Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Fentanyl”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed1997

Evaluation of morphine versus fentanyl for postoperative analgesia after ambulatory surgical procedures.

Adequate postoperative analgesia without side effects is necessary to facilitate same-day discharge of ambulatory patients after ambulatory surgery. This study compared the use of intravenous morphine and fentanyl after painful ambulatory procedures with respect to analgesic efficacy, the incidence of side effects, and impact on the patient's readiness for discharge. Fifty-eight patients undergoing ambulatory surgery were prospectively randomized to receive morphine or fentanyl for postoperative analgesia and studied in double-blind fashion. The drugs were administered in equipotent doses in the postanesthesia care unit (PACU) and were titrated against pain scores until a visual analog score < 40 mm was achieved and the patient was satisfied with the level of analgesia. In the ambulatory surgical unit, oral analgesia was available. Pain scores, amount of analgesia used, the incidence of side-effects (nausea and vomiting, sedation and dizziness), the times to achieve recovery milestones, and fitness for discharge were studied. Equal amounts of morphine and fentanyl were used in the PACU, but pain scores were higher in the fentanyl group in the ambulatory surgical unit. In addition, the fentanyl group required more oral analgesia than the morphine group (69% vs 17%; P < 0.0002). The incidence of in-hospital side effects was similar. However, the morphine group had a more frequent incidence of postdischarge nausea and vomiting than the fentanyl group (59% vs 24%; P < 0.016). There was no significant difference in the duration of stay in the PACU (morphine vs fentanyl, 69 +/- 15 min vs 71 +/- 20 min), the times to achieve recovery milestones, and fitness for discharge (morphine vs fentanyl, 136 +/- 41 min vs 132 +/- 40 min). The short duration of fentanyl was not associated with faster discharge times; most patients required additional analgesia to control pain. Morphine produced a better quality of analgesia but was associated with an increased incidence of nausea and vomiting, the majority of which occurred after discharge.

Adult↗
PubMed2002

Intravenous fentanyl increases natural killer cell cytotoxicity and circulating CD16(+) lymphocytes in humans.

UNLABELLED: Opioids, including fentanyl, are often administered to patients who may be at risk for the consequences of impaired immune function. We performed a clinical study to test the effects of the synthetic opioid fentanyl on human immune function. Participants received an IV fentanyl initial dose of 3 microg/kg followed by a 2-h IV infusion of 1.2 microg x kg(-1) x h(-1). Peripheral blood was drawn before and after fentanyl administration to test for neutrophil phagocytic function, neutrophil antibody-dependent cell cytotoxicity, natural killer cell cytotoxicity, percentage of lymphocyte populations, T-lymphocyte proliferative response, and in vivo antibody response to a pneumococcal vaccine inoculation given at the end of the fentanyl infusion. Fentanyl exposure under the conditions of this study caused a rapid and significant increase in natural killer cell cytotoxicity, which was coincident with an increase in the percentage of CD16(+) and CD8(+) cells in peripheral blood. Fentanyl did not significantly affect any of the other immune measurements. IMPLICATIONS: Many previous studies have suggested that opioid drugs can impair immune resistance in patients who may be at risk for infection. This study suggests that the opioid fentanyl, when given to healthy humans without coexisting diseases, does not suppress immune resistance. On the basis of these results, the use of fentanyl should not be restricted because of concerns that it may suppress immune function.

Adult↗
PubMed2002

The primary action of epidural fentanyl after cesarean delivery is via a spinal mechanism.

