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PubMed1985

Epidural fentanyl in labour. An evaluation of the systemic contribution to analgesia.

In a randomized double-blind trial in the first stage of labour, 20 patients given fentanyl 80 micrograms in the epidural test dose of bupivacaine, were compared with 20 patients receiving an intravenous infusion designed to produce comparable plasma fentanyl concentrations, at the same time as their epidural test dose. Despite slightly higher plasma fentanyl concentrations in the intravenous fentanyl group, epidural fentanyl produced analgesia which was more complete, more rapid in onset and slightly longer lasting. Supplementary doses of bupivacaine were needed to produce analgesia in 75% of the intravenous and 30% of the epidural fentanyl group. It is clear that epidural fentanyl produces satisfactory pain relief when added to the epidural test dose, but that the presence of fentanyl in the systemic circulation makes a negligible contribution to analgesia.

Adult↗
PubMed1992

Effect of fentanyl on the circulatory responses to orotracheal fibreoptic intubation.

The effectiveness of fentanyl in attenuating the pressor and heart rate response to orotracheal fibreoptic intubation under general anaesthesia was assessed in 60 healthy patients undergoing elective surgery. Patients were randomly assigned to receive either fibreoptic intubation with or without fentanyl 6 micrograms.kg-1 or traditional Macintosh intubation with fentanyl 6 micrograms.kg-1. A standardised general anaesthetic was administered which included temazepam premedication, thiopentone, atracurium, oxygen, nitrous oxide and isoflurane. The pressor response to fibreoptic intubation was suppressed in those patients who received fentanyl and was similar to that seen in the Macintosh-fentanyl group of patients. The heart rate response to fibreoptic intubation was also significantly reduced in the patients who received fentanyl, but, in contrast, was still significantly greater than that in the Macintosh-fentanyl group. Fentanyl 6 micrograms.kg-1 appears to have a useful place in attenuating the cardiovascular effects of fibreoptic intubation under general anaesthesia.

Adolescent↗
PubMed1997

Neonatal welfare and placental transfer of fentanyl and bupivacaine during ambulatory combined spinal epidural analgesia for labour.

To investigate current concerns that potent opioid drugs, such as fentanyl, used for labour regional analgesia may affect neonatal status, maternal and umbilical plasma concentrations of fentanyl and bupivacaine at delivery were measured in 40 nulliparous patients receiving low-dose combined spinal epidural analgesia. Neonatal assessments included Apgar scores, umbilical blood gases and neurobehavioural tests. All maternal and umbilical venous plasma concentrations were low. Maternal and umbilical vein total fentanyl concentrations increased with increasing doses of epidural fentanyl (r = 0.46 and 0.30, respectively, p < 0.01). There were no significant differences between maternal and umbilical venous plasma total or free concentrations of fentanyl. Mean umbilical vein/maternal fentanyl ratios were 1.12 for total drug and 1.20 for free drug and values were unrelated to the last epidural bolus to delivery interval (r = 0.12, p = 0.49). There were no correlations between Apgar scores, umbilical blood gases or neurobehavioural scores and umbilical venous concentrations of either fentanyl or bupivacaine. The dose of fentanyl used for ambulatory combined spinal epidural analgesia would appear to have a negligible effect on neonatal condition.

Ambulatory Care↗
PubMed2005

Pharmacokinetics and tolerability of different doses of fentanyl following sublingual administration of a rapidly dissolving tablet to cancer patients: a new approach to treatment of incident pain.

