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PubMed1998

Effect of epidural fentanyl on neonatal respiration.

BACKGROUND: The addition of opioids to epidural infusions for laboring mothers may reintroduce the problem of neonatal depression seen with systemic opioids. The authors studied neonatal respiration and neurobehavior in newborns of mothers randomized to receive epidural analgesia with or without fentanyl. METHODS: One hundred thirty-eight women in labor received loading doses of plain bupivacaine. When pain-free, they received an infusion of either 0.125% bupivacaine alone or 0.0625% bupivacaine with 2.5 microg/ml fentanyl. After delivery, transcutaneous oxygen tension and carbon dioxide tension were recorded in the newborns every 10 s until 90 min after delivery using a transcutaneous oxygen-carbon dioxide monitor. Umbilical venous and arterial acid-base status, Apgar scores, and Neurologic and Adaptive Capacity Scores 2 h and 24 h after delivery were measured. The umbilical venous plasma fentanyl concentration was correlated with indices of neonatal respiration and welfare in the fentanyl group. RESULTS: One hundred fourteen newborns delivered vaginally were studied. In the fentanyl group, the mean (range) maternal dose of fentanyl was 184 microg (range, 53-400), and the umbilical venous fentanyl concentration was 0.077 ng/ml (range, <0.021 to 0.244). There were no significant differences between the groups for any indices of neonatal respiration or neonatal welfare, and the plasma fentanyl concentration did not correlate with any of these indices. CONCLUSIONS: The results suggest that fentanyl added to epidural bupivacaine infusions during labor does not depress neonatal respiration or adversely affect neurobehavioral scores and other indices of neonatal welfare.

Adult↗
PubMed2000

Facilitated uptake of fentanyl, but not alfentanil, by human pulmonary endothelial cells.

BACKGROUND: Extensive pulmonary uptake of lipophilic basic amines, such as fentanyl, attenuates early blood drug concentrations after rapid intravenous administration. The basis of this phenomenon is poorly understood. The authors tested the hypothesis that fentanyl uptake into cultured human lung microvascular endothelial (HMVE-L) cells occurs by facilitated uptake in addition to passive diffusion. The authors compared fentanyl and alfentanil uptake with that of antipyrine, a diffusible marker of pulmonary tissue water. In addition, the authors determined the effect of verapamil, a nonspecific inhibitor of drug transport, and UIC2, a blocking antibody of the P-glycoprotein drug transporter, on the uptake of these drugs. METHODS: Human lung microvascular endothelial cells were incubated, with varying concentrations of antipyrine and fentanyl or alfentanil in the absence or presence of varying verapamil concentrations or of UIC2. Supernatants were collected and cells were rinsed and dissolved. Supernatant and cell-associated antipyrine, fentanyl, and alfentanil concentrations were measured. The data were fit to a model of cellular uptake that allowed for passive diffusion and facilitated uptake. RESULTS: Alfentanil uptake by HMVE-L cells was indistinguishable from that of antipyrine for the concentration ranges studied. In contrast, at low concentrations, fentanyl sequestration into HMVE-L cells was substantially greater than that of antipyrine. Facilitated fentanyl uptake was blocked by verapamil, but not by UIC2, in a concentration-dependent manner. CONCLUSIONS: The differential HMVE-L uptake of fentanyl and alfentanil is consistent with the observed differences in the pulmonary uptake of these drugs. This suggests that specific fentanyl uptake and sequestration by HMVE-L cells may be the mechanisms of its extensive pulmonary uptake.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Low doses of fentanyl block central sensitization in the rat spinal cord in vivo.

