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PubMed2007

The effects of buprenorphine on fentanyl withdrawal in rats.

RATIONALE: Fentanyl is a potent mu-opioid receptor agonist that is widely used for the treatment of severe chronic pain. Discontinuation of fentanyl administration has been shown to induce a negative emotional state. OBJECTIVES: The aim of the present studies was to investigate the effects of the partial mu-opioid receptor agonist buprenorphine on the negative emotional state associated with precipitated and spontaneous fentanyl withdrawal in rats. MATERIALS AND METHODS: Fentanyl and saline were chronically administered via osmotic minipumps. A discrete-trial intracranial self-stimulation procedure was used to provide a measure of brain reward function. Somatic signs were recorded from a checklist of opioid abstinence signs. RESULTS: Naloxone induced a deficit in brain reward function in rats chronically treated with fentanyl. Buprenorphine dose-dependently prevented the naloxone-induced deficit in brain reward function. Discontinuation of fentanyl administration was also associated with a deficit in brain reward function. After explantation of the minipumps, the administration of buprenorphine induced a potentiation of brain reward function in the fentanyl-withdrawing rats, but did not affect brain reward function of saline-treated control rats. Buprenorphine prevented the somatic withdrawal signs associated with spontaneous fentanyl withdrawal and attenuated the somatic signs associated with precipitated fentanyl withdrawal. CONCLUSIONS: Buprenorphine prevents affective and somatic fentanyl withdrawal signs. Moreover, buprenorphine is rewarding in rats previously exposed to fentanyl, but not in opioid-naïve rats. This pattern of results suggests that buprenorphine may be an effective treatment for the anhedonic-state associated with fentanyl withdrawal, but further study of buprenorphine's abuse potential is warranted.

Analgesics, Opioid↗

PubMed1989

The transdermal administration of fentanyl in the treatment of postoperative pain: pharmacokinetics and pharmacodynamic effects.

A transdermal formulation of fentanyl (TTS-fentanyl, Alza Corp., Palo Alto, CA) was evaluated in 13 surgical patients after an abdominal operation. An intraoperative dose of fentanyl (100-200 micrograms i.v.) was administered at the same time as the TTS-fentanyl systems (50-125 micrograms/h) were applied to the antero-lateral chest wall. The TTS-fentanyl systems remained in situ for 24 h and were then removed and a second lot of systems were applied to the contra-lateral chest wall. There was a mean (S.D.) delay time of 12.7 (9.6) h before minimum effective blood fentanyl concentrations (MEC) were obtained from the systems and pseudo-steady state was reached between 36 and 48 h. There was a decay time of 16.1 (7.1) h after the systems were removed for the blood fentanyl concentration to decrease to less than the mean MEC for the control of postoperative pain. There was marked variability between patients in the actual hourly fentanyl dose rate determined from the residual amount of fentanyl remaining in the system and the duration of application. Significantly more supplementary pethidine was administered for inadequate postoperative analgesia between 0 and 12 h compared to the 12-24, 24-36 and 36-48 h periods; this was consistent with the observed delay time. Three patients required a reduction in the hourly fentanyl dose rate because of bradypnoea while 1 patient required an increase in dose because of inadequate pain relief. Nausea was the most frequently reported side effect (85% of patients) while bradypnoea, drowsiness, unpleasant dreams and headache were also reported. These effects were due to the combined effects of a sustained blood fentanyl concentration and the intermittent supplementary pethidine doses. Side effects due to the topical formulation were transient and included erythema (8 patients) and a minor rash (2 patients) in the area occluded by the systems. The TTS-fentanyl systems provided a significant contribution to postoperative pain control but, at the TTS dose rates used, supplementary doses of pethidine were required by all patients probably to control 'incident' pain.

Administration, Cutaneous↗

PubMed1989

Pharmacokinetics of fentanyl in lumbar and cervical CSF following lumbar epidural and intravenous administration.