AIMS: It is estimated that two-thirds of cancer patients will at some point during their illness experience breakthrough pain. In this study, the pharmacokinetics of a novel sublingual dosage form of fentanyl developed for breakthrough pain was evaluated. METHODS: Eleven Caucasian patients (seven male and 4 female, aged 34-75 years, median 60 years) with metastatic malignant disease were recruited initially, but three patients withdrew. Prior to the study all patients were on continuous nonfentanyl opiate medication. The study was a double-blind, cross-over trial, consisting of three 1-day treatment periods. A new rapidly dissolving preparation of fentanyl, was administered sublingually in single doses of 100, 200 and 400 microg, respectively, on three separate occasions. Plasma fentanyl concentrations were determined using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated by noncompartment analysis. Tolerability and the occurrence of adverse events were monitored throughout the study by patient questionnaire. RESULTS: The data from nine subjects who completed at least two periods were used in the analysis of variance. There were no significant differences between doses (100, 200 and 400 microg) for dose adjusted AUC (F = 0.42, P = 0.6660), dose adjusted C(max) (F = 0.08, P = 0.9206) and Tmax (F = 0.94, P = 0.4107). Thus, these parameters showed dose proportionality. The differences (400-100microg) in dose adjusted AUC from the three-period crossover analysis was -0.016 min.ng/ml (t = 0.71, P = 0.8718). Interindividual variability in systemic exposure to fentanyl was fairly small (25-40%), which may be related to a good in vivo biopharmaceutical performance of the sublingual tablet, and a relatively small fraction of the dose being swallowed. The first detectable plasma concentration of fentanyl was observed between 8 and 11 min after administration. t(max) increased from 39.7 +/- 17.4 to 48.7 +/- 26.3 and 56.7 +/- 24.6 min for the 100, 200 and 400 microg doses, respectively. Adverse events were few and did not increase with increasing dose. CONCLUSION: With this rapidly dissolving fentanyl formulation, the first detectable plasma concentration of fentanyl was observed at 8-11 min after administration. The pharmacokinetics of the drug showed dose proportionately. This formulation of fentanyl seemed to be well tolerated by the patients.

Administration, Sublingual↗
PubMed2006

Pharmacokinetics of fentanyl delivered transdermally in healthy adult horses--variability among horses and its clinical implications.

The safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60-67 microg/kg, were investigated in six healthy adult horses. Three transdermal fentanyl patches (Duragesic), each containing 10 mg of fentanyl citrate, were applied to the mid-dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it gradually declined in a roughly linear manner over the next 72 h. There was much individual variation, however. The initial delay ranged from 0 to 5.1 h (mean, 1.91+/-2.0 h), Tcmax ranged from 8.5 to 14.5 h (mean, 11.4+/-2.7 h) and Cmax ranged from 0.67 to 5.12 ng/mL (mean, 2.77+/-1.92 ng/mL). In two horses, the plasma fentanyl concentration failed to reach even 1 ng/mL, whereas in the other four horses it was >1 ng/mL for at least 40 h and for at least 72 h in two of these horses. No adverse effects attributable to fentanyl were observed in any of the horses, indicating that this dosage is safe in systemically healthy adult horses. However, it failed to achieve plasma fentanyl concentrations generally considered to be analgesic (>or=1 ng/mL) in about one-third of horses.

Administration, Cutaneous↗
PubMed1982

Cardiovascular effects of high-dose fentanyl anaesthesia.

An anaesthetic technique using high-dose fentanyl for coronary artery surgery is described. Fentanyl 60 or 70 micrograms kg-1 was used as the sole anaesthetic agent, and patients were ventilated with air/O2 (fentanyl 70 micrograms kg-1) or N2O/O2 (fentanyl 60 micrograms kg-1). Cardiovascular data from 30 patients are presented. Fentanyl caused no significant cardiovascular depression. The only statistically significant changes in cardiovascular parameters were seen in the patients who received fentanyl 60 micrograms kg-1. Five minutes after skin incision there was an increase in peripheral resistance. Diastolic pressure was increased following sternotomy. Problems associated with this technique of anaesthesia are a 50% incidence of hypertension following sternotomy (requiring treatment with sodium nitroprusside) and prolonged respiratory depression. The lack of cardiovascular depression produced by fentanyl and the ability of fentanyl to reduce hormonal and metabolic responses to surgery make it a satisfactory technique for cardiac anaesthesia.

Anesthesia, General↗
PubMed2005

Effect of fentanyl on lidocaine-induced convulsions in mice.

