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PubMed1997

High-dose fentanyl does not adversely affect outcome from forebrain ischemia in the rat.

Fentanyl citrate has properties, including agonism of the mu-opioid receptor and proconvulsant activity, that theoretically could pose adverse effects in ischemic brain. This study examined the effects of high-dose fentanyl on outcome in rats subjected to transient near-complete forebrain ischemia. Rats were anesthetized with halothane and surgically prepared for ischemia. In one group (fentanyl; n = 15), intravenous fentanyl (400 micrograms/kg followed by an infusion of 16 micrograms/kg/min for 20 min) was administered and halothane was discontinued. In the remaining rats (control: n = 15), halothane administration was continued and no fentanyl was given. Following 10 min of bilateral carotid artery occlusion and profound systemic hypotension, animals were maintained normocapnic, normothermic, and mildly hyperoxemic for 8 h. Four days later, histologic and neurologic outcomes were assessed. In another group of rats also administered halothane (uncontrolled recovery; n = 15), no attempt was made to control physiologic variables during recovery from ischemia. Fentanyl caused preischemic evidence of epileptoid activity but decreased the percentage of neurons that died in the CA1 sector of the hippocampus relative to control (p = 0.0005). Damage in the cortex or caudoputamen was not different from that in the control group. Rats with an uncontrolled recovery had decreased damage in the cortex (p = 0.005) and caudoputamen (p = 0.00015) relative to control. In this model of forebrain ischemia, fentanyl caused no worsening of histologic damage in the cortex or caudoputamen and decreased hippocampal CA1 injury despite major electroencephalographic activation in the immediate preischemic period.

Anesthesia↗
PubMed2003

Moderate hypothermia may be detrimental after traumatic brain injury in fentanyl-anesthetized rats.

OBJECTIVES: To determine whether transient, moderate hypothermia is beneficial after traumatic brain injury in fentanyl-anesthetized rats. DESIGN: Prospective, randomized study. SETTING: University-based animal research facility. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: All rats were intubated, mechanically ventilated, and anesthetized with fentanyl (10 microg/kg intravenous bolus and then 50 microg.kg(-1).hr(-1) infusion). Controlled cortical impact was performed to the left parietal cortex, followed immediately by 1 hr of either normothermia (brain temperature 37 +/- 0.5 degrees C) or hypothermia (brain temperature 32 +/- 0.5 degrees C). Hypothermic rats were rewarmed gradually over 1 hr. Fentanyl anesthesia and mechanical ventilation were continued in both groups until the end of rewarming (2 hrs after traumatic brain injury). MEASUREMENTS AND MAIN RESULTS: Histologic assessment performed 72 hrs after traumatic brain injury was the primary outcome variable. Secondary outcome variables were physiologic variables monitored during the first 2 hrs after traumatic brain injury and plasma catecholamine and serum fentanyl concentrations measured at the end of both hypothermia and rewarming (1 and 2 hrs after traumatic brain injury). Contusion volume was larger in hypothermic vs. normothermic rats (44.3 +/- 4.2 vs. 28.6 +/- 4.0 mm, p <.05), but hippocampal neuronal survival did not differ between groups. Physiologic variables did not differ between groups. Plasma dopamine and norepinephrine concentrations were increased at the end of hypothermia in hypothermic (vs. normothermic) rats (p <.05), indicating that hypothermia augmented the systemic stress response. Similarly, serum fentanyl concentrations were higher in hypothermic (vs. normothermic) rats at the end of both hypothermia and rewarming (p <.05), demonstrating that hypothermia reduced the clearance and/or metabolism of fentanyl. CONCLUSIONS: Moderate hypothermia was detrimental after experimental traumatic brain injury in fentanyl-anesthetized rats. Since treatment with hypothermia has provided reliable benefit in experimental traumatic brain injury with inhalational anesthetics, these results indicate that the choice of anesthesia/analgesia after traumatic brain injury may dramatically influence response to other therapeutic interventions, such as hypothermia. Given that narcotics commonly are administered to patients after severe traumatic brain injury, this study may have clinical implications.

