A Comparison of Fentanyl, Sufentanil, and Remifentanil for
Fast-Track Cardiac Anesthesia
Milo Engoren, MD*, Glenn Luther, CRNA, MSA*,
Departments of *Anesthesiology and †Research, St. Vincent Mercy Medical Center, Toledo, Ohio
Cardiac surgery is estimated to cost $27 billion annually
in the United States. In an attempt to decrease the costs
of cardiac surgery, fast-track programs have become
popular. The purpose of this study was to compare the
effects of three different opioid techniques for cardiac
surgery on postoperative pain, time to extubation, time
to intensive care unit discharge, time to hospital dis-
charge, and cost. Ninety adult patients undergoing car-
diac surgery were randomized to a fentanyl-based,
sufentanil-based, or remifentanil-based anesthetic.
Postoperative pain was measured at 30 min after extu-
bation and at 6:30 am on the first postoperative day.
Pain scores at both times were similar in all three
groups (P ⬎ 0.05). Median ventilator times of 167, 285,
and 234 min (P ⬎ 0.05), intensive care unit stays of 18.8,
19.8, and 21.5 h (P ⬎ 0.05), and hospital stays of 5, 5, and
C
ardiac surgery, particularly coronary artery by-
pass grafting, has become one of the most com-
mon operations in the United States. Because of
its success and an aging population, cardiac surgery is
estimated to cost $27 billion annually in the United
States (1). In an attempt to decrease the costs of cardiac
surgery, fast-track programs have become popular.
They rely on an anesthetic technique that permits
prompt extubation instead of the traditional overnight
mechanical ventilation. Early success was achieved
with a propofol-based technique (2). However, an-
other study has suggested that a fentanyl/isoflurane
technique can achieve the same prompt extubation at
a much lower anesthetic cost (3). Remifentanil, an
ultra-short-acting opioid, was introduced to practice
in 1993 (4). This drug, which is metabolized by plasma
cholinesterases, permits more rapid emergence than
either fentanyl or sufentanil and may permit a more
prompt extubation. However, remifentanil is much
more expensive than either fentanyl or sufentanil, and
Accepted for publication May 22, 2001.
Address correspondence and reprint requests to Milo Engoren,
MD, Department of Anesthesiology, St. Vincent Mercy Medical
Center, 2213 Cherry St., Toledo, OH 43608. Address e-mail to
engoren@pol.net.
©2001 by the International Anesthesia Research Society
0003-2999/01
and Nancy Fenn-Buderer, MS†
5 days (P ⬎ 0.05) for the Fentanyl, Sufentanil, and
Remifentanil groups did not differ. Three patients
needed to be tracheally reintubated: two in the Sufen-
tanil group and one in the Fentanyl group. Median an-
esthetic costs were largest in the Remifentanil group
($140.54 [$113.54 –$179.29]) and smallest in the Fenta-
nyl group ($43.33 [$39.36 –$56.48]) (P ⱕ 0.01), but hospi-
tal costs were similar in the three groups: $7841 (Fenta-
nyl), $5943 (Sufentanil), and $6286 (Remifentanil) (P ⬎
0.05). We conclude that the more expensive but shorter-
acting opioids, sufentanil and remifentanil, produced
equally rapid extubation, similar stays, and similar
costs to fentanyl, indicating that any of these opioids
can be recommended for fast-track cardiac surgery.
(Anesth Analg 2001;93:859 –64)
its putative advantages to achieve more rapid extuba-
tion and discharge need to be evaluated to determine
whether use of remifentanil can produce sufficient
savings to justify its higher acquisition cost. We hy-
pothesized that remifentanil would produce a shorter
time to tracheal extubation and therefore designed this
study to compare the effects of three different opioid
techniques for cardiac surgery on time to tracheal
extubation, time to intensive care unit (ICU) dis-
charge, time to hospital discharge, postoperative pain,
and cost. Additionally, we sought to evaluate the re-
lationships among time of mechanical ventilation, ICU
length of stay, hospital length of stay, and cost.
