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Comparative analysis of costs of total intravenous anaesthesia with propofol and remifentanil vs. balanced anaesthesia with isoflurane and fentanyl

Epple, J.; Kubitz, J.; Schmidt, H.; Motsch, J.; Böttiger, B. W; Martin, E.; Bach, A.

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European Journal of Anaesthesiology: January 2001 - Volume 18 - Issue 1 - p 20-28



Remifentanil, a short-acting μ-opioid, provides haemodynamic stability and rapid postanaesthetic emergence and recovery when used as part of total intravenous anaesthesia (TIVA) [1–4] or a balanced anaesthesia regimen [5,6]. However, data on its cost-effectiveness are scarce and hospital budget restrictions in many countries have made it necessary to compare new drugs with established ones with respect to both benefits and costs [7]. Parameters for the evaluation of benefits have been established and these have been used in anaesthesia research for many years. The methods of cost evaluation, however, are still comparatively new. Concepts and guidelines for cost analysis have been suggested by many authors [8–12], but the design of pharmacoeconomic studies still requires further improvement. In particular, the exact evaluation of indirect costs [13] is very complex and thus remains an unsolved problem. Consequently, most economic studies have been content to produce a more or less comprehensive evaluation of direct costs.

This single-blind trial was conducted to determine the cost-effectiveness of total intravenous anaesthesia with remifentanil and propofol in comparison to balanced anaesthesia with fentanyl and isoflurane, which is currently the most inexpensive alternative for general anaesthesia in terms of drug costs and was the standard method of anaesthesia used in our department before the introduction of TIVA with propofol and remifentanil. Therefore, this balanced anaesthetic technique was selected for pharmacoeconomic comparison with TIVA with propofol and remifentanil even though the pharmacokinetic properties are different. Furthermore, we included the factors patient satisfaction and the ability of the two methods to improve the efficiency of an operating room schedule using a computer simulation to compare the cost-effectiveness of these anaestheia regimens.

Materials and methods

Anaesthesia regimen

After obtaining Institutional Review Board approval and written informed patient consent, 124 geriatric patients (age > 65 years, ASA physical status I, II or III) scheduled for elective cataract surgery under general anaesthesia were enrolled in this prospective, single-blind study. The patients were randomly allocated to receive either propofol and remifentanil or isoflurane and fentanyl, according to a computer-generated randomization schedule. Patients were excluded if they had a history of allergic reaction to one of the drugs used in this study.

Patients did not receive any other medication before surgery. When the patients arrived in the operating room, a peripheral intravenous (i.v.) cannula was inserted and standard monitoring consisting of pulse oximetry, non-invasive arterial pressure recording, and electrocardiogram was instituted. Systolic and diastolic arterial pressures, heart rate, and haemoglobin oxygen saturation were recorded during surgery and recovery. The inspired and end-tidal concentrations of oxygen, carbon dioxide, and isoflurane were measured with a calibrated infra-red gas analyser and recorded along with fresh gas flows at 5-min intervals. In the propofol and remifentanil group, patients received propofol 1.5 mg kg−1 and remifentanil 1 μg kg−1 over a period of 3 min for induction of anaesthesia. In the isoflurane and fentanyl group, anaesthesia was induced with etomidate 0.1–0.3 mg kg−1 and fentanyl 1.5 µg kg−1. In both groups, 0.15 mg kg−1 mivacurium was administered to facilitate orotracheal intubation. After intubation, patients' lungs were ventilated mechanically with a 1:2 oxygen–air mixture and 3 L min−1 fresh gas flow. Anaesthesia was maintained by continuous infusion of propofol 0.05–0.1 mg kg−1 min−1 and remifentanil 0.15–0.3 μg kg−1 min−1 in the propofol and remifentanil group, and with isoflurane 0.8–2.5 MAC and a bolus of 0.1 mg fentanyl at the beginning of surgery in the isoflurane and fentanyl group. No supplementary doses of muscle relaxant were administered.

After the conjunctival suture defining the end of surgery, all anaesthetics were discontinued and the lungs were ventilated manually with 100% oxygen. The effects of the muscle relaxant did not need to be antagonized. The orotracheal tube was removed as soon as the patients breathed spontaneously and opened their eyes on command.