Anesthesia, Intravenous↗
PubMed1983

Epidural versus intramuscular fentanyl. Analgesia and pharmacokinetics in labour.

In a randomised double blind trial, 36 patients in the first stage of labour received either epidural or intramuscular fentanyl at the same time as the epidural test dose of bupivacaine. Analgesia was more rapid in onset and more complete in the epidural fentanyl group. Supplementary doses of bupivacaine were required within the first hour in 62% of the intramuscular fentanyl group compared with only 16% in the epidural group. Plasma fentanyl concentrations showed wide interindividual variation, but after epidural fentanyl the peak occurred earlier. There was no correlation between analgesia and plasma fentanyl concentration, and epidural fentanyl produced superior analgesia but a systemic contribution to this effect cannot be ruled out.

Adult↗
PubMed1980

The role of thiopental and fentanyl in the production of balanced anaesthesia.

In order to clarify the interactions between various doses of thiopental and fentanyl in producing "balanced anaesthesia", their effects on consciousness, superficial nociception, and respiration and circulation were studied during N2O+O2 inhalation in connection with the induction of anaesthesia. Altogether 60 patients were studied; the drug combinations used were thiopental 5 mg/kg (TP5), thipental 3 mg/kg (TP3), thiopental 3 mg/kg and fentanyl 0.5 micrograms/kg (TP3F0.5), thiopental 2 mg/kg and fentanyl 1 micrograms/kg (TP2F1), thiopental 1 mg/kg and fentanyl 2 micrograms/kg (TP1F2), and fentanyl 3 micrograms/kg (F3). Five minutes after the i.v. supplementation of N2O+O2 anaesthesia, the depth of anaesthesia and analgesia (antinociception) were evaluated from the eyelid reflex and by pinching an inguinal skin fold. Cardiorespiratory parameters were measured during this study period at 1-min intervals. The balance between antinociception and anaesthesia was closest to optimum in groups TP2F1 and TP2F0.5. In pure thiopental groups, the analgesia was poor; only four patients did not respond to the nociceptive stimulus, whereas in group F3 anaesthesia (disappearance of the eyelid reflex) was obtained in only two patients. The respiratory depression was most pronounced in groups receiving 3, 2 and 1 micrograms/kg fentanyl and weakest in groups where only thiopental was used. Blood pressure decreased in all groups but no statistically significant differences were noted. On the basis of the results it seems obvious that attempts to achieve what is called "balanced anaesthesia" by the supplementation of an N2O+O2 mixture with fentanyl only leads to an unnecessarily prnounced respiratory depression, whereas supplementation with thiopental alone does not offer adequate antinociception.

Adult↗
PubMed1985

Isoflurane v fentanyl for outpatient laparoscopy.

Isoflurane and fentanyl have been compared as anaesthetic agents for outpatient laparoscopy. In 50 female patients anaesthesia was induced with thiopentone and maintained with nitrous oxide 66% in oxygen combined with either isoflurane 1-2% or fentanyl 0.3 mg according to a randomized list. Suxamethonium was used to facilitate intubation and for further muscle relaxation. Immediate recovery from anaesthesia was assessed by eye opening and time before giving the date of birth. Additional observations made hourly for 4 h were: nausea or vomiting; clinical assessment of wakefulness; psychic or motor agitation; antiemetic or analgesic drugs given; reaction time; respiratory depression. Immediate recovery was more rapid in the fentanyl group (P less than 0.05). Reaction times in the isoflurane patients returned to control by 3 h, whereas the fentanyl patients were 10% slower than control at 4 h (P less than 0.05 at 2 h, 3 h, 4 h). Nausea and vomiting were more frequent in the fentanyl group, and four of the fentanyl patients required naloxone. Both anaesthetic techniques provided satisfactory operating conditions, but isoflurane appeared to provide a better recovery with less side effects than fentanyl.

Adolescent↗
PubMed1986

Pharmacokinetics of intravenous, intrathecal and epidural morphine and fentanyl in the goat.