This study was undertaken to examine the effect of fentanyl on lidocaine-induced convulsions in mice. Seventy-five male mice were used and divided into five groups, 15 in each. Convulsions were obtained by lidocaine injection subcutaneously (150 mg/kg), in a dose volume of 0.1 ml/10 g body weight over the upper back. The five groups were: (a) control group: pretreated with normal saline; (b) F50 group: pretreated with fentanyl 50 microg/kg; (c) F100 group: pretreated with fentanyl 100 microg/kg; (d) F200 group: pretreated with fentanyl 200 microg/kg, and (e) F100+N group: pretreated with fentanyl 100 mug/kg plus naloxone 1 mg/kg. The pretreatments were given intraperitoneally (i.p.) 5 min prior to lidocaine injection. After lidocaine injection, the latency to the onset of generalized convulsions was observed for 12 min and recorded. The severity of convulsions was assessed and scored as 1 = mild, 2 = moderate, and 3 = severe. The recovery or death of the mice were also recorded. Student's t, Mann-Whitney U, and Fisher's exact tests were used to analyze the data. Compared with the control group (431.7 +/- 37.3 s), the latencies of onset of convulsions in the fentanyl groups were dose-dependently decreased (F50: 331.0 +/- 37.1 s; F100: 240.3 +/- 28.6 s, p < 0.001; F200: 188.7 +/- 19.4 s, p < 0.001), and the decreased latency was reversed by naloxone (F100+N: 412.9 +/- 34.1 s). Compared with the control group (1.13 +/- 0.19), the severities of convulsions in the fentanyl groups were also increased in a dose-dependent manner (F50: 1.47 +/- 0.19; F100: 1.93 +/- 0.21, p < 0.05; F200: 2.46 +/- 0.17, p < 0.001). Similarly, the increased severity was reversed by naloxone (F100+N: 1.33 +/- 0.16). There was no death in the control and naloxone-treated groups. The incidences of death were 2/15 in F50 group, 5/15 in F100 group, and 7/15 in the F200 group (p < 0.05). The results of this study demonstrated that fentanyl potentiates the lidocaine-induced convulsions in a dose-dependent manner in mice, and this effect may be mediated by an opioid mechanism.

Animals↗
PubMed1988

Induction using fentanyl to suppress the intubation response in the cardiac patient: what is the optimal dose?

Eighty patients undergoing coronary artery surgery were randomly allocated to receive either 0, 2, 5, 10 or 15 micrograms/kg of fentanyl with induction of anaesthesia. Heart rate and blood pressure were measured before induction, after induction, and after intubation. The effects of fentanyl dose on both heart rate and mean arterial pressure (MAP) were evaluated in terms of both the mean and group responses. At all doses of fentanyl, mean heart rate increased after induction and rose further on intubation. The mean increase after induction was minimal at doses of 5 micrograms/kg and greater. The increase in heart rate after intubation was more difficult to block but with a fentanyl dose of 15 micrograms/kg, 87% of patients had heart rates below 100 bpm. As a group, the percentage of patients in whom the postintubation heart rate remained below 100 bpm increased progressively with the fentanyl dose. In contrast, mean MAP fell at all dose levels after induction, the mean fall being about 30 mmHg at 5 micrograms/kg and greater. Mean MAP exceeded pre-induction values after intubation with 0 and 2 micrograms/kg, and progressive attenuation of the MAP rise was found as the dose of fentanyl increased. The percentage of patients who did not exceed their preinduction MAP rose progressively with increasing dose of fentanyl with an ED50 of 3.7 micrograms/kg. If a minimal fall in mean MAP after induction with no rise above preinduction MAP is the sole criterion, a fentanyl dose of about 3 micrograms/kg is recommended. If heart rate is to be kept below 100 bpm, a dose of at least 10 micrograms/kg should be used.2+ dose or greater will cause the MAP to fall in some patients to less

Blood Pressure↗
PubMed1999

Middle latency auditory evoked potentials during total intravenous anesthesia with droperidol, ketamine and fentanyl.

We investigated whether total intravenous anesthesia with ketamine, fentanyl and droperidol would affect middle latency auditory evoked potentials and explicit memory, and whether dreams during the anesthesia are related to plasma concentrations of fentanyl and the infusion technique. A total number of 40 patients were the subjects for this study. Twenty patients (group A) were maintained with intravenous ketamine 2 mg kg-1 hr-1 and fentanyl 5 micrograms kg-1 hr-1 for the first 60 min and 3 micrograms kg-1 hr-1 for the next 90 min, and droperidol 0.1 mg kg-1. The remaining 20 patients (group B) were maintained with intravenous ketamine 2 mg kg-1 hr-1, droperidol 0.1 mg kg-1 and fentanyl 50-100 micrograms in a bolus intermittently as needed by vital signs such as increases in heart rate and arterial blood pressure. Middle latency auditory evoked potentials, plasma fentanyl and ketamine levels were measured; explicit memory and dreams were also estimated. There were no patients who recollected explicit memories of intraoperative events in both groups. The middle latency auditory evoked potentials were not significantly changed during the anesthesia in both groups. We could find no significant differences in latencies and amplitudes of the middle latency auditory evoked potentials between the both groups. Plasma fentanyl levels of group B patients were significantly lower than those of group A patients and the incidence of the dreams was significantly higher in group B patients. We conclude that the anesthesia with ketamine, fentanyl and droperidol is not associated with the explicit memories, though the middle latency auditory evoked potentials were not significantly changed as compared with those in the waking state. In addition, dreams during the anesthesia may correlate with plasma fentanyl concentrations or the infusion technique.

