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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
J Pain Symptom Manage 1992 Apr
PMID:The history and development of the fentanyl series. 151 29

The transdermal therapeutic system (TTS) fentanyl has been designed for rate-controlled drug delivery. It provides a convenient regimen for the use of a drug previously limited by a short duration of action and a noninvasive parenteral route for a drug that is unsuitable for oral administration. TTS fentanyl has been developed to provide continuous controlled systemic delivery of fentanyl base for 72 hr. It is a rectangular, transparent unit composed of a protective peel strip and four functional layers. The amount of fentanyl released from each system (25 micrograms/hr per 10 cm2) is proportional to the surface area. So far, four patch sizes are available (10-40 cm2). When the system is applied, a fentanyl depot concentrates in the upper skin layers. Fentanyl plasma concentrations are not measurable until 2 hr after application, and it takes 8-16 hr latency until full clinical fentanyl effects are observed. Steady-state serum concentrations are obtained after several sequential 72-hr applications, and these are maintained for as long as a system is applied. Following removal, serum fentanyl concentrations decline gradually and fall about 50% in approximately 16 hr. This prolonged apparent elimination half-life occurs because fentanyl continues to be absorbed from the skin. Transdermal fentanyl transport is essentially the same between the chest, abdomen, and thigh. The skin-permeability constant is about 0.0125 mL/hr/cm2, much lower than the regional blood supply to a chest-skin area. Because of potential permeability variations among individuals, a special rate-controlling membrane in the system provides additional control of drug release.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pain Symptom Manage 1992 Apr
PMID:Transdermal fentanyl: clinical pharmacology. 151 37

Thirty-four patients undergoing thoracotomy were entered into a randomized, double-blind, placebo-controlled study to compare the effects of patient-controlled, lumbar epidural (PCA-E) fentanyl with patient-controlled intravenous (PCA-i.v.) fentanyl with respect to drug requirements, analgesic efficacy and respiratory function. Prior to chest closure patients received fentanyl 2 micrograms.kg-1 by the epidural or i.v. route. In the recovery room further doses of epidural or i.v. fentanyl, 50 micrograms, were administered by the patients who controlled two PCA pumps. Background fentanyl infusion rates were increased by 10 micrograms.hr-1 each time the patient administered a drug bolus and were decreased by 10 micrograms.hr-1 whenever visual analogue scale (VAS) pain scores were less than 2 on a maximum 10 scale. Twenty-nine patients completed the study. Patients in the PCA-E group (n = 14) required less total fentanyl than those in the PCA-i.v. (n = 15) group (1857 +/- 693 micrograms vs 2573 +/- 890 micrograms respectively, P less than 0.05). Fentanyl infusion rates were lower in the PCA-E group at most measurement times. There were no differences between groups in respiratory rates, PaCO2, VAS pain scores or changes in pulmonary function as measured by FVC and FEV1. It is concluded that satisfactory patient-controlled analgesia can be achieved with both epidural and i.v. fentanyl after thoracotomy but that fentanyl requirements are less when given via the epidural route. This supports a direct spinal cord site of action for lumbar epidural fentanyl.
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PMID:Patient-controlled lumbar epidural fentanyl compared with patient-controlled intravenous fentanyl for post-thoracotomy pain. 155 Nov 51

Epidural fentanyl is often added to epidural local anaesthetic agents to improve the quality of anaesthesia obtained during Caesarean section. Fentanyl may be given either before or after delivery of the infant. When given before delivery, fentanyl has not been reported to cause neonatal depression, although this remains a concern. A prospective, randomized, double-blind study was undertaken to determine if fentanyl was more effective if given before or after delivery of the baby in 64 women undergoing Caesarean section under lidocaine epidural anaesthesia. Maternal outcome was determined by time to achieve T4 neural blockade, the dose of lidocaine necessary to achieve this block and intraoperative scores for pain, nausea, vomiting, shivering, and sedation. Neonates were assessed by umbilical arterial blood pH and Apgar scores. No differences were detected in either group with respect to maternal or neonatal outcome. We recommend using only epidural local anaesthetic agents before delivery, and giving epidural fentanyl following delivery of the infant.
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PMID:Epidural fentanyl and caesarean section: when should fentanyl be given? 840 64