Intrathecal and epidural catheters and an intravenous cannula were inserted in 10 goats. After administration of either morphine 4 mg, intravenously, 1 mg intrathecally or 4 and 8 mg epidurally, or fentanyl 0.1 mg intravenously, 0.05 mg intrathecally or 0.1 and 0.2 mg epidurally, venous blood and CSF were sampled at 2, 5, 10, 15, 30 min and 1, 2, 4, 6, 8 and 24 h. The concentrations of the drugs were measured by radioimmunoassay. After administration of intravenous morphine the plasma concentration-time curve fitted a 3-compartment model (body clearance = 84 +/- 23 ml/min/kg, mean +/- s.d., N = 5), while after fentanyl the plasma concentration-time curve was best described by a 2-compartment model (body clearance = 3.9-5.8 ml/min/kg, N = 3]. After intrathecal injection the elimination rates of the opioids from CSF were 0.3 to 2.0 and 0.6 to 2.4 ml/h/kg for morphine and fentanyl, respectively (N = 3). The time to reach maximum CSF concentration after epidural administration was 0.22 +/- 0.14 h for morphine (N = 6) and 0.22 +/- 0.13 h for fentanyl (N = 8). In the same goat the CSF availability was 2.3 and 11.3% for morphine and 0.8 and 3.3% for fentanyl following epidural administration of the low and high doses, respectively. After epidural administration, morphine and fentanyl are absorbed into CSF at the same rate but the relative amount of drug absorbed may be higher for morphine than fentanyl. Bulk flow is supposed to be the principal mechanism of opioid elimination from CSF.

Animals↗
PubMed1986

The influence of fentanyl on the cardiovascular effect of suxamethonium.

The influence of fentanyl on the cardiovascular effect of a single dose of suxamethonium was evaluated during thiopentone N2O/O2 anaesthesia. Sixty adult patients were randomly allocated to three groups. In one group (control group) no fentanyl was given. In two groups fentanyl 0.002 mg/kg and 0.004 mg/kg, respectively, was given before induction of anaesthesia. Three minutes after the injection of suxamethonium 1 mg/kg, both heart rate (HR) and mean arterial pressure (MAP) in the two groups receiving fentanyl were significantly lower than in the control group. However, the absolute changes were small and no dose-related effect was seen. An estimation of the change in HR following suxamethonium was made using as predictors initial HR before induction of anaesthesia, age, sex, and the injection of fentanyl. The higher the initial HR, the greater was the chance of a decrease in HR following suxamethonium. Injection of fentanyl lowered the threshold HR above which a decrease was to be expected following injection of suxamethonium. This effect was most pronounced among the younger patients. It is concluded that injection of fentanyl potentiates the decrease in HR sometimes seen after a single dose of suxamethonium and that this effect is influenced by HR before induction of anaesthesia and by age of the patient.

Adult↗
PubMed1998

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomised, double-blind, cross-over study with and without adrenaline.

BACKGROUND: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. METHODS: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml.h-1 of bupivacaine 1 mg.ml-1, fentanyl 2 micrograms.ml-1, and adrenaline 2 micrograms.ml-1 were included. On the 1st and 2nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. RESULTS: The number of hypaesthetic dermatomal segments decreased (P < 0.001) and pain intensity at rest and when coughing increased (P < 0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15-20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng.ml-1 (P < 0.01), and there was more sedation during the period without adrenaline. CONCLUSIONS: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.

Adrenergic alpha-Agonists↗
PubMed2005

Intrathecal fentanyl added to hyperbaric ropivacaine for transurethral resection of the prostate.