Fentanyl (1 microgram/kg body weight) was administered intravenously and via a lumbar epidural catheter (in random order) on 2 separate occasions to 6 patients with chronic pain associated with non-terminal disease states. Frequent blood samples were collected from an indwelling intravenous catheter and CSF samples were collected via spinal needles inserted in the cervical (C7-T1 interspace) and lumbar (L3.4 interspace) regions at 0, 5, 10, 20, 30 and 45 min after fentanyl administration. The concentration of fentanyl in blood and CSF samples were quantified by a sensitive and selective gas-liquid chromatography assay. Visual analogue pain scores (VAPS) were recorded every 5 min for the first hour. Coded syringes (one containing the appropriate fentanyl dose while the other contained an equivalent volume of saline) allowed the investigator administering the fentanyl and assessing VAPS to remain blinded as to which route of administration actually contained the fentanyl. There was minimal vascular uptake of fentanyl following epidural administration. Similarly, the permeation of fentanyl into cervical and lumbar CSF following intravenous administration was minimal and erratic such that only 4 of the 60 CSF samples had detectable fentanyl concentrations. In contrast, there was a rapid penetration of fentanyl across the dura mater following lumbar epidural administration. There was significantly fentanyl in lumbar CSF samples by 10 min in 5 patients, and by 20 min in all 6 patients. The mean maximum lumbar CSF concentration was 19.1 ng/ml, while the time associated with these maximum concentrations was 22.5 min. The mean maximum cervical CSF fentanyl concentrations were 10% of the lumbar CSF concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Fentanyl↗

PubMed1993

Immunoassay evidence for fentanyl in hair of surgery patients.

Head hair samples obtained from surgery patients who received fentanyl during anesthesia were analyzed by immunoassay for the presence of fentanyl. Thirteen hair samples were collected from patients following intravenous administration of 1-6 mg of fentanyl. Additional hair samples were collected following the administration of 0.18 and 0.38 mg of sufentanil to 2 patients. The elapsed time after drug administration for all patients ranged from 7 to 273 days. Twenty control hair samples also were collected from staff members who reported no surgery or anesthesia during the previous year. All samples were initially washed with methanol, followed by extraction with methanol and reconstitution in citrate buffer. Analysis of wash and extract fractions was performed by radioimmunoassay (Coat-A-Count Fentanyl assay). Segmental analysis was performed on the surgery patients' hair samples. Eight of the fentanyl patients' hair samples contained fentanyl concentrations (equivalents) of 0.13-0.48 ng/10 mg of hair in the 'root' end. Fentanyl concentrations in the 'tip' segment were lower than those found in the 'root' segment with the exception of 1 subject whose hair sample had been collected only 7 days after surgery. The remaining 5 patients had fentanyl concentrations similar to those determined for the control subjects hair samples (0-0.08 ng/10 mg, n = 19). No correlation between hair fentanyl concentration and administered dose was found for the 13 fentanyl subjects. Both sufentanil subjects' hair samples tested negative. One control subject who had experienced environmental exposure to fentanyl had a fentanyl concentration of 0.29 ng/10 mg in the extract and 0.63 ng/10 mg in the wash fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1996

Controlled transdermal delivery of fentanyl: characterizations of pressure-sensitive adhesives for matrix patch design.

Transdermal delivery of fentanyl from various adhesive matrix formulations to achieve a steady-state skin flux was investigated. For this purpose, various pressure-sensitive adhesives selected from the three chemical classes of polymers (polyisobutylene (PIB), acrylate, and silicone adhesives) were characterized with respect to fentanyl's solubility, diffusion coefficient, and permeability coefficient. The solubility of fentanyl in various pressure-sensitive adhesives at 32 degrees C was determined by the drug absorption-desorption method. The solubilities of fentanyl in these adhesives were in the following order: acrylate > silicones > PIB. The permeability coefficient and diffusion coefficient of fentanyl in these adhesives were determined by the membrane diffusion method. The diffusion coefficient rank order was silicone-2920 > silicone-2675 > or = acrylate > PIB. The release profiles of fentanyl in the aqueous buffer from these adhesives with 2-4% drug loading was evaluated. The release rate of fentanyl from the acrylate polymer was significantly higher than those of silicone and PIB adhesives. The in vitro flux of fentanyl through cadaver skin from various adhesives with 2% drug loading was determined at 32 degrees C using modified Franz diffusion cells. The skin fluxes of fentanyl from silicone-2920 and PIB adhesives were 6.3 +/- 0.7 and 3.1 +/- 0.3 micrograms/cm2/h, respectively. On the other hand, the skin fluxes of fentanyl from acrylate and silicone-2675 adhesive matrices were about 1 microgram/cm2/h. The effect of drug loading on skin flux was investigated using PIB as a model adhesive. The drug released in the phosphate buffer (pH = 6.0) increased linearly as the drug loading in the PIB was increased from 1% to 4%; and as the drug loading exceeded 4%, an initial burst effect followed by a zero-order release was observed. The skin flux of fentanyl increased proportionally as the drug loading in the PIB adhesive was increased from 1 to 4%, and a plateau was reached beyond 4% drug loading. These results suggest that fentanyl concentration in the PIB adhesive might have reached saturation above 4% drug loading and that the optimum skin flux was accomplished from such a system because of attainment of maximum thermodynamic activity.