Haemodynamic parameters were monitored continuously at 5-min intervals from the beginning of induction until the patients were discharged from the postanaesthetic recovery room (PACU). Haemodynamic changes exceeding 20% of the preoperatively assessed baseline values were treated by adjusting the doses of anaesthetic agents (step 1) and administering specific cardiovascular medication, for example atropine or etilefrine (step 2). Any required concomitant drugs were recorded.

To permit calculation of the costs involved, anaesthetic and surgical time intervals were defined (Table 1) and recorded. Discharge fitness from the PACU was judged by the anaesthetist in charge – who was not blinded with respect to the anaesthetic technique – according to standard clinical discharge criteria. The total working hours per case of the anaesthetists and the anaesthesia nurses were noted. Additionally, emergence times from discontinuation of anaesthesia to eye opening, tracheal extubation and achievement of an Aldrete score > 8 [14] were noted. The Aldrete score was recorded when the patients arrived in the PACU and every 15 min thereafter.

Table 1
Table 1:
Definition of time intervals

Postanaesthetic period

Postanaesthetic adverse events and medication were recorded for a period of 24 h after anaesthesia. Adverse events were defined as any unintended changes in body function or well-being, such as hypertension, postoperative nausea and vomiting (PONV), shivering, or pain, in particular if clinical intervention or drug therapy was required. Any contact of the medical or nursing staff with the patient in the PACU and on the ward that was beyond the usual postoperative observation was recorded within the 24-h interval in order to compare the two anaesthesia techniques concerning work-load requirements.

Patient satisfaction

On the first postoperative day, patients were interviewed using a questionnaire. They were specifically asked about postoperative complaints (nausea, vomiting, headache, wound pain, muscle pain, pain at the venous cannula location, sore throat, hoarseness, coughing, thirst, and shivering). In addition, they were asked at what time they were able to resume everyday activities. Patients' satisfaction was assessed by asking if awaking from anaesthesia was ‘more pleasant’, ‘as pleasant as’ or ‘worse’ than expected and if they were fully satisfied and would choose the same anaesthesia technique again.

Cost analysis

A cost comparison was performed from the perspective of our anaesthesia department. The analysis considered direct cost as described by Macario [15]. Total direct costs comprised: (a) the actual acquisition costs of all drugs, including waste, administered by the anaesthesia staff from the beginning of anaesthesia to discharge from the PACU; (b) the actual acquisition costs of disposable material used during this period of time such as perfusion syringes, cannulas, etc.; and (c) costs of all anaesthesia staff involved in the individual case. Therefore, the evaluated total working hours of anaesthetists and anaesthesia nurses were converted to monetary terms using the clinical intern salaries and assuming a nurse-to-patient ratio of 1:4 in our PACU. The costs of drugs and materials were based on the acquisition costs of our department. Costs of isoflurane were calculated using the formula described by Kuhn and his colleagues [16]. Drugs and resources that were common to both groups (e.g. oxygen, air, pulse oximeter probes, anaesthetic circuit) were not included. Furthermore, the expenses for drugs were calculated, both including and excluding costs of waste. In accordance with Tang and his colleagues [17], we calculated the ‘costs per completely satisfied patient’ for each group by dividing the total costs per patient by the fraction of completely satisfied patients as assessed by the questionnaire. In this way, the cost-effectiveness of the anaesthetic techniques can be compared.

Model simulation

Simulation is a useful means of comparing utilization of the operating theatre and the PACU when different anaesthesia regimens are used [18]. Thus, we developed a model for simulating the patient flow through an operating suite with three operating theatres and one PACU over the course of one working day. The ‘ithink Analyst 4.0.2’ software developed by Altura Software was used to build the model and to run it. Several input parameters such as different time intervals or the number of operating theatres in use could be varied. The length of stay in the anaesthesia induction room, the operating theatres, and the PACU, and also the anaesthesiologists' active time staying with the patients were the parameters obtained from our study. Closing times of the operating theatres and of the PACU, staff overtime and total length of patients' stay within the operating suite represented the output parameters in this model. We analysed two different scenarios defined by different operating suite work schedules: one with a given number of cases per day with unlimited closing time and another in which the closing time of the operating suite was fixed.