BACKGROUND: Our purpose was to evaluate the effect of intrathecal fentanyl 25 microg added to 18 mg of 6 mg ml(-1) hyperbaric ropivacaine on the characteristics of subarachnoid block and postoperative pain relief in patients undergoing TURP surgery. METHODS: The patients were randomly assigned into two groups: Group S (saline group, n=16) received 3 ml of 18 mg hyperbaric ropivacaine + 0.5 ml saline--in total, a 3.5-ml volume intrathecally; and Group F (fentanyl group, n=15) received 3 ml of 18 mg hyperbaric ropivacaine + 0.5 ml of 25 microg fentanyl--in total, a 3.5-ml volume intrathecally. In both groups the onset and recovery times of the sensory block, degree and recovery times of the motor block and side-effects were recorded and statistically compared. RESULTS: There was no significant difference between the groups in achieving the highest level of sensory block, and in the times taken to reach the peak level. Regression to L1 was significantly prolonged in the fentanyl group compared with the saline group (P=0.004). Times to the first feeling of pain and the first analgesic requirement were significantly prolonged in the fentanyl group compared with the saline group (P=0.011 and P=0.016, respectively). The frequency of pruritus was significantly higher in the fentanyl group compared with the saline group (P=0.022). CONCLUSION: Addition of fentanyl 25 microg to hyperbaric ropivacaine 18 mg for spinal anesthesia in patients undergoing TURP may significantly improve the quality and prolong the duration of analgesia, without causing a substantial increase in the frequency of major side-effects.

Amides↗
PubMed2005

Less postoperative nausea and vomiting after propofol + remifentanil versus propofol + fentanyl anaesthesia during plastic surgery.

BACKGROUND: The effect of different opioids on postoperative nausea and vomiting (PONV) has not been conclusively determined yet, thus the aim of this study was to compare the incidence of PONV in propofol-anaesthetized patients receiving either fentanyl or remifentanil as opioid supplement. METHODS: Sixty ASA physical status I and II patients scheduled for plastic surgery gave their written informed consent for this prospective, randomized, double-blind study. Anaesthesia was induced with propofol, rocuronium and fentanyl (n = 30; 2 microg kg(-1)) or remifentanil (n = 30; 1 microg kg(-1)). After tracheal intubation, anaesthesia was maintained with propofol, oxygen in air and an infusion of the opioid studied, which was modified according to clinical criteria. Baseline postoperative analgesia was achieved with intravenous propacetamol + metamizol. Intravenous morphine was given if visual analogic scale (VAS) for pain was > or = 4 (scale 0-10) and metoclopramide was administered if a patient presented > or = 2 PONV episodes (nausea or vomiting) in less than 30 min. Postoperatively (2, 12 and 24 h), we registered VAS, rescue morphine consumption, number of patients with episodes of PONV and number of patients requiring metoclopramide. P < 0.05 was considered significant. RESULTS: There were no significant differences between groups in the demographic parameters, ASA physical status, propofol dose, VAS, and rescue morphine requirements. Fourteen patients in the fentanyl group and four in the remifentanil group presented PONV episodes 2-12 h postoperative hours' interval; (P < 0.05). Ten patients in the fentanyl group and four in the remifentanil group presented vomiting episodes in the same period (P < 0.05); and eight patients in the fentanyl group and one in the remifentanil group required metoclopramide; (P < 0.05). The number of postoperative PONV episodes were low, both in the 0-2-h period (n = 2 vs. n = 1, fentanyl and remifentanil, respectively) and in the 12-24-h period (n = 3 vs. n = 1). CONCLUSION: Propofol + fentanyl anaesthesia resulted in a higher incidence of PONV and requirements of antiemetic drugs in the period between 2 and 12 postoperative hours compared with propofol + remifentanil, in patients undergoing plastic surgery.

Adolescent↗
PubMed1982

The uptake of fentanyl by erythrocytes.

Fentanyl passed rapidly into and out of erythrocytes to equilibrate with plasma concentration, and a red cell/plasma partition coefficient of 1.01 +/- 0.0083 s.e.m. was found in 15 normal subjects. Most of the binding of fentanyl by red cells was by haemoglobin. 10% was bound by the cell membrane. Partition was unaffected by haematocrit, pH, or the concentration of fentanyl up to 0.5 mg ml-1 of blood. Dilution of plasma proteins, and replacement of plasma by buffer showed that uptake of fentanyl by red cells is a linear function of the concentration of free drug in plasma. A partition coefficient for red cells/buffer of 4.91 +/- 0.032 s.e.m. was found. This relation was confirmed where binding to plasma proteins was altered in uraemia or hyperlipoproteinaemia, or by competitive displacement of fentanyl by aspirin and phenylbutazone thereby changing the size of the free fraction of fentanyl in plasma. Quinidine, however, inhibited the binding of fentanyl to plasma proteins and red cells equally, to maintain a partition coefficient of unity.