Acrylates↗

PubMed2003

Effect of fentanyl on 5-HT efflux involves both opioid and 5-HT1A receptors.

1. Fentanyl is a micro -opioid analgesic that might disinhibit 5-HT neurons and thus increase 5-HT efflux. However, fentanyl also binds to 5-HT(1A) receptors, and if it activates 5-HT(1A) somatodendritic autoreceptors, the resultant inhibition might offset opioid-mediated increases in 5-HT efflux. To test this hypothesis, we used microdialysis to study effects of fentanyl on extracellular 5-HT in the dorsal raphe nucleus (DRN) of unanesthetized rats. 2. Systemic administration of fentanyl (0.01-0.2 mg kg(-1), s.c.) increased 5-HT efflux in the DRN. An intermediate dose of fentanyl (0.05 mg kg(-1)) produced the maximum increase in 5-HT to approximately 180% of baseline levels in the DRN. Naltrexone (10 mg kg(-1), s.c.) blocked the increase in response to systemic fentanyl (0.05 mg kg(-1)). 3. In contrast, during infusion into the DRN, fentanyl (10-1000 micro M) induced a dose-dependent decrease in 5-HT. Naltrexone and nor-binaltorphimine failed to block the decrease suggesting that micro - and kappa-opioid receptors did not mediate this effect. 4. Systemic (-)-pindolol (8 mg kg(-1), s.c.) or infusion of WAY-100635 (100 micro M) into the DRN blocked the decrease, and instead 5-HT increased in response to local infusion of fentanyl (100 micro M). WAY-100635 (0.3 mg kg(-1), s.c.) also potentiated the effect of systemic fentanyl (0.2 mg kg(-1), s.c.). (-)-Pindolol and WAY-100635 block 5HT(1A) receptors, indicating that inhibition of 5-HT neuronal activity resulting from fentanyl binding to somatodendritic autoreceptors attenuated opioid-mediated increases in 5-HT efflux. 5. These results provide novel evidence that besides stimulating micro -opioid receptors, fentanyl is a 5-HT(1A) receptor agonist. Possibly, this contributes to lethality of fentanyl overdose.

Analgesics, Opioid↗

PubMed2005

Pharmacokinetic mass of fentanyl for postoperative analgesia in lean and obese patients.

