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PubMed1992

Fentanyl-prilocaine mixture for intravenous regional anaesthesia in patients undergoing surgery.

The effect of the addition of 0.1 mg or 0.2 mg fentanyl to 40 ml 0.5% prilocaine in intravenous regional anaesthesia of the arm was investigated in 37 patients in a randomised, double-blind study. The characteristics of the sensory and motor block were studied. There was no difference in the speed of onset of analgesia in the groups (mean latency approximately 4 min in each group). However, significantly more patients in the fentanyl 0.2 mg group (7/12) had complete anaesthesia at 15 min than in the fentanyl 0.1 mg group (1/13) and the control group (2/12) (p less than 0.05). There were no differences in the incidence of tourniquet pain immediately before cuff deflation (tourniquet time 45-87 min). After cuff deflation, in those patients who complained of wound pain within 30 min, on average the pain appeared later in the fentanyl 0.2 mg group (six patients, mean 14.3 min) than in the control group (eight patients, mean 9.4 min) (ns). In the fentanyl groups, the incidence of central nervous system side effects was greater than in the control group (fentanyl 0.1 mg 7/13 patients, fentanyl 0.2 mg 6/12 patients, control 1/12 patients) (p less than 0.05). The plasma concentrations of prilocaine after cuff deflation were higher, in a dose-dependent fashion, in the fentanyl groups than in the control group, but the concentrations of prilocaine and fentanyl did not correlate with the symptoms. Postoperative nausea occurred only in the patients who had received fentanyl.

Anesthesia, Conduction↗

PubMed1996

High-dose fentanyl does not suppress interleukin-1 beta-induced increases in plasma ACTH and corticosterone in rats.

BACKGROUND: High-dose fentanyl anesthesia is reported to attenuate the metabolic and endocrinal responses to surgery. Interleukin-1 (IL-1) is one of the key mediators in the immunoneuroendocrine system, and may be involved in the stress responses to surgery. We studied whether high-dose fentanyl may influence the IL-1 beta-induced alterations in plasma ACTH and corticosterone in rats. METHODS: Plasma ACTH, corticosterone, blood pressure, heart rate and acid-base status were determined in either awake or fentanyl-anesthetized animals immediately before and after either phosphate buffered saline or IL-1 beta administration. Fentanyl anesthesia was induced by bolus intravenous injections of fentanyl at 50 micrograms/kg and pancuronium bromide at 0.2 mg/kg, and maintained by continuous administrations of fentanyl at 100 or 200 micrograms.kg-1.h-1 and pancuronium bromide at 0.4 microgram.kg-1.h-1. RESULTS: In awake rats, IL-1 beta at incremental doses of 0.25, 0.5 and 1 microgram/kg increased plasma ACTH in a dose-dependent manner, but heat-inactivated IL-1 beta at 4 micrograms/kg did not influence plasma ACTH. A noxious stimulus with tail clamping for 30 min did not significantly alter plasma ACTH in fentanyl-anesthetized rats. Fentanyl reduced the basal plasma corticosterone, but it did not modulate the increases in plasma ACTH and corticosterone after the administration of IL-1 beta at 1 microgram/kg. Fentanyl moderately increased the basal blood pressure and heart rate, but it moderately attenuated the IL-1 beta-induced elevations of blood pressure and heart rate. IL-1 beta moderately decreased PCO2 in awake animals. CONCLUSIONS: Fentanyl anesthesia, which is able to suppress the endocrine responses to noxious stimuli, does not attenuate the IL-1 beta-mediated activation of the pituitary-adrenal axis in rats.

