the maintenance of general anaesthesia, according to a computer-generated random numbers table. In the propofol group (Group P), anaesthesia was induced with propofol (2 mg kg−1), but after orotracheal intubation, it was maintained with continuous infusion of propofol (4-8 mg kg−1 h−1).
In the propofol/sevoflurane group (Group P/S), anaesthesia was also induced with propofol (2 mg kg−1), but after orotracheal intubation, it was maintained with sevoflurane (end-tidal concentration 0.6-1.2 vol.%).
In a third group (Group S), patients received a tidal breathing induction  and maintenance of anaesthesia using sevoflurane. After 1 min preoxygenation, the vaporizer was adjusted stepwise up to 8%. After the eyelash reflex was abolished and before orotracheal intubation, the vaporizer setting was reduced to 5%. Subsequently, anaesthesia was maintained with a 0.6-1.2% end-tidal concentration of sevoflurane.
All patients received their usual cardiac and antihypertensive medications, and no sedative drugs were given for premedication. After preoxygenation, induction of anaesthesia was started with a continuous infusion of remifentanil (20 μg kg−1 h−1). Subsequently, the induction of general anaesthesia was continued according to the protocol described above. Two minutes before orotracheal intubation, atracurium 0.3-0.5 mg kg−1 was given. For the maintenance of anaesthesia, the infusion rate of remifentanil was reduced to 10 μg kg−1 h−1. At the end of surgery, the administration of anaesthetics was discontinued and the spontaneously breathing patients were extubated once they had opened their eyes on command. To standardize the anaesthesia procedures described above, all cases were performed by the same anaesthetist (S. L.).
Data assessment in the perianaesthetic period
In the perianaesthetic period, comparative analyses focussed on heart rate, mean arterial blood pressure, the duration of anaesthesia induction, the duration of surgery and the emergence from anaesthesia.
During the recovery period, subjective aspects of well being, and the side-effects of anaesthesia or surgery (hypertension, postoperative nausea and vomiting (PONV), shivering, pain, etc.) as well as subsequent interventions were assessed. Changes in heart rate and mean arterial blood pressure of more than 30% of preoperative baseline values were treated with atropine 0.5 mg i.v. bolus, etilefrin 1 mg bolus and urapidil 5 mg bolus, respectively.
When individual visual analogue scales (VAS) (1-100) showed 30 or more, PONV was treated with dolasetron 12.5 mg and pain with metamizol 1000 mg .
The Aldrete score was measured every 10 min after patients' arrival in the postanaesthesia care unit . A score of nine or 10, measured twice in the course of 10 min, indicated that patients were fit to be discharged to the ward.
Each patient performed different tests for psychomotor ability at five different times: the day before surgery, 30, 60 and 120 min after extubation of the trachea, and the day after surgery. Individual reaction times to visual and auditory stimuli were measured, and critical flicker fusion frequency was evaluated . Moreover, long- and short-term memory performance and manual abilities using the ball-bearing test were assessed. In addition, patients were asked about pain, PONV and sedation using 100 mm VAS .
Patients' satisfaction with the entire anaesthetic procedure was assessed the morning after surgery by questionnaire asking about the occurrence of named side-effects of anaesthesia or surgery (PONV, pain, coughing, sedation, thirst), discomfort during induction and recovery from anaesthesia, and psychomotor abilities after anaesthesia. The final question was whether the patients would choose the same anaesthesia regimen again.
A cost analysis was based on the actual acquisition costs for our anaesthesia department. The analysis considered the consumption of anaesthetic agents and the consumption of drugs for treatment of side-effects of the anaesthetic, e.g. hypo- or hypertension, bradycardia and PONV. Disposable items were included in cost calculations. For the same patient, syringes and drugs were reused whenever additional drug doses were required. Drugs, materials and personnel resources common to all groups (endotracheal tube, remifentanil, atracurium, etc.) were not considered.
Total consumption of propofol was noted at the end of anaesthesia. Vaporizers for sevoflurane were calibrated before starting the investigation. Fresh gas flow and the vaporizer setting were recorded every 1 min during induction of anaesthesia until orotracheal intubation, and every 5 min until the end of surgery.
The costs for the periods of the different sevoflurane settings were calculated according to the formula described by Weiskopf and Eger  and Rosenberg et al.:
where P is the vaporizer dial setting (%), F is the fresh gas flow (L min−1), T is the duration of sevoflurane administration (min), M is the molecular weight (sevoflurane = 200), C is the cost (€ mL−1) of liquid agent and d is the density (sevoflurane = 1.52 g mL−1). The prices for each period were added to obtain the total costs for sevoflurane.
The actual amount of anaesthetic agent (sevoflurane and/or propofol) and the total costs of anaesthesia, including drugs and single-use material for the treatment of side-effects, were analysed separately.