Adult↗
PubMed2002

Longitudinal follow-up of TTS-fentanyl use in patients with cancer-related pain: results of a compassionate-use study with special focus on elderly patients.

GOALS OF THE WORK: This open compassionate-use prospective registration study evaluated the tolerability, ease of use and applied doses of transdermal (TTS) fentanyl in adult patients with cancer-related pain requiring strong opioid analgesia. Elderly patients were particularly focussed on. PATIENTS AND METHODS: Previous pain medication was converted to an appropriate dose of TTS-fentanyl. Immediate-release morphine rescue medication was allowed as needed for breakthrough pain. Dose adjustments of TTS-fentanyl, rescue morphine requirements, the ease of use and side-effects were assessed monthly, with special emphasis paid to the severity of constipation and the use of laxatives. MAIN RESULTS: A total of 663 patients with cancer-related pain, including 8% opioid-naive patients, were enrolled; 661 patients used at least 1 patch of TTS-fentanyl. Of these, 455 subjects were assessed at baseline and at 1 post-baseline visit at least. Individual treatment ranged from a few days to 2 1/2 years; TTS-fentanyl doses ranged from 25 to 950 microg/h. The major reason for study termination was non-drug-related death (61%). Approximately 40% of patients reported constipation. The frequency of constipation depended on the rescue morphine dose used, but no dose-relationship was found for TTS-fentanyl. Patient acceptance of the patches was high; around 85% of patients rated convenience as good to excellent The ease of use and tolerability of TTS-fentanyl in the elderly patients were comparable to that in the total population, except for a slight increase of non-serious adverse events. CONCLUSIONS: TTS-fentanyl can be applied as long-term therapy to patients with cancer-related pain, including the elderly.

Administration, Cutaneous↗
PubMed2003

Comparison of TTS-fentanyl with sustained-release oral morphine in the treatment of patients not using opioids for mild-to-moderate pain.

OBJECTIVE: This randomised, multicentre, direct open comparative trial evaluated the efficacy, treatment convenience, tolerability and safety aspects of transdermal therapeutic system (TTS)-fentanyl and sustained-release oral morphine (SRM) in both opioid-naïve patients with moderate-to-severe cancer-related pain and in patients who had already been using opioids for mild-to-moderate pain. The two treatment groups were run in parallel. Special attention was paid to constipation, nausea/vomiting, drowsiness and respiratory depression. PATIENTS AND METHODS: The 131 enrolled patients started the 4-week treatment at low doses of opioid (25 microg/h TTS-fentanyl for 3 days or 30 mg SRM every 12 h) and were individually titrated. Tolerability, efficacy and safety were assessed throughout the study period. Frequency of constipation was the primary study variable and accordingly the study was powered for this. Both patients and investigators made a global treatment evaluation. RESULTS: TTS-fentanyl and SRM were shown to be equally effective. Pain control and sleep quality improved with both treatments. None of the patients developed respiratory depression. Statistically significantly more patients in the SRM treatment group discontinued the trial prematurely (59% vs 27%; p < 0.001), particularly due to adverse events (36% vs 4%; p < 0.001). Fewer patients in the TTS-fentanyl than in the SRM treatment group reported constipation during the trial. This finding was statistically significant after 1 week of treatment (27% vs 57%; p = 0.003). The favourable tolerability profile of TTS-fentanyl was also reflected in both the patient and the investigator global evaluation of the treatment. Patient assessment favoured TTS-fentanyl treatment in terms of a significantly lower rate of troublesome side-effects ('quite a bit' to 'very much' troublesome side-effects in 14% vs 36% of patients; p = 0.003) and less interruption of daily activities (absence of any interruption of daily activities in 88% vs 63% of patients; p = 0.012). Investigators scored TTS-fentanyl as significantly better with respect to 'side-effects' (p = 0.039) and 'overall impression' (p = 0.013). Sub-analyses of opioid-naïve users gave similar results. CONCLUSION: These data indicate that TTS-fentanyl, when used as an opioid of first choice in the treatment of cancer-related pain, is as effective as, but better tolerated than, SRM, including in opioid-naïve patients.