Adrenocorticotropic Hormone↗

PubMed2004

Effect of transdermally administered fentanyl on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To determine the effect of two doses of fentanyl, administered transdermally, on the minimum alveolar concentration (MAC) of isoflurane in cats. STUDY DESIGN: Prospective, randomized study. ANIMALS: Five healthy, spayed, female cats. METHODS: Each cat was studied thrice with at least 2 weeks between each study. In study 1, the baseline isoflurane MAC was determined in triplicate for each cat. In studies 2 and 3, isoflurane MAC was determined 24 hours after placement of either a 25 or 50 microg hour(-1) fentanyl patch. In each MAC study, cats were instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Twenty-four hours prior to studies 2 and 3, a catheter was placed and secured in the jugular vein and either a 25 or 50 microg hour(-1) fentanyl patch was placed in random order on the left thorax. Blood samples for plasma fentanyl determination were collected prior to patch placement and at regular intervals up to 144 hours. After determination of MAC in studies 2 and 3, naloxone was administered as a bolus dose (0.1 mg kg(-1)) followed by an infusion (1 mg kg(-1) hour(-1)) and MAC redetermined. RESULTS: The baseline isoflurane MAC was 1.51 +/- 0.21% (mean +/- SD). Fentanyl (25 and 50 micro g hour(-1)) administered transdermally significantly reduced MAC to 1.25 +/- 0.26 and 1.22 +/- 0.16%, respectively. These MAC reductions were not significantly different from each other. Isoflurane MAC determined during administration of fentanyl 25 micro g hour(-1) and naloxone (1.44 +/- 0.16%) and fentanyl 50 micro g hour(-1) and naloxone (1.51 +/- 0.19%) was not significantly different from baseline MAC (1.51 +/- 0.21%). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl patches are placed to provide long-lasting analgesia. In order to be effective postoperatively, fentanyl patches must be placed prior to surgery. Plasma fentanyl concentrations achieved intraoperatively decrease the need for potent inhalant anesthetics in cats.

Administration, Cutaneous↗

PubMed2006

Pharmacokinetics of fentanyl after single intravenous injection and constant rate infusion in dogs.

OBJECTIVE: To determine the plasma concentration and define the pharmacokinetic characteristics of fentanyl (10 microg kg(-1)) administered as a single intravenous (IV) injection followed by: (a) no further drug; or (b) a constant rate infusion (CRI) of fentanyl 10 microg kg(-1) hour(-1) lasting 1, 3 or 4 hours in dogs. Animals Fourteen healthy adult beagles (seven males and seven females). EXPERIMENTAL DESIGN: Randomized cross-over design. MATERIALS AND METHODS: Dogs were randomly assigned to four treatment groups. Drugs were administered to each dog in a randomized cross-over design with at least a 14-day washout interval between experiments. All dogs received an IV loading dose of fentanyl (10 microg kg(-1)). One group received no further fentanyl. In others, the loading dose was followed by a CRI of fentanyl (10 microg kg(-1) hour(-1)) for 1, 3 or 4 hours. Blood samples were collected and plasma fentanyl concentrations determined using high-performance liquid chromatography-mass spectrometry. Plasma pharmacokinetic estimates were obtained by plotting plasma concentrations versus time data and by fitting the change in concentration to a pharmacokinetic model, using a purpose-built program written by the Graduate School of Pharmaceutical Sciences (Kyoto University) in Visual Basic (VBA) on Excel (Microsoft Corporation). RESULTS: Plasma fentanyl concentration decreased rapidly after single IV injection: the plasma concentration-time curve best fitted a two-compartment model. Pharmacokinetic variables for IV injection were characterized by a short distribution half-time (t1/2alpha was 4.5 minutes), a relatively long elimination half time (t1/2beta was 45.7 minutes), a large volume of distribution (approximately 5 L kg(-1)) and high total body clearance (77.9 mL minute(-1) kg(-1)). Stable plasma fentanyl levels were obtained in all CRI groups although pharmacokinetic variables were influenced by the duration of administration. CONCLUSIONS AND CLINICAL RELEVANCE: While this study clarified the pharmacokinetic features of rapid IV fentanyl injection and CRI in dogs, the plasma concentration achieving analgesia was not and so further research is needed. Further studies on the effects of other sedatives and/or anaesthetics on fentanyl's disposition are also required as the drug is commonly used with other agents.

Anesthesia, General↗

PubMed1995

Fentanyl remaining in a transdermal system following three days of continuous use.

