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PubMed1994

Impaired memory and behavioral performance with fentanyl at low plasma concentrations.

Fentanyl is commonly administered to conscious patients by continuous epidural or intravenous (i.v.) infusions, or by the transdermal route, which result in relatively constant, low, concentrations of the drug. Previous studies of memory and cognitive effects have not been performed at constant plasma concentrations of fentanyl. Based on simulated infusions using the pharmacokinetic modeling program IV-SIM, we administered fentanyl or placebo to nine healthy volunteers (aged 21-45 yr) by continuous i.v. infusion, targeting plasma concentrations of 1, 1.5, and 2.5 ng/mL in succession. A battery of memory and psychomotor tasks was administered at each plasma concentration of fentanyl, and at two points in the recovery phase while drug levels were decreasing. At increasing plasma concentrations of fentanyl, we found the following effects on memory (in comparison with placebo): a progressive decline in verbal learning (P < 0.03); decreased delayed recognition of words presented at different test times (P < 0.02); and decreased spontaneous recall of pictures shown during infusion (P < 0.03). Fentanyl at concentrations above 2.5 ng/mL caused a performance decrement of 15%-30% relative to baseline on all the psychomotor tests administered. Plasma concentrations less than 2.25 ng/mL had negligible effects on performance with the exception of the critical flicker fusion frequency, which decreased by 5 Hz at plasma concentrations between 1.5 and 2.25 ng/mL. Visual analog scale (VAS) measures of mental and physical sedation were significantly affected by fentanyl, but euphoria was not demonstrable. All subjects receiving fentanyl experienced severe nausea and four of six had one or more episodes of emesis (P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Minimum analgesic doses of fentanyl and sufentanil for epidural analgesia in the first stage of labor.

UNLABELLED: In this study, we sought to determine the minimum analgesic doses and relative potencies of fentanyl and sufentanil when they are used as the sole epidural analgesic during the first stage of labor. Nulliparous parturients (n = 66) in spontaneous labor at term gestation and requesting epidural analgesia were enrolled into this prospective, double-blinded, randomized, sequential-allocation study. Each woman received fentanyl or sufentanil diluted with 0.9% wt/vol saline to a volume of 10 mL. The initial dose was arbitrarily chosen to be 125 microg for fentanyl and 25 microg for sufentanil, with subsequent doses being determined by the response of the previous patient (testing interval, 5 microg for fentanyl and 1 microg for sufentanil). Efficacy was accepted if the visual analog score decreased to < or =10 mm on a 100-mm scale within 30 min. The minimum analgesic dose or median effective dose was 21.1 microg (95% confidence interval [CI], 20.2-21.9 microg) for sufentanil and 124.2 microg (95% CI, 118.1-130.6 microg) for fentanyl (P < 0.0001). The sufentanil/fentanyl potency ratio was 5.9 (95% CI, 5.6-6.3). In conclusion, we have established the equivalent doses and relative potencies of fentanyl and sufentanil for epidural analgesia in the first stage of labor. IMPLICATIONS: This study determined the minimum analgesic doses of fentanyl and sufentanil for epidural anesthesia in the first stage of labor. The sufentanil/fentanyl potency ratio was 5.9. This ratio may be used to establish the equivalent doses for fentanyl and sufentanil for epidural analgesia in labor.

Adult↗
PubMed2003

The site of action of epidural fentanyl infusions in the presence of local anesthetics: a minimum local analgesic concentration infusion study in nulliparous labor.