Methods
This study was approved by our IRB, and written,
informed consent was obtained from all patients be-
fore group assignment and surgery. Ninety adult pa-
tients undergoing cardiac surgery at our university-
affiliated tertiary care center were randomized to a
fentanyl-based, sufentanil-based, or remifentanil-
based anesthetic as chosen by a computer-generated
random number list designed to produce true ran-
domization rather than balanced groups. Patients
Anesth Analg 2001;93:859–64 859
860 CARDIOVASCULAR ANESTHESIA ENGOREN ET AL.
OPIOIDS FOR FAST-TRACK CARDIAC ANESTHESIA
were excluded if they were having nonelective sur-
gery, having combined carotid and cardiac surgery,
did not speak English, were mechanically ventilated
before surgery, or were not capable of understanding
instructions.
All patients had standard monitoring, including
electrocardiography, arterial and central venous ma-
nometry, pulse oximetry, and measurement of inspira-
tory and expiratory carbon dioxide and isoflurane
concentrations. Pulmonary artery catheterization was
at the discretion of the anesthesiologist and surgeon
(and was used in ⬍10% of the patients in each of the
three groups), and the decision for this was made after
enrollment in the study but before assignment to any
of the three groups. Surgery was performed via a
median sternotomy. Cardiopulmonary bypass, when
used, was normothermic.
All patients were premedicated with lorazepam
2 mg sublingually (1 mg if the patient was ⬍55 kg or
⬎70 yr). All patients had anesthesia induced with
diazepam 0 –5 mg, thiopental 0 –250 mg, and pancu-
ronium 0.1 mg/kg (median and interquartile ranges
are given in Table 1). Patients in the Fentanyl group
received fentanyl 7–10 ␮g/kg for the induction and
additional doses of 1–2 ␮g/kg as needed for intense
stimulus. The Sufentanil group patients received
sufentanil 1– 4 ␮g/kg for the induction and 0.1– 0.3
␮g/kg as needed for intense stimulus. Although
sufentanil is typically considered to be 5 to 10 times
more potent than fentanyl, it has a shorter half-life
than fentanyl—approximately half as long (5). There-
fore, we front-loaded sufentanil at approximately one
third the dose of the fentanyl to compensate for the
shorter half-life. Remifentanil patients had anesthesia
induced with a remifentanil infusion at 0.5–1.0
␮g · kg⫺1 · min⫺1 (on the basis of ideal body weight),
then maintained anesthesia by titrating the infusion
between 0.05 and 1.0 ␮g · kg⫺1 · min⫺1. Boluses of 0.5–
1.0 ␮g/kg could be given as needed for intense stim-
ulus. On arrival in the ICU, the infusion was de-
creased to 0.025– 0.2 ␮g · kg⫺1 · min⫺1. Then, 15 to
30 min later (after initial doses of ketorolac and mor-
phine), the remifentanil infusion was discontinued.
All Remifentanil group patients received fentanyl 250
␮g as part of the induction. We believed that this
would decrease the remifentanil dose needed for the
induction, provide some initial postoperative analge-
sia (when the remifentanil was discontinued), and
have minimal effects on the rest of the postoperative
course. In addition, patients in all three groups re-
ceived maintenance doses of diazepam 0 –5 mg, pan-
curonium 0.01 mg/kg as needed to maintain one to
three twitches of a train-of-four as measured by pe-
ripheral nerve stimulator, and isoflurane at an end-
tidal concentration of 0.3%– 0.7%.
Hemodynamic status was supported as previously
described (3). Briefly, nitroglycerin and nitroprusside
ANESTH ANALG
2001;93:859 –64
were used to maintain mean arterial blood pressure
(MAP) ⬍70 mm Hg during surgery and ⬍90 mm Hg
after surgery. Ephedrine and phenylephrine were
used to maintain MAP ⬎60 mm Hg during and after
surgery. During surgery, esmolol and propranolol
were used to keep heart rate ⬍100 bpm. After surgery,
propranolol 1 mg IV every 4 h was administered.