OBJECTIVE: To determine whether there was a sufficient amount of fentanyl remaining in a patch that had been used continuously for 3 days to warrant establishment of disposal policies to prevent diversion of fentanyl. DESIGN: Nine patches were applied and removed by hospice nurses after 3 days of continuous use on hospice patients with cancer. Patches were analyzed for the remaining fentanyl contents using the Coat-A-Count Fentanyl radioimmunoassay. Five 2.5-mg patches and four 10.0-mg patches were opened, solubilized with methanol, diluted with water, and analyzed in duplicate. An unused 2.5-mg patch also was analyzed as a control and showed a 94% recovery of fentanyl. A methanol blank was negative for fentanyl. MAIN OUTCOME MEASURES: The study determined the amount of fentanyl in milligrams remaining in a used patch. Using pharmacokinetics principles, this quantity was compared with a potential lethal dose of fentanyl. RESULTS: Analysis showed 0.7-1.22 mg remaining in the 2.5-mg patches and 4.46-8.44 mg remaining in the 10.0-mg patches. These numbers represent 28-84.4% of the original contents. Using the pharmacokinetic values of the volume of distribution of 4L/kg and a potential lethal blood concentration of 3.7 micrograms/L, one can calculate the potential lethal dose for a 70-kg person to be 1036 micrograms. This is well within the amount remaining in the patch. This study also demonstrated that a wide patient variability exists in the absorption of fentanyl from the patch. CONCLUSIONS: There is a sufficient amount of fentanyl available for abuse and misuse after 3 days of therapeutic use. Adequate disposal policies currently are not established and need to be implemented.

Administration, Cutaneous↗

PubMed2000

Sedative tolerance accompanies tolerance to the analgesic effects of fentanyl in infant rats.

Iatrogenic tolerance and physical dependence have been documented in human neonates and infants infused with fentanyl or morphine i.v. to maintain continuous analgesia and sedation during extracorporeal membrane oxygenation (ECMO) and mechanical ventilation for the treatment of life-threatening pulmonary diseases. Using postnatal d 17 infant rats, the hypothesis was tested that sedative tolerance accompanies tolerance to fentanyl analgesia in the tail-flick test. Postnatal d 14 infant rats remained naive or received osmotic minipumps infusing saline (1 microL/h) or fentanyl citrate (60 microg x kg(-1) h(-1)). Seventy-two hours later, fentanyl's antinociceptive potency was reduced 3.1-fold in fentanyl-infused rats. Conscious sedation and deep sedation were examined with the cliff-avoidance and the righting-reflex procedures, respectively. Fentanyl-infused infants were tolerant to both the conscious and deep sedative effects of fentanyl. Another hypothesis tested was that very high receptor intrinsic activity opioids are less likely to produce tolerance, or to be cross-tolerant to other opioids. Dihydroetorphine is 5,000 to 10,000 times more potent than morphine. However, fentanyl-infused infant rats were cross-tolerant to the analgesic and sedative effects of dihydroetorphine. Interestingly, dihydroetorphine's analgesic efficacy was significantly reduced to a maximum analgesic efficacy (Emax) value of 40% maximum possible effect (MPE). Another concern was whether fentanyl tolerance would generalize to another class of sedatives, the benzodiazepines. This was especially relevant considering the widespread use of benzodiazepines like midazolam in ECMO and mechanical ventilation. Midazolam elicited no analgesia in the tail-flick test. Furthermore, fentanyl-tolerant rats were not cross-tolerant to the conscious or deep sedative effects of midazolam.

Analgesics, Opioid↗

PubMed1992

Effects of fentanyl on alpha-aminoisobutyric acid transfer across the blood-brain barrier.