UNLABELLED: We have previously demonstrated that continuous epidural infusions of fentanyl without local anesthetics elicit analgesia by a systemic mechanism. In this study, we examined the hypothesis that, in the presence of epidural bupivacaine, continuous infusions of epidural fentanyl elicit analgesia by a spinal mechanism. Forty-eight nulliparous women in active labor participated in this prospective, randomized, double-blinded study. Women received lumbar epidural analgesia with 20-30 mL bupivacaine 0.125% until pain free. Subjects were then randomized to either IV or epidural (EPI) fentanyl infusion groups. Each infusion delivered fentanyl 30 microg/h. All women received an epidural infusion of bupivacaine at a rate of 20 mL/h, the concentration of which was determined by the response of the previous woman in the same group to the analgesic regimen used. Unlike previous studies that assessed the minimum local analgesic concentration (MLAC) for bolus administration at the initiation of analgesia, this study assessed MLAC(infusion) for the maintenance of analgesia throughout the first stage of labor. MLAC(infusion) was determined using the up-down sequential analysis described by Dixon and Massey. The MLAC(infusion) of epidural bupivacaine was 0.063% (95% confidence interval, 0.058-0.068) and 0.019% (95% confidence interval, 0.000-0.038) in the IV and EPI groups respectively. A continuous infusion of fentanyl was more than three times as potent when administered by the epidural than by the IV route. This marked increase in potency for the epidural route is highly suggestive for a predominantly spinal mechanism of action for infused epidural fentanyl under the conditions of this study. IMPLICATIONS: This study determined the median effective concentration for epidural infusions of bupivacaine during labor analgesia. Coadministered epidural fentanyl infusions were more than three times more potent than IV fentanyl infusions, suggesting a predominantly spinal mechanism of opioid action under these study conditions.

Adolescent↗
PubMed2004

The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial.

UNLABELLED: A noninvasive method of delivery of parenteral opioids for management of acute pain may offer logistic advantages for patients and nursing staff. A patient-controlled transdermal system (PCTS) under development consists of a preprogrammed, self-contained drug-delivery system that uses electrotransport technology (E-TRANS, ALZA Corp, Mountain View, CA) to deliver 40 micro g of fentanyl HCl over 10 min per on-demand dose for patient-controlled analgesia (PCA). In this randomized, double-blinded, placebo-controlled trial we compared the efficacy and safety of on-demand fentanyl HCl PCTS 40 microg against placebo for postoperative pain up to 24 h after major abdominal, orthopedic, or thoracic surgery in 205 patients. The primary efficacy measurement was the percentage of patients withdrawn from the study because of inadequate analgesia after completing at least 3 h of treatment. Secondary efficacy measures included mean pain intensity (using visual analog scales), patient global assessments, and investigator global assessments. Of 189 patients considered evaluable for efficacy, 25% of patients in the fentanyl HCl PCTS 40 microg group withdrew because of inadequate analgesia, compared with 40.4% of the placebo group (P < 0.05). Use of fentanyl HCl PCTS 40 micro g was associated with lower VAS scores and higher mean patient and investigator global assessment scores compared with placebo. No patient experienced clinically relevant respiratory depression. This study showed that a fentanyl HCl PCTS 40 microg for PCA was superior to placebo and well tolerated for the control of moderate to severe postoperative pain for up to 24 h after major surgery. IMPLICATIONS: This multicenter, randomized, double-blinded, placebo-controlled trial showed that an on-demand fentanyl HCl patient-controlled transdermal system (PCTS) was superior to placebo and well tolerated for the control of moderate to severe postoperative pain for up to 24 h after major surgery. This fentanyl HCl PCTS is a preprogrammed, needle free, self-contained drug-delivery system that uses electrotransport technology (iontophoresis) to deliver 40 microg of fentanyl per on-demand dose.

Acute Disease↗
PubMed2004

The pharmacokinetics of the intravenous formulation of fentanyl citrate administered orally in children undergoing general anesthesia.

The bioavailability of oral transmucosal fentanyl citrate (OTFC) in children is similar to that of fentanyl solution administered orally to adults. We hypothesized that administering an oral fentanyl solution to children would result in similar fentanyl plasma concentrations and pharmacokinetic variables as administering comparable doses of OTFC. In this pilot study, 10 healthy children requiring postoperative analgesia were enrolled. Each received the undiluted IV fentanyl formulation orally (approximately 10-15 microg/kg; maximum, 400 microg). Venous blood samples were collected from 15 to 600 min after administration. Pharmacokinetic variables were determined using noncompartmental analysis and were compared with a previously studied population of children who received a similar dose of OTFC. Pharmacokinetic variables for the orally administered IV fentanyl formulation were as follows: time to reach peak concentration = 1.7 +/- 1.6 h, peak concentration = 1.83 +/- 1.19 ng/mL, half-life = 4.7 +/- 2.8 h, area under the plasma concentration time curve = 6.46 +/- 3.96 h . ng(-1) . mL(-1), apparent oral volume of distribution (V/F) = 17.5 +/- 7.2 L/kg, apparent oral clearance (CL/F) = 3.33 +/- 2.25 L . kg(-1) . h(-1). Although both OTFC and orally administered IV fentanyl resulted in similar pharmacokinetic variables and plasma concentrations for a given dose, there was marked interpatient variability, particularly in the early hours after oral administration of the IV formulation of fentanyl. This suggests that this method of administration be used with caution until further data are available.