UNLABELLED: We tested the hypotheses that the primary mechanism of action of epidural fentanyl after cesarean delivery is spinal and that very small dose epidural bupivacaine with epinephrine enhances this effect. After elective cesarean delivery, 100 parturients were randomized in a double-blinded design to four groups. Group I and II patients received a continuous 12 mL/h epidural infusion of bupivacaine 0.015% with epinephrine 1 microg/mL for 48 h and Groups III and IV received a 12 mL/h saline epidural infusion instead. Fentanyl 20 microg/mL was administered via a patient-controlled analgesia device either into the epidural infusion (Groups I and IV) or IV (Groups II and III). When compared to patients receiving epidural fentanyl, those receiving IV fentanyl required larger mean infused and total dose of fentanyl (P < 0.0001), reported more pain (P < 0.001), and had a more frequent incidence of excessive sedation (P < 0.01), nausea (P < 0.01), and vomiting (P < 0.01). Plasma concentrations of fentanyl were larger for Group II and III than for Groups I and IV (P < 0.001) at 24 and 48 h. Our results support the hypothesis that the primary mechanism of analgesia of epidural fentanyl after cesarean delivery is spinal. Our data also show that the total required dose of epidural, but not IV, fentanyl is reduced by very small dose epidural bupivacaine and epinephrine (Group I versus Group IV, P < 0.02 and Group II vs Group III, not significant). IMPLICATIONS: Fentanyl administered epidurally to parturients after cesarean delivery has a primarily spinal mechanism of action and this effect is enhanced by very small dose epidural bupivacaine and epinephrine.

Anesthesia, Epidural↗
PubMed2002

Fentanyl attenuates the hemodynamic response to endotracheal intubation more than the response to laryngoscopy.

UNLABELLED: We examined the effectiveness of avoiding laryngoscopy in reducing the hemodynamic responses to orotracheal intubation during the induction of anesthesia. One hundred surgical patients who required orotracheal intubation were randomly allocated into four groups. The first and third groups underwent fiberoptic intubation, in which an anesthesiologist inserted the endotracheal tube into the trachea under TV monitoring through a bronchoscope, and the second and fourth groups underwent conventional orotracheal intubation using a rigid laryngoscope. The third and fourth groups were pretreated with 2 microg/kg fentanyl IV immediately before the induction of anesthesia. Blood pressure and heart rate were measured noninvasively. A significant reduction in hemodynamic response was seen in only the group treated with fentanyl and intubated using the fiberoptic technique. Without fentanyl, there was no significant difference in hemodynamic changes between the groups. We conclude that the administration of fentanyl suppresses the hemodynamic responses to endotracheal intubation more than it does to laryngoscopy. There was no significant difference in the hemodynamic responses to orotracheal intubation by fiberscopy and laryngoscopy without fentanyl pretreatment, whereas 2 microg/kg fentanyl significantly reduced the hemodynamic responses in the group intubated by fiberscopy. IMPLICATIONS: We assessed the effectiveness of avoiding laryngoscopy for orotracheal intubation. There was no significant difference in the hemodynamic responses to orotracheal intubation by fiberscopy and laryngoscopy without fentanyl pretreatment, whereas 2 microg/kg fentanyl significantly reduced the hemodynamic responses in the group intubated by fiberscopy. Pretreatment of fentanyl and fiberoptic intubation might be recommended for avoiding hyperdynamic responses.

Adult↗
PubMed1982

The anesthetic potency of fentanyl in terms of its reduction of enflurane MAC.

Infusion rates for fentanyl were calculated to produce stable plasma concentrations at which the ability of fentanyl to reduce enflurane MAC could be studied utilizing the tail clamp method and measurement of end-tidal enflurane. Following the determination of control enflurane MAC in each animal, an infusion of fentanyl was begun. Group 1 received continuous successive infusion rates of 0.05, 0.1, and 0.2 micrograms . kg-1 . min-1 with respective loading doses (given over 20 min) of 15, 15, and 30 micrograms/kg; Group 2 received infusions of 0.2, 0.8, and 3.2 micrograms . kg-1 . min-1 with loading doses of 30, 90, and 270 micrograms/kg, respectively. Group 3 was studied in the same manner except that fentanyl was omitted from the infusion solution. Enflurane MAC was determined at each infusion level and blood samples were analyzed for the concentration of fentanyl. Fentanyl concentrations in plasma were proportional to the infusion rate. Enflurane MAC was decreased significantly in proportion to fentanyl plasma concentrations up to 30 ng/ml where a reduction of MAC by 65% was evident. A threefold higher concentration produced a minimal further reduction. In Group 3 dogs, no change in enflurane MAC was seen. It was concluded that predictable, stable levels of fentanyl in plasma can be achieved, that there is a close relationship between the concentration of fentanyl in plasma and its enflurane sparing effect, and that there is a ceiling to this concentration-response relationship.

