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Anesth Analg 1999;88:77-82
© 1999 International Anesthesia Research Society

ECONOMICS AND HEALTH SYSTEMS RESEARCH

Cost Analysis of Target-Controlled Infusion-Based Anesthesia Compared with Standard Anesthesia Regimens

Stefan Suttner, MD, Joachim Boldt, MD, Christian Schmidt, MD, Swen Piper, MD, and Bernhard Kumle, MD

Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Akademisches Lehrkrankenhaus der Universität Mainz, Ludwigshafen, Germany

Address correspondence and reprint requests to Prof. Dr. Joachim Boldt, Department of Anesthesiology and Intensive Care Medicine, Akademisches Lehrkrankenhaus der Universität Mainz, Klinikum der Stadt Ludwigshafen, Bremserstr. 79, D-67063 Ludwigshafen, Germany.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Appendix
 References
 
With the development of new computer-assisted target-controlled infusion (TCI) systems and the availability of short-acting anesthetics, total IV anesthesia (TIVA) has become increasingly popular. The aim of this study was to compare costs of TCI-based anesthesia with two standard anesthesia regimens. Sixty patients undergoing elective laparoscopic cholecystectomy were randomly divided into three groups. Group 1 (TIVA/TCI) received TIVA using a propofol-based TCI system and continuous administration of remifentanil; Group 2 (isoflurane) underwent inhaled anesthesia with isoflurane, fentanyl, and N2O; Group 3 (standard propofol) received fentanyl and N2O and a continuous infusion of propofol using a standard delivery system. Maintenance doses for anesthetics were adjusted according to the patient's need. Isoflurane consumption was measured by weighing the vaporizer by using a precision weighing machine. Duration of surgery and of anesthesia was similar in the three groups. Time from stopping administration of anesthetics until tracheal extubation (6 ± 2 min) and stay in the postanesthesia care unit (PACU; 70 ± 12 min) were shorter in Group 1 than in the Groups 2 (15 ± 3 and 87 ± 13 min, respectively) and 3 (10 ± 4 and 81 ± 14 min, respectively) (P < 0.05). Episodes of postoperative nausea and vomiting in the PACU and on the surgical ward were less common in Group 1 than in the other two groups. Intraoperative costs were higher in Group 1 ($62.19/patient; $0.55/min of anesthesia) than in Groups 2 ($16.97/patient; $0.13/min of anesthesia) and 3 ($34.68/patient; $0.32/min of anesthesia). Cost for discarded anesthetic drugs accounted for almost 18% of total intraoperative costs in Group 1. We conclude that TIVA/TCI anesthesia using propofol/remifentanil was associated with the highest intraoperative costs but the fewest postoperative side effects. An overall cost-effectiveness analysis of new anesthetic regimens must balance the direct cost of anesthetics and beneficial effects leading to improved patients' comfort.

Implications: In today's climate of cost-consciousness, careful economic evaluation of new anesthetic regimens is necessary. A target-controlled infusion (TCI)-based total IV anesthesia (TIVA) regimen using propofol and remifentanil was compared with a standard propofol anesthesia regimen and an inhaled anesthetic technique using isoflurane. Target-controlled infusion/total IV anesthesia was associated with the largest intraoperative costs but allowed the most rapid recovery from anesthesia, was associated with fewest postoperative side effects, and permitted earlier discharge from the postanesthesia care unit.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Appendix
 References
 
With the introduction of new, short-acting anesthetics and the development of computer-assisted target-controlled infusion (TCI) systems, total IV anesthesia (TIVA) is gaining increasing acceptance. TCI systems for propofol consist of averaged pharmacokinetic models derived from large population samples, a set of specific pharmacokinetic variables for propofol, and infusion-control algorithms (1,2). The use of propofol-based TCI anesthesia results not only in more rapid induction of anesthesia with less propofol, but is also associated with less movement in response to surgical stimuli due to a deeper level of anesthesia (3,4). Propofol has a favorable pharmacokinetic profile for TIVA. It is associated with more rapid recovery and less nausea and vomiting than standard anesthetic regimens (5–7).