Propranolol was withheld for MAP ⬍70 mm Hg, sys-
tolic blood pressure ⬍110 mm Hg, or heart rate
⬍70 bpm. Dobutamine, epinephrine, and dopamine
were used per the surgeon’s choice as inotropes.
All patients were weaned from mechanical ventila-
tion by our standard protocol (3). Briefly, mechanical
ventilation was started in synchronized intermittent
mandatory ventilation mode with a rate of 10 breaths/
min and a tidal volume of 10 –12 mL/kg. Fraction of
inspired oxygen was adjusted to maintain oxygen sat-
uration by pulse oximetry ⱖ95%. Positive end-
expiratory pressure was set at 5 cm H2O. End-tidal
CO2 measurements were used to adjust tidal volume
to maintain predicted arterial CO2 between 35 and
40 mm Hg. When patients were hemodynamically
stable and rousable, they were changed to continuous
positive airway pressure. If patients were awake but
showed clinical signs of residual neuromuscular
blockade, glycopyrrolate 0.4 mg and neostigmine
2.5 mg were given IV. If end-tidal CO2 remained
within 5 mm Hg and the patient was alert, mechanics
were checked, and if these were acceptable (respira-
tory rate 10 –28 breaths/min, tidal volume ⬎5 mL/kg,
vital capacity ⬎10 mL/kg, and negative inspiratory
force ⱕ20 cm H2O), the patient was extubated. If
end-tidal CO2 increased by more than 5 mm Hg, a
synchronized intermittent mandatory ventilation rate
was reinstituted until the patient was more awake and
continuous positive airway pressure could be retried.
Ventilator hours were defined as time from arrival in
cardiovascular ICU (CVICU) until tracheal extubation.
Prolonged ventilation was defined as continued me-
chanical ventilation at 6:30 am the day after surgery.
Ketorolac and morphine were used for analgesia,
and the doses between arrival in the ICU and 6:30 the
next morning were recorded. Ketorolac 15 mg IV was
given on arrival in the CVICU, on first complaint of
pain, and then every 6 h as needed. Ketorolac was not
used if the patient had a history of aspirin intolerance,
recent peptic ulcer disease, or an increased creatinine.
Morphine 1–2 mg IV as needed was used if ketorolac
was insufficient.
Thirty minutes after extubation and at 6:30 am on
the first postoperative day, each patient was asked to
rate his or her pain on the 101-point numeric rating
pain scale: 0 as no pain and 100 as pain as bad as it
could be (6).
Hospital cost was calculated as the sum of the direct
variable cost for each item and service used by the
ANESTH ANALG
2001;93:859 –64
Table 1. Anesthetic Drug Doses
Anesthetic Fentanyl group
Diazepam (mg) 5 (5–5)
Thiopental (mg) 250 (250–250)
Pancuronium (mg) 10 (8–10)
Fentanyl (␮g/kg) 9.0 (7.6–10.0)
Sufentanil (␮g/kg) 0 1.7 (1.4–2.0)
Remifentanil (␮g/kg) 0 0
Data are presented as median (interquartile range).
patient from preoperative preparation through dis-
charge or death and was obtained from the hospital’s
internal accounting system.
The a priori power calculation was based on 90%
power, 1.7% type I error (to control for multiple com-
parisons among groups), and an sd estimate of
202 min in time of mechanical ventilation from a pre-
vious study (3). This yielded 90 patients. For patient
characteristics and primary outcome of the continuous
type, groups were compared by using a nonparamet-
ric Kruskal-Wallis test and were presented as median
and interquartile range. If there was evidence, with P
⬍ 0.05, for at least some group differences, then a
Bonferroni multiple comparisons procedure was used
to examine which groups differed. Groups were com-
pared by using ␹2 or Fisher’s exact tests for categoric-
type data. Spearman correlation coefficients were
used.
Results
Patients in the Fentanyl group were slightly younger
(P ⫽ 0.04) than those in either the Sufentanil or
Remifentanil groups. The other preoperative demo-
graphics and types of surgery were similar (Table 2).