Anesthesia, General↗
PubMed1983

Dose-independent pharmacokinetics of fentanyl.

Fentanyl is used as an analgesic in small doses (1-2 micrograms X kg-1) and as an anesthetic in very large doses (greater than 150 micrograms X kg-1). It has been demonstrated that the effects of fentanyl correlate with its concentrations in plasma. It is important, therefore, to know whether or not the pharmacokinetics of fentanyl vary with dose size in order to predict the plasma concentrations and effects produced by various dosage regiments. The authors studied the pharmacokinetics of fentanyl in dogs. 3H-fentanyl (2.5-640 micrograms X kg-1) was injected intravenously in dogs anesthetized at a stable level with enflurane-O2. Arterial plasma and urine were analyzed for unchanged 3H-fentanyl. Kinetic indices were derived by nonlinear least-squares analysis of log concentration of fentanyl in plasma (ng X ml-1) versus time after a bolus injection. The terminal elimination half-time (t 1/2 beta = 211 min), the apparent volume of distribution (9.5 l X kg-1), the volume of the central compartment (1.14 l X kg-1), and the clearance (37 ml X kg-1 X min-1) of fentanyl were independent of dose over the 6.4-640 micrograms X kg-1 dose range. The distribution volume and distribution half-times were lower for the 2.5 micrograms X kg-1 than for some of the larger doses; this was attributed to differences in experimental conditions. The authors conclude that the pharmacokinetics of fentanyl are dose independent certainly over the 6.4-640 micrograms X kg-1 dose range. There is no evidence of saturation of biotransformation or tissue uptake mechanisms for doses in the range of 2.5 to 640 micrograms X kg-1.

Animals↗
PubMed1985

Cardiovascular and pharmacodynamic effects of high-dose fentanyl in newborn piglets.

To understand better the hemodynamic effects of fentanyl anesthesia on the developing newborn, the authors studied the changes in cardiac output and its four determinants (preload, afterload, heart rate, and contractility) and plasma fentanyl kinetics in newborn piglets following the administration of high-dose fentanyl with or without atropine premedication. Twenty-five healthy farm piglets were divided into four groups. Hemodynamic studies were conducted on five who received 50 micrograms/kg intravenous fentanyl, five controls who received only 0.01-0.03 mg/kg intravenous atropine, and nine who received both agents. Fentanyl pharmacokinetics were determined by radioimmunoassay in six additional piglets. Mean plasma fentanyl concentrations were 25.4, 12.7, and 7.9 ng/ml at 5, 15, and 30 min postbolus, respectively, with an elimination phase half-life of 35.8 min. In piglets given fentanyl alone, the maximum significant (P less than 0.05) hemodynamic changes from baseline occurred at 5 min: mean aortic pressure (MAP) +42%, cardiac output -42%, heart rate -36%, left ventricular end-diastolic pressure +81%, and total peripheral resistance index +93%. The latter four hemodynamic variables were highly correlated with the logarithm of the plasma fentanyl concentration (R2 greater than 0.96, P less than or equal to 0.05). In control animals given atropine alone, only MAP changed significantly (+12-14%) during the study. Contractile indices (echocardiographic shortening fraction and left ventricular peak dP/dT) did not change significantly in any group. Piglets given fentanyl-atropine had no significant hemodynamic change during the study other than a 7-15% increase in MAP.

Anesthesia, Intravenous↗
PubMed1986

Epidural injections of bupivacaine, morphine, fentanyl, lofentanil, and DADL in chronically implanted rats: a pharmacologic and pathologic study.

