Clinical Therapeutics/Volume 30, Number 9, 2008

Low Fresh Gas Flow Balanced Anesthesia Versus Target

Controlled Intravenous Infusion Anesthesia in Laparoscopic
Cholecystectomy: A Cost-Minimization Analysis
Predrag D. Stevanovic, MD, PhD1; Guenka Petrova, PhD2; Branislava Miljkovic, PhD3;
Radisav Scepanovic, MD, PhD4; Radoslav Perunovic, MD, PhD4;
Dragos Stojanovic, MD, PhD4; and Janja Dobrasinovic, MD 1
1Clinicof Anaestkesiology and Reanimatology, Clinical Center "Dr D. Misovic"-DEDINJE, Universityof
Belgrade, Belgrade, Republic of Serbia; 2Medical University Facultyof Pharmacy, Sofia, Bulgaria; 3Institute
for Pharmacokinetics, Facultyof Pharmacy, Universityof Belgrade, Belgrade, Republicof Serbia; and 4Surgery
Clinic, ClinicalCenter "Dr D. Misovic"-DEDINJE, Universityof Belgrade, Belgrade, Republicof Serbia
ABSTRACT
Background: Laparoscopic surgery is widely recognized as a well-tolerated and effective method for
cholecystectomy. It is also considered cost saving because it has been associated with a decreased hospital
length of stay. Variables that might lead to increased
costs in laparoscopic surgery are the technique and
drugs used in anesthesia.
Objective: The goal of this study was to compare the
costs of 2 anesthetic techniques used in laparoscopic
cholecystectomy (LC)--balanced versus IV anesthesia-from the standpoint of an outpatient surgical department, with a time horizon of 1 year.
Methods: Patients scheduled to undergo elective LC
were enrolled in this prospective case study. Patients
were randomly allocated to receive balanced anesthesia, administered as low fresh gas flow (LFGF)
with inhalational sevoflurane and IV sufentanil in a
target controlled infusion (LFGF SS group), or IV
anesthesia, administered as IV propofol/sufentanil
in a target controlled infusion (TCI group). We used
a microcosting procedure to measure health care
resource utilization in individual patients to detect
treatment differences. The costs of medications used
for the induction and maintenance of anesthesia
during surgery were considered for LFGF SS and
TCI. Other end points included duration of anesthesia; mean times to early emergence, tracheal extubation, orientation, and postanesthesia discharge
(PAD); pain intensity before first analgesia; number
of analgesics required in the first 24 hours after
surgery; and prevalences of nausea, vomiting, and
agitation.
1714

Results: A total of 60 patients were included in this

analysis (male/female ratios in the LFGF SS and TCI
groups: 11/19 and 12/18, respectively; mean [SD] ages,
48 [7.9] and 47 [8.6] years; and mean [SD] body mass
indexes, 26 [2.0] and 26 [3.0] kg/m2). The costs of anesthetics were significantly lower with LFGF SS compared with TCI (C17.40 [C2.66] vs C22.01 [C2.50]
[2006 euros]). Times to early emergence and tracheal
extubation were significantly shorter with LFGF SS than
TCI (5.97 [1.16] vs 7.73 [1.48] minutes and 7.57 [1.07]
vs 8.87 [1.45] minutes, respectively). There were no significant between-group differences in mean duration of
anesthesia; times to orientation and PAD; pain intensity
before first analgesia; number of analgesics required in
the first 24 hours; or prevalences of nausea, vomiting,
and agitation. Because no clinically significant differences in the anesthetic results were observed, a costminimization analysis was conducted and found that
using LFGF SS, the outpatient surgical department could
realize a budget savings of C454 per 100 patients. For the
nearly 1000 expected patients per year, the savings for
the department was calculated as C4540.
Conclusion: The results from this cost analysis in
these patients who underwent elective LC suggest that
the use of sevoflurane through the LFGF technique
would be cost saving in this outpatient surgical department. (Clin Ther. 2008;30:1714-1725) 2008
Excerpta Medica Inc.
Accepted for publicationJune 7, 2008.
doi:l 0.1016/j.clinthera.2008.09.009

0149-2918/$32.00
2008 Excerpta Medica Inc. All rights reserved.