In the era of healthcare reform, the ability to demonstrate the economic value of new technologies is essential. As total costs for anesthesia comprise direct and indirect costs, an initial step of precise cost calculation is to tally the direct costs for the anesthetics used (8). This is especially important for IV anesthetics, which are, in part, discarded after their use. Furthermore, indirect costs derived from postoperative side effects such as nausea and vomiting should also be assessed (9–11). Several cost-analysis studies with varying anesthesia techniques have been published (12–17), but there is only limited information about the costs associated with propofol-based TCI anesthesia. Thus, we designed the present study to compare the costs and side effects of a TCI-based TIVA anesthesia technique with standard anesthesia regimens.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Appendix
 References
 
After approval of the study by our hospital's ethics committee, 60 ASA physical status I or II patients scheduled for elective laparoscopic cholecystectomy gave written, informed consent to participate in the study. Renal and liver insufficiency (creatinine >1.5 mg/dL; alanine aminotransferase/aspartate aminotransferase >40 U/L), abuse of alcohol and drugs, unstable angina pectoris, and a history of myocardial infarction within the last 6 mo were defined as exclusion criteria. All patients were premedicated with lorazepam (1–2 mg) orally 1 h before induction of anesthesia.

The patients were randomly assigned to one of the following groups. In Group 1 (TIVA/TCI; n = 20), TIVA was used with propofol administered by a continuous computer-assisted TCI system (Graseby® 3500 syringe pump; Graseby Medical Ltd, Watford, UK) and additional continuous infusion of remifentanil. Before induction of anesthesia, the patient's weight, age, and the desired blood concentration of propofol were entered into the TCI system. Anesthesia was induced using 1 µg/kg remifentanil administered over 1 min using a regular syringe pump. Thereafter, propofol-TCI was started. The initial target (plasma) concentration was set at 4–6 µg/mL, titrated against clinical effects. Atracurium (0.5 mg/kg) was administered to achieve muscle relaxation before endotracheal intubation. Maintenance of anesthesia was achieved by adjusting the anesthetics to the individual patient's need (target plasma concentration of propofol 2.5–5 µg/mL, remifentanil dose 0.25–0.5 µg · kg-1 · min-1). During wound closure, the target propofol concentration was set to 2 µg/mL. Remifentanil and propofol infusions were discontinued with the last suture at the end of surgery. Ventilation was controlled with a fraction of inspired oxygen (FIO2) of 0.4. In Group 2 (isoflurane; n = 20), anesthesia was induced by thiopental (5 mg/kg), fentanyl (2–3 µg/kg), and atracurium (0.5 mg/kg). Isoflurane (inspiratory concentration 0.5%–1.5%) was used for maintenance of anesthesia. Isoflurane/nitrous oxide delivery was stopped during wound closure. Isoflurane concentration was measured using a PM 8050 monitor (Drägerwerke, Lübeck, Germany). Ventilation was controlled with 60% nitrous oxide in oxygen using a semiclosed rebreathing circuit. Muscle relaxation for endotracheal intubation was achieved as described in Group 1. A constant fresh gas flow of 2 L/min was used during maintenance of anesthesia. In Group 3 (standard propofol; n = 20), anesthesia was induced with propofol 2 mg/kg, fentanyl 2–3 µg/kg, and atracurium 0.5 mg/kg. Using a conventional delivery system (regular syringe pump), maintenance of anesthesia was achieved by a continuous infusion of propofol according to the patient's needs. Propofol infusion and nitrous oxide were stopped during wound closure. Ventilation was controlled as described in Group 2. In all groups, a nasogastric tube was inserted after intubation of the trachea and left in place until before extubation. Doses for anesthetics (propofol, isoflurane, fentanyl, remifentanil) were adjusted according to patient need: anesthetics were increased stepwise when heart rate and/or systolic blood pressure increased by 20% of baseline values and when sweating or lacrimation occurred. The ventilation pattern was adjusted to keep arterial oxygen saturation >95% (continuous oximetry) and end-expiratory carbon dioxide concentration between 35 and 40 mm Hg (continuous capnography). Intraoperative muscle relaxation was provided by administration of additional doses of atracurium, aiming to maintain two twitches of the train-of-four assessment. No more fentanyl was given approximately 30 min before the end of surgery. Tracheal extubation occurred when patients demonstrated suitable alertness and strength. Time from discontinuation of the anesthetics until extubation was defined as extubation time. Anesthesia was provided by anesthesiologists with a minimum of 3 yr training who were not involved in the study and who did not know the nature of the study.