A new technique of epidural catheterization in rats is described. The pharmacologic characterizations of the model were established after epidural injection of bupivacaine, morphine, fentanyl, lofentanil, and D-Ala2-D-Leu5-enkephalin (DADL) on hot plate (HP) and tail flick (TF). In addition, rostral spread, motor function, behavior, and reproducibility of the effects over time were assessed. The time-response curves showed an almost immediate onset of action for bupivacaine, fentanyl, and lofentanil and a delayed onset for morphine and DADL. Morphine and lofentanil displayed a significantly longer duration of action than bupivacaine, fentanyl, and DADL. The dose-response curves were monotonic and the slopes were log-linear. Based on the ED50 values, the following rank order of potency was obtained 1 day after catheterization for both HP and TF: lofentanil much greater than fentanyl greater than morphine much greater than DADL greater than bupivacaine. Intraperitoneal (IP) administration of naloxone antagonizes the agonist effects of epidural morphine, fentanyl, and lofentanil. To assess the role in analgesia played by epidural vascular uptake after epidural administration of morphine, fentanyl, and lofentanil, the lowest maximally effective epidural dose of these agents was given intravenously. After iv fentanyl and lofentanil, the analgesic and behavioral effects were not different from the values obtained after epidural administration. By contrast, the effects were negligible after iv morphine when compared with the epidural route. Epidural vascular uptake is thought to be low for morphine and high for fentanyl and lofentanil. The reproducibility of the analgesic and behavioral effects over time was assessed by epidurally injecting the lowest maximally effective dose of bupivacaine, morphine, fentanyl, and lofentanil 1 day and 10 days after catheterization. After 10 days, a significant reduction of analgesic and behavioral effects was noted and was thought to be due to a complete fibrotic sheath surrounding the epidural catheter.

Analgesia↗
PubMed1988

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. VI. Verapamil and fentanyl-pancuronium.

To assess the interaction between verapamil and fentanyl-pancuronium, dogs were chronically instrumented to measure heart rate; PR interval; aortic, left ventricular, and left atrial pressures; and coronary, carotid, and renal blood flows. The effect of fentanyl citrate infusion on single-dose verapamil pharmacokinetics was examined in six animals. The effects of verapamil infusion (3 micrograms.kg-1.min-1 and 6 micrograms.kg-1.min-1) were examined in the conscious state and during fentanyl infusion plus pancuronium on two separate occasions in nine dogs. In addition, the effects of fentanyl citrate (500 micrograms.kg-1 followed by 1.5 micrograms.kg-1.min-1) were examined over 1 h of infusion. Fentanyl infusion did not affect single-dose verapamil pharmacokinetics. In the conscious animals, verapamil increased heart rate and PR interval, and slightly decreased LV dP/dt. Fentanyl combined with pancuronium increased mean arterial pressure and LV dP/dt. During fentanyl infusion, verapamil decreased mean arterial pressure and LV dP/dt, increased PR interval, and did not change heart rate. The hemodynamic effects of fentanyl infusion were steady over 1 h. In contrast to the inhalational anesthetics, which alter verapamil pharmacokinetics and have mainly additive effects with verapamil on left ventricular contractility, cardiac conduction, and regional blood flows, fentanyl-pancuronium had no effect on verapamil pharmacokinetics and minimal effect on verapamil pharmacodynamics in healthy dogs.

Animals↗
PubMed1988

Fentanyl suppression of nociceptive neurons in the superficial dorsal horn of the cat.