BACKGROUND: mu-Opioid receptor agonists are strong analgesics. However, their usefulness for preemptive analgesia is controversial. The authors tested antinociceptive and preemptive properties of fentanyl as a mu-opioid receptor agonist in a model of spinal nociception in vivo. METHODS: C fiber-evoked potentials were recorded in the superficial laminae I-II of the rat lumbar spinal cord with glass microelectrodes in response to electrical stimulation of the sciatic nerve. High-frequency stimulation was applied on the sciatic nerve to induce long-term potentiation of C fiber-evoked field potentials, a form of central sensitization. To test the effect of fentanyl on acute nociception, fentanyl was infused intravenously at increasing doses (6-192 microg.kg(-1).h(-1)). One hour after start of infusion, high-frequency stimulation was applied to evaluate effects of fentanyl on the induction of long-term potentiation. RESULTS: In the absence of fentanyl, high-frequency stimulation potentiated C fiber-evoked field potentials to 149 +/-12% of controls (mean +/-SEM; n = 6) for at least 1 h. Increasing doses of fentanyl led to a significant reduction of C fiber-evoked potentials in a dose-dependent manner. The induction of long-term potentiation was blocked by low doses of fentanyl (infusion 12-48 microg.kg(1).h(-1)). At high doses, fentanyl did not block the induction of long-term potentiation (infusion 96-192 microg.kg(-1).h(-1)). CONCLUSIONS: : Low doses of fentanyl block the synaptic form of central sensitization in the rat spinal cord in vivo, but higher doses do not have this effect.

Animals↗
PubMed2004

Inhibitory effect of fentanyl on acetylcholine-induced relaxation in rat aorta.

BACKGROUND: Previous study has shown that fentanyl attenuates acetylcholine-induced vasorelaxation. The goal of the current in vitro study was to identify the muscarinic receptor subtype that is mainly involved in the fentanyl-induced attenuation of endothelium-dependent relaxation elicited by acetylcholine. METHODS: The effects of fentanyl and muscarinic receptor antagonists on the acetylcholine concentration-response curve were assessed in aortic vascular smooth muscle ring preparations precontracted with phenylephrine. In the rings pretreated independently with pirenzepine, 4-diphenylacetoxyl-N-methylpiperidine methiodide, and naloxone, acetylcholine concentration-response curves were generated in the presence and absence of fentanyl. The effect of fentanyl on the concentration-response curve for calcium ionophore A23187 was assessed. RESULTS: Fentanyl (0.297 x 10 0.785 x 10 m) attenuated acetylcholine-induced vasorelaxation in ring preparations with or without 10 m naloxone. Pirenzepine (10 to 10 m) and 4-diphenylacetoxyl-N-methylpiperidine methiodide (10 to 10 m) produced a parallel rightward shift in the acetylcholine concentration-response curve. The concentrations (-log M) of pirenzepine and 4-diphenylacetoxyl-N-methylpiperidine methiodide necessary to displace the concentration-response curve of an acetylcholine by twofold were estimated to be 6.886 +/- 0.070 and 9.256 +/- 0.087, respectively. Methoctramine, 10 m, did not alter the acetylcholine concentration-response curve. Fentanyl, 0.785 x 10 m, attenuated acetylcholine-induced vasorelaxation in the rings pretreated with 10 m pirenzepine but had no effect on vasorelaxation in the rings pretreated with 10 m 4-diphenylacetoxyl-N-methylpiperidine methiodide. Fentanyl, 0.785 x 10 m, did not significantly alter calcium ionophore A23187-induced vasorelaxation. CONCLUSIONS: These results indicate that fentanyl attenuates acetylcholine-induced vasorelaxation via an inhibitory effect at a level proximal to nitric oxide synthase activation on the pathway involving endothelial M3 muscarinic receptor activation in rat aorta.

Acetylcholine↗
PubMed2005

Fentanyl attenuates alpha1B-adrenoceptor-mediated pulmonary artery contraction.