BACKGROUND: We previously proposed dosing weights for fentanyl, termed 'pharmacokinetic mass', that span the total body weight (TBW) range from 40 to 210 kg. In this study, we examined the relationships among fentanyl doses needed to achieve postoperative analgesia, corresponding plasma fentanyl concentrations, and pharmacokinetic mass in lean and obese patients undergoing abdominal surgery. METHODS: A total of 69 patients were studied, with TBW ranging from 48 to 181 kg. Fentanyl infusion was used during surgery. After surgery, fentanyl infusion rates were titrated to achieve analgesia without significant respiratory depression. Plasma fentanyl concentrations were measured when an apparent steady analgesic state was obtained. Comparisons were made for dosing requirements and effective plasma concentrations for 37 lean patients (body mass index < 30, TBW < 85 kg) and 33 obese patients (body mass index > 30, TBW > or = 85 kg). RESULTS: The average fentanyl dose (microg h(-1)) required to achieve and maintain analgesia over the 4 h postoperative period had a non-linear relationship to TBW; in comparison, fentanyl dose had a strong linear relationship to pharmacokinetic mass: dose (microg h(-1)) = 1.22 x pharmacokinetic mass - 7.5; r = 0.741, P < 0.001. Based on results from our earlier study, the corresponding values of TBW and pharmacokinetic mass are: 52 kg--52 kg; 70 kg--65 kg; 100 kg--83 kg; 120 kg--93 kg; 140 kg--99 kg; 160 kg--104 kg; 180 kg--107 kg; 200 kg--109 kg. In the group comparisons, there was no statistically significant difference in the postoperative fentanyl dose per unit of pharmacokinetic mass between lean and obese patients. The plasma concentration of fentanyl required for analgesia was approximately 1.5 ng ml(-1), and was similar in the two groups. CONCLUSION: The relationship between dose and pharmacokinetic mass, compared with that of dose vs TBW, may provide confidence for the use of pharmacokinetic mass as a dosing approximation for fentanyl. Fentanyl dose based on TBW may cause overdosing in obese patients.

Adult↗

PubMed1979

Fentanyl concentrations in brain and serum during respiratory acid--base changes in the dog.

It is a clinical impression that less fentanyl is needed for anesthesia during hyperventilation and hypocarbia. If true, it might be due to both increased penetration of fentanyl, a highly lipid-soluble agent, into the brain and increased brain tissue binding. Serum and brain concentrations of fentanyl were determined in dogs anesthetized with halothane during normocarbia, hypocarbia by hyperventilation, and hypercarbia by addition of CO2 to the inspired mixture. Fentanyl, 12.5 micrograms/kg, was injected iv, and serum and brain samples were taken for fentanyl analysis by radioimmunoassay. Brain fentanyl values peaked latest (15--20 min) and were highest during hypocarbia; brain fentanyl values peaked earliest (0--5 min) and were lowest during hypercarbia; values during normocarbia were intermediate in time to peak (10--15 min) and concentration. Thereafter, brain levels declined, but during hypocarbia were significantly higher and during hypercarbia were significantly lower than during normocarbia. Interestingly, serum fentanyl levels were also significantly higher during hypocarbia. The brain--blood fentanyl ratios for each of the three CO2 levels increased for 30 min and thereafter stayed relatively constant. The brain--blood ratios were highest with hypocarbia and lowest with hypercarbia. At 35 min, when clinical analgesia may be considered terminated, hypocarbic brain levels were double those of normocarbia. The authors feel this reflects, to a large extent, higher serum fentanyl concentrations and delayed cerebral wash-out because of decreased blood flow. To a small but unknown extent the higher brain fentanyl levels result from increased brain--blood penetration due to increased lipid solubility, and increased brain tissue binding of fentanyl during respiratory alkalosis.

Alkalosis, Respiratory↗

PubMed1981

Tissue redistribution of fentanyl and termination of its effects in rats.

The kinetics of fentanyl elimination from plasma suggest its rapid and extensive uptake by tissues. The authors determined the relationships between tissue and plasma concentrations of fentanyl. Six rats injected iv with 3H-fentanyl citrate (50 micrograms/kg) were sacrificed at each of the following times: 1.5, 5, 15, 30, 60, 120, and 240 min after injection. Tissues were analyzed for unchanged 3H-fentanyl citrate and for total 3H-radioactivity. Fentanyl effects were evident 10 s after injection; recovery began at 5 min and was complete within 60 min. Fentanyl concentrations in brain, heart, and lung equilibrated with that in plasma before 1.5 min and declined at the same rate (t 1/2 alpha = 8 min, t 1/2 beta = 45 min). Fentanyl uptake by muscle and fat was slower and equilibration with plasma occurred by 120 min. Muscle accumulated 56 per cent of the dose within 5 min by which time brain fentanyl levels had declined by 90 per cent. Only 6 per cent of the dose was in fat at 5 min but this increased to a maximum of 17 per cent at 30 min. Fentanyl was extensively metabolized; metabolites represented 25 per cent of body 3H-radioactivity at 15 min, and 80 per cent at 4 h. The authors conclude that the short duration of fentanyl effect is due to its rapid redistribution from sites of action in the brain to sites of storage (muscle and fat) and biotransformation (liver). The elimination of fentanyl from the body is governed by its reuptake from storage sites and its metabolism in the liver. Most of the dose is ultimately excreted in the form of fentanyl metabolites in urine.