Statistical analysis

Our a priori power analysis was based on data from an earlier remifentanil/propofol study with a mean of about 50 min and a standard deviation of about 26 min for the time from end of surgery until PACU discharge readiness. We calculated that a minimum of 51 patients needed to be enrolled in each group in order to provide 80% power to detect a difference of at least 15 min in the primary endpoint at α = 0.05 (two-tailed test). Demographic data were compared using the Chi-squared test for categorical variables and Student's t-test for continuous variables. Time intervals and expenses for drugs, materials, and staff were evaluated using Student's t-test for a comparison of mean values, F-test for standard deviations, and U-test for medians. Adverse events and questionnaire results were analysed using the Chi-squared test. Data are expressed as mean ± standard deviation unless stated otherwise. P < 0.05 was considered statistically significant.


A total of 124 geriatric patients undergoing elective cataract surgery and scheduled for general anaesthesia participated in this study. The demographic characteristics were similar among the groups (Table 2). The drug consumption for both groups is shown in Table 3.

Table 2
Table 2:
Demographic data
Table 3
Table 3:
Drug consumption (without waste)

There was no significant difference in the mean duration of presurgical anaesthesia-controlled time (ACT, time from the beginning of the anaesthetist's presence until the completion of induction of anaesthesia) and surgically controlled time (SCT; time from the beginning until the end of surgery). Recovery times and postsurgical ACT I (time from the end of surgery until the end of the anaesthetist's presence) were significantly shorter in the propofol and remifentanil group. The time from the end of surgery until transfer to the ward was reduced by a mean of 17 min in the propofol and remifentanil group compared with the isoflurane and fentanyl group. Furthermore, the anaesthetists were occupied for an average of 9 min less per case in the propofol and remifentanil group, and the total working time of the anaesthesia nurses was also significantly lower due to a faster recovery from anaesthesia and, hence, a faster transfer to the PACU.The duration of PACU stay alone, i.e. the postsurgical ACT II, did not differ significantly among the study groups (Table 4); however, the time in the PACU until an Aldrete Score > 8 was achieved differed significantly between the two groups, with a difference of 10 min per case in favour of propofol and remifentanil.

Table 4
Table 4:
Time intervals (min)

There were no significant differences regarding the work-load requirement in the PACU and the ward during the observation period. The time the anaesthesia nurses needed for an individual patient beyond routine postanaesthetic observation was similar among the groups (median 3 vs. 2 min, P = 0.234). The same applies to the ward, where the total time for patient care was identical in the two groups (median 31 vs. 31 min, P = 0.223). The requirement for additional medical treatment did not differ significantly among the study groups: additional treatment by ophthalmologists 3 vs.1, anaesthetists 1 vs. 0, and internists 2 vs. 0 (propofol and remifentanil vs. isoflurane and fentanyl respectively).

Occurrence of adverse events and related drug therapy differed significantly among the groups. In the PACU, more patients needed cardiovascular medication after propofol and remifentanil (52 vs. 27%), whereas antiemetic therapy was only required after isoflurane and fentanyl (0 vs. 13%). More patients in the propofol and remifentanilI group needed analgesics for postoperative pain than did patients in the isoflurane and fentanyl group (16 vs. 8%); however, this difference was not statistically significant. The incidence of postoperative shivering was significantly higher in the propofol and remifentanil group (10 vs. 0%). One patient in the propofol and remifentanil group experienced a myocardial infarction 23 h postoperatively. Coronary angiography performed on the first postoperative day demonstrated a previously unknown three-vessel coronary disease. The patient recovered without any sequelae.

One hundred and twenty questionnaires (97%) were returned. Significant differences between the groups were found for the incidence of nausea (10 vs. 34%, P = 0.001), vomiting (3 vs. 23%, P = 0.002), coughing (45 vs. 20%, P = 0.003), and shivering (24 vs. 2%, P < 0.001, propofol and remifentanil vs. isoflurane and fentanyl respectively). Other complaints were similar among groups. Time intervals until patients could think clearly (P = 0.045) and conduct a conversation after the end of surgery (P = 0.039) differed significantly among the study groups in favour of propofol and remifentanil. In the propofol and remifentanil group, a higher percentage of patients experienced recovery from anaesthesia as more pleasant than expected (56 vs. 33%, P = 0.022), were fully satisfied and would be happy to have the same anaesthesia regimen again (93 vs. 66%, P < 0.001). No patient in the study population recalled any intraoperative event.

The cost of anaesthesia differed significantly concerning both the individual cost factors and the total cost. Although expenses for drugs and materials were higher in the propofol and remifentanil group, the total cost of anaesthesia per case was € 12.25 less than in the isoflurane and fentanyl group due to lower personnel expenses to the amount of € 23.60. The proportion of wasted anaesthetics which were included in this comparison (see Table 5) amounted to 39% of total costs for anaesthetics in the propofol and remifentanil group and 13% in the isoflurane and fentanyl group.