This study was designed to examine the influence of spinally administered fentanyl on the spontaneous and noxiously evoked activity of high threshold (HT) and wide dynamic range (WDR) neurons in the superficial layers (lamina I and II) of the dorsal horn of cats made decerebrate and in which the spinal cord had been transected. Single unit activity was recorded using extracellular microelectrode recording techniques. Neuronal activity was evoked by the presentation of noxious radiant heat (51 degrees C) to the cells' receptive fields on the hind paws. Evoked activity of WDR neurons was monitored, both before and after the spinal administration of either 10 micrograms (n = 9) or 25 micrograms (n = 10) of fentanyl. HT neurons were examined before and after either 25 micrograms (n = 7) or 50 micrograms (n = 7) of spinally administered fentanyl. In all cases 31 min after fentanyl administration naloxone (0.1 mg) was administered intravenously (iv), and its antagonistic effect on the fentanyl suppression was determined. All doses of fentanyl tested suppressed both spontaneous and evoked activity of both types of neurons. Within 30 minutes 10 and 25 micrograms of fentanyl reduced the mean evoked activity of WDR neurons to 61% and 19% of control values, respectively, and 25 and 50 micrograms of fentanyl reduced the mean evoked activity of HT neurons to 70% and 47% of control values, respectively. Naloxone reversed the suppression seen in all cells studied. The results of the present study demonstrate that HT neurons are significantly less suppressed by the spinal administration of fentanyl than WDR neurons located in the same superficial layers of the dorsal horn.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Fentanyl is devoid of major effects on coronary vasoreactivity and myocardial metabolism in experimental animals.

Experiments were designed to determine the effects of fentanyl on coronary vascular tone and energetic state of the heart. Both arterial and arteriolar responses were assessed; particular attention was directed to epicardial vessels. Four experimental methods and three animal species were used. Isolated canine coronary artery rings with and without endothelium were suspended in organ chambers, and changes in their tension were measured. Fentanyl (100 ng/ml) had no effect on resting tension of unstimulated rings on a contraction evoked by serotonin 10(-8) to 10(-4) M. In rings with endothelium, the opioid had a minimal depressant effect on the contractile response to phenylephrine. Tension of vessels precontracted with serotonin (3 x 10(-7) M), or phenylephrine (10(-5) M) was unchanged following fentanyl at 10, 30, 70, or 150 ng/ml. Computerized quantitative angiography was used in intact pigs anesthetized with ketamine to determine the effects of fentanyl on coronary artery diameters of vessels with or without endothelium. Intravenous fentanyl 50 and 250 micrograms/kg had no effect on vessel diameters. Isolated perfused rat hearts were used to assess fentanyl effects upon coronary flow and arteriolar tone and upon myocardial energy state. Coronary blood flow was not altered by fentanyl (100 ng/ml) and was unchanged following washout of the drug. The heart maintained a normal energy status prior to and following fentanyl treatment. These data demonstrate that, under the conditions tested, fentanyl is devoid of major effects on the coronary circulation and upon myocardial metabolism.

Animals↗
PubMed1990

Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation.

We undertook a retrospective chart review of 37 neonates who received fentanyl by continuous infusion while undergoing extracorporeal membrane oxygenation (ECMO) between May 1986 and October 1988. We quantified the doses of all sedatives utilized, determined the incidence of neonatal abstinence syndrome (NAS), and identified risk factors associated with NAS. We determined peak fentanyl infusion rate, mean fentanyl infusion rate, total fentanyl dose, and duration of ECMO therapy. NAS was observed in 21 of 37 neonates (57%). In both the NAS and non-NAS neonates, mean infusion rate increased steadily during ECMO therapy, from a mean of 11.6 +/- 6.9 (SD) micrograms.kg-1.h-1 on day 1 to a mean of 52.5 +/- 19.4 (SD) micrograms.kg-1.h-1 by day 8. Total fentanyl dose and duration of ECMO were significantly greater in neonates with NAS. We found that neonates with a total dose greater than 1.6 mg/kg or an ECMO duration greater than 5 days had a significantly greater incidence of NAS (chi-squared test, P less than 0.01 and P less than 0.005; odds ratios = 7.0 and 13.9, respectively). With multiple logistic regression, ECMO duration was found to be the most powerful predictor of the occurrence of NAS. We also measured plasma fentanyl concentrations in a separate group of 5 neonates receiving fentanyl by continuous infusion for sedation. Fentanyl concentrations increased steadily during the period of infusion, suggesting the development of tolerance to the sedating effects. We conclude that continuous administration of fentanyl for sedation is associated with the uniform development of tolerance and a significant incidence of dependence. Alternative approaches to sedation should be investigated.