No patient had reoperative cardiac surgery. They re-
ceived similar doses of diazepam, thiopental, and pan-
curonium (Table 1). We found no differences in the
ability of fentanyl, sufentanil, and remifentanil to pro-
mote faster liberation from mechanical ventilation,
shorter ICU stays, and shorter hospital stays (Table 3).
However, patients who received sufentanil during
surgery required less morphine in the ICU compared
with fentanyl (P ⫽ 0.02) and remifentanil (P ⬍ 0.001).
Patients in the Remifentanil group were more likely to
require bolus doses of phenylephrine during surgery
(83% vs 55% for the Fentanyl group and 43% for the
Sufentanil group, P ⬍ 0.01). They were also more
likely to receive bolus doses of nitroglycerin in the
CVICU (41% vs 21% for the Fentanyl group and 14%
for the Sufentanil group, P ⬍ 0.05). Use of all other
hemodynamic drugs was similar among the three
groups.
There were six patients with complications in the
Fentanyl group: one patient required propofol for
CARDIOVASCULAR ANESTHESIA ENGOREN ET AL. 861
OPIOIDS FOR FAST-TRACK CARDIAC ANESTHESIA
Sufentanil group Remifentanil group P Value
5 (5–5) 5 (2.5–7.5) 0.8
250 (175–250) 250 (250–250) 0.3
9 (8–10) 9 (8–10) 0.9
0 2.9 (2.7–3.5) —
0 —
88 (67–116) —
emergence delirium, one with reexploration for hem-
orrhage, and one with intraoperative insertion of an
intraaortic balloon pump. The fourth patient was re-
intubated (3 days after extubation), had a partial
bowel resection for ischemia, and needed a tracheos-
tomy before recovering. The fifth patient had isolated
acute respiratory distress syndrome. The sixth patient
had an intraoperative myocardial infarction, pro-
gressed to multisystem organ dysfunction, and ulti-
mately died 4 days after surgery (he was included in
all analyses; excluding him did not change any re-
sults). Two patients in the Remifentanil group had
complications: one required propofol for emergence
delirium, and the other had a postoperative encepha-
lopathy. Five patients in the Sufentanil group had
complications: two patients needed to be reintubated
(2 and 7 days after extubation, respectively), the third
required propofol for emergence delirium, the fourth
required a permanent pacemaker, and the fifth devel-
oped ischemic hepatitis and renal failure necessitating
hemodialysis. Two patients in each of the Sufentanil
and Remifentanil groups required reversal of residual
neuromuscular block in the CVICU.
Although the highest opioid (P ⬍ 0.001) and anes-
thetic (P ⬍ 0.01) costs were in the Remifentanil group
and the lowest in the Fentanyl group, total direct
variable costs were similar (P ⫽ 0.3) among all three
groups (Table 3). The study also found that although
there were statistically significant correlations be-
tween time of mechanical ventilation and ICU length
of stay (r ⫽ 0.50, P ⬍ 0.0001), hospital length of stay (r
⫽ 0.32, P ⫽ 0.002), and direct variable cost (r ⫽ 0.25, P
⫽ 0.02), the Spearman correlations, which made no
assumptions about linearity, were fair to poor (Fig. 1).
Also, ICU length of stay correlated poorly with hos-
pital length of stay (r ⫽ 0.38, P ⫽ 0.0002) (Fig. 1,
bottom right).
Discussion
The use of more expensive but shorter-acting anes-
thetics may be justified if they permit faster extubation
and shorter ICU and hospital stays and these shorter
stays translate into lower total costs. However, this
study found that the use of the shorter-acting opioids,
sufentanil and remifentanil, was not associated with
862 CARDIOVASCULAR ANESTHESIA ENGOREN ET AL. ANESTH ANALG
OPIOIDS FOR FAST-TRACK CARDIAC ANESTHESIA 2001;93:859 –64

Table 2. Patient Demographics and Types of Surgery

Variable Fentanyl group Sufentanil group Remifentanil group P value
a
Age (yr) 58 (51–66) 68 (60–74) 66 (59–72) 0.04
Height (cm) 172 (165–178) 159 (159–178) 170 (160–178) 0.3
Weight (kg) 83 (75–99) 86 (80–100) 86 (72–93) 0.4
BMI (kg/m2) 28 (26–33) 32 (27–39) 28 (26–32) 0.2
Sex (M/F) 23/10 17/11 17/12 0.6
CPB/no CPB 26/7 25/3 25/4 0.5
CABG/Valve/C&V 27/5/1 23/3/2 24/4/1 0.9
Data are presented as median (interquartile range).