Adipose Tissue↗

PubMed1995

Pharmacokinetics of inhaled liposome-encapsulated fentanyl.

BACKGROUND: Pulmonary administration of fentanyl solution can provide satisfactory but brief postoperative pain relief. Liposomes are microscopic phospholipid vesicles that can entrap drug molecules. Liposomal delivery of fentanyl has the potential to control the uptake of fentanyl by the lungs and thus provide sustained drug release. To demonstrate that inhalation of a mixture of free and liposome-encapsulated fentanyl can provide a rapid increase and sustained plasma fentanyl concentrations (CfenS), this study determined the pharmacokinetic profiles after the inhalation of free and liposome-encapsulated fentanyl in healthy volunteers. METHODS: After obtaining institutional approval and informed consent, ten healthy volunteers (five men, five women) were studied. Each subject received 200 micrograms intravenous fentanyl and inhaled 2,000 micrograms of free (50%) and liposome-encapsulated fentanyl (50%) on separate occasions. Frequent venous blood samples were collected, and CfenS were determined by radioimmunoassay. The pharmacokinetics and absorption characteristics of the inhaled mixture of free and liposome-encapsulated fentanyl were determined using moment analysis and least-squares numeric deconvolution. RESULTS: The mean (+/- SD) volume of distribution at steady-state and clearance of fentanyl after the intravenous administration were comparable to previous studies: 435 +/- 1821 and 0.584 +/- 0.209 l.min-1, respectively. The mean (+/- SD) peak Cfen was significantly greater for the intravenous administration compared to the aerosol mixture of free and liposome-encapsulated fentanyl (4.67 +/- 1.87 vs. 1.15 +/- 0.36 ng.ml-1). However, CfenS at 8 and 24 h after aerosol administration were greater compared to intravenous (0.25 +/- 0.14 and 0.12 +/- 0.16 ng.ml-1 for aerosol versus 0.16 +/- 0.10 and 0.05 +/- 0.06 ng.ml-1 for intravenous). The peak absorption rate, time to peak absorption, and bioavailability after inhalation were 7.02 (+/- 2.34) micrograms.min, -1(16) (+/- 8.0) min, and 0.12 (+/- 0.11), respectively. CONCLUSIONS: The data suggest that this analgesic method offers a simple and noninvasive route of administration with a rapid increase of Cfen and a prolonged therapeutic fentanyl concentration. Future studies are required to determine the optimal liposome composition that would produce a sustained stable Cfen within analgesic therapeutic concentrations.

Adult↗

PubMed2000

Effect of intravenous versus epidural fentanyl on the minimum local analgesic concentration of epidural bupivacaine in labor.

BACKGROUND: The minimum local analgesic concentration (MLAC) has been defined as the median effective local analgesic concentration (EC50) in a 20-ml volume for epidural analgesia in the first stage of labor. The aim of this study was to determine the relative local anesthetic sparing efficacies of intravenous and epidural fentanyl by comparison of their effects on the MLAC of bupivacaine. METHODS: In this double-blind, randomized, prospective study, 84 parturients at < or = 7-cm cervical dilation who requested epidural analgesia were allocated to one of two groups. After lumbar epidural catheter placement, 20 ml bupivacaine (n = 44) or bupivacaine with 3 microg/ml (60 microg) fentanyl (n = 40) was administered. The plain bupivacaine group then received 60 microg intravenous fentanyl. The bupivacaine-fentanyl group received intravenous saline. The concentration of bupivacaine was determined by the response of the previous patient in that group to a higher or lower concentration using up-down sequential allocation. Analgesic efficacy was assessed using 100-mm visual analog pain scores, with < or = 10 mm within 30 min define as effective. RESULTS: The MLAC of bupivacaine-intravenous fentanyl was 0.064% wt/vol (95% confidence interval, 0.049-0.080), and the MLAC of bupivacaine-epidural fentanyl was 0.034% wt/vol (95% confidence interval, 0.017-0.050). Epidural fentanyl significantly increased the analgesic potency of bupivacaine by a factor of 1.88 (95% confidence interval, 1.09-3.67) compared with intravenous fentanyl. The epidural fentanyl group demonstrated significantly higher dermatomal spread (P = 0.0064) and increased pruritus (P = 0. 01). CONCLUSIONS: Epidural fentanyl significantly reduced the MLAC of bupivacaine when compared with intravenous fentanyl for the parturients in this study. The significantly enhanced local anesthetic sparing, dermatomal level, and pruritus with epidural fentanyl suggest a primarily spinal site of action.