Blood Proteins↗
PubMed2005

Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of buprenorphine and fentanyl in rats: role of receptor equilibration kinetics.

The objective of this investigation was to characterize the pharmacokinetic/pharmacodynamic correlation of buprenorphine and fentanyl for the antinociceptive effect in rats. Data on the time course of the antinociceptive effect following intravenous administration of buprenorphine or fentanyl was analyzed in conjunction with plasma concentrations by nonlinear mixed-effects analysis. For fentanyl, the pharmacokinetics was described on the basis of a two-compartment pharmacokinetic model. For buprenorphine, a three-compartment pharmacokinetic model best described the concentration time course. To explain time dependencies in pharmacodynamics of buprenorphine and fentanyl, a combined effect compartment/receptor binding model was applied. A log logistic probability distribution model is proposed to account for censored tail-flick latencies. The model converged, yielding precise estimates of the parameters characterizing hysteresis. The results show that onset and offset of the antinociceptive effect of both buprenorphine and fentanyl is mainly determined by biophase distribution. The k(eo) was 0.024 min(-1) [95% confidence interval (CI): 0.018-0.030 min(-1)] and 0.123 min(-1) (95% CI: 0.095-0.151 min(-1)) for buprenorphine and fentanyl, respectively. On the other hand, part of the hysteresis in the buprenorphine pharmacodynamics could be explained by slow receptor association/dissociation kinetics. The k(off) was 0.073 min(-1) (95% CI: 0.042-0.104 min(-1)) and k(on) was 0.023 ml/ng/min (95% CI: 0.013-0.033 ml/ng/min). Fentanyl binds instantaneously to the OP3 receptor because no reasonable values for k(on) and k(off) were obtained with the dynamical receptor model. In contrast to earlier reports in the literature, the findings of this study show that the rate-limiting step in the onset and offset of buprenorphine's antinociceptive effect is distribution to the brain.

Analgesics, Opioid↗
PubMed1998

Pharmacodynamic effects and pharmacokinetic profile of continuous infusion fentanyl in newborn piglets.

The objective of this study was to determine hemodynamic effects and pharmacokinetic profiles of fentanyl with continuous infusion in 1- to 3-day-old newborn piglets. The piglets (n = 6) were administered a loading dose of fentanyl at 30 microg/kg i.v. over 15 min followed by a continuous i.v. infusion at 10 microg/kg/h for 6 h. The control group (n = 8) received equivalent volume bolus and infusion of 5% dextrose. Blood samples were obtained serially from systemic circulation and sagittal sinus vein for measurement of plasma fentanyl, pH and blood gases. Plasma fentanyl achieved steady state levels by 30 min of infusion both in the systemic (202.7 +/- 39.1 ng/ml) and sagittal sinus vein (136.7 +/- 20.7 ng/ml). Fentanyl caused a transient increase in respiratory rate at 2 h. Heart rate was significantly elevated at 30 min and 6 h during infusion but systemic and sagittal sinus vein blood pressure remained unchanged. Systemic and sagittal sinus vein PO2 were significantly decreased from 2 through 6 h of infusion. Compared to the control group, there was a 56% (p < 0.01) decrease in sagittal sinus vein O2 content at 30 min of infusion, an effect which lasted up to 6 h (47%, p < 0.01). Fractional O2 extraction by the brain increased significantly at 30 min (26%, p < 0.01) and remained elevated throughout the infusion time (22%, p < 0.05 at 6 h). Brain fractional O2 extraction increased as a function of brain fractional fentanyl extraction (r2 = 0.40, p < 0.001). Mean clearance was estimated as 56.2 +/- 13.7 ml/kg/h (range 43.5-76.9 ml/kg/h), mean volume of distribution at steady state was 1.29 +/- 0.6 liters/kg (range 0.78-2.15 liters/kg) and the mean half-life was 15.7 +/- 5.7 h (range 9.4-22.5 h). These data suggest that increased systemic oxygen may be necessary to maintain normal cerebral oxygen extraction during fentanyl anesthesia/analgesia.

