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CARDIOVASCULAR ANESTHESIA

The Efficacy and Resource Utilization of Remifentanil and Fentanyl in Fast-Track Coronary Artery Bypass Graft Surgery: A Prospective Randomized, Double-Blinded Controlled, Multi-Center Trial

Davy C. H. Cheng, MD^*, Mark F. Newman, MD, Peter Duke, MD^¶, David T. Wong, MD, Barry Finegan, MD, Michael Howie, MD^#, Jane Fitch, MD^**, T. Andrew Bowdle, MD, Charles Hogue, MD, Zak Hillel, MD, Eric Pierce, MD^¶¶, and Deo Bukenya, PharmD^||

*Division of Cardiac Anesthesia & Intensive Care, Toronto General Hospital, University of Toronto, Toronto, Ontario; Medical/Surgical Intensive Care Unit, University Health Network, University of Toronto, Toronto, Ontario; and Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta; Division of Cardiac Anesthesia, Duke University Medical Center, Durham; and ||Glaxo Wellcome, Research Triangle Park, North Carolina; ¶Division of Cardiac Anesthesia, University Health Science Center, University of Manitoba, Manitoba; #Division of Cardiovascular Anesthesia, The Ohio State University Medical Center, Columbus, Ohio; **Division of Cardiovascular & Thoracic Anesthesiology, Baylor College of Medicine, Houston, Texas; Department of Anesthesiology, University of Washington School of Medicine, Seattle, Washington; Division of Cardiothoracic Anesthesia, Washington University School of Medicine, St. Louis, Missouri; Division of Cardiothoracic Anesthesia, St. Luke’s-Roosevelt Hospital Center, New York, New York; and ¶¶Department of Anesthesiology, Boston University Medical Center, Boston, Massachusetts

Address correspondence and reprint requests to Dr. Davy Cheng, Department of Anesthesia, Toronto General Hospital, University Health Network, 200 Elizabeth Street, EN3-464, Toronto, Ontario, M5G 2C4. Address e-mail to davy.cheng{at}uhn.on.ca

	Abstract

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We compared (a) the perioperative complications; (b) times to eligibility for, and actual time of the following: extubation, less intense monitoring, intensive care unit (ICU), and hospital discharge; and (c) resource utilization of nursing ratio for patients receiving either a typical fentanyl/isoflurane/propofol regimen or a remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in 304 adults by using a prospective randomized, double-blinded, double-dummy trial. There were no differences in demographic data, or perioperative mortality and morbidity between the two study groups. The mini-mental status examination at postoperative Days 1 to 3 were similar between the two groups. The eligible and actual times for extubation, less intense monitoring, ICU discharge, and hospital discharge were not significantly different. Further analyses revealed no differences in times for extubation and resource utilization after stratification by preoperative risk scores, age, and country. The nurse/patient ratio was similar between the remifentanil/isoflurane/propofol and fentanyl/isoflu-rane/propofol groups during the initial ICU phase and less intense monitoring phase. Increasing preoperative risk scores and older age (>70 yr) were associated with longer times until extubation (eligible), ICU discharge (eligible and actual), and hospital discharge (eligible and actual). Times until extubation (eligible and actual) and less intense monitoring (eligible) were significantly shorter in Canadian patients than United States’ patients. However, there was no difference in hospital length of stay in Canadian and United States’ patients. We conclude that both anesthesia techniques permit early and similar times until tracheal extubation, less intense monitoring, ICU and hospital discharge, and reduced resource utilization after coronary artery bypass graft surgery.

Implications: An ultra-short opioid technique was compared with a standard fast-track small-dose opioid technique in coronary artery bypass graft patients in a prospective randomized, double-blinded controlled study. The postoperative recovery and resource utilization, including stratification of preoperative risk score, age, and country, were analyzed.