Volume 30 N u m b e r 9

P.D. Stevanovic

Key words: anesthesia, cost-minimization analysis,

sevoflurane fresh gas flow anesthesia, propofol anesthesia, pharmacotherapy, laparoscopic cholecystectomy.

INTRODUCTION

Laparoscopic surgery has been widely recognized as a

reliable and efficient method for cholecystectomy. It is
considered cost saving because it has been associated
with decreased hospital length of stay (LOS) compared with conventional surgery. Variables that might
lead to cost increases in laparoscopic surgery are the
anesthetic technique and anesthetic drugs used.
The choice of anesthetic agent depends on its pharmacodynamic properties, route of administration, and
costs; depth of anesthesia required; a patient's willingness to comply with anesthesia; and clinical factors (eg,
time to emergence, LOS). 1,2 Anesthesia may be maintained using IV agents alone, inhaled agents alone, or a
combination of both. Any of these approaches can provide excellent conditions for outpatient surgery, but the
clinical and economic results might differ.3-5 It is difficult
to make a direct comparison between IV and inhaled
anesthetics due to the inability to measure IV drug concentrations in real time and the complicated measurement of total amount of inhaled anesthetic delivered. 6-8
Manual adjustment and maintenance of anesthesia
by syringe pump infusion is sometimes viewed as less
convenient than using a vaporizer with an inhalational agent. A more convenient method--target controlled infusion (TCI)--was developed and applied in
1995. 9,1 The basic principle of TCI is that the anesthesiologist sets and adjusts the target blood anesthetic concentration according to the depth of anesthesia
required. The infusion rate is altered automatically
according to a validated pharmacokinetic model. 11
The TCI system was designed as a substitution for the
vaporizer, administering the correct dosage at a regular interval. The clinical skills required in varying
target blood anesthetic concentration according to a
patient's response are learned during the administration of volatile agents from a calibrated vaporizer.
Results from numerous studies 12-14 designed to
determine the anesthetic method optimal for outpatient surgery are contradictory, and this leads to a
wide variation in practice. Differences in the prevalences of short-term effects, such as early emergence
and tracheal extubation, might influence patient outcomes and the overall costs of anesthesia. 15
September 2008

et

al.

Propofol is considered a standard IV anesthetic

agent. It has been found to have antiemetic properties
and to be associated with low frequencies of postoperative nausea and vomiting (PONV), 16 which may
lead to faster recovery and reduced intervention costs.
Gokce et al 2 analyzed the hemodynamic effects, recovery profile, and costs of remifentanil-based anesthesia
with propofol or desflurane and found no statistically
significant differences between the 2 agents with respect to hemodynamic parameters, recovery profile,
adverse effects, Aldrete Recovery Score, or costs. Gokce
et al considered that both anesthetics provided perioperative hemodynamic stability and early and easy recovery and had similar cost profiles in septorhinoplasty.
Sevoflurane was introduced in anesthesia within
the past 15 years. As an anesthetic drug is introduced
into anesthetic practice, the manufacturer typically
sponsors research to determine the advantages of the
product. However, as White and Smith 17 noted, "anesthesia practitioners, as well as pharmacy and therapeutic committees, are demanding proof that a new,
more costly drug or medical device is superior to existing products in achieving its desired effect, is associated with fewer adverse effects, enhances efficiency,
and reduces health care costs."
The issue of cost is of particular importance.
Motsch et al 5 found that in urologic and ophthalmologic outpatient surgery, recovery and the return of
mental and psychomotor function within the first
hour after the end of anesthetic administration are
significantly faster with sevoflurane than propofol.
They found no significant between-treatment differences in ambulation times and concluded that sevoflurane may offer clinical advantages over propofol if
used for the maintenance of anesthesia during outpatient surgical procedures. 5
The results from a study by Watson and Shah 18
suggested that recovery from anesthesia may be faster
with sevoflurane than propofol. In another study,
Wandel et a119 compared extubation and recovery
times in 2 groups of 25 patients randomized to receive
propofol or sevoflurane for the maintenance of anesthesia. They found that the time intervals from the end
of anesthesia to tracheal extubation (6.6 vs 9.8 minutes), eye opening (7.2 vs 12.6 minutes), hand squeezing (8.2 vs 13.8 minutes), and providing the correct
date of birth (8.6 vs 14.6 minutes) were significantly
shorter with sevoflurane (P < 0.01 for each interval).
Those results provided appropriate evidence for the
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Clinical Therapeutics