Adult↗

PubMed2000

Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

BACKGROUND: Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. METHODS: In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. RESULTS: In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. CONCLUSIONS: Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during halothane or sevoflurane anesthesia for BMT is associated with diminished postoperative agitation without an increase in vomiting, hypoxemia, or discharge times.

Administration, Intranasal↗

PubMed2002

A comparison of intrathecal fentanyl and sufentanil for labor analgesia.

BACKGROUND: The use of intrathecal opioids for labor analgesia continues to gain popularity, but there are limited data to guide this use. Previously, the authors established the ED50 for 60 min of labor analgesia from intrathecal sufentanil using an up-down sequential allocation study design. The current study first establishes an ED50 for intrathecal fentanyl using this same study design to establish an intrathecal potency ratio for fentanyl and sufentanil and then uses this ratio to compare the efficacy, duration of analgesia, and side effects from comparable doses of intrathecal fentanyl and sufentanil. METHODS: Seventy-five healthy nulliparous women requesting labor analgesia were enrolled in this two-part study. In phase I, 20 women received varying doses of fentanyl to establish an ED50 for 60 min of labor analgesia. In phase II, 55 women were randomized to receive either 36 microg intrathecal fentanyl or 8 microg sufentanil (2 times the ED50s) via a combined spinal-epidural technique and by double-blinded design. Pain relief, side effects, block height, maternal hemodynamics, and fetal heart rate were assessed throughout the study. The duration of spinal analgesia was considered to be the time from injection of study drug to the time of the patient's first request for additional analgesia. RESULTS: The ED50 of intrathecal fentanyl for 60 min of labor analgesia was found to be 18.2 microg, and therefore, the potency ratio of intrathecal sufentanil to intrathecal fentanyl at the ED50 level is 4.4:1. The duration of spinal analgesia was significantly longer from 8 microg intrathecal sufentanil than from 36 microg intrathecal fentanyl (104 +/- 34 vs. 79 +/- 34 min, P = 0.009). Otherwise, patient demographics, maternal hemodynamics, duration of labor, mode of delivery, motor block, subjective leg weakness, pruritus, nausea, pinprick sensory levels, visual analog scale pain scores, fetal bradycardia, and Apgar scores were similar between groups. CONCLUSION: The relative potency of intrathecal sufentanil to fentanyl for labor analgesia is 4.4:1. When using intrathecal opioids alone for early labor analgesia, 8 microg sufentanil produces labor analgesia lasting approximately 25 min longer than from 36 microg fentanyl, without a statistically significant increase in side effects. However, when making a choice between fentanyl and sufentanil, one must consider other important factors, such as the higher cost of sufentanil and the greater risk of dosing error due to the higher potency of sufentanil compared with fentanyl.

Adult↗

PubMedDate not supplied

The efficacy and safety of fentanyl for the management of severe procedural pain in patients with burn injuries.