Administration, Oral↗
PubMed2005

The effect of mild hypothermia on plasma fentanyl concentration and biotransformation in juvenile pigs.

Therapeutic hypothermia may alter the required dosage of analgesics and sedatives, but no data are available on the effects of mild hypothermia on plasma fentanyl concentration during continuous, long-term administration. We therefore assessed in a porcine model the effect of prolonged hypothermia on plasma fentanyl concentration during 33 h of continuous fentanyl administration. Seven female piglets (weight: 11.8 +/- 1.1 kg) were anesthetized by IV fentanyl (15 microg . kg(-1) . h(-1)) and midazolam (1.0 mg . kg(-1) . h(-1)). After preparation and stabilization (12 h), the animals were cooled to a core temperature of 31.6 degrees +/- 0.2 degrees C for 6 h and were then rewarmed and kept normothermic at 37.7 degrees +/- 0.3 degrees C for 6 more hours. Plasma fentanyl concentrations were measured by radioimmunoassay, cardiac index by thermodilution, and blood flows of the kidney, spleen, pancreas, stomach, gut, and hepatic artery by a colored microspheres technique. Furthermore, in an additional 4 pigs, temperature dependency of hepatic microsomal cytochrome P450 3A4 (CYP3A4) was determined in vitro by ethylmorphine N-demethylation. Plasma fentanyl concentration increased by 25% +/- 11% (P < 0.05) during hypothermia and remained increased for at least 6 h after rewarming. Hypothermia reduced the cardiac index (41% +/- 15%, P < 0.05), as well as all organ blood flows except the hepatic artery. A strong temperature dependency of CYP3A4 was found (P < 0.01). Mild hypothermia induced a distribution and/or elimination-dependent increase in plasma fentanyl concentration which remained increased for several hours after rewarming. Consequently, a prolonged increase of the plasma fentanyl concentration should be anticipated for appropriate control of the analgesia/sedatives during and early after therapeutic hypothermia.

Analgesics, Opioid↗
PubMed2005

Epidural fentanyl speeds the onset of sensory and motor blocks during epidural ropivacaine anesthesia.

In this study we examined the onset times of sensory and motor block during epidural ropivacaine anesthesia with and without the addition of fentanyl to the epidural solution. Forty-five young male patients undergoing knee arthroscopic surgery were randomly allocated into 3 groups of 15 patients each: epidural fentanyl (EF; epidural administration of 15 mL of 1% ropivacaine plus 100 mug fentanyl followed by IV injection of 2 mL of normal saline); IV fentanyl (IF; epidural administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline followed by IV injection of 100 mug fentanyl); and control (C; epidural administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline followed by IV injection of 2 mL of normal saline). The sensory and motor blocks were assessed by pinprick and modified Bromage scale, respectively. The hemodynamic changes, postepidural shivering, and side effects of epidural fentanyl were also recorded. There was no difference in the distribution of age, weight, and height among the 3 groups. The onset time of sensory block to the T10 dermatome was significantly more rapid in the EF group (13.0 +/- 3.0 min) than in the IF group (16.2 +/- 3.5 min, P < 0.05) or C group (17.7 +/- 3.6 min, P < 0.05). The onset times of motor block up to Bromage scale 1 and 2 were significantly more rapid in the EF group (11.9 +/- 4.6 and 24.4 +/- 5.9 min) than in the IF group (16.9 +/- 4.7 and 30.8 +/- 5.6 min, P < 0.05) or C group (18.3 +/- 4.9 and 32.7 +/- 5.7 min, P < 0.05). There was no difference in the incidence of shivering among the three groups. Pruritus was observed in three patients of the EF group and one patient of the IF group. No nausea, vomiting, respiratory depression, urinary retention, or hypotension was observed in any patient. We conclude that epidural administration of the mixture of 100 mug fentanyl and 1% ropivacaine solution accelerated the onset of sensory and motor blocks during epidural ropivacaine anesthesia without significant fentanyl-related side effects.