The effect of fentanyl on the transfer of small hydrophilic molecules across the blood-brain barrier was studied in rats by measuring the blood-brain transfer coefficient (Ki) and the regional cerebral blood flow (rCBF) and by calculating the capillary permeability-surface area product. In the control group (n = 14), after a femoral artery and vein were catheterized under isoflurane anesthesia, the rats were allowed to remain awake for 1.5 h before measuring Ki (n = 8) using intravenous 14C-alpha-aminoisobutyric acid or rCBF (n = 6) using 14C-iodoantipyrine. In the fentanyl groups, rats were injected with 25 micrograms/kg (low (n = 6) or 100 micrograms/kg (high dose) of fentanyl (n = 14), followed by a continuous infusion at a rate of 50 or 200 micrograms.kg-1.h-1, respectively. Their lungs were mechanically ventilated. The Ki (low dose, n = 6; high dose, n = 8) and rCBF (high dose, n = 6) were measured 1 h after fentanyl infusion. The Ki was lower in 9 of 13 brain regions in the low-dose fentanyl group and in 7 of 13 brain regions in the high-dose fentanyl group than in the control animals. The average value of Ki in all the brain regions was 8.6 +/- 4.6 microL.g-1.min-1 in the control group, 5.2 +/- 2.9 microL.g-1.min-1 in the low-dose fentanyl group, and 5.7 +/- 2.9 microL.g-1.min-1 in the high-dose fentanyl group. High-dose fentanyl did not significantly affect rCBF in any brain region studied. The value of the regional permeability-surface area product was similar to the corresponding regional Ki in the groups studied. In conclusion, fentanyl decreased the transfer of small hydrophilic molecules across the blood-brain barrier, as demonstrated by a decreased Ki and permeability-surface area product, without significant changes in rCBF.

Aminoisobutyric Acids↗

PubMed2004

A study of transdermal fentanyl in cancer pain at Aichi-Cancer Center.

In Japan, transdermal fentanyl (Durotep Patch) was launched in March 2002, and it was regarded as making opioid rotation possible. When changing from morphine to transdermal fentanyl, the efficacy ratio of 1:150 is used in Japan as well as in many other countries. However, the ratio of 1:100 is used in Germany. As a result, a dose increase in transdermal fentanyl is often required to control pain. We studied transdermal fentanyl use in the Aichi Cancer Center (ACC) to investigate the actual conversion ratio and appropriate switching by following up 144 patients (81 men, 63 women) who had received transdermal fentanyl in the ACC from March 19, 2002, to April 30, 2003. Transdermal fentanyl improved pain control in patients who had difficulty in tolerating oral medication or in continuing morphine because of side effects. Regression analysis indicated that the efficacy ratio of oral morphine to transdermal fentanyl was 1:78. As the fentanyl dosage was excessive even in some patients who followed the recommended morphine/fentanyl conversion of 150:1, it is dangerous to use the conversion ratio of 78:1 at first. Morphine side effects were reduced in some patients who changed to transdermal fentanyl, but there was no reduction in those who needed high-dose morphine for rescue analgesia. Therefore it is safe and effective to use low-dose transdermal fentanyl in the beginning and to control pain promptly using rescue morphine based on the present recommended dosage. For opioid rotation, quick-acting opioids other than morphine are expected to be launched in Japan.

Administration, Cutaneous↗

PubMed2000

Antinociceptive activity of the novel fentanyl analogue iso-carfentanil in rats.

A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful antinociceptive drugs. In this study, the newly synthesized fentanyl analogue 3-carbomethoxy fentanyl (iso-carfentanil) was compared to fentanyl for its antinociceptive activity (tail-immersion test) in rats. It was revealed that the introduction of a 3-carbomethoxy group in the piperidine ring of fentanyl skeleton reduced the potency and shortened the duration of action of the parent compound, i.e., fentanyl. The antinociceptive potency of 3-carbomethoxy fentanyl is influenced mainly by the steric factor (voluminosity of the carbomethoxy group and the cis/trans isomerism), while the chemical nature of the group is probably irrelevant. This is in agreement with SAR studies of other 3-substituted fentanyl analogues. In contrast to potency, the duration of action is not affected by cis/trans isomerism. It is assumed that the time course of action of 3-carbomethoxy fentanyl is influenced by the nature of the carbomethoxy group. Since the potency and the duration of action of this novel antinociceptive compound are interesting from the aspect of SAR studies and have potential promise for clinical application, 3-carbomethoxy fentanyl deserves to be extensively evaluated.

Analgesics↗

PubMed2003

The L-arginine/nitric oxide/cyclic-GMP pathway apparently mediates the peripheral antihyperalgesic action of fentanyl in rats.