use of sevoflurane. However, when this inhalational

anesthetic is administered using high flesh gas flow
(HFGF), the cost of anesthesia increases. 2 For this
reason, in developing countries, it is difficult to convince hospital management to supply the anesthesia
department with sevoflurane rather than propofol.
The cost of inhalational anesthesia depends on the
mode of administration used. Inhalational anesthesia
is typically administered using HFGF (4-6 L/rain).
However, this rate might exceed gas requirements by
a large margin, 8 while homeostasis of the breathing
circuit with carbon dioxide absorption could be maintained with a flesh gas flow (FGF) rate similar to a
patient's gas requirements for oxygen and anesthetic
gases (ie, the closed-circuit technique). Some practitioners advocate the use of the closed-circuit technique,
citing as its advantages the conservation of resources,
increased awareness on the part of the clinician of the
physiologic status of the patient, and an increased
awareness of the functioning of the anesthetic machine. The closed-circuit technique, however, is labor
intensive. 2
The low FGF (LFGF) and minimal FGF (MFGF)
(0.5-2.0 L/rain) techniques are alternatives to the
HFGF and closed-circuit techniques. Relative to HFGF,
LFGF conserves a patient's body heat and humidity
and reduces costs. 21
Studies of anesthetic drugs have aimed at establishing tolerability, but few data on the pharmacoeconomic characteristics of the available medicines
have been published, 22-24 based on a literature
search. One available study compared the cost of
3 anesthetic techniques developed by Demeere et al. 25
The author found that in total hip replacement, the
cost of the anesthetic medication was "ridiculously
small" considering the total cost of the procedure,
but this is not the case in outpatient surgery using
laparoscopy. Because 2 of the major and variable
costs of anesthetic care are the cost of the anesthetic
used and the technique used, the present study compared the costs of 2 anesthetic dosing regimens using
interchangeable drugs--sufentanil, sevoflurane, and
propofol.
We tested the hypothesis that balanced sevoflurane
LFGF anesthesia and sufentanil TCI would provide
clinical results similar to those found with propofol/
sufentanil TCI anesthesia, but at a lower cost, in patients undergoing outpatient surgery. The secondary
end point was risk/benefit ratio.
1716

MATERIALS AND METHODS

The prospective case study (no. CR 10-014) was

conducted at the Surgery Clinic, Clinical Center
"Dr. D. Misovic"-DEDINJE, University of Belgrade,
Belgrade, Republic of Serbia, from the prospective of
the outpatient surgical department (ie, choice of anesthetic technique for outpatient laparoscopic cholecystectomy [LC] in the clinic when there is already available LFGF equipment for the 2 anesthetic techniques
under consideration), with a time horizon of 1 year.
Approval of the study protocol was obtained from the
clinic's ethics committee.

Patient Selection
Male and female patients aged 18 to 65 years,
weighing 40 to 150 kg, and scheduled to undergo elective outpatient LC were enrolled per the criteria defined
in physical status classes I and II as classified by the
American Society of Anesthesiologists. Patients were
excluded if they had a history of chronic active hepatitis
B or C virus; known or suspected cardiovascular, pulmonary, renal, hepatic, metabolic, or neuromuscular disorder that may have affected the study results; known or
suspected allergy to any of the medications used in the
course of treatment; clinically significant laboratory
abnormalities that classified the patient as high risk
(ie, those with possible impaired organ function that
might influence the outcomes of anesthesia); or alcohol
or drug abuse within the previous 2 years; were pregnant, possibly pregnant, or breastfeeding (in women);
and/or were unwilling to participate in the study.
Eligible patients provided written informed consent
before entering the study.
Study Medications and Surgical Procedures
Patients were randomized, using a table of random
numbers, to 1 of 2 groups: LFGF anesthesia with
sevoflurane or sufentanil TCI (LFGF SS group) and
propofol/sufentanil TCI (TCI group).
Maintenance of Anesthesia
All patients were premedicated using atropine sulfate 0.5 rag, metoclopramide 10 rag, and midazolam
0.07 mg/kg administered IM 30 minutes prior to the
induction of anesthesia per routine hospital practice.
LFGF SS Group
In the LFGF SS group, anesthesia was induced using an infusion of sufentanil TCI 0.15 ng/mL and a
Volume 30 Number 9