BACKGROUND: The authors tested the hypothesis that the intravenous anesthetic fentanyl would attenuate the pulmonary vasoconstrictor response to alpha1-adrenoceptor activation. They also investigated the alpha1-adrenoceptor subtypes that could potentially mediate this effect of fentanyl. METHODS: Endothelium-denuded canine pulmonary arterial rings were suspended for isometric tension recording. Dose-response curves for the alpha1-adrenoceptor agonist phenylephrine were generated in the absence and presence of fentanyl. The effects of inhibiting alpha2 (rauwolscine), alpha1 (prazosin), alpha1A (5-methylurapidil), alpha1B (chloroethylclonidine), and alpha1D (BMY 7378) adrenoceptors on phenylephrine contraction were also investigated. Receptor "protection" studies were performed to investigate the specific role of alpha1B adrenoceptors in mediating fentanyl-induced changes in phenylephrine contraction. Finally, competition binding studies were performed in rat-1 fibroblasts stably transfected with human alpha1-adrenoceptor complementary DNAs corresponding to the alpha1A-, alpha1B-, or alpha1D-adrenoceptor subtypes to directly assess whether fentanyl can compete for the alpha1-adrenoceptor activation pocket. RESULTS: Fentanyl attenuated phenylephrine contraction in a dose-dependent fashion. Rauwolscine had no effect on phenylephrine contraction. Phenylephrine contraction was inhibited by prazosin and abolished by chloroethylclonidine but was relatively resistant to inhibition by 5-methylurapidil and BMY 7378. Pretreatment with fentanyl before exposure to chloroethylclonidine increased the maximal contractile response to phenylephrine compared to chloroethylclonidine pretreatment alone. Competition binding studies revealed that fentanyl binds to all three alpha1-adrenoceptor subtypes, with a fivefold greater affinity for the alpha1B-adrenoceptor compared with the alpha1D-adrenoceptor subtype. CONCLUSION: Phenylephrine-induced contraction is primarily mediated by alpha1B-adrenoceptor activation in canine pulmonary artery. Fentanyl attenuates phenylephrine contraction by binding to alpha1B adrenoceptors.

Anesthetics, Intravenous↗
PubMed1999

The clinical outcome of abdominoplasty performed under conscious sedation: increased use of fentanyl correlated with longer stay in outpatient unit.

The objective of this study was to present data supporting the effectiveness of performing mini and full abdominoplasties under conscious sedation with local anesthesia. The authors performed 20 such operations between 1994 and 1996, using a combination of midazolam (Versed) and fentanyl instead of general anesthesia (without an anesthesiologist or nurse anesthetist present). At 5- to 10-minute intervals, the surgeon would order the injection of 1 cc (1 mg/ml) of midazolam and 1 cc (50 microg/ml) of fentanyl. The amount and the interval varied based on the patient's level of sedation. Blood pressure, oxygen saturation, and the patient's response to verbal and physical stimuli were used to assess the sedation level. Average operating time was 147.5 minutes, and mean length of stay in the outpatient recovery room was 235.5 minutes. The average amounts of midazolam and fentanyl used were 9.4 mg (6 to 12.5 mg) and 532 microg (300 to 800 microg), respectively. The average age of patients in this group was 41.7 years (28 to 63 years). Nineteen patients were discharged the same day. There were no surgical complications and no complication related to the sedation (such as respiratory or cardiac compromise). The average follow-up of these patients was 1.2 years (range, 3 to 21 months). Correlation coefficient rates and regression rates were calculated. The longer the procedure, the more midazolam was used intraoperatively (r = 0.5, p = 0.03). However, there was no correlation between the length of the procedure and the amount of fentanyl used. Rather, there was a positive correlation demonstrating that patients who received more fentanyl stayed longer in the outpatient recovery area after surgery (r = 0.6, p < 0.01). The age of the patients and the amount of midazolam did not correlate with how fast they went home from the outpatient area. In conclusion, full and mini abdominoplasties can be performed safely using conscious sedation without compromising patient care or surgical outcome. Second, the survey revealed that patient satisfaction with these procedures performed under conscious sedation was very high. Third, the increased use of fentanyl, not midazolam, resulted in a longer stay in the outpatient unit after surgery. Nausea is a known side effect of narcotic analgesics, and it correlated with a higher dose of fentanyl administration in the patients. The authors are now routinely administering a dose of either droperidol or odansetron (Zofran) preoperatively (both are antiemetics). Previously, the ratio of midazolam and fentanyl injection was 1:1 every 5 to 10 minutes, but now it is 2: 1 to 4: 1 every 5 to 10 minutes (a smaller dose of fentanyl is administered). The conscious sedation technique should be an option for patients and plastic surgeons in academic and community hospital settings if they desire.