Administration, Cutaneous↗
PubMed2004

Use of transdermal fentanyl without prior opioid stabilization in patients with cancer pain.

OBJECTIVE: To determine the safety and efficacy of transdermal fentanyl for pain relief in cancer patients and to compare the effects on patients according to whether they had previously received strong opioids, weak opioids or non-opioid analgesia. METHODS: Cancer patients requiring strong analgesia were recruited into an open-label, multicentre study, conducted in eight countries. Patients received transdermal fentanyl treatment for 28 days. Pain severity, overall satisfaction with pain control, convenience of use of patches and treatment preferences were recorded daily. RESULTS: Of the 292 participants, 135 had previously received a strong opioid, 84 had previously received a weak opioid and 73 had received no regular opioids. Thirty-eight patients did not complete the study, mainly due to adverse events. For all groups the proportion of patients with 'good to excellent' pain control increased after transdermal fentanyl treatment. Transdermal fentanyl was well tolerated, with the most common treatment-related adverse events being nausea, vomiting and constipation. The percentage of strong-opioid-tolerant patients with constipation decreased following transdermal fentanyl treatment and increased slightly in the strong-opioid-naïve groups. Most patients rated the convenience of the patches as 'good to excellent', and most preferred transdermal fentanyl to their previous therapy. CONCLUSIONS: Transdermal fentanyl is an effective and well-tolerated treatment for cancer-related pain for patients regardless of whether they have previously received opioids. Previous guidelines have often advocated initial dose finding with short-acting opioids but this study demonstrates that such a complex titration and conversion schedule may not be necessary,and that treatment may be initiated directly with long-acting formulations such as transdermal fentanyl when previous analgesic therapy fails to provide adequate relief.

Administration, Cutaneous↗
PubMed1987

Inhibition of the adrenocorticotropin response to surgery in humans: interaction between dexamethasone and fentanyl.

We examined the plasma ACTH and cortisol responses to surgery in 25 patients with atherosclerotic heart disease undergoing myocardial revascularization. The patients were all premedicated with diazepam, and general anesthesia was induced with thiopental. They were randomly assigned to one of four groups: I) no dexamethasone (DEX), enflurane anesthesia, II) 40 mg DEX, iv, 45-60 min before sternotomy, enflurane anesthesia, III) no DEX, fentanyl [N-(1-phenethyl-4-piperidyl)propionanilide] anesthesia (50-100 micrograms/kg), and IV) DEX, fentanyl anesthesia. Isokalemic hemodilution of significant magnitude occurred during cardiopulmonary bypass. All groups had significant increases in plasma ACTH during surgery, which returned to control levels 22 h after the bypass. Group I (no DEX, no fentanyl) and group III (no DEX, fentanyl) patients had large similar increases in plasma ACTH, which peaked 2-4 h postbypass [400 +/- 83 (+/- SEM) pg/mL; 88 +/- 18 pmol/L]. The group II (DEX, no fentanyl) patients also had large increases in ACTH which were similar to those in groups I and III, except 2-4 h postbypass (183 +/- 91 pg/mL; 40 +/- 20 pmol/L). The group IV (DEX, fentanyl) patients had a significantly attenuated ACTH response to surgery; the mean plasma ACTH level 2-4 h postbypass was only 54 +/- 21 pg/mL (12 +/- 5 pmol/L). Therefore, although DEX or fentanyl alone had a minimal effect on the ACTH response to surgery, a significant attenuation occurred when DEX and fentanyl were used in combination. We conclude that glucocorticoids and morphine agonists exert interactive inhibitory effects on ACTH release in humans, probably by virtue of their suppression of CRH release from the hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1990

Differences in magnitude and duration of opioid-induced respiratory depression and analgesia with fentanyl and sufentanil.