Adult↗
PubMed1998

Continuous fentanyl infusion: use in severe cancer pain.

OBJECTIVE: To describe the use of a continuous fentanyl infusion in an adult cancer patient. CASE SUMMARY: A 66-year-old white woman diagnosed with metastatic pancreatic carcinoma required hospital admission for pain control after receiving five different chemotherapy regimens. Morphine 2 mg/h i.v. was initiated and the dosage was titrated upward to a total of 6613 mg/d by hospital day 16. As hospital supplies of opioids became depleted over a holiday weekend, therapy was changed to a continuous infusion of hydromorphone 70 mg/h on hospital day 17, then changed to a continuous fentanyl infusion beginning with a dosage of 500 micrograms/h. The fentanyl dosage was titrated to 4250 micrograms/h by hospital day 20. She died comfortably on hospital day 22 while receiving this dosage. DISCUSSION: Continuous infusions of opioids, particularly morphine and hydromorphone, are frequently used for control of cancer pain and are safe and effective when administered by this route. Transdermal fentanyl has been shown to effectively manage chronic cancer pain, and use of continuous subcutaneous fentanyl has been reported. However, reports of continuous intravenous fentanyl infusion in the cancer pain literature are limited. Our patient achieved good pain control with a continuous infusion of fentanyl 4250 micrograms/h. CONCLUSIONS: Continuous fentanyl infusion should be considered for the treatment of cancer pain in patients requiring high doses who become refractory to other opioids, when other opioids cause intolerable adverse effects, when patients have a true morphine allergy, or when high-dose requirements threaten to deplete existing stock of alternate opioids.

Aged↗
PubMed2000

Gestational age and birth weight effects on plasma clearance of fentanyl in newborn infants.

OBJECTIVE: To provide a rational basis for the dosage of fentanyl in newborn infants by determining clearance in the first days of life. STUDY DESIGN: A continuous infusion of fentanyl for 2 to 3 days (10. 5 microg/kg over a 1-hour period followed by 1.5 microg/kg/h) was administered to 38 newborn infants who had undergone ventilation (gestational ages 26 to 42 weeks and birth weights 835 to 3550 g). Fentanyl concentrations were measured in arterial blood samples collected at 2, 12, 24, 48, and 60 hours after the start of fentanyl infusion. Fentanyl levels were correlated with a pain score. RESULTS: The mean (+/-SD) steady-state fentanyl concentration of 2.5 (+/-1) ng/mL achieved between 24 and 48 hours of infusion correlated significantly with the concomitant pain score (r = -0.57, P <.01). The clearance, 11.5 (+/-4.0) mL/min/kg, correlated significantly with the gestational age (r = 0.46, P <.01) and birth weight (r = 0. 48, P <.01). CONCLUSIONS: Because plasma fentanyl clearance increases with maturity, gestational age should be taken into account when fentanyl is administered to newborn infants.

Analgesics, Opioid↗
PubMed2003

Propofol requirement for insertion of cuffed oropharyngeal airway versus laryngeal mask airway with and without fentanyl: a dose-finding study.

BACKGROUND: The cuffed oropharyngeal airway (COPA) is a modified Guedel-type oral airway with a cuff at its distal end. The objectives of this prospective, randomized study were to compare the COPA and the laryngeal mask airway (LMA) in terms of propofol requirement with and without fentanyl pretreatment for smooth insertions. METHODS: Seventy-five patients undergoing general anaesthesia were randomly assigned to either a COPA (n=38) or LMA (n=37) group for airway management, and each group was further randomized to a saline-propofol or fentanyl-propofol group for anaesthesia induction. The saline-propofol group received i.v. saline and the fentanyl-propofol group received i.v. fentanyl 1 micro g kg(-1) followed 30 s later by i.v. propofol. Insertion of the device was attempted 90 s after propofol administration without the use of neuromuscular blocking agents or other adjuvants, and the responses of 'movement' or 'no movement' were judged by three observers blinded to the drug dose. Each dose of propofol at which insertion was attempted was predetermined by modification of Dixon's up-and-down method with 0.5 mg kg(-1) as the step size, and 2 mg kg(-1) as an initial dose. RESULTS: Without fentanyl pretreatment, propofol requirement [mean (SD), 95% CI] for COPA placement [2.17 (0.38), 1.77-2.56 mg kg(-1)] was significantly less than for LMA insertion [3.42 (0.26), 3.15-3.69 mg kg(-1), P<0.001]. In contrast, propofol requirements after fentanyl were comparable between the COPA and LMA groups [1.50 (0.42), 1.06-1.94 and 1.42 (0.26), 1.15-1.69 mg kg(-1), respectively], but were less than for the placebo group with both devices (P<0.05). Haemodynamic changes and duration of apnoea were similar with both devices irrespective of fentanyl pretreatment. CONCLUSIONS: Insertion of the COPA can be accomplished with a smaller bolus dose of propofol compared with the LMA, but propofol requirements are similar with both devices after a small dose of fentanyl.