Abdomen↗
PubMed1995

Methoctramine, a cardioselective muscarinic cholinergic antagonist, prevents fentanyl-induced bradycardia in the dog.

A controlled study examining the effects of the cardioselective muscarinic cholinergic antagonist methoctramine on fentanyl-induced bradycardia was performed in six dogs. Five doses of methoctramine (6, 10, 20, 30 and 60 micrograms/kg) followed by fentanyl (20 micrograms/kg) were administered randomly on separate days. Fentanyl caused a significant reduction in heart rate from baseline values. Moreover, fentanyl produced a variety of arrhythmogenic actions indicative of vagal hyperactivity, including sinus bradycardia, second-degree atrioventricular block and ventricular and supraventricular escape beats. Administration of methoctramine 5 min before fentanyl injection prevented the bradycardic effects of fentanyl in a dose-dependent manner, with high doses of methoctramine causing sinus tachycardia. Using regression analysis, the dose of methoctramine necessary to prevent fentanyl-induced bradyarrhythmias without causing tachycardia was calculated as 14.4 micrograms/kg. The study confirmed that fentanyl administration in the conscious dog causes profound bradycardia with bradyarrhythmias. The cardioselective muscarinic antagonist agent methoctramine prevented the bradycardic effects of fentanyl.

Analysis of Variance↗
PubMed2005

Relationship between plasma concentrations and analgesia after intravenous fentanyl and disposition after other routes of administration in cats.

Data allowing rational use of analgesics in cats are limited. Pharmacokinetics and pharmacodynamics of fentanyl were studied in cats. Plasma fentanyl concentrations were measured using radioimmunoassay in a crossover study in six cats after 10 microg/kg (i.v.) or by application of fentanyl in pluronic lecithin organogel (PLO) to the inner ear pinna. On a separate occasion thermal thresholds were measured after i.v. fentanyl (10 microg/kg) or saline. Plasma fentanyl concentrations reached 4.7-8.31 ng/mL 2 min after i.v. administration and were undetectable after 95 min. Fentanyl was not detected in plasma at any time after PLO use. Thermal thresholds did not change following saline administration but were increased above baseline from 5 to 110 min after i.v. fentanyl. In this model a plasma concentration of >1.07 ng/mL was required to provide analgesia. Plasma concentrations were measured in additional cats after intranasal or oral dosing (2 microg/kg) and after 30 microg/kg in PLO gel. After oral and nasal dosing, Cmax values were 0.96 and 1.48 ng/mL at 5 and 2 min, respectively. Plasma fentanyl was not detected after application of the higher dose of fentanyl in PLO.

Administration, Cutaneous↗
PubMed1998

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits.

BACKGROUND: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e.g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. METHODS: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 microgram.kg-1 i.v. or midazolam 0.05 mg.kg-1 i.v. on the effects of propofol and fentanyl respectively on PNA were studied. RESULTS: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg.kg-1 i.v. and 32 micrograms.kg-1 i.v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg.kg-1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg.kg-1. The mean ED50s, calculated from dose-response curves, were 5.4 mg.kg-1, 3.9 micrograms.kg-1 and 0.4 mg.kg-1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 microgram.kg-1 i.v. or midazolam 0.05 mg.kg-1 i.v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg.kg-1 and 8 micrograms.kg-1, respectively. CONCLUSION: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.

Action Potentials↗
PubMedDate not supplied

Total intravenous anesthesia in greyhounds: pharmacokinetics of propofol and fentanyl--a preliminary study.