Analgesics, Opioid↗
PubMed2004

Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Dose and timing study.

OBJECTIVES: Opiates, which serve an integral role in anesthesia, suppress immune function, particularly natural killer cell cytotoxicity (NKCC). NK cells play an important role in tumor and metastasis surveillance. We reported that large-dose fentanyl anesthesia induced prolonged suppression of NKCC in patients undergoing abdominal surgery. The immune modulatory effects of opiates may depend on the interaction between dose and time of administration. The present study examined the effects of different doses of fentanyl, administered at different time points relative to tumor inoculation, on NKCC and on experimental tumor metastasis in rats. METHODS: Fischer 344 rats were injected with low or high doses of fentanyl, 6 or 2 h before, simultaneously with or 1 h after being inoculated intravenously with MADB106 tumor cells. Lung tumor retention (LTR) was assessed 4 h after, and lung tumor metastases were counted 3 weeks after tumor inoculation. NKCC was assessed 1 h after the fentanyl injection. RESULTS: At all time points, except 6 h before tumor inoculation, fentanyl (0.1-0.3 mg/kg) induced a dose-dependent increase in MADB106 LTR (2.3- to 74-fold). An intermediate dose of fentanyl (0.15 mg/kg) doubled the number of lung metastasis, and, within animal, suppressed NKCC and increased MADB106 LTR in a correlated manner. CONCLUSION: These findings indicate that fentanyl suppresses NKCC and increases the risk of tumor metastasis. Suppression of NK cells at a time when surgery may induce tumor dissemination can prove to be critical to the spread of metastases. It is suggested that the acute administration of a moderate dose of opiates during surgery should be applied cautiously, particularly in cancer patients.

Adenocarcinoma↗
PubMed1991

Analgesia and sedation in neonatal intensive care using fentanyl by continuous infusion.

To determine the effects of fentanyl in newborn and premature infants, we compared two groups of 20 newborn and premature babies under artificial ventilation for severe respiratory distress syndrome: a prospective group receiving fentanyl for analgesic and sedation and a historical control group, who did not receive fentanyl. Fentanyl serum levels during steady state were determined by radioimmunoassay. Average time of infusion was 86 +/- 47 h with a mean dosage of 0.68 +/- 0.24 micrograms/kg/h. The fentanyl group needed much less sedatives and catecholamines. Heart rate and blood pressure were not significantly changed by fentanyl. Meconium was excreted later, and higher values of bilirubin were reached earlier than in the control group. Although fentanyl proved to be helpful in the neonatal intensive care unit, the administration should remain under strict indication.

Bilirubin↗
PubMed1982

Effect of fentanyl on myocardial metabolism during ischemia.

In this survey, the effect of fentanyl, a potent morphinomimetic, on myocardial metabolism and some hemodynamic variables during ischemia is described. The data presented were derived from open-chest experiments on dogs. Ischemia was induced by partial occlusion (stenosis) of a coronary artery. Inducing the stenosis twice in the same animal after a certain interval made it possible to use the animal as its own control. Control and compound series are discussed. In the compound series, fentanyl (25 microgram/kg-1) was injected IV 5 minutes before induction of the second stenosis. Fentanyl decreased the oxygen demand of the ischemic myocardium, mainly due to a reduction in heart rate, which resulted in a decrease in the breakdown of energy-rich phosphates and in the anaerobic breakdown of glucose. The latter resulted in a less pronounced production of lactate by the ischemic myocardium and hence in a diminished acidity of this tissue. The release of potassium ions during ischemia was reduced after fentanyl. The uptake of glucose by the ischemic myocardium was not affected by fentanyl, but the uptake of free fatty acids was diminished. During ischemia, the arterial free fatty acid concentration decreased after fentanyl, indicating that the compound may suppress stress responses. Although extrapolation to clinical anesthesia should be handled with care, the described findings suggest that the use of fentanyl may benefit patients with coronary artery disease during anesthesia.