CPB/NO CPB ⫽ cardiopulmonary bypass used versus cardiopulmonary bypass not used; CABG/Valve/C&V ⫽ isolated coronary artery bypass surgery
versus isolated valve surgery versus coronary artery bypass surgery combined with valve surgery; BMI ⫽ Body Mass Index.
a
Comparing age between groups two at a time: fentanyl versus sufentanil, P ⫽ 0.03; fentanyl versus remifentanil, P ⫽ 0.03; sufentanil versus remifentanil,
P ⫽ 0.8.

Table 3. Analgesic Use, Pain, Ventilation, ICU and Hospital Length of Stay (LOS) and Cost
Fentanyl group Sufentanil group Remifentanil group P value
Ketorolac (mg) 45 (0–90) 30 (0–68) 45 (0–60) 0.5
Morphine (mg)* 8 (8–12) 6 (4–9) 12 (9–16) ⬍0.001
CPK (units) 798 (408–1185) 688 (472–891) 749 (470–1023) 0.9
CPK-MB (units) 15 (7–29) 15 (9–41) 19 (11–32) 0.9
CPB time (min) 92 (62–118) 87 (61–109) 91 (65–112) 0.9
Vent time (h) 2.78 (1.9–6.68) 4.75 (3.67–6.37) 3.90 (2.03–6.25) 0.4
Prolonged ventilation 21% 10% 7% 0.13
Pain at 30 min 10 (4–35) 15 (3.5–50) 25 (8–40) 0.5
Pain at 6:30 am 20 (3–37.5) 10 (3–40) 25 (4–40) 0.7
ICU stay (h) 18.8 (10.1–25.7) 19.8 (14.2–22.6) 21.5 (11.3–23.7) 0.5
Hospital LOS (days) 5 (4–6) 5 (4–7.5) 5 (4–7) 0.6
Hospital cost ($) 7841 (4957–9482) 5943 (4394–8658) 6286 (4546–7819) 0.3
Opioid cost ($)† 1.29 (1.29–1.29) 15.00 (15.00–15.00) 78.35 (48.04–104.14) ⬍0.001
Anesthetic cost ($)‡ 43.33 (39.36–56.48) 51.41 (48.72–57.14) 140.54 (113.54–179.29) ⬍0.01
ICU ⫽ intensive care unit; CPK ⫽ creatine phosphokinase; CPK-MB ⫽ myocardial band enzymes of CPK.
Data are given as median and (interquartile range) or percentages. CPB time is cardiopulmonary bypass time presented as median (interquartile range).
* P ⫽ 0.001 for morphine use in the Sufentanil group compared with the other two groups.
† P ⬍ 0.001 for fentanyl compared with both Sufentanil and Remifentanil groups and for Sufentanil compared with Remifentanil groups.
‡ P ⬍ 0.0001 for remifentanil compared with both Fentanyl and Sufentanil groups and P ⫽ 0.01 for the Fentanyl group compared with the Sufentanil group.
Prolonged ventilation was defined as receiving mechanical ventilation at 6:30 am the day after surgery. Eight patients in the Fentanyl, four in the Remifentanil,
and four in the Sufentanil groups could not give a numeric pain score 30 min after extubation, and nine, four, and three in the Fentanyl, Remifentanil, and
Sufentanil groups could not give a numeric pain score or had not been extubated by 6:30 the morning after surgery. Pain was rated by each patient on a 101-point
numeric pain scale: 0 as no pain and 100 as pain as bad as it could be (4).

shorter ventilator times, ICU stays, or hospital stays.