OBJECTIVE: To evaluate concomitant propofol and fentanyl infusions as an anesthetic regime, in Greyhounds. ANIMALS: Eight clinically normal Greyhounds (four male, four female) weighing 25.58 +/- 3.38 kg. DESIGN: Prospective experimental study. METHODS: Dogs were premedicated with acepromazine (0.05 mg/kg) by intramuscular (i.m.) injection. Forty five minutes later anesthesia was induced with a bolus of propofol (4 mg/kg) by intravenous (i.v.) injection and a propofol infusion was begun (time = 0). Five minutes after induction of anesthesia, fentanyl (2 microg/kg) and atropine (40 microg/kg) were administered i.v. and a fentanyl infusion begun. Propofol infusion (0.2 to 0.4 mg/kg/min) lasted for 90 minutes and fentanyl infusion (0.1 to 0.5 microg/kg/min) for 70 minutes. Heart rate, blood pressure, respiratory rate, end-tidal carbon dioxide, body temperature, and depth of anesthesia were recorded. The quality of anesthesia, times to return of spontaneous ventilation, extubation, head lift, and standing were also recorded. Blood samples were collected for propofol and fentanyl analysis at varying times before, during and after anesthesia. RESULTS: Mean heart rate of all dogs varied from 52 to 140 beats/min during the infusion. During the same time period, mean blood pressure ranged from 69 to 100 mm Hg. On clinical assessment, all dogs appeared to be in light surgical anesthesia. Mean times (+/- SEM), after termination of the propofol infusion, to return of spontaneous ventilation, extubation, head lift and standing for all dogs were 26 +/- 7, 30 +/- 7, 59 +/- 12, and 105 +/- 13 minutes, respectively. Five out of eight dogs either whined or paddled their forelimbs in recovery. Whole blood concentration of propofol for all eight dogs ranged from 1.21 to 6.77 microg/mL during the infusion period. Mean residence time (MRTinf) for propofol was 104.7 +/- 6.0 minutes, mean body clearance (Clb) was 53.35 +/- 0.005 mL/kg/min, and volume of distribution at steady state (Vdss) was 3.27 +/- 0.49 L/kg. Plasma concentration of fentanyl for seven dogs during the infusion varied from 1.22 to 4.54 ng/mL. Spontaneous ventilation returned when plasma fentanyl levels were >0.77 and <1.17 ng/mL. MRTinf for fentanyl was 111.3 +/- 5.7 minutes. Mean body clearance was 29.1 +/- 2.2 mL/kg/min and Vdss was 2.21 +/- 0.19 L/kg. CONCLUSION AND CLINICAL RELEVANCE: In Greyhounds which were not undergoing any surgical stimulation, total intravenous anesthesia maintained with propofol and fentanyl infusions induced satisfactory anesthesia, provided atropine was given to counteract bradycardia. Despite some unsatisfactory recoveries the technique is worth investigating further for clinical cases, in this breed and in mixed breed dogs.

Anesthetics, Intravenous↗
PubMed2004

Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia.

Mu-opioid receptor activation increases body temperature and affects cardiovascular function. In the present study, fentanyl was administered intravenously [100 mug/kg (300 nmol/kg) iv] and intracerebroventricularly [3.4 mug (10 nmol) in 10 microl icv] in urethane-chloralose-anesthetized, artificially ventilated rats. Increases in brown adipose tissue (BAT) sympathetic nerve activity (SNA) (peak, +326% of control), BAT temperature (peak, +0.8 degrees C), renal SNA (peak, +146% of control), and heart rate (HR; peak, +32 beats/min) produced by intravenous fentanyl were abolished by premamillary transection of the neuraxis but were mimicked by intracerebroventricular administration of fentanyl, which also increased arterial pressure (AP; peak, +12 mmHg). Pretreatment with the opioid antagonist naloxone (100 nmol in 10 microl icv) eliminated the intracerebroventricular fentanyl-evoked responses. Microinjection of glycine (0.5 M, 60 nl) to inhibit local neurons in the rostral raphe pallidus (RPa) selectively reversed the intracerebroventricular fentanyl-evoked increases in BAT SNA and HR, while the fentanyl-evoked excitation in RSNA, the pressor responses, and the tachycardic responses were reversed by inhibition of neurons in the rostral ventrolateral medulla (RVLM). Prior inhibition of neurons in the dorsomedial hypothalamus eliminated the intracerebroventricular fentanyl-evoked increases in BAT SNA, BAT temperature, and HR, but not those in RSNA or AP. These results indicate that activation of central mu-opioid receptors with fentanyl can elicit BAT thermogenesis and cardiovascular stimulation through excitation of the sympathetic outflows to BAT, kidney, and heart. Activation of neurons in the rostral RPa and RVLM are essential for the increases in BAT thermogenesis and renal sympathoexcitation, respectively, induced by activation of central mu-opioid receptors. BAT thermogenesis could contribute to fentanyl-evoked hyperthermia, particularly in infants where BAT plays a significant role in thermoregulation.