	Introduction

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Potent synthetic opioids, such as fentanyl and sufentanil, are often used with a concomitant hypnotic drug for cardiac surgery anesthesia. Earlier research investigated a range of remifentanil infusion rates for cardiac surgery, but did not include an opioid comparison.¹ Currently, coronary artery bypass graft (CABG) patients who are expected to be extubated shortly after surgery are given relatively decreased opioid doses (such as fentanyl 10–15 µg/kg), with concomitant inhaled anesthetics and/or propofol, with hemodynamic control facilitated by vasoactive drugs (1,2). This technique has become common anesthesia practice in fast-track cardiac surgery. Fast-track cardiac anesthesia is safe and cost effec-tive (2–4). Decreased catecholamine levels and excellent control of intraoperative hemodynamics suggest that the intraoperative stress control benefits of an opioid-based anesthetic regimen can be achieved with remifentanil (5).

This trial was designed to study the safety, efficacy, and resource utilization of remifentanil infusion compared with fentanyl for CABG surgery. The objectives were to compare the following endpoints between the opioid groups in subjects undergoing elective CABG surgery (stratified for age, preoperative risk score, and country) with either remifentanil boluses and infusion or fentanyl intermittent boluses as the opioid component of a balanced anesthetic technique: (a) perioperative complications; (b) times to eligibility for, and actual time of extubation, intensive care unit (ICU) and hospital discharge; and (c) nursing ratio in resource utilization.

	Methods

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Study Design and Patient Population
This study was a multi-center, prospective randomized, double-blinded, double-dummy study in ASA physical status III–IV subjects undergoing elective CABG surgery, with cardiopulmonary bypass (CPB) with either remifentanil boluses and infusion or fentanyl intermittent boluses as the opioid component of a balanced anesthetic technique. After IRB approval, 304 subjects >18 yr old scheduled for elective CABG surgery were randomized at 14 centers [10 in the United States and 4 in Canada]. A preoperative risk score was recorded, using information from medical history and physical examination (6). Exclusion criteria consisted of simultaneous valve repair, replacement, or any other combined surgical procedure (e.g., simultaneous carotid endarterectomy or left ventricular aneurysm repair); >50% ideal body weight; medical conditions such as preoperative intraaortic balloon counterpulsation, severely impaired left ventricular function (ejection fraction 0.30), or severe congestive heart failure (pulmonary edema on clinical evaluation supported by chest radiographic findings); as well as any condition that would preclude administration of ketorolac. Hypersensitivity to fentanyl analogs; women of child-bearing potential; substance abuse; history of a psychiatric illness which might impair a patient’s ability to provide informed consent, or presence of a mental deficit that would preclude completing the screening mini-mental state examination (score <26); and previous study participation within 4 wk were also exclusions.

A computer-generated random code determined which opioid assignment was identified by each treatment number. Subjects were assigned the treatment numbers in ascending, chronological order of admission into the induction period of the study. A double-dummy technique was necessary to blind this study, because standard fentanyl dosing is by intermittent bolus whereas standard remifentanil dosing is by continuous infusion. Subjects were given a double-blinded induction/maintenance infusion, double-blinded induction and preextubation boluses, and simultaneous double-blinded/double-dummy boluses/infusion increases for prevention or treatment of responses during maintenance of anesthesia.