P.D. Stevanovic et al.

bolus of propofol 2 mg/kg. Endotracheal intubation

was performed after administration of rocuronium
bromide 0.6 mg/kg. After anesthetic induction, the
anesthetic bag was emptied, and manual ventilation
was started using an 02 FGF of 2 L/min and a sevoflurane vapor concentration of 8 vol%.
After equilibrium of anesthetic gas in-circuit was
achieved (-1 minute or when the 2.3-L bag was nearly
full), mechanical ventilation was started using minimal FGF (02, 0.5 L/min; fraction of inspiratory oxygen [FiO2] , 60%) over the remainder of anesthesia.
Because of the risks for postoperative ileus and nausea
and vomiting, nitrous oxide was not used. (The new
inhalational anesthetics diminish the need for nitrogen
oxide.) Sevoflurane vapor was set to achieve a minimal alveolar concentration of 0.8 to 1.2 during the
course of anesthesia. Analgesia was provided using an
infusion of sufentanil TCI (0.15-0.25 ng/mL). Sufentanil infusion and sevoflurane delivery were stopped
15 minutes before the end of surgery, but an FGF of
0.5 L/min was maintained, and sevoflurane washout
was started 5 minutes before the end of surgery.

TCI Group
Anesthesia was induced using propofol TCI 5 tlg/mL
and an infusion of sufentanil TCI 0.15 ng/mL. Endotracheal intubation was performed after administration of rocuronium bromide 0.6 mg/kg. After anesthetic induction, IV infusion of propofol TCI 3.5 to
5 tlg/mL was continued, and analgesia was provided
using an infusion of sufentanil TCI 0.15 to 0.25 ng/mL.
Anesthesia was maintained with oxygen/air (FiO2,
60%) using MFGF (0.5 L/min). Sufentanil infusion
was stopped 15 minutes before the end of surgery and
propofol infusion was stopped at the end of surgery
using slow step-down regulation.
To compare the 2 anesthetic regimens, a comparable depth of anesthesia was needed. All patients were
maintained equally between 40 and 60 points on the
Datex-Ohmeda (Louisville, Colorado) $5 entropy monitoring scale (scale: 0-100 points, with 0 = awake and
100 points = excessive deep anesthesia) during the
course of anesthesia.
A half-hour before the end of surgery, analgesia
was provided using the same nonsteroidal analgesics
(ketorolac) intravenously. The same dose was used in
all patients.
Artificial ventilation (pressure-controlled ventilation) and ETCO 2 were maintained between 35 and
September 2008

40 mm Hg by making necessary adjustments of ventilator parameters during the procedure. All patients
received continuous IV infusion of isotonic crystalloid
solution 5 mL/kg h -I. The patient's position was altered from supine to head uptilt (20 degrees) after the
induction of anesthesia and before pneumoperitoneum was induced. Pneumoperitoneum was induced by
inserting a Veress needle at the umbilical level and
connecting it to the CO 2 insufflator, which achieved
and maintained an intra-abdominal pressure of
14 mm Hg. TCI infusions of propofol and sufentanil
were performed using Fresenius Vial infusion technology (Base Primea Orchestra system, Fresenius Vial SAS,
Brezins, France). A Solar 8 monitor (Datex-Ohmeda)
was used to follow up cardiovascular parameters. All
data from the monitor and the anesthetic machine
were recorded using a computerized Anesthesia Information Management System (Recall AIMS, Driger
Medical AG & Co. KG, Libeck, Germany) for followup of the anesthetic process.

Cost Identification and Analysis

Only the cost of anesthetic medications was considered for both LFGF SS and TCI. The costs of anesthesia included medications for the induction and maintenance of anesthesia during surgery. After propofol
or sufentanil quantity was obtained from the infusion
pump, the microcosting procedure was applied, and
sevoflurane spending was calculated in each patient.
The microcosting procedure allows for the detection
of treatment differences between patients and differences in costs associated with them. For obtaining the
results via microcosting, we recorded the quantity of
medications used in each patient during surgery.
The local market prices of anesthetics were recorded. At the end of surgery, the mean costs of the
medications per patient were calculated by multiplying the quantities of consumed drugs by the respective
market price and dividing by the number of patients.
Cost Calculations