Anesthesia↗
PubMed1992

Transdermal fentanyl.

OBJECTIVE: To review the use of transdermal fentanyl for the treatment of moderate to severe chronic pain. The article provides background on the pharmacology and pharmacokinetics of the drug, as well as the properties of the transdermal system. In addition, clinical trials, adverse effects, and therapeutic considerations and recommendations are presented. DATA SOURCES: Clinical trials, review articles, and reference texts. STUDY SELECTION: Comparative clinical trials involving the use of transdermal fentanyl on postoperative and chronic pain patients. DATA EXTRACTION: Data from clinical human trials published in the English language were reviewed. Trials were assessed by sample size, opioid dosage regimen, and therapeutic outcome. DATA SYNTHESIS: Transdermal fentanyl was found to be effective in the control of chronic and postoperative pain. In one trial the overall patient satisfaction with pain control was 79 percent for the transdermal fentanyl group and 44 percent for the placebo group. In another trial, the amount of additional parenteral morphine was significantly lower for the group receiving transdermal fentanyl than for the placebo group (49.9 +/- 4.9 vs. 77.0 +/- 6.3 mg, respectively, p < 0.01). The most common adverse effects recorded were nausea (45-85 percent), pruritus (14-60 percent), and sedation (40-59 percent). The cost of analgesic therapy with this delivery system is higher than that of parenteral opioid analgesia, but less than patient-controlled analgesia. CONCLUSIONS: The transdermal fentanyl formulation offers some minor advantages over other forms of conventional pain management. Results of early clinical trials are promising, but more studies are needed to evaluate its long-term effectiveness and adverse effects. Specifically, comparisons with standard parenteral and patient-controlled opioid analgesia in chronic malignant and nonmalignant pain are necessary for adequate evaluation of transdermal fentanyl.

Administration, Cutaneous↗
PubMed2006

A Phase III study to assess the clinical utility of low-dose fentanyl transdermal system in patients with chronic nonmalignant pain.

BACKGROUND: The transdermal fentanyl delivery system (fentanyl TTS; Duragesic) is currently widely available in patch strengths of 25, 50, 75, and 100 microg/h. However, a lower dose of 12 microg/h would allow optimal titration and fine tuning of the analgesic effect, and may be beneficial in certain patient populations such as the elderly or opioid-naïve. A 12 microg/h fentanyl TTS patch has been developed, and the clinical efficacy and safety tested in this single-arm, non-randomized, open-label, multicenter, 28-day trial in opioid-exposed and -naïve patients with moderate to severe pain for at least 6 months. PATIENTS: Patients were treated with fentanyl TTS for 28 days in an intent-to-treat manner starting at 12 microg/h (one patch), titrated upwards in increments of 12 mug/h to a maximum dose of 36 microg/h (three patches). RESULTS: A total of 227 patients were enrolled. The majority of patients with a "global assessment of therapy" of fair/poor at baseline (63.4%) improved to good/very good, while 28.9% of patients with an assessment of good/very good at baseline worsened to fair/poor at endpoint. The average pain intensity levels for the efficacy evaluable population steadily decreased over the course of the trial. The adverse event (AE) profile of fentanyl TTS in this trial was generally similar to that identified in previous fentanyl TTS trials, and no unexpected safety issues or AEs were noted. Furthermore, the drop-out rate in this trial was lower than has been noted in previous trials. CONCLUSION: This trial demonstrated that the lower 12 microg/h dose of fentanyl TTS provided a therapeutic benefit in non-malignant chronic pain, with a similar AE rate but a lower drop-out rate than that seen in trials at higher doses. This lower dose may, therefore, be of particular benefit to elderly or opioid-naïve patients.

Administration, Cutaneous↗