Anesthesia Induction and Maintenance
Both groups received standardized preoperative premedication with 1–3 mg IV midazolam and 0.05 mg/kg IV morphine before invasive instrumentation. Anesthesia was induced with propofol 0.5 mg/kg over 1 min plus 10 mg bolus every 10 s until loss of consciousness. In a double-dummy manner, remifentanil/isoflurane/propofol (REMI) regimen induction consisted of 1 µg · kg^-1 · min^-1 and titrated during maintenance; whereas, fentanyl/isoflurane/propofol (FENT) regimen induction consisted of 10 µg/kg bolus. Cisatracurium besylate (0.2 mg/kg) or vecuronium (0.15 mg/kg) was administered, and the trachea was intubated no sooner than 3 min after starting the induction/maintenance infusion. After intubation, isoflurane was administered to achieve an end-tidal concentration of 0.5%. Propofol was started at rewarming on bypass, and isoflurane discontinued at the end of CPB. Opioid maintenance boluses and rate increases were given to prevent or control responses to surgical stimuli. The maintenance bolus consisted of 1 µg/kg (REMI) and 2 µg/kg (FENT). Isoflurane 0.5% end-tidal was titrated if needed. Propofol and the blinded study maintenance infusion were continued until patients were settled in the ICU. The maximal opioid administration was the rate equivalent to 4 µg · kg^-1 · min^-1 remifentanil. Isoflurane or propofol were increased if opioid treatment did not prevent or control a response; vasodilator or ß-blocking drugs were given only if needed after titration of opioid and hypnotic drugs. Hypotension was treated as necessary with isoflurane/propofol rate decreases, study opioid infusion rate decreases, then ephedrine or phenylephrine.

A volatile anesthetic (isoflurane or enflurane) was generally administered as needed via the CPB circuit throughout the bypass period. Upon the start of rewarming (or approximately mid-bypass if normothermic CPB was used), propofol was started at an initial rate of 2 mg · kg^-1 · h^-1 and titrated for control of anesthesia responses through the remainder of surgery. Sites that did not have CPB machines equipped with vaporizers would start propofol at the beginning of bypass.

Postoperative ICU and Follow-Up Period
In ICU, study opioid rate equal to 1 µg · kg^-1 · min^-1 remifentanil and 0.5 mg · kg^-1 · h^-1 propofol were titrated to minimal requirement. When criteria for eligibility to start an extubation regimen were met (>36°C, hemodynamically stable, chest tube drainage <100 mL/h, urine output 0.5 mL · kg^-1 · h^-1), ketorolac 30 mg IV (or IM if required) was given, and any residual neuromuscular blockade was reversed. After 10–15 min, propofol was turned off and study opioid infusion was titrated down at 10-min intervals (50% decrements three or four times, then off). Patients were extubated when the following extubate criteria were achieved: responds to command, SpO₂ >95% at FIO₂ <0.5; pH >7.25–7.3; PaCO₂ <55 mm Hg, adequate respiratory effort. Vital signs were recorded. Time was recorded when criteria for eligibility for ICU discharge were met: SpO₂ >90% at FIO₂ <0.5; no uncontrolled arrhythmia; chest tube drainage <50 mL/h; urine output 0.5 mL · kg^-1 · h^-1; no inotropes or vasopressor. Actual time until ICU discharge was also recorded. On postoperative days (POD) 1, 2, and 3, vital signs, pain score, mini-mental examinations, adverse event assessment, and POD-3 interview for recall and satisfaction were recorded. The time and date of hospital discharge were documented.

Outcome and Utilization Measurements
The efficacy and morbidity variables between the Remifentanil and Fentanyl groups were compared. Resource utilization in terms of the time of eligibility for, and actual tracheal extubation, transfer to less intensive monitoring, ICU and hospital discharge, and mini-mental examinations (7), were analyzed. After stratification [by preoperative risk score, age (less than versus more than 70 yr old), and US versus Canada], resource utilization, including nurse/patient ratio and number of arterial blood gas samples, were compared between the two groups.

Hypotension was defined as systolic blood pressure <80 mm Hg for >1 min. Bradycardia was defined as heart rate <40 bpm for >1 min. Apnea was defined as <6 breaths per min. Adverse events, such as confusion, hallucination, muscle stiffness, and pain documented by the nursing staff or reported by study personnel, were compared. Oliguria was defined by urine output <0.5 mL · kg^-1 · h^-1 in 8 h. Renal insufficiency was defined as serum creatinine 133 µmol/L. The mini-mental state examination was administered by the same study personnel to all subjects. On POD 3, study personnel interviewed each subject for recall of intraoperative events, by asking the following standard question: "Do you remember anything that happened during the operation?" Subjects reporting recall were questioned to determine the extent and nature of the memory, and to determine as best as possible the time of the events remembered.