The magnitude and duration of analgesia and respiratory depression induced by fentanyl (1.0, 2.0, and 4.0 micrograms/kg) and sufentanil (0.1, 0.2, and 0.4 microgram/kg) after intravenous administration over 30 s were measured in 30 healthy young adult male volunteers divided into three groups and studied in a double-blind, randomized fashion. Each volunteer received one dose of fentanyl or sufentanil and no sooner than 48 h later, the corresponding equipotent dose of the other opioid. End-tidal CO2 and ventilatory and occlusion pressure responses to CO2 rebreathing were used to measure drug-induced respiratory effects. Analgesic effects were assessed by changes in the pain threshold to electric shock applied to the forearm. Plasma levels of fentanyl and sufentanil were measured by radioimmunoassay. Testing and sampling intervals were 5, 30, 60, 90, 120, 240, 300, and 360 min after drug administration. The magnitude and duration of depression of the ventilatory and occlusion pressure response were significantly less with sufentanil compared with fentanyl, irrespective of dose. Ventilatory and occlusion pressure responses returned to control values by 30 and 30 min, respectively, after sufentanil and by 240 and 120 min, respectively, after fentanyl. Statistically significant elevations of the pain threshold were, however, greater and longer lasting after sufentanil compared with fentanyl. Pain threshold returned to control values 180 min after sufentanil but only 90 min after fentanyl. These results suggest that sufentanil may provide better patient comfort with less respiratory depression than does fentanyl.

Adolescent↗
PubMed1991

Comparison of nalbuphine and fentanyl anesthesia for coronary artery bypass surgery. Hemodynamics, hormonal response, and postoperative respiratory depression.

To determine whether nalbuphine might replace fentanyl as the principal opioid for anesthesia during coronary artery bypass surgery, 20 patients undergoing myocardial revascularization were anesthetized with flunitrazepam and with a continuous infusion of either nalbuphine (an opioid agonist-antagonist) or fentanyl (a pure opioid agonist) in equipotent dosage ratio of 333:1. During endotracheal intubation, all patients given nalbuphine, but only one given fentanyl (P less than 0.05), required nitroglycerin to control arterial blood pressure. Two minutes after tracheal intubation, plasma values of epinephrine, norepinephrine, vasopressin, and cortisol did not change in the fentanyl group compared with the awake (baseline) levels, whereas catecholamines and vasopressin significantly increased with nalbuphine compared with the baseline and with the values in the fentanyl group. A steady state of anesthesia (30 min after intubation), when compared with the baseline, was characterized by unchanged systemic and pulmonary blood pressures and increased systemic vascular resistance with nalbuphine, by decreased systemic and pulmonary pressures and resistances with fentanyl, and by comparably decreased cardiac index with both opioids. Hormone values returned to baseline levels but norepinephrine remained significantly higher in the nalbuphine than in the fentanyl group. A bolus injection of either nalbuphine (2.5 mg/kg) or fentanyl (7.5 micrograms/kg) given during the steady-state period of anesthesia provoked only minimal hemodynamic changes. Before skin incision, 7 of 10 patients receiving nalbuphine required nitroglycerin to control arterial blood pressure. After sternotomy, both groups required nitroglycerin, but additional antihypertensive drugs were necessary mainly in the nalbuphine group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1992

Fentanyl does not alter the "sleep" plasma concentration of thiopental.