Adipose Tissue, Brown↗
PubMed1989

Effects of fentanyl on carotid sinus baroreflex control of circulation in rabbits.

The effects of intravenous administration of fentanyl on carotid sinus baroreflex control of hemodynamics were investigated in chronically instrumented rabbits. Carotid sinus baroreflex was assessed by bilateral carotid occlusion (BCO), and the responses of mean arterial pressure (MAP), heart rate (HR), mean ascending aortic flow (MAF), and total peripheral resistance (TPR) were obtained. Hemodynamic responses to BCO were examined with cumulative doses of 5, 10, and 15 micrograms/kg of fentanyl. Fentanyl did not affect MAP and TPR but reduced HR and MAF dose dependently. Fentanyl did not attenuate the MAP response to BCO significantly. In contrast, fentanyl significantly attenuated the TPR response from 0.126 +/- 0.003 to 0.104 +/- 0.005 mmHg.min-1.ml-1 and augmented the HR response from 31 +/- 2 to 47 +/- 3 beats/min in the conscious state and at 15 micrograms/kg of fentanyl, respectively. The administration of atropine after the fentanyl attenuated MAP and HR responses to 79.9 and 27.7% of those of 10 micrograms/kg of fentanyl, respectively. We suggest that these dissociated hemodynamic responses reflect the vagotonic and sympatholytic effects of fentanyl on the baroreflex pathways.

Animals↗
PubMed1991

Dose-dependent effects of fentanyl on indomethacin-induced gastric damage.

Whilst developing a rat model for studies of gastric protection, we noticed that the anaesthetic agent 'Hypnorm', containing the opiate fentanyl 0.315 mg/ml and the butyrophenone fluanisone 10 mg/ml, was itself protective against indomethacin-induced damage: unrestrained animals given indomethacin (20 mg/kg) subcutaneously had an ulcer score of 9 +/- 1 mm2, compared with 1 +/- 1 mm2 in animals pre-treated with Hypnorm (0.8 ml/kg) and then given indomethacin (p less than 0.01). Further investigation showed this effect to be due to fentanyl-inhibiting gastric acid secretion: doses of fentanyl (90 and 180 micrograms/kg) which decreased indomethacin-induced damage also caused a rise in intragastric pH from 2.7 +/- 0.6 in controls to 5.1 +/- 0.8 and 5.0 +/- 0.8, respectively. However, the response of fentanyl varied depending on the dose given: fentanyl, 3.6 micrograms/kg did not affect indomethacin-induced damage, 8 +/- 2 vs. 9 +/- 1 mm2; fentanyl, 18 micrograms/kg potentiated damage, 15 +/- 4 mm2 (p less than 0.05), whereas fentanyl, 90 micrograms/kg and 180 micrograms/kg decreased damage, 2 +/- 1 mm2 and 0.1 +/- 0.1 mm2, respectively (p less than 0.01). Neither the butyrophenone haloperidol (8.3 mg/kg) nor the alpha-adrenergic receptor antagonist phenoxybenzamine (3 mg/kg) protected against indomethacin-induced damage. We conclude that fentanyl affects intragastric pH and can both potentiate and protect against indomethacin-induced damage. Furthermore, the potentiation of gastric damage by fentanyl occurred at doses similar to those used for human anesthesia, so clinical studies are suggested.