After surgery, all patients were transferred to a postanesthesia care unit (PACU). Postoperative recovery was evaluated by an independent PACU nurse blinded to the patient's study group. Postanesthesia recovery was scored according to the Aldrete scoring system, which is based on the patient's activity, blood pressure, consciousness, and color (18) on arrival at the PACU and on discharge. Criteria for discharge from the PACU was defined as Aldrete score >8 with pain, shivering, nausea, and vomiting controlled. Postoperative pain was assessed by using a visual analog scale (VAS) ranging from 0 to 10 (0 = no pain; 10 = worst pain imaginable). Pain scores were obtained on arrival at the PACU, on discharge to the surgical ward, and within a 6-h period at the surgical ward. Pain was treated either by diclofenac (100-mg suppository) or IV administration of piritramide (incremental doses of 7.5 mg). Episodes of undesired side effects, such as shivering and postoperative nausea and vomiting, were recorded throughout the stay in the PACU and within a 6-h period at the surgical ward. For shivering, 10 mg of nefopam (a nonopioid analgesic) was given; for nausea and vomiting, 10 mg of metoclopropamide was given IV. If nausea and vomiting were persistent, dehydrobenzperidol was added (incremental doses of 2.5 mg).

Consumption of isoflurane was measured by weighing the vaporizer (Vapor 19.3; Drägerwerke, Lübeck, Germany) using a precision weighing machine (SG 16001; Mettler-Toledo, Greifensee, Switzerland; exactness to 0.1 mg). Conversion from grams to milliliters was performed by using the specific weights of isoflurane (1.50 g/mL). Cost analyses did not include costs for N2O and O2, staff (physicians, nurses), and disposables (cannula, infusion lines, etc.). Fixed costs for anesthesia machines and monitoring equipment or overhead costs were also not taken into consideration. Prices for all anesthetic drugs were taken from our hospital's pharmacy list (Table 2). The exchange rate from the German Deutsche Mark (DM) to the American dollar was $1 = 1.83 DM.


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  		Table 2. Intraoperative Drug Requirements
 
Data are presented as mean ± SD. A computer-based statistical program was used for statistical analyses (SPSS version 4.0; SPSS, Inc. Chicago, IL). Analyses of variance, {chi}2 test, Mann-Whitney U-test, or t-test were used for statistical analyses. P values <0.05 were considered significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Appendix
 References
 
There were no differences among the groups regarding ASA class, age, weight, and duration of surgery and anesthesia (Table 1). Seven anesthesiologists performed the 60 anesthetics. The surgical procedure was performed by 10 surgeons.


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  		Table 1. Patient Demographics and Data from the Perioperative Perid
 
There were no differences in amount of muscle relaxants or fluid replacement (Table 2). Muscle antagonism was not necessary at the end of surgery in any of the patients. No differences were seen with regard to propofol consumption between patients in Groups 1 and 3. The time from the end of administration of anesthetics to tracheal extubation was longest in Group 2 (15 ± 3 min). Patients in Group 1 spent a significantly shorter period of time in the PACU than the other patients (Table 3). The Aldrete score at transfer to the PACU was significantly smaller in Group 2 than in Group 1 (Table 3). Baseline VAS score for pain assessment and the requirement for additional analgesics were similar for all groups on arrival and on discharge from the PACU. The incidence of postoperative nausea and vomiting was less frequent in Group 1 than in the other two groups (Table 3). Only 10% of patients in Group 1 vomited in the PACU, whereas 40% in Group 2 and 20% in Group 3 had at least one episode of vomiting. Vomiting at the surgical ward occurred significantly less frequently in Group 1 (5%) than in Groups 2 (60%) and 3 (25%). There was no difference in the incidence of postoperative shivering among the groups (Table 3). In the PACU, significantly more analgesics were used in Group 1 patients (total piritramide 135 mg) than in Group 2 (total piritramide 120 mg) and Group 3 patients (total piritramide 105 mg).