Drug Tolerance↗
PubMed1991

Absorption and bioavailability of oral transmucosal fentanyl citrate.

Oral transmucosal fentanyl citrate (OTFC) is a novel, noninvasive dosage form of fentanyl used to provide children and adults with sedation, anxiolysis, and analgesia. In order to determine the bioavailability and absorption of fentanyl from OTFC, 12 volunteers were given intravenous fentanyl citrate or OTFC 15 micrograms/kg on each of two occasions. On a third occasion, the authors assessed oral administration (gastrointestinal absorption) by giving eight of the same volunteers the same dose of a solution of fentanyl citrate to swallow. In each study, arterial blood samples were taken over 24 h for analysis of plasma fentanyl. After intravenous (iv) administration of fentanyl, clearance (mean +/- standard deviation) was 0.67 +/- 0.15 l/min; volume of distribution at steady state was 287 +/- 79 l; and the terminal elimination half-life was 425 +/- 102 min. Peak plasma concentrations of fentanyl were higher (3.0 +/- 1.0 vs. 1.6 +/- 0.6 ng/ml, P = 0.01) and occurred sooner (22 +/- 2.5 vs. 101 +/- 48.8 min, P = 0.003) after OTFC than after oral solution administration. Plasma concentrations of fentanyl after OTFC decreased rapidly, to less than 1.0 ng/ml within 75-135 min after the beginning of administration. Peak absorption rate was greater (11.1 +/- 4.3 vs. 3.6 +/- 2.1 micrograms/min, P = 0.004) and occurred much sooner after OTFC than after oral solution administration (19 +/- 2.6 vs. 87.5 +/- 38.1 min, P = 0.001). Systemic bioavailability was greater after OTFC administration than after the oral solution (0.52 +/- 0.1 vs. 0.32 +/- 0.1, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Fentanyl-induced rigidity and unconsciousness in human volunteers. Incidence, duration, and plasma concentrations.

BACKGROUND: Muscle rigidity frequently accompanies induction of anesthesia with opioids. The authors sought to determine whether unconsciousness and amnesia occur when humans develop rigidity and apnea after intravenous fentanyl (without other concomitant anesthetics). METHODS: The incidence and duration of rigidity and level of consciousness were evaluated and associated plasma concentrations of fentanyl were measured in 12 healthy adult male volunteers given only intravenous fentanyl. Fentanyl was infused at a rate of 150 micrograms/min until a total of 15 micrograms/kg had been administered. Arterial blood samples for fentanyl assay were drawn and responsiveness, heart rate (HR), and systolic and diastolic arterial blood pressures were determined at frequent intervals during and after infusion. If rigidity was accompanied by an Spo2 < 90%, positive pressure ventilation with 100% O2 with a mask was instituted until spontaneous ventilation resumed. RESULTS: The incidence of muscular rigidity was 50% (6/12). All subjects who developed rigidity were apneic, unresponsive, and had no recall of commands to breathe or of positive pressure ventilation. Subjects not developing rigidity remained awake and responsive. No subject developing rigidity required neuromuscular blockade to allow positive pressure ventilation and adequate oxygenation (Spo2 > 90%). When rigidity occurred, it started 3 +/- 0.9 (range 1-4) min after the peak plasma fentanyl concentration and lasted for 11.5 +/- 5.8 (range 7-23) min. Rigidity started at a plasma fentanyl concentration of 21.5 +/- 4.4 (range 16-28) ng/ml and ended at 6.9 +/- 1.5 (range 5.2-8.7) ng/ml. Baseline HR was less in the subjects who subsequently developed rigidity (56.7 +/- 7.8 vs. 67.2 +/- 7.8 P = 0.04). No differences in fentanyl plasma concentrations or predicted effect site concentrations for rigidity were detected between subjects who developed rigidity and those who did not. CONCLUSIONS: These findings support the hypothesis that unconsciousness occurs in the unstimulated subject during fentanyl-induced apnea and rigidity.

