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An action of fentanyl, a short-acting narcotic, on the reflex discharge in the digastric nerve induced by the inferior alveolar nerve stimulation was investigated in alpha-chloralose anesthetized cats. In the ipsilateral digastric reflex discharge, there were an early phase induced by stimulus exciting Aalpha fibers and a late phase appearing when Adelta fibers were also stimulated. Following dorso-lateral cordotomy at the obex level, an isolation of the spinal trigeminal nucleus caudalis, a total area in the digastric reflex discharge decreased, while its first peak amplitude was little affected, indicating a disappearance of the late phase and a preservation of the early phase. Fentanyl depressed both the total discharge area and the first peak amplitude. After dorso-lateral cordotomy, the depression of the area decreased considerably, whereas that of the amplitude decreased slightly. Results indicate that fentanyl depressed both the early phase which is activated by the Aalpha fiber stimulation, not via the subnucleus caudalis and the late phase which is activated by the Adelta fiber stimulation via the sub-nucleus caudalis or its surroundings. The latter action would be related to the analgesic action of fentanyl.
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PMID:Effect of fentanyl, a narcotic analgesic, on two components of the jaw opening reflex. 118 4

The effects of Halothane, Fentanyl and droperidol in combination on the circulatory system, the preganglionic sympathetic nerve activity and the respiratory centre were examined in 21 experiments carried out on cats which were relaxed and artificially ventilated with nitrous oxide in oxygen. The results showed that even the minimal dosage of 0.5 vol-% Halothane combined with 0.0042 mg/kg Fentanyl and 0.15 mg/kg droperiodol led to a significant decrease of blood pressure and a depression of the sympathetic and phrenic nerve activity both in rest and in stress during asphyxia. A dosage of 1 vol-% Halothane produced a significant increase in the above mentioned effects when at rest, while the doubled dosage of Fentanyl and droperidol combined with the original Halothane dosage of 0.5 vol-% produced no marked increase in its effects. A comparison of these results with those of previous experiments using only the inhalation of Halothane shows that an anaesthesia consisting of 0.5 vol-% Halothane combined with Fentanyl and droperidol has virtually equal effects on the decrease of blood pressure and on the depression of central sympathetic nerve activity as the inhalation of 1 vol-% Halothane alone. Using a combination of 1 vol-% Halothane, Fentanyl and droperidol the effects induced by 2 vol-% Halothane are reached.
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PMID:[The effects of combining halothane and neuroleptanalgesia on the preganglionic sympathetic activity, the respiratory centre and the circulation (author's transl)]. 121 4

The effects of i.v. injected Fentanyl and droperidol used either singly or in combination were observed in 50 experiments carried out on cats which had been relaxed and artificially respirated. The preganglionic discharges of the cervical sympathetic nerve and action potentials of the phrenic nerve, the mean arterial pressure and the heart rate were recorded. The experiments showed that with the dosage of 0.0042-0.0083 mg/kg Fentanyl no significant change in the recorded functions took place. The dosage of 0.0166 mg/kg Fentanyl led to an activation of the central sympathetic activity and to a inhibition of the respiratory centre which persisted for as long as 60 min after the injections. Other than as above, a dosage of 0.15-0.6 mg/kg droperidol led to a decrease of the blood pressure and a depression of the sympathetic nerve activity, while the activity of the phrenic nerve remained unchanged. The effect on the blood pressure was mainly influenced by the central nervous system as the inhibition of the pressor effect of noradrenaline was only minimally. The dosage of 0.0083 mg/kg Fentanyl combined with 0.3 mg/kg dropendol as administered for neuroleptanalgesia led to a decrease in blood pressure and a depression of the central sympathetic and phrenic nerve activity both in rest and in stress during asphyxia. The effects were minimal and accorded virtually to the effects produced by 0.5 vol-% Halothane during the first 25 min of inhalation, which had been registered in previous experiments. Contrary to the effects of Halothane, neuroleptanalgesia produced no decrease in the heart rate, no depression on the pressor effects of noradrenaline and no accumulation of irregularities in cardiac rhythm after administration of noradrenaline.
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PMID:[The effects of neuroleptanalgesia on the sympathetic activity and the circulation in animals (author's transl)]. 121 5