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  		Table 3. Time of Postanesthesia Care Unit (PACU), Incidence of Postoperative Side Effects, and Recovery Characteristics
 
Costs of all anesthetic drugs, costs per patient, and costs per minute of anesthesia were significantly higher in Group 1 (Table 4). TCI/TIVA using propofol and remifentanil was the most expensive anesthesia regimen, with total intraoperative costs almost twofold compared with the standard IV propofol regimen and almost four times larger compared with a standard inhaled anesthetic. Adding the cost for discarded substance in each group, wastage (opened ampules with remainders of anesthetics) accounted for almost 18% of total intraoperative costs in Group 1, only 5% in Group 2, and 17% in Group 3. Total costs of drugs administered postoperatively did not differ significantly among the groups (Table 4).


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  		Table 4. Costs of Anesthesia and Postoperative Care
 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Appendix
 References
 
Despite some benefits of TIVA regimens, standard anesthetic regimens using volatile anesthetics are still widely used. This may be due to the fear of increasing costs in today's climate of cost-consciousness and cost-containment. Therefore, cost analyses are needed to clearly identify the potential benefits and subsequent costs of new drugs and new anesthesia strategies. In recent years, several efforts have been undertaken to estimate the costs of different anesthetic techniques. The results, however, are not conclusive (12–17,19,20). Determination of costs is relatively straightforward for IV drugs, whereas it is more difficult to assess the consumption of inhaled anesthetics. We measured the consumption of isoflurane by measuring the vaporizer by using a precision weighing machine, which records changes up to 0.1 mg. This allows a more precise measurement of the consumed liquid quantity of inhaled anesthetics than the use of formulas.

Direct costs of all used drugs were significantly higher in Group 1. Intraoperative costs per patient and per minute of anesthesia were almost four times higher compared with a standard inhaled anesthesia regimen using isoflurane and approximately two times higher compared with a standard propofol anesthesia using fentanyl and nitrous oxide. Other studies comparing the direct costs of TIVA and inhaled anesthesia showed similar results. Alhashemi et al. (17) found a fourfold difference in direct costs of anesthetic drugs between TIVA with propofol and alfentanil and inhaled anesthesia with isoflurane, fentanyl, and N2O. No TCI-based technique and no remifentanil were used. As in the present study, no group differences concerning indirect costs (costs for postoperative drugs) were demonstrated. Rosenberg et al. (19) reported drug acquisition costs for the maintenance period of a desflurane-based anesthesia technique to be four times more expensive than a standard propofol-based technique. Newson et al. (16) demonstrated that a computerized TCI/TIVA-based sedation regimen was associated with greater drug usage than a standard propofol anesthesia technique. In the study by Newson et al., local anesthesia was used, and no additional opioids were given for pain control. It is very difficult to compare results from the different studies because of the varying use of anesthetics (propofol, desflurane, isoflurane) and additional drugs (remifentanil, alfentanil, fentanyl, N2O). For example, the costs for propofol for the induction and maintenance of anesthesia in the present study did not differ significantly between Groups 1 and 3. Remifentanil accounted for approximately 44% of total intraoperative costs in Group 1. Acquisition costs of anesthetic drugs vary widely from area to area and may also change rapidly. Costs for propofol have decreased by almost 50% within the last years in several countries. This may also happen with remifentanil within the next years. Wastage due to discarded substance accounted for 18% of total intraoperative costs in Group 1 and 17% in Group 3. This finding is consistent with data reported by Rosenberg et al. (19) and by Johans (20), who calculated a percentage of propofol waste of 19% and 20%, respectively. Waste of expensive anesthetics may be an important cost factor in TIVA regimens and is an unsolved problem.

Overhead costs for staff salaries, which are by far the largest costs in the hospital, were not taken into consideration in our cost analyses. Earlier recovery of psychomotor function and fewer postoperative side effects, such as nausea and vomiting, may lead to earlier discharge from the PACU or even from the hospital. The use of a TIVA/TCI anesthetic regimen may be an important step toward fast-track eligibility and shortening of PACU time. This may result in increased efficacy in busy surgical centers. This cost-reducing factor should be taken into account when these three anesthetic regimens are compared because it may compensate for the higher intraoperative costs with this new anesthetic strategy. Moreover, in times of increasing competition among hospitals, increased patient satisfaction due to fewer negative postoperative side effects may become increasingly important.