Animals↗
PubMed1988

Fentanyl pretreatment modifies anaesthetic induction with etomidate.

Haemodynamic changes and side-effects of induction of anaesthesia with etomidate were evaluated in 60 ASA Class I or II patients. The objective was to find an optimal pre-induction dose of fentanyl which eliminated haemodynamic changes and side-effects during induction and intubation without introducing other problems. Patients were randomly assigned to four groups according to the pretreatment dose of fentanyl (Group I = 2 ml normal saline; Group II = 100 micrograms of fentanyl; Group III = 250 micrograms of fentanyl; Group IV = 500 micrograms of fentanyl) administered intravenously five minutes prior to induction of anaesthesia with etomidate, 0.3 mg/kg. There was an increasing incidence of apnoea (53, 87, 87 and 100% in Groups I-IV respectively) and a decreasing incidence of myoclonus (60, 33, 13 and 0% in Groups I-IV respectively) and injection pain (53, 13, 7 and 0% in Groups I-IV respectively), P less than 0.002 chi-square test for linear trends, with increasing fentanyl dosage. The incidences of postoperative nausea and vomiting were similar in the four groups. There were also significant linear regression relationships (P less than 0.01 ANOVA for linear regression) between increasing doses of fentanyl administered before etomidate and the prevention of increases in systolic blood pressure and heart rate during the induction-intubation sequence. The data demonstrate that increasing pre-induction doses of fentanyl are more effective at minimising side-effects and preventing increases in systolic arterial blood pressure and heart rate but also increase the incidence of apnoea during induction. The results suggest that 500 micrograms of fentanyl is an ideal pretreatment dose in fit patients prior to anaesthetic induction with etomidate.

Adult↗
PubMed1997

Rapid loss of fentanyl citrate admixed with fluorouracil in polyvinyl chloride containers.

OBJECTIVE: To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with fentanyl citrate 12.5 micrograms/mL in dextrose 5% and in sodium chloride 0.9% injection. DESIGN: Test solutions of the drugs in dextrose 5% injection and in sodium chloride 0.9% injection were prepared in triplicate and stored at -20, 4, 23, and 32 degrees C. Samples were removed immediately and at various times over 7 days and stored at -70 degrees C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter; particle content was measured with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC. RESULTS: Fentanyl citrate was rapidly lost when admixed with fluorouracil in polyvinyl chloride (PVC) containers, losing about 25% in the first 15 minutes and about 50% in the first hour. The loss of fentanyl citrate was so rapid that accurate time zero determinations were not possible. The extent of fentanyl loss increased with time and occurred more rapidly at the higher temperatures (i.e., 23, 32 degrees C). Losses of 70% or more occurred in all samples within 24 hours. Fentanyl underwent rapid sorption to the containers at the high pH (9.0-9.5) of the fluorouracil admixtures. Adjusting the pH of a fentanyl citrate solution (containing no fluorouracil) in PVC containers to pH 9 with sodium hydroxide also resulted in rapid sorption loss. Fentanyl citrate sorption did not occur when admixtures were prepared in polyethylene containers. Fluorouracil remained stable for at least 7 days at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any time. CONCLUSIONS: When admixed with fluorouracil 1 and 16 mg/mL in dextrose 5% injection and sodium chloride 0.9% injection, fentanyl citrate 12.5 micrograms/mL underwent rapid and extensive loss due to sorption to the PVC containers, making the combination unacceptable within minutes of mixing. The sorption results from the alkaline pH of the admixture and, presumably, could occur from the admixture of fentanyl citrate with any sufficiently alkaline drug.

Analgesics, Opioid↗
PubMed2004

Radiotherapy plus either transdermal fentanyl or paracetamol and codeine for painful bone metastases: a randomised study of pain relief and quality of life.