Adolescent↗
PubMedDate not supplied

Fentanyl and lidocaine versus lidocaine for Bier block.

BACKGROUND AND OBJECTIVES: The present study was designed to assess the efficacy of fentanyl combined with dilute lidocaine solution for intravenous regional anesthesia of the arm. METHODS: In ten volunteers, the nondominant arm was exposed to three treatments: 100 mg lidocaine, 42 ml; 100 mg lidocaine plus 100 micrograms fentanyl, 42 ml; and 100 micrograms fentanyl, 42 ml. Each subject was tested on three occasions with three or more days between experiments. Sensory and motor function was tested to determine whether the neural effects of the particular treatments differed. RESULTS: When lidocaine and lidocaine plus fentanyl results were compared, no significant differences were found. However, anesthesia, analgesia, and loss of motor function generally were less complete and slower in onset with the fentanyl alone treatment. Two subjects became nauseated after tourniquet cuff deflation when lidocaine plus fentanyl was tested, as did one subject when fentanyl was tested. CONCLUSION: Results of this and other studies indicate there is no value in adding fentanyl to local anesthetics for intravenous regional anesthesia.

Adult↗
PubMed2004

[Home palliative care--2 case reports: a long-term cancer pain management with transdermal fentanyl].

Transdermal Fentanyl was released in March 2002 in Japan after the acceptance of the insurance under the office of public health. Transdermal therapy is especially effective for patients having difficulty of oral intakes, and for home care cancer patients who suffer from chronic pain only if the therapy is feasible on the long-term basis. We report our cases for long-term cancer pain management with transdermal fentanyl. A total of 52 long-term patients with chronic cancer pain (28 men and 24 women with an average age of 63.5 years, range 46-74 years) were evaluated. The most prevalent cancers were colorectum (n=14), stomach (n=10), breast (n=8), esophagus (n=6), pancreas (n=6), and others. The duration of the transdermal therapy varied from minimum of 2 days to maximum of 630 days. Two patients on this therapy were longer than 500 days. The transdermal therapy was discontinued 2-37 days for 8 patients due to uncontrolled pain relief. Case report 1: A 72-year-old woman suffering from a relapse of pancreatic cancer with chronic back pain experienced a good pain relief after switching from 60 mg/day sustained oral release morphine to 2.5 mg transdermal fentanyl. During the long-term treatment, the transdermal fentanyl dosage had to be increased. Transdermal therapy was continued until the patient's death on day 601. The last fentanyl dosage was 7.5 mg. Transdermal therapy was given 319/601 days at home and 282/601 days in the hospital. Meanwhile, a little rescue suppository morphine was used as an adjuvant during the duration of transdermal therapy. Case report 2: A 73-year-old man suffered a relapse of rectal cancer. He experienced adequate pain relief with 40 mg oral sustained release morphine, but he was switched to 2.5 mg transdermal fentanyl. Transdermal therapy was continued until today on day 630. At present, fentanyl dosage is 20 mg. The patient has been treated at home for 622/630 days. He was hospitalized only once for 8 days because of dehydrations, and has been treated at home. Only a little rescue powder morphine was needed as an adjuvant during the duration of transdermal therapy. In these 2 cases of long-term cancer pain management, transdermal therapy has resulted in good pain reduction and the side effects with transdermal therapy were not noted. Transdermal fentanyl can be recommended for treatment of palliative cancer pain at home.

Administration, Cutaneous↗
PubMed2005

[The optimal dose of fentanyl added to 0.2% ropivacaine for postoperative epidural analgesia after gynecological surgery].