Table 5
Table 5:
Data for the economic analysis (per case in €)

The costs per completely satisfied patient, defined as one who would choose the same anaesthesia regimen again, were significantly lower in the propofol and remifentanil group with € 176 compared with € 269 in the isoflurane and fentanyl group (Table 5).

The patient flow simulation for one working day in an operating suite showed that the operating theatre and the PACU could be closed down approximately 1 h earlier if propofol and remifentanilI were used instead of isoflurane and fentanyl in all six consecutive cases in a single operating theatre or 18 consecutive cases in three operating theatres respectively. On the other hand, if the operating theatre and the PACU have to be closed down after an 8.5-h shift, one more patient per day in a single operating theatre and three more patients per day in three operating theatres could be treated if propofol and remifentanil were used. Table 6 presents the results of the simulation in detail for the two described working time scenarios.

Table 6
Table 6:
Operating theatre and PACU organization according to patient flow modelModel 1. Fixed number of cases


This study evaluated the recovery profiles, the patient satisfaction, and the costs of drugs and other resources used for TIVA with remifentanil and propofol compared with a balanced anaesthesia regimen with fentanyl and isoflurane. The geriatric population of this study represents the typical patient population treated at a tertiary eye care centre with regard to the prevalence of systemic comorbidity [19]. Currently, a substantial variation in anaesthesia care for cataract surgery is being observed [20]. Local and regional anaesthesia are most commonly used, but due to the high incidence of unanticipated complications and interventions, monitored anaesthesia care seems to be necessary [21]. If the presence of an anaesthetist is required to monitor a patient under local anaesthesia, there are almost similar direct costs per case compared with a general anaesthesia technique, because personnel costs represent 67% of the total direct costs in our department. In our study, patients not eligible for local or regional anaesthesia in cataract surgery were included and randomized to receive either isoflurane and fentanyl or propofol and remifentanil.

Due to the trend towards minimally invasive surgery, on one hand, and budget restrictions in many health care systems, on the other, outpatient surgery and anaesthesia are gaining in importance. Outpatient anaesthesia requires early postoperative discharge from hospital, which means rapid recovery of psychomotor functions, low probability of postoperative adverse events, and rapid resumption of everyday activities. Due to a markedly shorter half-life of esterase-metabolized remifentanil [22–24] as compared with fentanyl and the pharmacokinetic properties of propofol and isoflurane, the expected faster emergence and recovery from anaesthesia were verified. The recovery parameters were similar to those described in previous studies [1–5] and were associated with an earlier discharge. Differences between the time of achievement of the discharge criteria according to the Aldrete score and actual discharge from the PACU were demonstrated, as pain and PONV — the main reasons for delayed discharge from the PACU [25] and therefore of great importance for cost calculation of postoperative patient care [26,27] — do not directly affect the Aldrete Score. On the other hand, deficiencies in the hospital infrastructure, for example intrahospital patient transport service or problems on the ward the patient is to be transferred to, can cause a delay in discharge from the PACU that is unrelated to the medical condition of the patient, as we observed in our study.

The high incidence of nausea after isoflurane and fentanyl in comparison to propofol and remifentanil in this study is consistent with the results of previous studies [25]. We assume that PONV and the long duration of postoperative sedation are the major reasons for lower patient satisfaction in the isoflurane and fentanyl group and are well-known factors influencing the patients' preferences in the recovery period [28–32]. As a consequence of remifentanil's short half-life, more patients in the propofol and remifentanil group complained of postoperative pain and required analgesics. The early recovery of alertness and sympathetic activity explains the higher incidence of postoperative hypertension and antihypertensive treatment. Postoperative shivering was comparatively frequent after propofol and remifentanil, but its incidence in this study was still lower than previously reported [6,33,34].

Patient satisfaction should also be included in a pharmacoeconomic analysis: Satisfaction with surgery and anaesthesia probably determines which hospital a patient will choose in the future. Furthermore, it is increasingly being used by third-party payers as a guide for selective contracting to high-performance institutions. Therefore, comparing the costs to ‘produce’ a completely satisfied patient could be of increasing interest for departments of anaesthesia and hospitals in general.