We conclude that healthcare reform has placed increasing pressure on anesthetists to consider the cost impact of current anesthesia strategies, new drugs, and new technologies. Aside from cost considerations, quality of care is an important but complex issue. A TCI/TIVA technique using propofol/remifentanil was associated with the highest costs compared with a standard propofol technique and especially compared with isoflurane-based anesthesia. The TIVA/TCI technique was associated with fewer postoperative side effects. New anesthesia regimens should be considered economically and in terms of outcome, side effects, or value. Despite significantly higher costs, the propofol/remifentanil TCI/TIVA regimen may have considerable benefits.


   Appendix
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix
References
 
Go


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  		Table 1. Drug Acquisition Costs from Our Hospital's Pharmacy List
 


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix
 References
 

  1. Coetzee JF, Glen JB, Wium CA, Boshoff L. Pharmacokinetic model selection for target controlled infusion of propofol. Anesthesiology 1995;82:1328–45.[ISI][Medline]
  2. White M, Kenny GNC. Intravenous propofol anesthesia using a computerised infusion system. Anaesthesia 1990;45:204–9.[ISI][Medline]
  3. Russell D, Wilkes MP, Hunter SC, et al. Manual compared with target-controlled infusion of propofol. Br J Anaesth 1995;75:562–6.[Abstract/Free Full Text]
  4. Struys M, Versichelen L, Thas O, et al. Comparison of computer-controlled administration of propofol with two manually controlled infusion techniques. Anaesthesia 1997;52:41–50.[ISI][Medline]
  5. Sung YF, Reiss N, Tillette T. The differential cost of anesthesia and recovery with propofol-nitrous oxide anesthesia versus thiopental sodium-isoflurane–nitrous oxide anesthesia. J Clin Anesth 1991;3:391–4.[Medline]
  6. Kortilla K, Östman P, Faure E, et al. Randomized comparison of recovery after propofol-nitrous oxide versus thiopentone-isoflurane-nitrous oxide anesthesia in patients undergoing ambulatory surgery. Anaesthesiol Scand 1990;34:400–3.
  7. Chan VWS, Chung FF. Propofol infusion for induction and maintenance of anesthesia in elderly patients recovery and hemodynamic profiles. J Clin Anesth 1996;8:317–23.[ISI][Medline]
  8. Vitez TS. Principles of cost analysis. J Clin Anesth 1994;6:357–63.[ISI][Medline]
  9. Hirsch J. Impact of postoperative nausea and vomiting in the surgical setting. Anaesthesia 1994;49 (Suppl):30–3.
  10. Carroll NV, Miederhoff PA, Cox FM, Hirsch JD. Costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting. J Clin Anesth 1994;6:364–9.[ISI][Medline]
  11. Watcha MF, Smith I. Cost-effectiveness analysis of antiemetic therapy for ambulatory surgery. J Clin Anesth 1994;6:370–7.[ISI][Medline]
  12. Boldt J, Jaun N, Kumle B, et al. Economic considerations of the use of new anesthetics a comparison of propofol, sevoflurane, desflurane, and isoflurane. Anesth Analg 1998;86:504–9.[Abstract]
  13. Bach A, Böhrer H, Schmidt H, et al. Cost effectiveness of modern inhalational anesthetics using sevoflurane as an example. Anaesthesist 1997;46:21–8.[ISI][Medline]
  14. Weiskopf RB, Eger EI II. Comparing the cost of inhaled anesthetics. Anesthesiology 1993;79:1413–8.[ISI][Medline]
  15. Broadway PJ, Jones JG. A method of costing anesthetic practice. Anaesthesia 1995;50:56–63.[ISI][Medline]
  16. Newson C, Joshi GP, Victory R, White PF. Comparison of propofol administration techniques for sedation during monitored anesthesia care. Anesth Analg 1995;81:486–91.[Abstract]
  17. Alhashemi JA, Miller DR, O'Brien HV, Hull KA. Cost-effectiveness of inhalational, balanced and total intravenous anaesthesia for ambulatory knee surgery. Can J Anaesth 1997;44:118–25.[Abstract/Free Full Text]
  18. Adrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg 1970;49:924–33.[Free Full Text]
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  20. Johans TG. The cost of propofol. Anesth Analg 1995;80:1248–53.[ISI][Medline]
Accepted for publication September 30, 1998.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press