OBJECTIVE: To compare the effects of providing analgesia with either transdermal fentanyl (TTS-fentanyl) or paracetamol and codeine (P/C) in addition to radiotherapy in patients with metastatic bone pain. METHODS: In a prospective study, 26 patients with radiologically confirmed bony metastases received radiotherapy (R/T). They were randomised to receive either 500 mg paracetamol and 30 mg codeine four times per day (P/C group), or transdermal fentanyl patches delivering 25 microg fentanyl/h (TTS-fentanyl group). Pain was assessed using visual analogue pain ratings (VAS) and the Greek Brief Pain Inventory (G-BPI) questionnaire administered before R/T and after 3 months. RESULTS: Data were available from 24 eligible patients. Use of TTS-fentanyl was associated with significantly superior pain relief. Mean VAS fell from 7.0 to 1.1 with TTS-fentanyl and from 8.3 to 4.3 with P/C, p< 0.01. The TTS-fentanyl group also showed significantly greater improvements of important G-BPI domains including global quality of life, pain, and physical, cognitive, and role functioning, than the P/C group (p< 0.01). Four patients receiving TTS-fentanyl and three receiving P/C reported severe nausea/vomiting. CONCLUSIONS: Transdermal fentanyl combined with R/T was more effective in reducing metastatic bone pain and resulted in greater improvements in quality of life than paracetamol and codeine.

Acetaminophen↗
PubMed2005

The effect of transdermal delivery of fentanyl on activity in growing pigs.

Recently, decreased activity levels have been observed in pigs treated postoperatively with transdermal delivery of fentanyl (TD-fentanyl) after isoflurane anaesthesia. Whether the change in behaviour is related to opioid-induced sedation or to insufficient pain relief remains to be investigated. This study was therefore undertaken to evaluate the effect of TD-fentanyl 50 microg h(-1) on the activity level with and without isoflurane anaesthesia. Eight pigs (25.4 +/- 5.2 kg) were submitted to a cross-over study and given two treatments; 1) fentanyl patch applied after 30 minutes of anaesthesia (treatment A/F) and 2) fentanyl patch without anaesthesia (treatment F). The pigs' behaviour was observed from a video recording instantaneously every 10 minutes for 24 h before treatments and up to 72 h after the patch attachment. Venous blood samples were taken 1, 6, 12, 24, 48 and 72 h after the patch application. The behaviour recordings showed that TD-fentanyl did not produce sedation in any pig. No differences were found between the two treatments in activity level, weight gain or serum fentanyl concentration. This concentration measured after 24 h was 0.27 +/- 0.11 ng ml(-1) and 0.47 +/- 0.40 ng ml(-1) in the A/F and F group, respectively. In conclusion, transdermal delivery of 50 microg h(-1) fentanyl did not cause inactivity in growing pigs. However, the large variations in serum fentanyl concentration indicate that drug absorption from transdermal patches is unpredictable and sometimes deficient.

Administration, Cutaneous↗
PubMed2001

Transdermal fentanyl for pain relief in a paediatric palliative care population.

This multicentre, observational study examined the efficacy of the therapeutic transdermal fentanyl system (TTS-fentanyl) in children requiring opioids for pain in life-threatening disease. Forty-one children receiving oral morphine (median dose 60 mg/day) transferred to transdermal fentanyl (median dose 25 micrograms/h according with the manufacturer's dose conversion guidelines). Twenty-six children completed the 15-day treatment phase, seven died due to disease progression and eight were withdrawn because of adverse events, inadequate analgesia or a change to parenteral opioids. After 15 days, the median fentanyl dose was 75 micrograms/h (range 25-250). No serious adverse events were attributed to fentanyl. There was a trend toward improved side-effects and convenience with fentanyl. Twenty-three of 26 parents (three missing) and 25 of 26 investigators considered transdermal fentanyl to be better than previous treatment. For all records available (at 15 days or on withdrawal if earlier), 75% (27/36) reported that fentanyl treatment was 'good' or 'very good'. The findings suggest that transdermal fentanyl is both effective and acceptable for children and their families.

Administration, Cutaneous↗