There are only a few studies on the molecular mechanisms underlying the peripheral antihyperalgesic effect of opioids. The aim of this study was to investigate the molecular bases of the peripheral antihyperalgesic effect of fentanyl in a model of prostaglandin-induced chemical hyperalgesia. Prostaglandin E2 (1.4 nmol) injected into one hind paw of male Wistar rats (200-250 g, N = 6 in each experimental or control group) pretreated with indomethacin (2.5 mg/kg) potentiated the nocifensive response to formalin (1%) injection made 60 min later. Drugs applied locally 30 min after prostaglandin E2 induced the following effects: fentanyl (0.1-1.0 nmol) caused a dose-dependent reversal of the hyperalgesic state, naloxone (2 nmol) co-injected with fentanyl (1 nmol) completely reversed the antihyperalgesic effect, Nomega-nitro-L-arginine (NOARG, 0.05-0.2 mol) in combination with fentanyl (1.0 nmol) caused a dose-dependent inhibition of the antihyperalgesic effect of fentanyl, co-administration of L-arginine (0.5 mol) with NOARG (0.2 mol) plus fentanyl (1.0 nmol) fully restored the antihyperalgesic effect, and the cyclic-GMP phosphodiesterase inhibitor UK-114,542-27 (5-[2-ethoxy-5-(morpholinylacetyl) phenyl]-1,6-dihydro-1-methyl-3-propyl-7H-pyrazolo [4,3-d]-pyrimidin-7-one methanesulfonate monohydrate; 0.5-2.0 mol) potentiated a subeffective dose of fentanyl (0.1 nmol) in a dose-dependent manner. However, UK-114,542-27 (2.0 mol) injected alone did not produce this antihyperalgesic effect. Systemically administered fentanyl (1.0 nmol, sc) did not cause antinociception. Taken together, these results support the view that fentanyl reverses prostaglandin E2-induced hyperalgesia, probably by activating an opioid receptor at the periphery, and furthermore the L-arginine/nitric oxide/cyclic-GMP pathway may mediate this peripheral effect of fentanyl.

Analgesics, Opioid↗

PubMed1999

[Fentanyl reduces the MAC of sevoflurane].

OBJECTIVE: To determine the interaction between fentanyl and sevoflurane following a bolus injection of fentanyl after induction iwth sevoflurane inhalation only. METHODS: Sixty children aged 5-10 years who were diagnosed as having VSD or ASD were randomly allocated into three groups. The first group received sevoflurane in oxygen without any other drugs. The second group received sevoflurane in oxygen with fentanyl 3 ng/kg, and the third group received sevoflurane in oxygen with fentanyl 6 ng/kg. MAC determination, in response to the stimulus of skin incision, was made using the "up-down" method. RESULTS: The MAC of sevoflurane in oxygen was (2.72 +/- 0.08)%. Fentanyl 3 ng/kg bolus injection produced a fentanyl plasma concentration of (0.64 +/- 0.13) microgram/L at skin incision and resulted in a MAC for sevoflurane of (1.03 +/- 0.07)%. Fentanyl 6 ng/kg bolus injection produced a fentanyl plasma concentration of (1.51 +/- 0.18) micrograms/L at skin incision and resulted in a MAC for sevoflurane of (0.64 +/- 0.01)%. By the stimulation of skin incision, the Hr, MAP of group I increased 39%, 29%, compared with group II 14%, 15%, group III 20%, 14%, respectively. These results were significantly different (P < 0.01). CONCLUSION: The MAC of sevoflurane is significantly reduced 20 minutes after a single dose of 3 ng/kg of fentanyl and that increasing the fentanyl dose to 6 ng/kg produces a little further decrease in MAC of sevoflurane.

Anesthesia, Inhalation↗

PubMed2001

Evaluation of fentanyl transdermal patches in rabbits: blood concentrations and physiologic response.