Fentanyl, sufentanil, and remifentanil all produced
similar outcomes with similar direct variable costs.
Prompt extubation has been touted as the first step in
fast-track cardiac surgery. However, we found that
time to extubation explained only 6.3% of the variance
(r ⫽ 0.25) in cost and 10.2% of the variance (r ⫽ 0.32)
in hospital length of stay. As Cheng (7) has pointed
out and Arom et al. (8) have shown, process of care
and intermediate outcomes (chest tube drainage, ar-
rhythmias, and so on) may have a greater effect on
cost and hospital length of stay than does choice of
anesthetic. This suggests that further efforts to de-
crease already short ventilation time might have min-
imal effects on decreasing hospital direct variable
costs. In addition, anesthetic cost was only a small
fraction (0.6% for the Fentanyl group, 1.0% for the
Sufentanil group, and 2.2% for the Remifentanil
group) of the total cost.
A previous study has found that patients who re-
ceive remifentanil may have more postoperative pain
(9). However, we found similar pain scores among the
three groups, with the Remifentanil group receiving
more morphine than the Sufentanil group. The similar
pain scores may be related to the residual effects of the
250 ␮g fentanyl used as part of the induction in the
Remifentanil group.
Only a few previous studies have compared
remifentanil or sufentanil with fentanyl (10,11). In a
small study of 27 patients (another 9 patients were
excluded for death or prolonged hospital stay), the
Remifentanil group had shorter (by an average of
2.5 hours) times to extubation and shorter (6.6 ⫾ 0.26
vs 8.4 ⫾ 0.5 days, mean ⫾ sem, P ⫽ 0.015) hospital
stays compared with patients receiving fentanyl (10).
However, we achieved shorter hospital length of stays
in all three of our groups; this probably reflects differ-
ences in process of care or criteria for discharge. Our
ANESTH ANALG
2001;93:859 –64
Figure 1. (Upper right) Direct variable cost versus time of mechan-
ical ventilation. One patient in the Fentanyl group who required
⬎72 h of mechanical ventilation (and died) is not shown. (Bottom
right) Hospital length of stay versus time of mechanical ventilation.
Two patients in the Fentanyl group are not shown: one required
⬎31 days in the hospital, and the second required ⬎72 h of me-
chanical ventilation. (Bottom left) Intensive care unit (ICU) length of
stay versus time of mechanical ventilation. Five patients are not
shown: one in the Sufentanil group and three in the Remifentanil
group stayed in the ICU ⬎96 h, and one in the Fentanyl group
required ⬎72 h of mechanical ventilation. (Upper left) Hospital
length of stay versus ICU length of stay. Six patients are not shown:
one in the Fentanyl group required ⬎21 days in the hospital, one in
each of the Fentanyl, Sufentanil, and Remifentanil groups stayed
⬎96 h in the ICU, and two in the Sufentanil group required
⬎21 days in the hospital and ⬎96 h in the ICU. F ⫽ Fentanyl group;
E ⫽ Sufentanil group;  ⫽ Remifentanil group.
results differ from those of Butterworth et al. (11), who
found that sufentanil produced a quicker extubation
than did fentanyl (geometric mean 12.2 vs 14.2 hours)
but likewise found no association between time of
mechanical ventilation and ICU or hospital length of
stay. We expected a very rapid emergence and tra-
cheal extubation in the Remifentanil group, but we did
not find this. Although our median time to tracheal
extubation in the Remifentanil group of 3.90 hours
was longer than expected, it was similar to the
3.3 hours found by Cheng et al. (12) and the 5.3 hours
found by Möllhoff et al. (13). Additionally, Zarate et
al. (14) found a mean time to tracheal extubation of 5.1
⫾ 4.3 hours in patients receiving remifentanil and
intrathecal morphine. Reasons for this delayed emer-
gence and extubation found with remifentanil after
cardiac surgery remain to be elucidated.