Sufentanil
In both groups, the mean cost of sufentanil per
patient was calculated by multiplying the market price
per microgram by the mean amount of sufentanil infused in the study group (calculated as the sum of the
amounts of sufentanil in each patient [automatically
provided by the TCI pump] divided by the number of
patients per group).
1717

Clinical Therapeutics

Propofol
The mean cost of propofol per patient in the LFGF
SS group was calculated by multiplying the local market price per milligram by the mean amount of propofol bolus infused in the group (calculated as the sum
of the boluses [in milligrams] divided by the number
of patients in the group). In the TCI group, propofol
cost was calculated by multiplying the market price
per milligram by the mean amount of propofol infused in the group (calculated as the sum of the propofol infusions [as read from the TCI pump] divided by
the number of patients in the TCI group).

Mean cost per vapor delivery was calculated using

the following formula2:
Cost per vapor delivery = (Cost/min) x
Delivery time (min)
Mean cost per sevoflurane delivery was calculated
using the following formula2:
Cost per sevoflurane delivery = (Cost/min) x
Delivery time (min)
Overall anesthetic cost was the sum of all delivery
time costs.

Sevoflurane
The mean cost of sevoflurane used per patient was
calculated by multiplying the local market price by the
mean amount used per patient in the LFGF SS group.
The amount of sevoflurane used was calculated according to the vaporizer delivery setting (%vap) using
the following formula2:
Vapor delivery (mL)/min = FGF/(100 - %vap) x
%vap
Vapor cost was calculated as vapor delivery (in milliliters per minute) multiplied by market price (in euros
per milliliter of vapor).
We identified the mean time periods with equal
FGF and sevoflurane delivery.
Mean values of anesthetic regimen parameters in the
LFGF SS group (delivery time intervals with different
FGFs and vaporizer settings) are represented in Figure 1.

Anesthetic Outcomes Measurements

Each patient's recovery profile was assessed using

several parameters: mean duration of anesthesia (in
minutes); times to early emergence (defined as verbal
command responses [eye opening, head uptilt]), tracheal extubation, orientation (defined as providing
correct date of birth), and postanesthesia discharge
(PAD), and use of first analgesia (all in minutes); pain
intensity score before first analgesia, as measured on a
10-cm visual analog scale; number of analgesics required in the first 24 hours after the end of surgery;
and prevalences of postoperative nausea, vomiting,
and agitation (all in %).
Statistical Analysis
A sample size calculation determined that a difference of C1.5 (2006 euros) in overall cost of anesthesia

FGF
L/min
7.6 / 5.4

13.4

19.0

7.6

(-- min (delivery times)

DEL
%vap
0Figure 1. Mean values of anesthetic variables (FGF and delivery [ordinate]) and time intervals in the group
that received low FGFwith inhalational sevoflurane and IV sufentanil in a target controlled infusion.
FGF = fresh gas flow; DEL = delivery; %vap = vaporizer settings.

1718

Volume 30 Number 9

P.D. Stevanovic et al.

would be detectable if the samples consisted of

29 patients at Cronbach o = 0.05 and a study power
of 80%. Therefore, we included 30 patients per
group.
The data were analyzed using SPSS version 10.0
(SPSS Inc., Chicago, Illinois). According to type and
distribution of data, the Z2 test, t test for independent
samples, and Mann-Whitney U test were applied.
RESULTS
Characteristics o f the Selected Patients

A total of 60 patients were enrolled. The LFGF SS

and TCI groups did not differ significantly with regard to demographic characteristics (male/female ratios, 11/19 and 12/18, respectively; mean [SD] ages,
48 [7.9] and 47 [8.6] years; and mean [SD] body mass
indexes, 26 [2.0] and 26 [3.0] kg/m2).

Cost Analyses
The costs of the anesthetics studied are shown in
Table I.

Sevoflurane
The mean volume of sevoflurane used per patient
was 1544 mL (range, 1128-2117 mL) (Figure 2). The
mean (SD) cost per patient of sevoflurane was C6.64
(C1.04) (range, C4.85-C9.12) (Figure 3). The time intervals of each FGF and vaporizer setting are shown
in Figure 1.

Propofol
The mean (SD) cost of propofol in the LFGF SS
group was C3.69 (C0.56); in the TCI group, propofol
cost was C14.87 (C1.57) (Table II).