BACKGROUND: Combined administration of local anesthetics and an opioid is frequently used in order to minimize the dose of each drug and to reduce adverse effects. Although fentanyl is commonly administered with local anesthetic, side effects of fentanyl increase in a dose-dependent manner. In this study, we determined the optimal dose of epidural fentanyl after gynecological surgery. METHODS: One hundred and sixteen adult patients scheduled for elective gynecological surgery were divided into 3 groups according to postoperative epidural analgesics; 0.2% ropivacaine (group R), 0.2% ropivacaine with 2 microg x ml(-1) fentanyl (group RF 2), or 0.2% ropivacaine with 5 microg x ml(-1) fentanyl (group RF 5). Each analgesic was infused at 5 ml x hr(-1) for 48 hr. Pain scores , incidence of NSAIDs administration and side effects were recorded for 48 hr after the surgery. RESULTS AND CONCLUSIONS: Ropivacaine alone could not provide sufficient analgesia. Although the addition of 5 microg x ml(-1) fentanyl to 0.2% ropivacaine at a rate of 5 ml x hr(-1) improved postoperative pain, side effects caused by fentanyl increased. Supplementing 2 microg x ml(-1) fentanyl provided sufficient analgesia with the least incidence of side effects.

Adult↗
PubMed2006

Effects of pressure sensitive adhesives and chemical permeation enhancers on the permeability of fentanyl through excised rat skin.

Drug-in-adhesive patches (DIAPs) of fentanyl were formulated using various pressure sensitive adhesives (PSAs) and various chemical permeation enhancers (CPEs). The effects of PSAs and CPEs on skin permeation of fentanyl from DIAPs were evaluated using modified jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that the permeation rate or steady state flux (J(ss)) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak 2054 and Duro-Tak 2516 showed the highest J(ss) of 1.95 microg cm(-2) h(-1) and the lowest J(ss) of 1.43 microg cm(-2) h(-1), respectively. Among the various CPEs used, propylene glycol and polyethylene glycol 400 showed 1.61 and 1.18, the highest and the lowest enhancement ratios (ER) of the skin permeation of fentanyl, respectively. Oleic acid and cetyl alcohol moderately increased the skin permeation of fentanyl. It was also shown that increasing the concentration of CPE led to reduction in the adhesion property of PSA as measured by the 180 degrees peeling strength test. Moreover, it was found that the permeation rate increased as the fentanyl loading increased from 1 to 3%. The skin permeation rate of fentanyl did not increase significantly beyond 3% drug loading. It was concluded that propylene glycol as a CPE and cosolvent in 10% (m/m) with 3% fentanyl loading in Duro-Tak 2054 showed an effective monolithic DIAP for the development of a transdermal therapeutic system for fentanyl.

Administration, Cutaneous↗
PubMed1992

Paradoxical effect of chronic fentanyl treatment on naltrexone-induced supersensitivity and upregulation.

The present study sought to evaluate the influence of chronic opioid antagonist treatment upon the discriminative stimulus and analgesic effects of the opioid receptor agonist fentanyl. Male Wistar rats were trained to discriminate fentanyl (0.04 mg/kg) from saline in a two-lever food reinforced paradigm. After acquisition of the discrimination, they were implanted with osmotic minipumps which delivered either naltrexone (0.07 mg/h) or distilled water, and the sensitivity of discrimination was assessed at various times after pump removal. The influence of chronic naltrexone treatment upon the antinociceptive effects of fentanyl was assessed in drug-naive (control) rats and in rats which had received fentanyl in the same dosage schedule as those in drug discrimination experiments. Chronic infusion of naltrexone for 7 days did not modify the dose-response curve for the fentanyl vs. saline discrimination. Algesiometric tests revealed a significant increase in the antinociceptive effect of fentanyl in control rats after naltrexone treatment. In contrast, such supersensitivity was not observed in rats which had previously received fentanyl injections. Autoradiographic data revealed a naltrexone-induced upregulation of mu opioid receptors in control animals. Paradoxically, this effect was significantly increased in fentanyl-pretreated rats. These data suggest that prior drug experience can affect the development of antagonist-induced supersensitivity to the behavioral actions of opioid agonists. Furthermore, it would appear that after chronic agonist treatment the phenomena of opioid receptor upregulation and functional supersensitivity are dissociated.

