Original contributionHemodynamics and emergence profile of remifentanil versus fentanyl prospectively compared in a large population of surgical patients☆
Introduction
Remifentanil hydrochloride (Ultiva) is a short-acting opioid of the phenylpiperidine class. The phenylpiperidines are more potent than alkaloid opiates, provide pure mu-opioid receptor agonist effects, and find wide usage in general anesthesia and conscious sedation techniques.1, 2 Remifentanil possesses an ester bond on a side chain from the phenylpiperidine ring unlike other members of this class (e.g., alfentanil, sufentanil, and fentanyl). This ester bond is readily hydrolyzed by nonspecific plasma and tissue enzymes. Remifentanil has a terminal half-life of 8 to 20 minutes,3 and a context-sensitive half-time of approximately 3 minutes.4 The principal metabolite of remifentanil is the deesterified carboxylic acid GR90291, which has no clinically observable opioid properties.5 Like other anesthetic agents, age influences pharmacokinetic-pharmacodynamic relationships for remifentanil.6, 7
Hemodynamic stability and absence of somatic responses may be achieved by inducing profound anesthetic states; however, this usually carries the penalties of slow emergence and delayed recovery. The effectiveness of intravenous opioid anesthetic regimens must, thus, be compared during both the intraoperative and recovery stages of anesthesia.8 This study was designed as a Phase IV prospective trial in a large surgical population to investigate whether the desired intraoperative characteristics of remifentanil, in comparison with fentanyl, could be obtained while achieving a fast, predictable recovery from anesthesia.
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Ethical and regulatory considerations
This study complied with the Declaration of Helsinki (as amended) and was approved by the institutional review board of each of the participating institutions. All patients provided written informed consent.
Overview of study design
Anesthesiologists first participated in an open-label, remifentanil-based balanced infusional technique on ten patients to gain experience using the drug. In the next phase of the study, two balanced anesthetic regimens were compared using a parallel-group, 1:1 randomized, controlled
Demographics
For inpatients, the safety and intent-to-treat populations were 477 and 465 for remifentanil and fentanyl, respectively. For outpatients, the safety population was 752 and 744 for remifentanil- and fentanyl-based regimens, respectively. For one outpatient, the surgical procedure was emergently canceled, and the intent-to-treat populations were 751 and 744 for remifentanil and fentanyl, respectively. Demographic characteristics of these populations were comparable between treatment groups,
Discussion
We compared hemodynamics and recovery outcomes observed during and after remifentanil- versus fentanyl-based balanced anesthesia regimens in a large-scale, multicenter, randomized, single-blind study. This is the largest study to date (2,438 patients) comparing intraoperative and recovery profiles of two phenylpiperidine opioids. Inpatients and outpatients were studied separately because of predictable demographic differences in age, ASA status, and type and duration of surgery. Statistically
Acknowledgements
We thank the investigators, other advisory panel members (Kenneth Tuman, Michael Roizen, Peter Glass), Deborah Thompson (Project Leader), study site coordinators, and patients who took part in this study.
References (21)
- et al.
Remifentanil versus alfentanil in a balanced anesthetic technique for total abdominal hysterectomy
J Clin Anesth
(1997) - et al.
Does functional ability in the postoperative period differ between remifentanil- and fentanyl-based anesthesia?
J Clin Anesth
(2001) Principles of cost analysis
J Clin Anesth
(1994)- et al.
A randomized, blind comparison of remifentanil and alfentanil during anesthesia for outpatient surgery
Anesth Analg
(1997) - et al.
A randomized multicenter study of remifentanil compared with alfentanil, isoflurane, or propofol in anesthetized pediatric patients undergoing elective strabismus surgery
Anesth Analg
(1997) - et al.
A review of the pharmacokinetics and pharmacodynamics of remifentanil
Anesth Analg
(1999) - et al.
Measured context-sensitive half-times of remifentanil and alfentanil
Anesthesiology
(1995) - et al.
Pharmacokinetics and pharmacodynamics of remifentanil in persons with renal failure compared with healthy volunteers
Anesthesiology
(1997) - et al.
Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development
Anesthesiology
(1997) - et al.
Pharmacokinetics and pharmacodynamics of remifentanil. II. Model application
Anesthesiology
(1997)
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This study was sponsored by GlaxoWellcome Inc., Research Triangle Park, NC, USA, under protocol number USAA4001.
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Professor of Clinical Anesthesiology, Department of Anesthesiology, SUNY Health Science Center at Brooklyn
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Head, Clinical Development, Neurosciences Medical Affairs, GlaxoSmithKline, Triangle Park, NC
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Professor of Anesthesiology, Department of Anesthesiology, Duke University Medical Center, Durham, NC
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Associate Professor of Anesthesiology, Joint Appointments in Medicine, Biomedical Information Sciences and Health Policy & Management, Clinical Director of Operating Rooms, Johns Hopkins Medicine
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Senior Analyst, Principal Health Outcomes Scientist, GlaxoSmithKline