Background demographics (sex, age, height, weight, ethnic origin, ASA physical status) and surgical procedure were compared between study groups. Recovery from anesthesia was evaluated by time to meet criteria for starting the extubation sequence, time to achieve criteria for extubation, actual time until extubation, time to achieve ICU discharge criteria, time until actual ICU discharge, and time until hospital discharge. Survival analysis technique was applied. Two-sided statistical tests were performed to detect a difference between treatment groups. Cox proportional hazards modeling, adjusting for site effects, was used to detect between-treatment differences in nonnormally distributed continuous variables, e.g., time until extubation or time until discharge. Success risk ratios relative to fentanyl, 95% confidence intervals, and P values were obtained from Wald ² statistics. Logistic regression analysis, adjusting for site effects, was used to detect between-treatment differences in dichotomous response variables, e.g., proportion of subjects with treated responses. Odds ratio relative to fentanyl, 95% confidence intervals, and P values were obtained from Wald ² statistics. Fisher’s exact test was performed when logistic regression exhibited convergence problems, e.g., when every subject had the same dichotomous response within at least one treatment group. The Cochran-Mantel-Haenszel test was applied when more than two levels of ordinal response were of interest. Analysis of variance, adjusting for sites and baseline, was used to detect between-treatment differences in normally distributed continuous variables.

	Results

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In this double-blinded randomized controlled trial, 150 patients in the REMI group and 154 patients in the FENT group were analyzed. Three REMI and two FENT deaths, of cardiovascular or surgical causes (e.g., myocardial infarction, hemorrhage), were reported during the study. None of the deaths were related to study medication. There were no differences in the demographic and surgical characteristics between the REMI and FENT groups ( Table 1). There were no differences in postoperative mortality and morbidity between the two study groups except an increased incidence of confusion in the FENT group and an increased incidence of muscle aches (pain) in the REMI group ( Table 2). The mini-mental status examination from POD 1 to 3 were similar between the two groups.

Resource Utilization: Nurse/Patient Ratio and Arterial Blood Gas Samples
The nurse/patient ratio was similar between the REMI and FENT groups during the initial ICU phase (1:1, 1:2) and less intense monitoring phase (1:2, 1:3, 1:4, 1:5, 1:6). The median and range of number of arterial blood gas samples within 24 h of induction of anesthesia were similar between the REMI and FENT groups (11, 4–33 vs 10.5, 4–22).

	Discussion

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Patient Characteristics, Safety, and Morbidity
Patient characteristics and morbidity were similar between the two study groups. The only significant differences noted were that patients in the REMI group had less confusion and more muscle aches compared with the FENT group during the hospital stay. However, further analyses of mental status at baseline, POD 1 to 3, showed no differences in overall mini-mental status examination: orientation, registration, attention, recall, and language scores between the two study groups. Therefore, it is possible that patients in the REMI group might have transiently exhibited less episodes of mental confusion, but the differences did not persist from POD 1 to 3. Postoperative nausea and vomiting were quite frequent in both study groups, consistent with other published reports (8,9).