Analgesia↗
PubMed1991

[The perimedullary vascular channel does not play a particularly important role in causing respiratory depression after epidural fentanyl].

The authors studied the role of the perimedullary vascular channel on long-lasting respiratory depression after the epidural administration of fentanyl 0.2 mg. At the first step, we compared the blood concentration of fentanyl in the azygos vein after thoracic epidural and that after caudal administration. After thoracic epidural administration, the peak concentration usually occurred at 3 min post-injection and averaged 7.6 +/- 1.6 ng.ml-1. After caudal administration, fentanyl concentrations were always below the limit of detection (1 ng.ml-1) in all patients throughout the course. At the second step, based on the results of the first step, we compared the respiratory effects of thoracic epidural fentanyl with those of caudal fentanyl. Th11-12 epidural fentanyl depressed ventilatory response to CO2 in the same fashion and to the same degree as caudal fentanyl. All these results suggest that the perimedullary vascular channel does not play a particularly important role in causing respiratory depression after epidural fentanyl.

Adult↗
PubMed1990

[Use of fentanyl for anesthesia induction in cesarean section. Pharmacokinetics and pharmacodynamics in mother and child].

A group of 36 patients in the last trimester of pregnancy and scheduled for cesarean section were examined during the induction of standardized general anesthesia (methohexitone 1.5 mg/kg, succinylcholine 1.5 mg/kg). No other inhalation anesthetics than N2O/O2 (50%:50%) were administered. In addition, 18 of the women received 0.005 mg/kg fentanyl prior to intubation. The remaining 18 patients served as a control group. In the study group maternal fentanyl plasma levels were determined 1 min after injection and again at the time of omphalotomy (radioimmunoassay). Immediately after clamping of the umbilical cord the fetal fentanyl plasma levels and the pH, pCO2 and pO2 values in both umbilical vein and artery were measured. The feto-maternal ratio and the fetal uptake were calculated. RESULTS. Maternal fentanyl plasma levels decreased significantly, from 7.84 (3.55-17.24) ng/ml 1 min after injection to 5.92 (2.01-14.15) ng/ml during omphalotomy. The corresponding fentanyl plasma levels in the umbilical vein were 2.08 (0.88-3.42) ng/ml. The feto-maternal ratio was 0.44 (0.08-1.00). The induction-delivery time ranged from 2 to 8 min. There was a significant correlation between umbilical-venous fentanyl concentration and the induction-delivery time: the longer the induction-delivery time the lower the fentanyl concentration in the umbilical vein. The 1-min Apgar score was 8 (5-9), the 5-min Apgar score 9 (8-10) and the 10-min Apgar score 10 (9-10) in neonates born to the fentanyl group. Only the 1-min Apgar score was significantly lower than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Stability of fentanyl citrate in glass and plastic containers and in a patient-controlled delivery system.

This study determined the stability of fentanyl citrate stored in glass or polyvinyl chloride containers and the concentrations of fentanyl citrate delivered by the Janssen on-demand analgesic computer (ODAC) system. Solutions containing 500 micrograms of fentanyl citrate (10 mL) were added to 100-mL three glass containers each of 5% dextrose injection or 0.9% sodium chloride injection and to three 100-mL polyvinyl chloride containers of 5% dextrose injection or 0.9% sodium chloride injection. All containers were stored under usual light conditions and at room temperature. Samples were taken immediately and at 0.25, 0.5, 1, 6, 12, 24, 36, and 48 hours. To determine the concentration of fentanyl delivered via the ODAC system, fentanyl citrate injection 2500 micrograms (50 mL) was added to a 500-mL polyvinyl chloride bag containing 5% dextrose injection. The solution was connected to the ODAC system, and samples of bolus demand doses were collected at various times during a 30-hour period. All the samples were assayed by a stability-indicating gas-liquid chromatographic method. For both glass and plastic containers, the mean +/- S.D. recovery of fentanyl after 48 hours was 98.6 +/- 2.3% when the drug was diluted in 5% dextrose injection and 97 +/- 1.5% when the drug was diluted in 0.9% sodium chloride injection. There was no significant difference between the amount of fentanyl recovered from glass containers and the amount recovered from polyvinyl chloride containers. Nor was there any significant difference between the amount of fentanyl recovered from solutions containing 5% dextrose injection and the amount recovered from solutions containing 0.9% sodium chloride injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Gas↗