The data were analysed to determine statistically significant differences. Patient characteristics data were compared using the χ2-test. For continuous variables, two-way analysis of variance (ANOVA) followed by Scheffé's test were used, and for categorical variables Fisher's exact test was applied. The results of repeated measurements of psychomotor ability were compared with each patient's baseline performance obtained on the day before anaesthesia. P < 0.05 was considered as statistically significant.
Ninety-six geriatric patients were investigated, 32 in each group (Group P, 74 ± 7 yr; Group P/S, 76 ± 6 yr; Group S, 77 ± 7 yr). No patient was withdrawn from the study. There were no significant differences between the patient groups with regard to age, gender, height, weight and ASA physical status. Additionally, there were also no differences between these groups with regard to the duration of surgery (Group P, 24.3 ± 6.5 min; Group PS, 26.4 ± 5.4; Group S, 26.4 ± 3.1 min).
Compared with Group S, mean arterial pressure following induction of anaesthesia until the beginning of surgery was significantly lower in Groups P and P/S (Fig. 1).
Additionally, significantly fewer medical interventions to increase mean arterial pressure were required in Group S during induction (P < 0.05 versus Groups P and P/S, respectively) and maintenance (P < 0.05 versus Group P/S) (Table 1).
Before the induction of anaesthesia, the heart rate in Group P patients was significantly lower than that in Group S patients (P < 0.05) (Fig. 2). During maintenance, patients in the propofol group (Group P) required atropine significantly more often than patients in the sevoflurane group (Group S, P < 0.05) (Table 1).
There were no differences in the incidence of shivering and pain in the postoperative period (Table 1). In the postanaesthesia care unit, patients had significantly more severe nausea after inhalation (Group S) than after intravenous induction of anaesthesia using propofol (Fig. 3). Therefore, most interventions to treat PONV were necessary in Group S (P < 0.05 versus Groups P and P/S) (Table 1).
There were no differences between all groups with regard to the duration of anaesthesia induction, the duration of surgery and the total time for anaesthesia (data not shown). After discontinuing administration of anaesthetic drugs at the end of surgery, the patients of Group P were extubated 1 min earlier than those in Group P/S (P < 0.05). According to the Aldrete score results, all the patients could be discharged from the recovery room without any significant differences.
The results of psychomotor recovery tests did not reveal any significant differences between any groups. All patients showed similar test performances on the day before and 24 h after surgery.
In the questionnaire 24 h after surgery, Group S patients more often reported periods of nausea (P < 0.01 versus Groups P and P/S) or vomiting (P < 0.05 versus Groups P and P/S) during recovery from anaesthesia (Table 2). When asked for their opinion about the general anaesthesia, 50% of Group S patients were highly satisfied with the induction (P < 0.05, versus 71% in Group P and 76% in Group P/S). In Group S, 22% of patients expressed a preference for another type of anaesthetic should a further operation be required (P < 0.01 versus 3% in Group P and 0% in Group P/S).
Cost analysis focussed on group-specific drug costs for anaesthesia, interventions and single-use materials. Personnel costs did not have to be considered because of the similar time schedules for patient management in all groups.
The consumption of anaesthetics for induction and the maintenance of anaesthesia are listed in Table 3. Anaesthesia induction using propofol (Groups P and P/S) required at least one 20 mL vial of propofol, and for maintenance another 50 mL vial of propofol had to be used. The costs for sevoflurane could be based on the consumption without any waste. In total, the anaesthetic costs were highest in Group P and lowest in Group P/S (Table 3).
A further aspect of cost analysis considered the group-specific consumption of additional drugs and single-use material according to the anaesthetic administered, and the incidence of treatment for hypotension, bradycardia and PONV. The total costs for general anaesthesia in Group P/S were lower than those in Groups P and S. The potential savings were about 14% (Table 3).
The present investigation in the elderly has demonstrated that the use of sevoflurane - for the maintenance of anaesthesia after an induction with propofol - showed advantageous results similar to those of propofol for both periods of general anaesthesia. However, the total costs could be reduced by 14% using a combination of propofol and sevoflurane. Therefore, the combination of propofol-induced and sevoflurane-maintained anaesthesia is the most cost-effective method in elderly patients without compromising safety, clinical outcome or satisfaction.
Depending on the anaesthesia regimen, the haemodynamic variables differed significantly, but ultimately patient safety and recovery did not seem to be affected. For all three groups, bradycardia during induction of anaesthesia required similar treatment, but with propofol for the maintenance of anaesthesia (Group P), atropine medication was required significantly more often. Both propofol and sevoflurane are known to cause a decrease in heart rate, but although our study population was quite old, bradycardia was not associated with haemodynamic instability in any patient and it could be treated effectively using small doses of atropine [13-15]. It cannot be denied that when combining propofol or sevoflurane with N2O, bradycardia might be more severe [15,16], but according to our protocol, N2O was not used in any group [17-19].