Fentanyl has been shown to be effective for the management of intense pain of short duration. We have recently used intravenous fentanyl for burn wound procedures because of its rapid onset, high potency, and short duration. In this report, we reviewed our experience with fentanyl in a variety of procedural burn pain settings to develop specific recommendations about its effectiveness and safety for the treatment of pain in patients with burn injuries. The medical records of patients with burn injuries who received fentanyl for wound procedures over a 2-year period were retrospectively reviewed. Patient demographics, the amount of fentanyl administered, the level of analgesia achieved, and the incidence of adverse effects were analyzed. Fifty-five patients who were 9 months to 75 years old with burn wounds (range, 1%-90% of total body surface area) received 148 doses of fentanyl for the treatment of procedural pain. An average of 8.0 +/- 7.0 microg/kg of fentanyl (range, 0.7 to 38.0 microg/kg) was required for the first wound procedure with fentanyl. No correlation between dosage of fentanyl given and either age or percentage of total body surface area burned was observed. Transient respiratory depression was observed in 17 patients (31%). No patient required intubation or additional supplemental oxygen after the conclusion of the procedure. High doses of fentanyl are required to achieve adequate analgesia during some burn wound procedures. Respiratory depression associated with fentanyl use is transient but requires adequate preparation and trained personnel. Fentanyl may be effectively integrated into the pain control strategy for patients with burn injuries.

Adolescent↗

PubMed2001

Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain.

OBJECTIVES: To compare patients' preference for transdermal fentanyl or sustained release oral morphine, their level of pain control, and their quality of life after treatment. DESIGN: Randomised, multicentre, international, open label, crossover trial. SETTING: 35 centres in Belgium, Canada, Denmark, Finland, the United Kingdom, the Netherlands, and South Africa. PARTICIPANTS: 256 patients (aged 26-82 years) with chronic non-cancer pain who had been treated with opioids. MAIN OUTCOME MEASURES: Patients' preference for transdermal fentanyl or sustained release oral morphine, pain control, quality of life, and safety assessments. RESULTS: Of 212 patients, 138 (65%) preferred transdermal fentanyl, whereas 59 (28%) preferred sustained release oral morphine and 15 (7%) expressed no preference. Better pain relief was the main reason for preference for fentanyl given by 35% of patients. More patients considered pain control as being "good" or "very good" with fentanyl than with morphine (35% v 23%, P=0.002). These results were reflected in both patients' and investigators' opinions on the global efficacy of transdermal fentanyl. Patients receiving fentanyl had on average higher quality of life scores than those receiving morphine. The incidence of adverse events was similar in both treatment groups; however, more patients experienced constipation with morphine than with fentanyl (48% v 29%, P<0.001). Overall, 41% of patients experienced mild or moderate cutaneous problems associated with wearing the transdermal fentanyl patch, and more patients withdrew because of adverse events during treatment with fentanyl than with morphine (10% v 5%). However, within the subgroup of patients naive to both fentanyl and morphine, similar numbers of patients withdrew owing to adverse effects (11% v 10%, respectively). CONCLUSION: Transdermal fentanyl was preferred to sustained release oral morphine by patients with chronic non-cancer pain previously treated with opioids. The main reason for preference was better pain relief, achieved with less constipation and an enhanced quality of life.

Administration, Cutaneous↗

PubMed2007

Single-dose and steady-state pharmacokinetics of fentanyl buccal tablet in healthy volunteers.

This study evaluated the single-dose and steady-state pharmacokinetics of fentanyl buccal tablet 400 microg in healthy adult volunteers. After receiving naltrexone 50 mg to block opioid receptor-mediated effects of fentanyl, subjects received fentanyl buccal tablet 400 microg on day 1, then every 6 hours from day 4 to day 9 (21 doses). Naltrexone 50 mg was administered every 12 hours throughout the study. Plasma fentanyl concentrations were determined for 72 hours after administration of fentanyl buccal tablet 400 microg on day 1 and the last dose of fentanyl buccal tablet 400 microg on day 9. Following single- and multiple-dose administration of fentanyl buccal tablet, the median time to maximum concentration (tmax) was 52.2 and 49.8 minutes, respectively. Peak plasma concentration of fentanyl (Cmax) was 0.88 ng/mL for the single-dose regimen and 1.77 ng/mL for the multiple-dose regimen. Steady state was reached within 5 days, consistent with the observed median half-life of approximately 22 hours following multiple doses. Observed accumulation of fentanyl after multiple doses of fentanyl buccal tablet was slightly greater than would be expected based on the single-dose data. This was attributed to the redistribution of fentanyl from a deep tissue compartment into the plasma. This study indicates that fentanyl buccal tablet has predictable pharmacokinetics following multiple-dose administration.