In the study reported here, we sought to evaluate transdermal fentanyl patches for their ability to achieve detectable plasma concentrations with minimal adverse effects in New Zealand White rabbits. Fentanyl patches were applied to the dorsum after removing hair either by clipping or by application of a depilatory agent. Blood samples were collected every 12 h for a total of 96 h (24 h after patch removal) for determination of plasma fentanyl concentration. At those times, rabbits were assessed for changes in body temperature, heart rate, respiratory rate, and body weight. In rabbits with clipped hair, where rapid hair re-growth was not a mitigating factor, mean plasma fentanyl concentration reached a mean (+/- SEM) peak of 1.11 +/- 0.32 ng/ml at 24 h, decreased to 0.77 +/- 0.21 ng/ml at 72 h, and was negligible at 96 h. In rabbits with depilated hair, peak concentration was obtained at 12 h (6.7 +/- 0.57 ng/ml) and decreased gradually to 0.27 +/- 0.06 ng/ml at 72 h. In a second group of fentanyl-treated rabbits in which hair started growing back within 24 h, plasma fentanyl concentration was not detectable. Control and fentanyl-treated rabbits with clipped hair had no effect from the experimental manipulations other than slight loss in body weight. In the depilatory group, two rabbits appeared moderately sedated during the initial 12-h period, and had decreased respiratory rate for 24 h. In conclusion, rabbits tolerate the transdermal fentanyl patch well. Hair regrowth in rabbits may present a complicating factor that impedes dermal absorption of fentanyl. The application of a depilatory agent lead to early and rapid absorption of fentanyl causing undue sedation in some rabbits and lack of sustained plasma concentrations for the desired three-day period.

Administration, Cutaneous↗

PubMed2004

Evaluation of safety and efficacy of transdermal therapeutic system-fentanyl in adult patients with gynecological cancer-related pain.

OBJECTIVES: To assess the analgesic safety and efficacy of Transdermal Therapeutic System (TTS)-fentanyl in the treatment of chronic gynecological cancer-related pain. BACKGROUND: TTS-fentanyl is a Transdermal Therapeutic System, which contains a rate-limiting membrane that provides constant release of fentanyl. TTS-fentanyl can be properly used to control pain. Therefore, this trial was designed to establish the analgesic efficacy and safety of TTS-fentanyl in the treatment of chronic gynecological cancer-related pain. MATERIAL AND METHOD: Thirty patients were recruited into the study. This open study was comprised of two phases. Phase 1: an oral morphine stabilization phase where eligible patients, who took other opioids and/or analgesic drugs, were entered into the stabilization phase and should be converted to oral morphine according to the conversion chart. The patients were then titrated to a stable oral morphine dose. Phase 2: an open TTS-fentanyl treatment phase where the daily dose of oral morphine was switched to TTS-fentanyl according to the conversion chart. The efficacy parameters of pain score were assessed by visual analogue scale (VAS) and global assessments. The safety was evaluated by monitoring the patient's clinical conditions and adverse events. RESULTS: TTS-fentanyl was generally well tolerated. Only one patient was dropped out from the study due to lacking enrollment in the stabilization phase. The most frequent adverse events were mild nausea or vomiting (46%) and constipation (33%). The median pain VAS during TTS-fentanyl treatment was decreased from 8 to 3 and global assessments at the end of the treatment were better than at the start of the treatment. CONCLUSION: The results suggest that TTS-fentanyl is safe and effective in managing chronic gynecological cancer-related pain.

Administration, Cutaneous↗

PubMed2006

[Effects of different doses of fentanyl on the stress response in patients undergoing valve replacement].