The hypotensive effect of the intravenous anaesthetic propofol seems to be more severe than that of the volatile anaesthetic sevoflurane [20,21]. Therefore, sevoflurane-based inhalation induction (Group S) provided a beneficial effect by preventing a rapid decrease in blood pressure. More haemodynamic stability might be achieved by using a maximum of 4% sevoflurane for the induction of anaesthesia instead of 8%, but this approach is occasionally associated with prolonged and unsuccessful induction . Both bradycardia and hypotension might be an effect of a very deep level of anaesthesia. Although the depth of anaesthesia was not monitored, the three anaesthetic techniques used here are postulated as being equal, as in most other studies [15,23,24]. Our clinical and perioperative experience did not give any indication that patients had had insufficient anaesthesia.
Group P or P/S patients did not develop any significant side-effects associated with intraoperative bradycardia or hypotension, or even required a longer stay in the recovery room. Therefore, the use of propofol or sevoflurane for any period of anaesthesia in the elderly is safe if bradycardia and hypotension are treated adequately.
In the present study, severe postoperative nausea was found after inhalation induction and the maintenance of anaesthesia using sevoflurane (Group S). The higher incidence of PONV in Group S reflects an important difference in clinical outcome because it influenced patient satisfaction and increased treatment costs. Other studies using sevoflurane or propofol for general anaesthesia in middle-aged outpatients [14,16,17,25-27] showed similar results. Propofol exhibits a well-known antiemetic effect , whereas sevoflurane increases the incidence of postoperative nausea or vomiting . In Group P/S, the emetic effect of sevoflurane appeared to be prevented due to the antiemetic effect of propofol , and concomitantly also by the reduced inhaled concentration of sevoflurane .
Different tests were used, each dealing with another ability to discover differences in psychomotor recovery. It has been shown here that in the elderly, following general anaesthesia using sevoflurane or propofol, the decrease in cognitive and motor function is mild and temporary. Our observation is in agreement with the data of Loop and Priebe, who showed similar and quick psychomotor recovery in patients anaesthetized with either propofol or sevoflurane . Therefore, especially for day-case surgery, either anaesthetic can be used without compromising patient safety.
Many studies have investigated the practicability of inhalation induction using sevoflurane. The acceptance of this method using single-breath or tidal volume ventilation in young adult patients was reported to be high [31,32]. In the present study with elderly patients, satisfaction, as indicated by Smith and colleagues  by willingness to receive the same anaesthetic again, was significantly low when inhalation induction was performed (Group S). The elderly patients themselves mentioned the two main reasons: first, discomfort related to inhalation induction, e.g. a mask close to the face and an unusual odour of sevoflurane, and, second, the later incidence of PONV. However, patient comfort was obviously high when using propofol for induction and either propofol or sevoflurane for the maintenance of anaesthesia. It is interesting that the local intravenous pain due to propofol injection, which was observed in a subgroup of patients, could not be remembered the day after surgery.
It has been shown that excessive costs can be minimized without compromising clinical outcome and patient satisfaction. Using a certain anaesthetic might produce further costs for the treatment of side-effects of this drug, so that an inexpensive volatile anaesthetic ultimately might prove to be a more expensive choice [33,34]. Therefore, comparing anaesthesia costs is not a trivial matter: two studies published in 1999 investigated outpatients anaesthetized with propofol and/or sevoflurane [23,26]: Tang and colleagues  focussed on the total costs required to achieve complete patient satisfaction and found that propofol/propofol-N2O were the cheapest kind of anaesthesia, followed by propofol/sevoflurane-N2O and sevoflurane/sevoflurane-N2O. Smith and colleagues'  results were the opposite. The sevoflurane/sevoflurane group was nearly as inexpensive as the propofol/sevoflurane group, but the propofol/propofol group was much more expensive. The present study focussed on the total anaesthesia costs and considered the costs of everything that might be different between the groups. Therefore, only those costs that were identical in all three study groups were not considered, e.g. costs for remifentanil, personnel resources or room rental, after checking the particular results and perioperative time schedules of patient management. Finally, the present study showed that the use of sevoflurane for the maintenance of anaesthesia after induction with propofol (Group P/S) was less expensive than either propofol or sevoflurane for both induction and the maintenance of anaesthesia in the elderly. A further reduction in costs may be possible if instead of using 3 L min−1 fresh gas flow, only 1 L min−1 was used for the maintenance of anaesthesia .
In the elderly, it is safe to use either propofol or sevoflurane for each period of general anaesthesia. Different haemodynamic effects of the anaesthetics, e.g. hypotension and bradycardia, can be treated routinely and do not influence patient outcome. However, after inhalation induction of anaesthesia with sevoflurane (Group S), some patients complained of discomfort because of a higher incidence of PONV. Moreover, the present detailed cost analysis revealed that it is less expensive to use propofol for induction and sevoflurane for the maintenance of anaesthesia than either propofol or sevoflurane for both periods of anaesthesia. Therefore, the combination of a propofol-induced and sevoflurane-maintained anaesthetic is the most cost-effective method without compromising patient safety, clinical outcome and satisfaction in the elderly.
The study was supported in part by a grant from Abbott Laboratories, Wiesbaden, Germany.
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