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Departments of *Anesthesiology and
Research, St. Vincent Mercy Medical Center, Toledo, Ohio
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{at}pol.net
| Abstract |
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0.01), but hospital costs were similar in the three groups: $7841 (Fentanyl), $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. IMPLICATIONS: To conserve resources for cardiac surgery, fentanyl-, sufentanil-, and remifentanil-based anesthetics were compared for duration of mechanical ventilation, intensive care unit length of stay, hospital length of stay, and cost. The shorter-acting anesthetics, sufentanil and remifentanil, produced equally rapid extubation, similar stays, and similar costs to fentanyl; thus, any of these opioids can be recommended for fast-track cardiac surgery.
| Introduction |
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| Methods |
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All patients had standard monitoring, including electrocardiography, arterial and central venous manometry, pulse oximetry, and measurement of inspiratory 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 05 mg, thiopental 0250 mg, and pancuronium 0.1 mg/kg (median and interquartile ranges are given in Table 1). Patients in the Fentanyl group received fentanyl 710 µg/kg for the induction and additional doses of 12 µg/kg as needed for intense stimulus. The Sufentanil group patients received sufentanil 14 µg/kg for the induction and 0.10.3 µg/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 fentanylapproximately half as long (5). Therefore, 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 0.51.0 µg · kg-1 · min-1 (on the basis of ideal body weight), then maintained anesthesia by titrating the infusion between 0.05 and 1.0 µg · kg-1 · min-1. Boluses of 0.51.0 µg/kg could be given as needed for intense stimulus. On arrival in the ICU, the infusion was decreased to 0.0250.2 µg · kg-1 · min-1. Then, 15 to 30 min later (after initial doses of ketorolac and morphine), the remifentanil infusion was discontinued. All Remifentanil group patients received fentanyl 250 µg as part of the induction. We believed that this would decrease the remifentanil dose needed for the induction, provide some initial postoperative analgesia (when the remifentanil was discontinued), and have minimal effects on the rest of the postoperative course. In addition, patients in all three groups received maintenance doses of diazepam 05 mg, pancuronium 0.01 mg/kg as needed to maintain one to three twitches of a train-of-four as measured by peripheral nerve stimulator, and isoflurane at an end-tidal concentration of 0.3%0.7%.
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All patients were weaned from mechanical ventilation 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 1012 mL/kg. Fraction of inspired oxygen was adjusted to maintain oxygen saturation by pulse oximetry
95%. 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 (respiratory rate 1028 breaths/min, tidal volume >5 mL/kg, vital capacity >10 mL/kg, and negative inspiratory force
20 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 mechanical 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 12 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 patient from preoperative preparation through discharge or death and was obtained from the hospitals internal accounting system.
The a priori power calculation was based on 90% power, 1.7% type I error (to control for multiple comparisons among groups), and an SD estimate of 202 min in time of mechanical ventilation from a previous study (3). This yielded 90 patients. For patient characteristics and primary outcome of the continuous type, groups were compared by using a nonparametric 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 compared by using
2 or Fishers exact tests for categoric-type data. Spearman correlation coefficients were used.
| Results |
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Although the highest opioid (P < 0.001) and anesthetic (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 between 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 hospital length of stay (r = 0.38, P = 0.0002) (Fig. 1, bottom right).
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| Discussion |
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A previous study has found that patients who receive 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 µg 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 differences in process of care or criteria for discharge. Our 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 tracheal 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 emergence 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. Although this pattern of transfer before midnight or after 8:00 AM occurs because of nursing staffing requirements, it also minimizes patient sleep disturbances, 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 ventilation, these drugs may have different effects on cost. Previous studies examining cost have been limitedthey 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 financial 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 assignment of more of the hospitals 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 medications. 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 hospitals. 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 hypothermia, which may affect the pharmacokinetics and pharmacodynamics of the studied drugs and may limit the generalizability of this study. Also, low statistical power could account for the lack of statistically significant differences among groups for some of the outcome 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 extubation time was much larger than estimated. Among the three groups, the median SD was 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 important. Data were not available to calculate a priori sample size requirements for the other outcome variables. 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 produce similar outcomes and have similar direct variable costs.
| Acknowledgments |
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| References |
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