Adult↗
PubMed1993

Plasma concentration of fentanyl, with 70% nitrous oxide, to prevent movement at skin incision.

BACKGROUND: The Cp50 (minimal steady state plasma concentration of an intravenous analgesic/anesthetic required to prevent a somatic response in 50% of patients following skin incision) and the Cp50-BAR (minimal plasma concentration of an analgesic/anesthetic required to prevent either a somatic, hemodynamic, or autonomic response in 50% of patients following skin incision) have been recently proposed as a measure, like minimum alveolar concentration (MAC; and MAC-BAR), to establish the relative potency of intravenous analgesics. This study was conducted to establish the Cp50 for fentanyl. METHODS: Unpremedicated patients were administered fentanyl (in the presence of 70% N2O) via computer-assisted continuous infusion, a pharmacokinetic model-driven infusion device. After induction of anesthesia with fentanyl, the randomized target fentanyl concentration was entered into computer-assisted continuous infusion. This target fentanyl concentration was maintained until skin incision. Before induction, prior to skin incision, and immediately after skin incision, arterial blood samples were obtained for measurement of fentanyl and norepinephrine concentrations. At skin incision, patients were observed for a somatic, hemodynamic, or autonomic response. Only patients in whom the pre- and postincision fentanyl concentrations were within +/- 30% were included in the calculation of the Cp50. The Cp50 was calculated using logistic regression. RESULTS: The Cp50 for fentanyl was 3.26 ng/ml, and the Cp50-BAR was 4.17 ng/ml. CONCLUSIONS: Comparing these results with the previously published Cp50 of alfentanil, the potency of fentanyl relative to alfentanil is 1:58. Establishing the Cp50, once effect site equilibration has occurred, will allow pharmacodynamic comparisons between the opioids at equipotent concentrations.

Adult↗
PubMed1994

Radicular artery blood flow does not redistribute fentanyl from the epidural space to the spinal cord.

BACKGROUND: Epidural opioids must redistribute to the spinal cord to produce analgesia. It has been suggested that opioids may reach the spinal cord via the radicular arterial blood supply. This study was designed to test this hypothesis. METHODS: Microdialysis probes were placed in the lumbar and thoracic spinal cord of six anesthetized pigs and a ligature placed around the thoracic aorta. At t = 0, fentanyl (300 micrograms) was injected into the epidural space and the spinal cord and plasma were sampled over 90 min to determine resultant spinal cord dialysate fentanyl concentrations. At t = 90, the thoracic aorta was occluded to eliminate distal radicular artery blood flow and fentanyl was again injected into the epidural space. The spinal cord was sampled for an additional 90 min to determine spinal cord dialysate fentanyl concentrations. At t = 90 min the aortic cross-clamp was released and spinal cord samples were collected for another 30 min. RESULTS: There was no difference in lumbar spinal cord dialysate concentrations of fentanyl between the control and cross-clamp conditions over the first 20 min after epidural administration. Between 20 and 90 min, lumbar spinal cord fentanyl concentrations were significantly greater during aortic cross-clamp. Fentanyl was not detected in the thoracic cord. CONCLUSIONS: Radicular artery blood supply does not redistribute fentanyl from the epidural space to the spinal cord in this model. However, radicular artery blood flow does play a role in clearing fentanyl from the spinal cord.

Animals↗
PubMed1995

Effects of fentanyl on sympathetic activation associated with the administration of desflurane.