Resource Utilization Measured by Times Until Extubation and Discharges
Resource utilization as measured by time until extubation, less intense monitoring, ICU discharge, and hospital discharge were similar between the two study groups. Because REMI has a shorter and ß half-life compared with FENT, and has virtually no accumulation after prolonged infusion, REMI theoretically may allow shorter times to extubation and discharges compared with the FENT group (10–17). However, with the introduction and acceptance of fast-track cardiac anesthesia (FTCA) consisting of propofol infusion and reduced-dose fentanyl (10–15 µg/kg), times until extubation, ICU and hospital discharge have been substantially shortened (3). Cheng et al. (3) showed that time until extubation, resource utilization and costs were significantly decreased by using an FTCA compared with conventional large-dose fentanyl technique in a randomized controlled trial. The current study indicates that there is little difference in times until extubation and resource utilization comparing a REMI to FENT technique for FTCA. Of significance is that, independent of drug selection, the eligibility and actual times to the setting of less intense monitoring were substantially different. Therefore, valuable time was wasted before patients who were eligible to transfer to a step-down unit were actually transferred. If ICUs were restructured to have variable-care nursing ratio availability (ranging from 1:1 to 1:6), considerable savings might be realized because FTCA patients are suitable for a smaller nursing ratio at much earlier times (4).

Times Until Extubation and Reduced Resource Utilization Stratified by Preoperative Risk Scores
The preoperative risk score developed by Higgins et al. (6) at the Cleveland Clinic in the early 1990s is a useful prognosticator of postoperative morbidity and mortality for cardiac surgery patients based on preoperative cardiac risk factors. Our results showed that there were no differences in times until extubation and discharges between the two study groups with comparable risk scores (Table 4). Cox’s proportional hazards model followed by pairwise comparison showed that patients with risk scores of 2–3, 4–6, and >6 had longer hospital discharge times compared with those with scores of 0–1.

The preoperative risk score used in our analyses may not be the most appropriate measure to stratify for times until extubation and reduced resource utilization in cardiac surgical patients. It was developed as a prognosticator of morbidity and mortality and has not been prospectively validated for times until extubation and reduced resource use. Wong et al. (18) has recently developed and validated cardiac risk scores for times until extubation and ICU discharge in FTCA populations. Among the FTCA literature, London et al. (19) demonstrated that intraoperative clinical process variables are more important factors in determining the timing of extubation than preoperative risk factors. Among non-FTCA literature, Tuman et al. (20) showed that increasing risk scores were associated with prolonged ICU discharge, whereas Tu et al. (21) showed that increasing risk scores were associated with prolonged ICU and hospital discharge. Our results are therefore consistent with other published findings.

Times Until Extubation and Reduced Resource Utilization in US and Canadian Centers
We found that the times until eligibility for extubation, less intense monitoring and ICU discharge, and times until actual extubation, were shorter for Canadian compared with US centers whereas the actual times until less intense monitoring were longer for Canadian centers. It is unclear why the Canadian patients were eligible for extubation and less intense monitoring sooner, because the demographic and patient characteristics were similar between Canadian and US patients. Although criteria for eligibility of times until extubation and discharges were clearly defined in the study protocol, local practices, policies, and guidelines affected the actual times until outcomes were achieved. ICU practice, utilization of ICU resources, and costs vary between US and Canadian hospitals (22–24).

Times Until Extubation and Reduced Resource Utilization Stratified by Age
There were no differences in times to achieve outcomes between the study groups stratified into younger (<70 years) and older (70 years) patients. Cox’s proportional hazards model followed by pairwise comparison showed that patients 70 years of age had longer hospital discharge times compared with those <70 years of age. The actual difference in hospital discharge times between the two age groups was minimal. There were no differences in times until extubation, less intense monitoring, or ICU discharge between the age groups. Therefore, older patients are equally suitable for early extubation and discharge using REMI or FENT FTCA protocol. Reviewing the FTCA literature, Ott et al. (25) showed that age >70 years was associated with prolonged hospital length of stay (LOS) among survivors. In the non-FTCA literature, Tu et al. (21) demonstrated that age >75 years was associated with prolonged ICU and hospital LOS, whereas Lahey et al. (26) showed that age >60 years was associated with prolonged hospital LOS.