OBJECTIVE: To investigate the effects of different doses of fentanyl on the stress response in valve replacement surgery during cardiopulmonary bypass (CPB). METHODS: Thirty ASA II-III adult patients scheduled for cardial valve replacement were randomly divided into 3 groups: Group A (fentanyl 30 microg/kg), Group B (fentanyl 60 microg/kg), and Group C (fentanyl 100 microg/kg). Anesthesia was induced with medazalam 0.1 mg/kg, fentanyl 10 microg/kg and vecuronium 0.1 mg/kg; And were maintained with fentanyl and propofol infusion. Remained dose of fentanyl was used before the CPB. MAP, CVP, HR, P(ET)CO2, SpO2, nasal and rectal temperature were monitored continuously. Blood samples were taken before the operation (T1), before the CPB (T2), 30 min after the aortic declamping (T3), 2 h after the aortic declamping (T4), 24 h (T5) after the operation to determine the plasma levels of glucose, adrenocorticotropic hormone (ACTH), angiotensin II (AT II) and cortisol. RESULTS: Levels of glucose, ACTH, AT II and cortisol after the CPB (T3, T4 and T5) in 3 groups were significantly increased compared with that of T1 (P < 0.05 or P < 0.01). After CPB, at the same time point, among the 3 groups, the levels of the above index of Group A were the most highest, that of Group C were the most lowest. Glucose, ACTH, AT II and cortisol levels at T3 and T4 were significantly lower in Group B and C than those in Group A ( P < 0.05); But there was no significant difference between Group B and C. The duration of stay in the ICU and time of endotracheal extubation were significantly longer in patients of Group C than Group A and B (P < 0.05). CONCLUSION: Fentanyl (30-100 microg/kg) can completely suppress the stress response induced by intubation and intense surgical stimulus before CPB. Different doses of fentanyl seemed to be effective in reducing CPB-induced stress response. But the effect was not dependent on dose. So 60 microg/kg fentanyl seemed to be an ideal dose.

Adrenocorticotropic Hormone↗

PubMed1988

Ventilatory effects of continuous epidural infusion of fentanyl.

The effects of a continuous epidural administration of fentanyl on pain and on ventilation were studied in eight patients scheduled for orthopedic surgery of the knee. In each subject, epidural fentanyl was given by a bolus dose of 1 microgram.kg-1, followed by a continuous infusion of 1 microgram.kg-1.h-1 over 18 hours. Ventilatory measurements were performed during quiet breathing and during CO2 stimulation tests before surgery. After surgery measurements were made before epidural administration of fentanyl; 1, 2, 5, 18 hours after the start of epidural fentanyl infusion; and 6 hours after its discontinuation. Adequate pain relief was achieved in all patients during fentanyl administration. No significant change in ventilation was noted during quiet breathing. The slope of the ventilatory response to CO2 (VE/PaCO2) decreased significantly from 1.46 +/- 0.2 to 0.75 +/- 0.1 L.min-1.mm Hg-1 (mean +/- SEM; P less than 0.05) one hour after the onset of fentanyl administration, and remained stable throughout the infusion. Eighteen hours after the onset of epidural fentanyl infusion, VE/PaCO2 was still 0.76 +/- 0.14 L.min-1.mm Hg-1. At the end of fentanyl administration, plasma fentanyl levels measured in six patients had progressively increased from 0.42 +/- 0.02 ng.ml one hour after the onset of the infusion to 1.54 +/- 0.19 ng.ml at the end of the infusion. These results suggest that a continuous epidural administration of fentanyl is a technique of analgesia that can provide adequate pain relief but which is associated with ventilatory depression. However, with the doses used in this study, the ventilatory depression remained moderate and of no demonstrable clinical consequence.

Adult↗

PubMedDate not supplied

Fentanyl for epidural intravascular test dose in obstetrics.

BACKGROUND AND OBJECTIVES: Although dizziness and drowsiness may be produced with either intravenous or epidural fentanyl, their occurrence after an intravenous injection is more rapid and relatively more pronounced. The purpose of this study was to determine whether or not the difference between routes of administration would be a reliable method of detecting an accidental intravascular injection. METHODS: In part 1, using a double-blinded protocol, we prospectively assessed in laboring women the incidence of dizziness, drowsiness, or both associated with intravenous fentanyl (100 micrograms). In random order, subjects received two peripheral intravenous injections: 2 ml of fentanyl and 2 ml of saline, separated by a 3-minute observation period. RESULTS: In group 1 (18/18) and group 2 (22/22), all subjects reported a response to intravenous fentanyl within the one-minute assessment. In part 2, we evaluated in laboring patients the frequency of dizziness, drowsiness, or both to epidural fentanyl (100 micrograms). The study design was identical to part 1; however, the subjects received 2 ml of fentanyl and 2 ml of saline via a functional epidural catheter. In group 3 (1/18) and group 4 (1/22), one subject reported a response to epidural fentanyl within the 3-minute observation period. CONCLUSIONS: Overall, the responses to intravenous fentanyl (40/40) occurred in a remarkably more consistent fashion when compared to epidural fentanyl (2/40). Thus, the results suggest that in laboring patients, intravenous fentanyl produces predictable and easily detectable changes that may be useful in identifying an epidural catheter unintentionally placed intravascularly.