BACKGROUND: Activation of the sympathetic nervous system occurs when desflurane is inspired shortly after anesthetic induction and when the inspired concentration of desflurane is rapidly increased during steady-state periods of anesthesia. The purpose of this study was to determine the effectiveness and dose response of fentanyl pretreatment in attenuating the neurocirculatory responses to desflurane in healthy human volunteers. METHODS: After Institutional Research Review Board approval, three study groups were selected and, in random order, received either placebo (n = 10), a 2.5-micrograms.kg-1 intravenous bolus of fentanyl citrate followed by a continuous infusion of 1 microgram.kg-1.h-1 (n = 9), or a 5.0-micrograms.kg-1 intravenous bolus followed by an infusion of 2 micrograms.kg-1.h-1 (n = 11) before the administration of desflurane. Arterial (MAP) and central venous (CVP) pressures were measured directly, and heart rate (HR) was determined indirectly. Efferent muscle sympathetic nerve activity (SNA) was recorded from the peroneal nerve by microneurography. After neurocirculatory recordings at conscious unmedicated baseline and 12 min after fentanyl administration, anesthetic induction was carried out with 2.0 mg.kg-1 propofol and 0.2 mg.kg-1 vecuronium. Neurocirculatory measurements were repeated beginning 2 min after induction when desflurane was given via mask (semiclosed circle system, 61/min fresh gas flow, 100% O2) in three incremental 1-min steps (3.6%, 7.2%, and 11%). Intubation occurred 10 min after propofol administration. Twenty minutes after intubation, recordings were obtained during two steady-state periods during which end-tidal concentrations had achieved 5.4% (0.75 MAC) and 11% (1.5 MAC) desflurane for at least 10 min. Data also were obtained during the rapid increase in the inspired gas concentration from 5.4% to 11% ("transition"). RESULTS: Neurocirculatory variables did not differ between the three groups at conscious baseline, after fentanyl, and during steady-state periods of anesthesia. Propofol administration significantly reduced SNA and MAP. The MAP reduction was enhanced in the fentanyl-treated groups. After induction, the increases in SNA and MAP associated with the administration of desflurane by mask were not significantly reduced by fentanyl. The transition from 5.4% to 11% desflurane resulted in increases in SNA, HR, MAP, and fentanyl administration significantly attenuated the HR and MAP components. At the 11% steady-state measurement period, CVP was increased and MAP was decreased from conscious baseline, and these changes were not modified by fentanyl. CONCLUSIONS: The administration of desflurane was associated with increases in SNA, HR, MAP, and CVP. Maximum sympathetic activation and hemodynamic responses occurred 4-5 min after initiating desflurane during induction and 2-3 min after increasing the inspired concentration of desflurane during the "transition" period. Although fentanyl partially attenuated the hemodynamic component in a dose-dependent fashion during the "transition" period, it did not significantly diminish the response during induction.

Adult↗
PubMed1996

Pharmacokinetic model-driven infusion of fentanyl in children.

BACKGROUND: This study determined the accuracy of previously defined adult fentanyl pharmacokinetics in children having surgery; from this population, the pharmacokinetics of fentanyl were characterized in children when administered via a computerized assisted continuous-infusion device. METHODS: Twenty children between the ages of 2.7 and 11 y scheduled to undergo elective noncardiac surgery were studied. After induction, anesthesia was maintained with 60% nitrous oxide in oxygen supplemented with fentanyl (n = 10) or fentanyl plus isoflurane (n = 10). Fentanyl was administered via computerized assisted continuous-infusion to target concentrations determined by clinical requirements. Plasma fentanyl concentrations were measured and used to evaluate the performance of the fentanyl pharmacokinetics and then to determine a new set of pharmacokinetic parameters and the variance in the context-sensitive half-times simulated for these patients. RESULTS: The original adult fentanyl pharmacokinetics resulted in a positive bias (10.4%), indicating that measured concentrations were mostly greater than predicted. A two-compartment model with age and weight as covariates provided the optimal pharmacokinetic parameters. These resulted in a residual performance error of -1.1% and a median absolute performance error of 17.4%. The context-sensitive times determined from this pediatric population were considerably shorter than the context-sensitive times previously published for adults. CONCLUSIONS: The pharmacokinetics of fentanyl administered by computerized assisted continuous-infusion differ between adults and children. The newly derived parameters are probably more suitable to determine infusion schemes of up to 4 h in children between the ages of 2 and 11 y.

Anesthetics, Intravenous↗