Nurse/Patient Ratio in US and Canadian Patients
Overall, on initial entry into ICU, the nurse/patient ratio was 1.0 for all Canadian patients and for the majority of US patients. However, on transition to less intense monitoring, the median nurse/patient ratio was 1:2 for US patients and 1:4 for Canadian patients. Approximately 66% of US patients had a ratio of 1:2 whereas 50% of Canadian patients had a ratio of 1:4. This reflects differences in utilization of ICU resources in the two countries. There were no differences in the use of arterial blood gas testing between the two study groups.

Limitations of the Study
The concept of time interval until less intense monitoring is necessary and is a new concept. More widespread adoption of the concept of a variable care unit is necessary before any anesthetic technique can be used to maximize the benefits of FTCA. The study centers were all academic teaching facilities and the study population was relatively low risk (ejection fraction 0.55, 3%–5% repeat operation). Both of these factors necessitate caution in extrapolating the findings to general practice. Finally, we did not attempt to address the issue of cost. Instead, times until extubation, ICU and hospital discharges, and nurse/patient ratio were used as surrogates for hospital resource utilization.

	Conclusions

Top Abstract Introduction Methods Results Discussion Conclusions References

 
In this prospective randomized, double-blinded controlled trial, perioperative morbidity, time to extubation, and resource utilization were similar between a remifentanil infusion and a small-dose fentanyl technique for FTCA. These data indicate that remifentanil is safe and as effective as small-dose fentanyl when used as the opioid component of a balanced anesthetic technique for fast-track cardiac surgery. Both techniques allow earlier times to extubation, less intense monitoring, ICU discharge, and hospital discharge compared with a large-dose fentanyl technique. Post hoc analyses showed that increasing preoperative risk score and increasing age were associated with longer hospital LOS, and Canadian patients had shorter times to eligibility for extubation and ICU discharge compared with US patients.

	Acknowledgments

 
This study was supported in part by a research grant from Glaxo Wellcome, Inc.

The authors gratefully acknowledge the following coinvestigators for participating in this multicenter trial: Drs. Patrick McCoy, Gordon R. Haddow, Vance Nielsen, Lawrence Siegal, Normal Searle, and Kenneth Thielmemeir.

	Footnotes

 
¹ Royston D, Kirkham A, Adt M, et al. Extubation following CABG using remifentanil-based total intravenous anesthesia [abstract]. Anesthesiology 1996;83:A239.

	References

Top Abstract Introduction Methods Results Discussion Conclusions References

 