Similar to London et al. (15), we identified a sharp
break in ICU length of stay (Fig. 1, bottom left) on the
basis of whether patients were transferred out of the
ICU before midnight the day of surgery or transfer
was accomplished after 8:00 the next morning. Al-
though this pattern of transfer before midnight or after
8:00 am occurs because of nursing staffing require-
ments, it also minimizes patient sleep disturbances,
CARDIOVASCULAR ANESTHESIA ENGOREN ET AL. 863
OPIOIDS FOR FAST-TRACK CARDIAC ANESTHESIA
which can lead to ICU psychosis and delirium (16).
However, this did not seem to affect hospital length of
stay (Fig. 1, bottom right).
Prompt tracheal extubation is safe, and a variety of
drugs (opioids, inhaled vapors, and propofol) can be
used to achieve prompt extubation (2,3,17). However,
although they have similar effects on mechanical ven-
tilation, these drugs may have different effects on cost.
Previous studies examining cost have been limited—
they use only costs of anesthetic drugs (3) or use
arbitrary assignment to different patient locations of
fixed overhead costs (2). This is the first study to
examine total direct variable cost for cardiac surgery.
Study has shown that charge/cost ratios have a large
variation from department to department (18). We
chose to use direct variable costs as the outcome fi-
nancial measure of interest (19). These are the costs
that are actually spent by the hospital to perform a
particular task. It ignores factors such as overhead that
are not reduced or eliminated by changes in process of
care. For example, if a patient is tracheally extubated
and transferred from the ICU to the stepdown unit
and the nurse/patient ratio is not changed, no direct
variable cost is saved, although charges may be lower
on the stepdown unit, reflecting an arbitrary assign-
ment of more of the hospital’s overhead to the ICU.
Unfortunately, the vast majority of costs in hospitals
may be fixed overhead and are not lowered when the
anesthetic technique is changed (20).
A major limitation of this study is that the costs may
be applicable to only this hospital. Hospitals may pay
different prices for disposable equipment and medi-
cations. Different nurse/patient staffing ratios and
mixtures of nurses to paraprofessionals will affect the
labor component of the costs. The determination of the
labor associated with any laboratory test or procedure,
such as a radiograph, may even differ between hospi-
tals. Hospitals may need to develop their own cost
models and evaluate the effectiveness of changes in
the process of care or in drug use to determine the cost
benefits of any change.
Another limitation was the use of normothermic
cardiopulmonary bypass. Most centers use hypother-
mia, which may affect the pharmacokinetics and phar-
macodynamics of the studied drugs and may limit the
generalizability of this study. Also, low statistical
power could account for the lack of statistically signif-
icant differences among groups for some of the out-
come variables. Our sample size was chosen a priori to
detect a large effect size of 1 between any two groups
for time to extubation (202 minutes or 3.37 hours). The
n was calculated on the basis of 90% power, 1.7% type
I error (to control for multiple comparisons among
groups), and an sd estimate of 3.37 hours from a
previous study (3). However, the observed sd for ex-
tubation time was much larger than estimated.
Among the three groups, the median sd was
864 CARDIOVASCULAR ANESTHESIA ENGOREN ET AL.
OPIOIDS FOR FAST-TRACK CARDIAC ANESTHESIA
5.37 hours. Therefore, the post hoc power to detect a
difference of 3.37 hours (as chosen a priori) was only
46%. Yet the largest observed difference in extubation
time among groups was only 1.97 hours, which is
smaller than we had originally deemed clinically im-
portant. Data were not available to calculate a priori
sample size requirements for the other outcome vari-
ables. However, similar post hoc analysis shows that
we would have needed to study 942 patients to detect
a $1500 difference in direct variable costs among the
three groups or 2115 patients for a $1000 difference.
The pain analysis was limited because several patients
could not provide a numeric estimate of their pain.
Our power to detect pain scale differences of 15
points, a clinically important difference, with ␣ ⫽
0.017 was only 35%.
In conclusion, this study found no differences in
the outcomes from fentanyl-, sufentanil-, and
remifentanil-based cardiac anesthetics. They all pro-
duce similar outcomes and have similar direct vari-
able costs.
We would like to thank the CVICU nurses, the anesthesiologists,
and nurse anesthetists for their help and participation in this study.
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