Data on the economics of TIVA with remifentanil and propofol are scarce. Suttner and his colleagues [33] found TIVA using remifentanil and propofol was associated with higher intraoperative costs than an anaesthesia technique using isoflurane. However, these authors only compared the drug costs and did not take into account material or personnel costs. Tang and his colleagues [17] included these cost components in a cost-effectiveness analysis of propofol vs. sevoflurane in office-based anaesthesia. In our study, actual acquisition costs of drugs and disposables and the costs for the management of side-effects were included. In addition, the labour costs of physicians and nurses were evaluated. The latter is of particular economic interest because personnel costs constitute a major proportion of total anaesthetic costs, in our department 67%. Previous studies have suggested that the advantageous recovery profile of remifentanil and propofol can be converted into savings on personnel expenses [6,17,33,35]. By calculating personnel costs per minute for the anaesthetist and the anaesthesia nurse, this could be verified for our department. The savings in personnel expenses outweighed the higher drug acquisition costs of propofol and remifentanil and rendered the direct costs even less than those of isoflurane and fentanyl. The direct costs could be decreased even more if the percentage of wasted drugs, which was high in the propofol and remifentanil group, could be reduced. On the other hand, the personnel cost reduction of € 23.60 is assumed to be linear, with personnel costs directly proportional to the time intervals in the OR and PACU. A more realistic scenario, as in our department, is to calculate personnel costs on the basis of a fixed salary for an 8.5-h shift plus additional overtime payments. This decreases the savings in personnel costs in favour of propofol and remifentanil to € 20.45 in our department. As the number of operations that can be performed within a defined time interval, i.e. per 8.5 h shift, is higher if propofol and remifentanil is used instead of isoflurane and fentanyl, it can be assumed that indirect costs per case such as costs for the facilities, administrative clerks, etc. are lower if propofol and remifentanil are used; yet, the objective of this study was not to evaluate indirect costs. However, work-load requirements on the ward to which the patients were transferred after their PACU stay were recorded: The amount of consumed resources was the same for the two groups and, thus, cost shifting did not occur.

A remaining problem of cost analysis is that the results cannot always be applied to other hospitals due to different drug, material and personnel costs [36]. Drug prices differ even among hospitals in the same country and change frequently. Actually, drug acquisition costs at our department decreased up to 42% after the study period. This would result in a 19% reduction of drug costs for propofol and remifentanil and 16% for isoflurane and fentanyl. Furthermore, the reduction in physicians' and nurses' working hours due to propofol and remifentanil as presented in the patient flow simulation discussion above enables the savings in labour costs to be calculated for different salary schedules. Also, in some countries, e.g. in Germany, prospective contracts with third-party payers which include limitations regarding the number of cases make it difficult to achieve cost advantages simply by increasing the number of cases per day. However, closing down the operating theatre and the PACU earlier may be turned into reduced overtime payments or into additional available time for research, education, administration or other tasks.

After the end of our study, patients scheduled for cataract surgery under general anaesthesia only received TIVA with propofol and remifentanil. The reduction of anaesthesia-controlled time as shown in our study proved to be a stable effect: The daily caseload of 18 patients in three operating theatres is managed as described in our study protocol, and as a result the operating theatre and PACU could be closed down 1 h earlier as compared with a previous control group with patients who received isoflurane and fentanyl. The waste of i.v. drugs could be reduced to approximately 10% in the poststudy period as a lesser amount of drug had to be filled in the syringe pumps according to the estimated time of surgery. This reduced the difference in direct costs for anaesthetics from about € 10 to € 2.36 per case, although the cost of drugs for TIVA with propofol and remifentanil was still higher. Replacing isoflurane by desflurane or sevoflurane would lower the difference in drug costs even further to about € 1 to € 2 per case, depending on the fresh gas flow. Use of low flow instead of a 3-L min−1 fresh gas flow with isoflurane would increase the difference in drug costs in comparison with propofol and remifentanil to about € 4 per case.

In conclusion, this study demonstrates that TIVA with remifentanil and propofol used in general anaesthesia for cataract surgery had advantages over balanced anaesthesia with fentanyl and isoflurane, combining lower total costs, higher patient satisfaction, and a more efficient operating theatre schedule.


The study was supported by a grant from Glaxo Wellcome GmbH & Co., Hamburg, Germany.


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© 2001 European Academy of Anaesthesiology