Analgesia, Epidural↗

PubMed1993

Fentanyl attenuates porcine coronary arterial contraction through M3-muscarinic antagonism.

The "antimuscarinic effect" of fentanyl and its dependence on subtypes of receptors were characterized in isolated porcine coronary arteries. Left anterior descending coronary arteries were dissected from the hearts of 60 adult pigs obtained at a slaughterhouse and prepared for isometric tension studies. The effects of fentanyl on the cumulative concentration-response curve for acetylcholine were obtained in the presence and absence of muscarinic blockade by atropine. Fentanyl shifted the concentration-response curve to the right in a concentration-dependent fashion. Atropine shifted the concentration-response curve to the right, and no further shift was caused by fentanyl. To investigate the dependence on muscarinic receptor subtypes, the effect of fentanyl on acetylcholine-induced contraction was examined in the presence of specific M1-, M2-, and M3-muscarinic antagonists. The pA2 values for fentanyl decreased significantly in the presence of atropine (a nonspecific antagonist) and also in the presence of p-F-HHSiD (an M3-antagonist). In contrast, no significant change of pA2 value for fentanyl was observed in the presence of both pirenzepine (an M1-antagonist) and methoctramine (an M2-antagonist). We conclude that fentanyl has an antimuscarinic effect, and that this antagonism occurs in a competitive manner. Furthermore, the significant decrease of the pA2 value for fentanyl in the presence of M3-, but not in the presence of M1 + M2-antagonists, suggests that the attenuation of cholinergic contraction of porcine coronary arteries by fentanyl is mediated through the M3-muscarinic receptor subtype.

Acetylcholine↗

PubMedDate not supplied

Thoracic versus lumbar administration of fentanyl using patient-controlled epidural after thoracotomy.

BACKGROUND AND OBJECTIVES: Epidural fentanyl injection can provide analgesia following thoracotomy, but where to insert the catheter is a matter of debate. The study compares the effects of thoracic and lumbar patient-controlled epidural fentanyl on analgesia, fentanyl requirements, and plasma levels after thoracotomy. METHODS: Thirty patients were randomized into two groups to receive either thoracic or lumbar patient-controlled epidural fentanyl for postoperative analgesia. Postoperative pain (10 cm, visual analog scale [VAS]) and fentanyl requirements were assessed every 4 hours for 24 hours and at 12-hour intervals for the next day. Fentanyl plasma levels were measured at 8 and 16 hours after surgery. Results were expressed as mean +/- 1 SD and analyzed using Student's t-test, ANOVA, and chi-square analysis at P < .05. RESULTS: Twenty-nine patients completed the study (14 in the lumbar and 15 in the thoracic group). The VAS scores and fentanyl requirements were not significantly different at any time interval in the thoracic group as compared to the lumbar group. VAS scores at 0 hours (4.6) and 4 hours (4.6) in the lumbar group were higher than VAS scores at 12 hours (2.8; P = .04), 16 hours (2.5; P = .02), and 20 hours (2.2; P = .01) in the same group. No significant difference was found between the fentanyl plasma levels of the two groups after 8 hours (lumbar, 0.26 +/- 0.37 ng/mL; thoracic, 0.22 +/- 0.20 ng/mL) or 16 hours (lumbar, 0.36 +/- 0.17 ng/mL; thoracic, 0.44 +/- 0.32 ng/mL). CONCLUSIONS: The authors concluded that there is little if any advantage of thoracic over lumbar patient-controlled epidural fentanyl administration in patients after thoracotomy with respect to analgesia, fentanyl requirements, and plasma levels.

Analgesia, Epidural↗