The acute effect of Fentanyl and Althesin upon haemodynamics, inotropism of the heart and myocardial oxygen consumption has not been studied in man so far. Healthy premedicated pateints (n = 16) were lightly anaesthetized with nitrous oxide-oxygen (ratio 2:1), 0.3 Vol.-% forane and 0.3 Vol.-% halothane respectively. In order to avoid any interference with respiratory depression all subjects were normoventilated via an orotracheal tube. In a circulatory steady state a single dose of 0.01 mg/kg Fentanyl (n = 7) and 0.075 mg/kg Althesin (n = 9) respectively was injected intravenously within 20 sec. After the application of Fentanyl there was a delayed (5th min) fall in blood pressure by 23%, which was due to a reduction in total peripheral resistance (12%) and in cardiac output (thermodilution technique) by 13%. The decrease in cardiac output was the result of a bradycardia (18%). Considering heart rate, pre- and afterload simultaneously, the fall in max dp/dt (catheter-tip manometer) by 20% could not be explained as a decrease in myocardial contractility. The altered haemodynamics led to a decrease of the myocardial oxygen consumption (control 6.4 ml O2/min x 100 g) by 31%. The energy demand of the heart was quantitatively calculated using the formula of the complex haemodynamic parameter developed by Bretschneider. Immediately after the administration of Althesin the cardiac output rose on account of tachycardia slightly, while stroke volume (19%), total peripheral resistance (32%) and mean arterial pressure (24%) reacted reversely. Since heart rate increased (11%), preload remainded unchanged and afterload decreased, the fall in dp/dt max (20%) has to be understood as a moderate reduction in myocardial inotropism. The energy demand of the heart decreased only initially by 15%. The clinical implications of the results were discussed.
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PMID:[The effect of Fentanyl and Althesin on haemodynamics, inotropism of the heart and myocardial oxygen consumption in man (author's transl)]. 125 26

The safety and efficacy of patient-controlled analgesia used for postoperative pain relief were evaluated. Cumulative 24-hour requirements were analyzed for possible correlation with patient characteristics. All patients who used a patient-controlled analgesia device for postoperative pain relief were reviewed from June to October 1991. The device Baxter's basal/bolus infusor with patient control module, was used to deliver fentanyl in 379 patients. The fentanyl requirement, verbal analog pain score, first passage of flatus, side effects, sedative score, and degree of satisfaction were examined. The fentanyl requirement during the first 24 hours after operation was analyzed with regard to age, body weight, and sex. The daily fentanyl consumption in the first three postoperative days was 928 +/- 352 micrograms (n = 338), 553 +/- 259 micrograms (n = 220), and 490 +/- 222 micrograms (n = 71), respectively. The requirement for fentanyl during the first 24 hours after surgery was significantly higher than for the next two days (p-value < 0.001). Fentanyl consumption correlated well with body weight, and inversely with age. No difference was found between fentanyl consumption and sex (p-value = 0.4687). The mean time to the first passage of flatus in patients with abdominal surgery was 54.6 +/- 26.4 hours. The incidence of nausea, vomiting, and dizziness was similar, about 20% of patients. Itching was noted in 7% of patients. Oversedation (class 4) was found in three patients during the first operative day, the sedative score for other patients were around class 1-3. No patient exhibited signs of respiratory depression or withdrawal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The efficacy of intravenous fentanyl patient-controlled analgesia for postoperative pain relief]. 134 40

The administration of epidural and intrathecal opioids for the management of postoperative pain is well established. Fentanyl, because of its greater lipophilicity, offers a number of advantages over morphine for epidural analgesia, including a lower incidence of side effects and reduced risk of delayed-onset respiratory depression. The relatively short duration of action of epidural fentanyl makes this agent more ideally suited for continuous infusion or patient-controlled epidural analgesia (PCEA). The effective doses and adverse effects profile of epidural fentanyl are reasonably well understood. Because of the lack of spread through the cerebrospinal fluid (CSF) and hence the segmental nature of the analgesia achieved, location of epidural catheter placement is of paramount importance when this agent is used. Prolonged epidural infusion of fentanyl may result in high systemic concentrations not dissimilar to IV infusion, and, therefore, the greatest efficacy of epidural fentanyl administration may be in combination with low concentrations of bupivacaine, an approach that achieves a synergistic effect. 2-Chloroprocaine has been shown to antagonize epidural fentanyl analgesia. Intrathecal fentanyl for postoperative analgesia is limited by its short duration of action with single-bolus administration. The widespread international increase in the use of epidural fentanyl for postoperative analgesia promises further improvements and refinement in techniques.
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PMID:Fentanyl: clinical use as postoperative analgesic--epidural/intrathecal route. 148 96

Fentanyl and morphine were administered epidurally to the patients after upper abdominal surgery for postoperative pain management. One hundred and ninety patients were divided into 3 groups; F group: bolus and continuous administration of fentanyl, M group: bolus and continuous administration of morphine, FM group: bolus of fentanyl and morphine and continuous administration of morphine. Pain scores of 1, 2, 3, 4, 8, 12 hours after administration and of the next morning were examined and side effects were recorded. Pain scores at 1 and 2 hours in F and FM group were significantly lower than those in M group. There were no significant differences in the scores among 3 groups from 3 hours to the next morning. The incidence of itching in F group was significantly less than in other groups. Respiratory depression (less than respiratory rate 8.min-1) occurred in 2 cases in M and FM group, but no case in F group. FM group had no advantage compared with F group. We conclude that continuous epidural infusion of fentanyl is more useful than morphine for postoperative pain management after upper abdominal surgery.
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PMID:[Comparison of continuous epidural fentanyl and morphine for postoperative pain management after upper abdominal surgery]. 149 76