Sufentani!
The total costs of sufentanil did not vary significantly between the 2 groups and would not have had
any influence on total cost of anesthetic technique.
However, when the costs of anesthetic induction and
maintenance were compared between the 2 groups, a
statistically significant difference was found (LFGF SS
[propofol + sevoflurane], C10.33 [C1.16]; TCI [propofol only], C14.87 [C1.57]; P = 0.001). The difference
in mean anesthetic drug costs per patient was significantly less with LFGF SS (C17.40 [C2.66] vs C22.01
[C2.50]; P = 0.001) (Table II).
Anesthetic Outcomes

The between-group differences in mean duration of

anesthesia and time to early emergence were not statistically significant. However, early emergence time
was significantly less in the LFGF SS group than the
TCI group (5.97 [1.16] vs 7.73 [1.48] minutes; P =
0.001). The times to tracheal extubation were 7.57
(1.07) minutes in the LFGF SS group and 8.87
(1.45) minutes in the TCI group (P = 0.001). Those differences did not affect the cost of the medication. Times
to orientation and PAD were not significantly different
between the 2 groups, and there was no significant influence of anesthetic technique on time to hospital discharge (all patients were discharged from the hospital
1 day after surgery) (Table III).
Pain intensity before first use of analgesia and the
numbers of analgesics administered in the first 24 hours
after surgery were comparable between the 2 groups.
Time to first use of analgesia was significantly longer
with the TCI technique (Table IV); this finding was
not considered to be of clinical significance.

Table I. Market prices of anesthetics available in the Republic of Serbia. Values are 2006 C
Drug
Sevoflurane
250-mL capsules
Propofol
20-mL 1% ampule
Sufentanil forte
0.05-mg/mL ampule

Price per Package

Price per Unit

Price per Subunit

194.65 Per bottle

0.78 Per milliliter

181 Per milliliter of vapor or liquid;

0.004302 per milliliter of vapor*

23.93 Per 5-ampule box

4.79 Per ampule

0.02 Per milligram

39.31 Per 5-ampule box

Z86 Per ampule

1.57 Per milliliter; 0.03 per

microgram

*Presented as the amount of-vapor and its price per unit.

September 2008

1719

Clinical Therapeutics

[]
[]
[]

600 500 -

500-600
400-500
300-400
200-300
100-200

[] 0-I00

400 300 >

200 -

100-

5000
0

Fresh Gas Flows

(mL/min)

Vaporizer Settings (vol%)

Figure 2. A m o u n t o f v a p o r per minute u n d e r various fresh gas f l o w s and v a p o r i z e r settings.

[]
[]
[]

2.5 - J

~"

2.0-

1.5-

1.0-

>

0.5-

?.~J

0-

2.0-2.5
1.5-2.0
1.0-1.5
0.5-1.0
0-0.5

000
Fresh Gas Flows
(mL/min)

Vaporizer Settings (m L)

Figure 3. Costs o f various fresh gas f l o w s and v a p o r i z e r settings.

1720

Volume 30 N u m b e r 9

P.D. Stevanovic et al.

Table II. Costs of-various anesthetics in the Republic of-Serbia. Values are mean (SD) 2006 C.
Anesthetic

LFGF SS

TCI

P*

3.69 (0.56)

14.87 (1.57)

0.001

Sufentanil

7.07 (1.56)

7.14 (1.30)

0.856

Sevoflurane

6.64 (1.04)

Propofol

Total cost per patient

17.40 (2.66)

22.01 (2.50)

0.001

LFGF SS = low fresh gas flow with inhalational sevoflurane and IV sufentanil in a target controlled infusion;
TCI = target controlled infusion ofpropofol/sufentanil.
*t Test.