1. Westaby S, Pillai R, Parry A, et al. Does modern cardiac surgery require conventional intensive care? Eur J Cardiothorac Surg 1993; 7: 313–8.[Abstract]
2. Cheng DCH, Karski J, Peniston C, et al. Morbidity outcome in early versus conventional tracheal extubation following coronary artery bypass graft: a prospective randomized controlled trial. J Thorac Cardiovasc Surg 1996; 112: 755–64.[Abstract/Free Full Text]
3. Cheng DCH, Karski J, Peniston C, et al. Early tracheal extubation after coronary artery bypass graft surgery reduces costs and improve resource use: a prospective randomized controlled trial. Anesthesiology 1996; 85: 1300–10.[Web of Science][Medline]
4. Cheng DCH. Fast-track cardiac surgery pathways: early extubation, process of care, and cost containment. Anesthesiology 1998; 88: 1429–33.[Web of Science][Medline]
5. Hillel Z, Howie M, Hogue C, et al. A multicenter trial comparing the safety and efficacy of remifentanil and fentanyl in elective CABG surgery patients. Anesth Analg 1999; 88: SCA76.
6. Higgins TL, Estafanous FG, Loop FD, et al. Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients: a clinical severity score. JAMA 1992; 267: 2344–8.[Abstract/Free Full Text]
7. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–98.[Web of Science][Medline]
8. Schuttler J, Albrecht S, Breivik H, et al. A comparison of remifentanil and alfentanil in patients undergoing major abdominal surgery. Anaesthesia 1997; 52: 307–17.[Web of Science][Medline]
9. Bowdle TA, Camporesi EM, Maysick L, et al. A multicenter evaluation of remifentanil for early postoperative analgesia. Anesth Analg 1996; 83: 1292–7.[Abstract]
10. Egan TD, Lemmens HJM, Fiset P, et al. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology 1993; 79: 881–92.[Web of Science][Medline]
11. Egan TD, Minto CF, Hermann DJ, et al. Remifentanil versus alfentanil: comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers. Anesthesiology 1996; 84: 821–33.[Web of Science][Medline]
12. Glass PSA, Hardman D, Kamiyama Y, et al. Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: remifentanil (GI87084B). Anesth Analg 1993; 77: 1031–40.[Abstract/Free Full Text]
13. Bowdle TA, Camporesi EM, Maysick L, et al. A multicenter evaluation of total intravenous anesthesia with remifentanil and propofol for elective inpatient surgery. Anesth Analg 1996; 83: 279–85.[Abstract]
14. Minto CF, Schnider TW, Egan TD, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 1997; 86: 10–23.[Web of Science][Medline]
15. Philip BK, Scuderi PE, Chung F, et al. Remifentanil compared with alfentanil for ambulatory surgery using total intravenous anesthesia. Anesth Analg 1997; 84: 515–21.[Abstract]
16. Westmoreland CL, Hoke JF, Sebel PS, et al. Pharmacokinetics of remifentanil (GI87084B) and its major metabolite (GI90291) in patients undergoing elective inpatient surgery. Anesthesiology 1993; 79: 893–903.[Web of Science][Medline]
17. Yarmush J, D’Angelo R, Kirkhart B, et al. A comparison of remifentanil and morphine sulfate for acute postoperative analgesia after total intravenous anesthesia with remifentanil and propofol. Anesthesiology 1997; 87: 235–43.[Web of Science][Medline]
18. Wong DT, Cheng DCH, Kustra R, et al. Predictors of early extubation, ICU length of stay and mortality in CABG patients undergoing fast track cardiac anesthesia: a new cardiac risk score. Anesthesiology 1999; 91: 911–4.[Web of Science][Medline]
19. London MJ, Shroyer AL, Jernigan V, et al. Fast track cardiac surgery in a Department of Veterans Affairs patient population. Ann Thorac Surg 1997; 64: 134–41.[Abstract/Free Full Text]
20. Tuman KJ, McCarthy RJ, March RJ, et al. Morbidity and duration of ICU stay after cardiac surgery: a model for preoperative risk assessment. Chest 1992; 102: 36–44.[Abstract/Free Full Text]
21. Tu JV, Jaglal SB, Naylor CD. Multicenter validation of a risk index for mortality, intensive care unit stay, and overall hospital length of stay after cardiac surgery: Steering Committee of the Provincial Adult Cardiac Care Network of Ontario. Circulation 1995; 91: 677–84.[Abstract/Free Full Text]
22. Wong DT, Crofts SL, Gomez M, et al. Evaluation of predictive ability of APACHE II system and hospital outcome in Canadian intensive care unit patients. Crit Care Med 1995; 23: 1177–83.[Web of Science][Medline]
23. Jacobs P, Noseworthy TW. National estimates of intensive care utilization and costs: Canada and the United States. Crit Care Med 1990; 18: 1282–6.[Web of Science][Medline]
24. Redelmeier DA, Fuchs VR. Hospital expenditures in the United States and Canada. N Engl J Med 1993; 328: 772–8.[Abstract/Free Full Text]
25. Ott RA, Gutfinger DE, Miller MP, et al. Rapid recovery after coronary artery bypass grafting: is the elderly patient eligible? Ann Thorac Surg 1997; 63: 634–9.[Abstract/Free Full Text]
26. Lahey SJ, Borlase BC, Lavin PT, Levitsky S. Preoperative risk factors that predict hospital length of stay in coronary artery bypass patients > 60 years old. Circulation 1992; 86 (Suppl 5): II181–5.

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