Whereas the efficacy of flumazenil (Fl) for improving vigilance in the presence of other benzodiazepine agonists (BZA) is undoubted, its effect on BZA- and/or opioid agonists (OA)-induced respiratory depression is the subject of controversies. Some authors describe an improvement of a midazolam (Mi)-induced increase in paCO2, whereas others cannot find any influence on diazepam-induced respiratory depression. In two studies in which Fl was used to antagonize Mi/Fentanyl (Fe) anaesthesia we found even worse oxygen saturation values than with placebo (Pl). All our previous studies indicate a slight intrinsic activity of Fl on respiration in the presence of opioids. We therefore investigated the influence of Fl and Pl on expiratory pCO2 and oxygen saturation (SAT). METHODS. A group of 15 male, healthy volunteers aged 20-30 years gave written informed consent to participate in this double blind study, which was approved by our Institutional Review Board. Each subject received 3 micrograms/kg body wt. Fe + 0.5 mg Fl and 1 week later 3 micrograms/kg body wt. Fe + 5 ml NaCl 0.9% (Pl) i.v., in random order. They were undisturbed and breathed spontaneously. The following parameters were measured: SAT, pCO2 and heart rate (HR) continuously, using a pulse oximeter (SAT, H) and CO2 infrared absorption monitor (Oscar, Messrs., Datex). The blood pressure was recorded before and after a 5-min preinjection period (baseline) and at the end of the procedure (25 min). The data were stored in a microcomputer (Multitalent, Messrs. ZAK) and transmitted to a PC after each trial. STATISTICS. The groups were compared with the Wilcoxon rank sum test. P less than 0.05 is significant. RESULTS. In trials 1 and 2 there was an increase of pCO2 and a drop in SAT. The changes in pCO2 and SAT were more pronounced after Fe+Fl in 12 subjects (80%), as against 1 subject with the opposite result. There were 2 subjects who showed no difference between trials 1 and 2. The combination of Fe and Fl caused significantly higher increases in pCO2 (P = 0.007) and more pronounced decreases in SAT (P = 0.04) than Fe and Pl. DISCUSSION. These results indicate a slight enhancement of Fe-induced respiratory depression by Fl. In a previous study it could be shown that Fl antagonized the respiratory depressive effect of Mi, but baseline paCO2 was not completely recovered. In previous studies respiratory function impaired by Mi+Fe was initially improved by Fl, but rebound effects on SAT were observed, which were more pronounced than those after Pl. Therefore, respiratory function must be closely monitored in Fl-antagonized patients after Mi/Fe anaesthesia.
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PMID:[The action of flumazenil in combination with fentanyl on spontaneous respiration]. 149 27

The transdermal therapeutic system (TTS) is a novel technique of drug administration that can mimic long-term continuous intravenous infusions in maintaining stable drug plasma concentrations. Fentanyl, a potent lipid-soluble synthetic opioid, has been incorporated into such a system and has undergone preliminary clinical trials in postoperative patient populations to assess analgesic efficacy and incidence of undesirable side effects (pruritus, nausea and vomiting, urinary retention, respiratory depression). In general, when applied 2 hr preoperatively, a TTS (fentanyl) patch (in different doses) provides moderate-to-good analgesia for a variety of surgical procedures for periods of up to 3 days. Most patients will require small amounts of systemically administered opioids for supplementary analgesia, especially in the first 24 postoperative hr. The incidence of side effects such as nausea and vomiting varies between studies but can be as high as 70%. Clinically significant respiratory depression is rare but was reported in several of the studies. TTS (fentanyl) is a simple and useful technique for the control of postoperative pain.
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PMID:Transdermal fentanyl: acute analgesic clinical studies. 151 28

In the last two decades, opioid analgesics have assumed an important place in general anesthetic practice in the United States. Part of the reason for this has been the introduction of the potent new agonists fentanyl, sufentanil, and alfentanil. Because of problems with morphine-oxygen anesthesia (incomplete amnesia, occasional histamine-related reaction, marked increases in intra- and postoperative respiratory depression), a suitable alternative was sought but not found among existing opioids. A breakthrough came in 1960, when fentanyl was synthesized, laying the foundation for a better understanding of the structure-activity relationships of narcotic analgesics and stimulating interest in developing compounds with even greater potency and safety margins. Investigators interested in opioid anesthesia began to study fentanyl in animals and then in humans. Fentanyl (50-100 micrograms/kg) with oxygen (100%) was evaluated as an anesthetic in patients undergoing mitral valve and coronary artery surgery. Changes in cardiovascular dynamics with induction doses ranging from 8 to 30 micrograms/kg consisted of small decreases in heart rate and arterial blood pressure. All other cardiovascular variables studied, including cardiac output, remained unchanged, even with additional doses up to 100 micrograms/kg. It was determined that fentanyl had use as a narcotic anesthetic, despite its potential for cardiovascular depression and stimulation, respiratory depression, muscle rigidity, and, occasionally, incomplete anesthesia. Since the introduction of fentanyl, two other potent synthetic opioids have been introduced into clinical practice--sufentanil and alfentanil.
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PMID:The history and development of the fentanyl series. 151 29


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