The prevalences of nausea, vomiting, and agitation

were not significantly different between the 2 groups
(Table V).
Cost Minimization
Cost minimization was analyzed because the outcomes of the 2 anesthetic options were similar, and so

the less costly option would be selected. Based on the

results obtained in the 2 patient groups, the costs of
the anesthetics differed significantly (Tables III-V).
The expected budget savings for the hospital department with LFGF SS, calculated from the differences in the mean costs per patient (Table II), was
C454 per 100 patients. Thus, for the nearly 1000 ex-

Table III. Statistical comparisons of anesthetic recovery parameters in patients undergoing elective laparoscopic cholecystectomy. Values are minutes.
End Point

LFGF SS

TCI

Duration o f anesthesia
Mean (SD)
Range

73.17 (9.35)
56-94

75.20 (8.02)
62-93

Time to early emergence

Mean (SD)
Range

5.97 (1.16)
4-8

7.73 (1.48)
4-10

Time to tracheal extubation

Mean (SD)
Range

P
0.370*

0.001"

0.001f
7.57 (1.07)
5-10

8.87 (1.45)
5-11

Time to orientation
Mean (SD)
Range

10.63 (1.71)
8-14

10.30 (1.42)
7-13

Time to postanesthesia discharge

Mean (SD)
Range

22.13 (2.25)
18-26

23.17 (1.80)
19-26

0.415"

0.055*

LFGF SS = low fresh gas flow with inhalational sevoflurane and IV sufentanil in a target controlled infusion;
TCI = target controlled infusion ofpropofol/sufentanil.
*t Test.
f Mann-Whitney U test.

September 2008

1721

Clinical Therapeutics

Table IV. Statistical comparisons of postsurgical anesthetic parameters in patients undergoing

elective laparoscopic cholecystectomy.
Parameter
Pain intensity VAS score ~ before
first analgesia
Mean (SD)
Range

LFGF SS

TCI

3.49 (0.58)
2.20-4.40

3.38 (0.49)
2.70-4.30

55.53 (10.15)
36.00-75.00

61.23 (10.79)
39.00-81.00

3.00 (0.47)
2-4

3.03 (0.61)
2-4

0.405f

0.039f

Time o f first analgesia, min

Mean (SD)
Range
No. o f analgesics in first 24 hours
after surgery
Mean (SD)
Range

0.857 t

LFGF SS = low fresh gas flow with inhalational sevoflurane and IV sufentanil in a target controlled infusion;
TCI = target controlled infusion of propofol/sufentanil; VAS = visual analog scale.
*Scale: 0 = no pain to 10 = worst possible pain.
f t Test.
$Mann-Whitney U test.

pected patients per year, the savings for the department would be C4540.
DISCUSSION
In this selected patient population undergoing elective
LC, there was a small but significant difference in
times to early emergence and tracheal extubation be-

Table V. Postoperative morbidity in patients undergoing elective laparoscopic cholecystectomy.~ Values are no. (%) of patients.

Event

LFGF SS
(n = 30)

TCI
(n = 30)

Pf

Nausea

4 (13.33)

2 (6.67)

0.389

2 (6.67)

0.389

Agitation

LFGF SS = low fresh gas flow with inhalational sevoflurane and IV sufentanil in a target controlled infusion;
TCI = target controlled infusion of propofol/sufentanil.
*No vomiting was reported in either treatment group.

fz 2 Test.

1722

tween the LFGF SS and TCI techniques, with no significant differences in recovery end points or PAD. It
seems likely that after short-duration anesthetic exposure, the LFGF SS group would experience a faster
recovery because there would be little time to saturate
deep tissue groups with volatile anesthetic administered using LFGE This was pointed out by Eger and
Johnson 2s in a study in rodents, in which the kinetic
advantages of the less-soluble anesthetics--sevoflurane
and desflurane--were more difficult to find after anesthetic exposures of <1 hour versus >1 hour.
The recovery end points between patients who received sevoflurane and those who received propofol
support results from a previously published multicenter study 13 (emergence time was significantly shorter
with sevoflurane than with propofol [8.8 (1.2) vs 13.2
(1.2) minutes]). The current results also are consistent with those from several similar studies that
compared recovery end points between desflurane
and propofol. 2,14,27-29 One, a meta-analysis 14 of
multiple studies of recovery after anesthesia with
desflurane and propofol, found no statistical differences in recovery end points. These similarities
between anesthetics led to the cost-minimization
analysis.

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P.D. Stevanovic et al.