Thiopental and fentanyl are commonly combined for induction of anesthesia. The effect of an analgesic concentration of fentanyl on the plasma concentration of thiopental to induce sleep was studied in 46 unpremedicated patients. As a measure of drug effect, sleep (the lack of response to open eyes to a verbal command) was used. Forty-six patients were randomized to receive thiopental infused to one of several predetermined plasma concentrations. Twenty-two of these patients also received a fentanyl infusion to a desired analgesic concentration of 1 ng/mL. Thiopental and fentanyl were infused by means of a pharmacokinetic model-driven infusion device (computer-assisted continuous infusion, CACI). Venous blood samples were taken from the contralateral antecubital fossa at 5 and 10 min after the start of the infusion. At 10 min, the patients' names were firmly spoken, and they were instructed to open their eyes. If they did not respond to this command, they were considered to be asleep. Only patients in whom the 5- and 10-min measured plasma concentrations of thiopental and fentanyl, respectively, were within +/- 30% of each other were used for the determination of the Cp50(asleep), the plasma concentration at which 50% of the patients were asleep. The Cp50(asleep) with and without fentanyl was calculated by logistic regression. The Cp50(asleep) for patients in whom concentrations were maintained within +/- 30% for thiopental alone (n = 17) was 7.32 micrograms/mL (95% confidence interval, 5.53-10.95); for thiopental in the presence of fentanyl (n = 18 with a measured fentanyl concentration of 1.27 +/- 0.5 ng/mL), this was 7.22 micrograms/mL (95% confidence interval, 4.83-10.15).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Comparative effects of ketorolac, dezocine, and fentanyl as adjuvants during outpatient anesthesia.

The comparative effects of ketorolac, dezocine, and fentanyl were evaluated in 136 healthy female patients undergoing outpatient laparoscopic procedures according to a randomized, double-blind protocol. Patients received ketorolac (60 mg) or dezocine (6 mg) or fentanyl (100 micrograms, control group) before the start of the operation. A standardized general anesthetic technique consisting of midazolam (2 mg), fentanyl (50 micrograms), and propofol (2 mg/kg) for induction of anesthesia followed by propofol (120 micrograms.kg-1.min-1), vecuronium (1-2 mg), and 67% nitrous oxide in oxygen for maintenance of anesthesia, was used. In the postanesthesia care unit, 61% of patients in the fentanyl group received analgesic drugs for persistent pain, compared with 34% and 25% in the ketorolac and dezocine groups, respectively. Similarly, less postoperative fentanyl (mean +/- SD) was required in the ketorolac (22 +/- 33 micrograms) and dezocine (18 +/- 35 micrograms) groups, compared with the fentanyl (58 +/- 71 micrograms) group. However, 52% of the patients receiving dezocine required antinausea therapy in the postanesthesia care unit, compared with 20% and 18% in the fentanyl and ketorolac groups, respectively. Finally, recovery times were significantly shorter in the ketorolac (vs dezocine) group. Although both ketorolac and dezocine were effective alternatives to fentanyl when administered during outpatient laparoscopy, dezocine was associated with an increased incidence of postoperative nausea and a delayed discharge time compared with ketorolac.

Adjuvants, Anesthesia↗
PubMed1993

Minimum effective combination dose of epidural morphine and fentanyl for posthysterectomy analgesia: a randomized, prospective, double-blind study.

Recent studies have produced conflicting results regarding whether the addition of epidural fentanyl improves postoperative analgesia from epidural morphine. Therefore, we prospectively determined the dose-response relationship and the minimum effective combination dose of epidural morphine and fentanyl (fentanyl given after morphine) for posthysterectomy analgesia. We studied 120 patients undergoing radical abdominal hysterectomy. All patients had epidural lidocaine 1.5% with epinephrine (1:200,000) for surgical anesthesia followed by light general anesthesia with endotracheal intubation. They were assigned randomly into six groups according to the combination of each narcotic dose: morphine 2 mg, morphine 2 mg/fentanyl 50 micrograms, morphine 2 mg/fentanyl 100 micrograms, morphine 4 mg, morphine 4 mg/fentanyl 50 micrograms, and morphine 4 mg/fentanyl 100 micrograms. Morphine and fentanyl were given epidurally in a double-blind manner approximately 60 and 15 min, respectively, before the completion of surgery. For 2 mg of morphine, the addition of 50 or 100 micrograms of fentanyl improved pain relief during the first 6 h postoperatively (P < 0.05), provided longer duration of analgesia (P < 0.05), and required less analgesic supplement (P < 0.05), but did not alter the incidence of side effects. For 4 mg of morphine, the same conclusion was drawn, except that vomiting occurred more frequently with addition of 100 micrograms of fentanyl (P < 0.05). Among fentanyl groups, there was no significant difference in pain scores, duration of analgesia, and analgesic requirements. Therefore, we conclude that epidural fentanyl given after morphine improves early postoperative analgesia from epidural morphine, and the minimum effective combination dose is morphine 2 mg/fentanyl 50 micrograms for posthysterectomy surgery analgesia.

Adolescent↗