Administration, Buccal↗

PubMedDate not supplied

Transdermal fentanyl combined with nonsteroidal anti-inflammatory drugs for analgesia in horses.

This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum fentanyl concentrations. Pharmacokinetic values were determined by noncompartmental analysis. Physical examination findings were recorded in all horses, and pain and lameness grading systems were used to assign scores to 8 and 6 horses, respectively. All horses tolerated the administration of fentanyl TTS, in that no clinically significant adverse effects attributable to fentanyl were observed. Use of the TTS resulted in variable serum concentrations of fentanyl, with a peak serum concentration of 2.2+/-1.1 ng/mL (mean+/-SD) and a time to peak serum concentration of 26+/-13 hours. After transdermal fentanyl administration, mean time to reach serum fentanyl concentrations consistent with analgesia in other species (1 ng/mL) was 14 hours. In addition, serum fentanyl concentrations of 1 ng/mL or greater were maintained in all but one horse for at least 18 hours. Pain scores were significantly decreased after fentanyl TTS and NSAID administration (P < .05), but lameness scores were not significantly different (P > .05). Overall, administration of fentanyl TTS had a favorable pharmacokinetic profile in horses with clinical pain, and the fentanyl TTS in combination with NSAIDs appeared to provide safe and effective analgesia in most of the horses with pain that was refractory to NSAID therapy alone.

Administration, Cutaneous↗

PubMed2003

Benefit-risk assessment of transdermal fentanyl for the treatment of chronic pain.

Transdermal fentanyl is effective and well tolerated for the treatment of chronic pain caused by malignancy and non-malignant conditions when administered according to the manufacturer's recommendations. Compared with oral opioids, the advantages of transdermal fentanyl include a lower incidence and impact of adverse effects (constipation, nausea and vomiting, and daytime drowsiness), a higher degree of patient satisfaction, improved quality of life, improved convenience and compliance resulting from administration every 72 hours, and decreased use of rescue medication. Transdermal fentanyl is a useful analgesic for cancer patients who are unable to swallow or have gastrointestinal problems. Transdermal fentanyl forms a depot within the upper skin layers before entering the microcirculation. Therapeutic blood levels are attained 12-16 hours after patch application and decrease slowly with a half-life of 16-22 hours following removal. Patients with chronic pain should be titrated to adequate relief with short-acting oral or parenteral opioids prior to the initiation of transdermal fentanyl in order to prevent exacerbations of pain or opioid-related adverse effects. Transdermal fentanyl can then be initiated based on the 24-hour opioid requirement once adequate analgesia has been achieved. The prolonged elimination of transdermal fentanyl can become problematic if patients develop opioid-related adverse effects, especially hypoventilation. Adverse effects do not improve immediately after patch removal and may take many hours to resolve. Patients who experience opioid-related toxicity associated with respiratory depression should be treated immediately with an opioid antagonist such as naloxone and closely monitored for at least 24 hours. Because of the short half-life of naloxone, sequential doses or a continuous infusion of the opioid antagonist may be necessary. Transdermal fentanyl should be administered cautiously to patients with pre-existing conditions such as emphysema that may predispose them to the development of hypoventilation. Transdermal fentanyl is indicated only for patients who require continuous opioid administration for the treatment of chronic pain that cannot be managed with other medications. It is contraindicated in the management of acute and postoperative pain, as pain may decrease more rapidly in these circumstances than fentanyl blood levels can be adjusted, leading to the development of life-threatening hypoventilation. Cognitive and physical impairments such as confusion and abnormal co-ordination can occur with transdermal fentanyl. Therefore, patients should be instructed to refrain from driving or operating machinery immediately following the initiation of transdermal fentanyl, or after any dosage increase. Patients may resume such activities once the absence of these potential adverse effects is documented.

Administration, Cutaneous↗