Speed and quality are important elements of anesthetic recovery. The current study did not find the
benefit of propofol in the prevalence of PONV. This
finding was likely the result of the administration of
an antiemetic in each patient before the end of surgery. The cost of the antiemetics was not considered
because it was similar in all of the patients.
Postanesthesia recovery times were similar between
the groups that received sevoflurane and propofol, but
early recovery end points were significantly shorter in
patients who received sevoflurane than in those who
received propofol. The prevalence of PONV was not
considered in the power analysis because the betweengroup difference was nonsignificant and was without
cost implications.
Modern anesthetics and anesthetic adjuvants may
decrease the overall cost of outpatient surgery by expediting the recovery process. 3
The use of TCI pumps might allow a decrease in
the minimal possible quantity, such as wastage, and
that was the case in the present study. The quantities
left at the end of the day were extremely small and did
not affect the cost of anesthesia. With regard to the
inhaled sevoflurane, the quantities left in the vaporizer
were used for subsequent surgeries. We also did not
consider the cost of the surgical suite and apparatus
because they were equally used by the patients.
Cost savings is a primary goal of outpatient surgery.
From the perspective of the institution, personnel costs
(labor costs and the time spent providing a service) are
more important than drug costs. 23,31 However, it is also
important to have in mind the least-costly alternatives
for surgical procedures and medications. The costs of
equipment and other start-up costs should also be considered as necessary. Start-up/equipment costs did not
apply in the present study because the equipment was
already available. Thus, the primary goal of the present
study was to calculate the costs of anesthesia for further establishment of the protocol at the clinic.
From a clinical point of view, the recovery profiles
of the 2 types of anesthesia used in this study were
similar. The cost of sufentanil was comparable between the 2 groups. There was a significant decrease
in total cost of anesthetic drug in the LFGF SS group
compared with the TCI group because sevoflurane
was less expensive than propofol. 32 The LFGF technique is useful in almost all patients except infants
and small children and in those undergoing short procedures. Limitations of LFGF include the need for an

September 2008

anesthetic machine that provides LFGF and the need

for training in its use. There are some absolute contraindications (eg, malignant hyperthermia, septicemia, smoke or gas intoxication) and some relative
contraindications (eg, decompensated diabetes mellitus, long-term starvation, acute and chronic alcoholism) to using the LFGF technique. 2
With regard to savings on medications, the present
results are important because of the significant difference in costs (C10.33 [1.16] with LFGF SS vs 14.87
[1.57] with TCI; P = 0.001). Although the savings
per patient would be small, the potential for savings
over the course of a year would be large. 33
The lower direct cost of the sevoflurane technique
may not accurately reflect total cost of the LFGF SS
technique, as the cost of probable delayed discharge
and increased PONV 24 with sevoflurane must be considered. The present analysis studied only direct medication costs because of a preconception of the high
cost of sevoflurane anesthesia, based on its market
price. A larger series is needed to confirm the cost
benefit found in the present study.
Although physicians are responsible for health care
expenditures, they often remain unaware of either the
specific costs or charges associated with interventions. 34 It has been suggested that a perceived direct
reward for cost minimization would be required because there might be strong opposition to any rigid
system that might place arbitrary restrictions on drug
or equipment use. 35
Study Limitations
One limitation of this study was the small patient
group in comparison with the overall patient flow at
the hospital. This small sample size was due to the
recommendations of the ethics committee. Based on
our results, however, we will attempt to increase the
size of the patient groups in future studies of sevoflurane costs. Another limitation was the standard requirement that the anesthetic concentration be kept at
"surgical depth" until the last suture or the dressing
was placed. Primary anesthetics (propofol and sevoflurane) are titrated down near the completion of surgery,
which might result in awakening and extubation occurring at or near the time of wound dressings.
CONCLUSION
In this cost analysis of 2 anesthetic techniques in these
patients who underwent elective LC, we found a cost

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Clinical Therapeutics

savings of C4540 per year with the use of LFGF SS

over TCI in this outpatient surgical department.
A C K N O W L E D G M ENT

The authors thank the residents and staff of the Clinic

of Anaesthesiology and Reanimatology and Surgery
Clinic, Clinical Center "Dr D. Misovic'-DEDINJE,
University of Belgrade, Belgrade, Republic of Serbia.
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Address c o r r e s p o n d e n c e to: Stevanovic D. Predrag, M D , PhD, Clinical

Center " D r D. M i s o v i c ' - D E D I N J E , Clinic of Anaesthesiology and
R e a n i m a t o l o g y , 1 H. M i l a n a Tepica Street, 11000 Belgrade, Republic of
Serbia. E-mail: batica@eunet.yu

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