Control of pain, discomfort, and agitation is an integral part of the postoperative management of critically ill patients. We examined the sedative and analgesic practices in a surgical ICU during two six-month periods, one in 1986-1987 and the other in 1989-1990. Narcotics, especially morphine and Fentanyl, were the most commonly used drugs. The amount of Fentanyl received by the endotracheal patients in the 1986-1987 group was quite large, 5.5 +/- 4.3 (SD) mg/day. The use of midazolam during the second survey period was associated with a reduced dose of narcotics in artificially ventilated patients receiving continuous intravenous Fentanyl and morphine. The use of epidural Fentanyl, especially following thoracic surgery, was greatly increased during the second study period. More work is needed to assess the effects and effectiveness of ICU sedative and analgesic regimens.
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PMID:Patterns of sedation and analgesia in the postoperative ICU patient. 160 Jul 84

One hundred and sixty-four patients scheduled for elective termination of pregnancy under general anaesthesia were randomly assigned to receive one of three different supplements to propofol and oxygen in nitrous oxide anaesthesia: 0.1 mg fentanyl, 0.5 mg alfentanil or placebo. Postoperative pain and nausea, as well as complications during anaesthesia were studied. There were no differences in complications or complaints by surgeons during anaesthesia, and no patient in any group reacted unsatisfactorily to surgery. The patients in the placebo group consumed significantly more propofol during the procedure (P less than 0.001). No differences were seen in time until hospital discharge between the three groups. Complaints about postoperative pain were significantly less frequent among patients receiving fentanyl (P less than 0.01). The number of patients requesting postoperative analgetics, however, did not differ. There was no difference in the frequency of nausea or vomiting, but postoperative pain was found significantly to increase complaints of nausea (P less than 0.01) and also time until hospital discharge (P less than 0.01). In conclusion, opioid supplementation lowered the amount of propofol needed for anaesthesia. Alfentanil 0.5 mg did not improve the postoperative course. Fentanyl 0.1 mg decreased the frequency of postoperative pain without increasing the time to hospital discharge.
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PMID:Opioid supplementation to propofol anaesthesia for outpatient abortion: a comparison between alfentanil, fentanyl and placebo. 176 99

Transdermal fentanyl 75 micrograms/h (Fentanyl-TTS) was compared with placebo in a randomized double-blind study in the early postoperative period, using 50 patients recovering from major urological operations. Analgesic efficacy was individually titrated with intravenous fentanyl by means of a PCA pump (demand dose 34 micrograms, lockout time 5 min). The test systems were applied 8 h before anaesthesia and were left in situ for 24 h. During the PCA period (18.2 h) patients with Fentanyl-TTS required significantly less additional fentanyl (0.48 vs 0.93 micrograms.kg-1.h-1) and reported less pain than patients in the placebo-group. Patient acceptance was high in both groups. Side-effects were of only minor intensity and did not differ between the two groups. In particular, there was no case of clinically relevant respiratory depression.
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PMID:Transdermal fentanyl for the treatment of pain after major urological operations. A randomized double-blind comparison with placebo using intravenous patient-controlled analgesia. 178 72

The pharmacokinetics, pharmacodynamics, and clinical uses of fentanyl, sufentanil, and alfentanil are reviewed. The fentanyl derivatives have reduced or eliminated many of the disadvantages of opioid anesthetics, such as incomplete amnesia and undesirable hemodynamic responses to surgery. Fentanyl is 50-100 times as potent as morphine and was the first of the three to be marketed. Sufentanil is even more potent than fentanyl. Alfentanil has the fastest onset of action, followed by sufentanil and then fentanyl. Alfentanil also has the shortest duration of action of the group. Most studies of these agents have been done to assess their role as anesthetics in cardiac surgery. All three provide cardiovascular stability when administered before noxious surgical stimuli, except when given as a single bolus during the induction of anesthesia. All seem to produce adequate anesthesia, particularly when used in combination with nitrous oxide. Because of its short duration of action, alfentanil is preferred for brief procedures or when rapid changes in the level of consciousness are desired. All three agents have also been used for analgesia; epidural administration provides adequate relief of pain. Fentanyl has been formulated as a transdermal patch that seems to provide the same degree of analgesia as a continuous i.v. infusion. Fentanyl has also been formulated as an investigational lozenge that has shown advantages as a preoperative sedative in children. As more is learned about these agents, their perioperative uses for anesthesia, analgesia, and sedation will continue to be refined.
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PMID:Clinical uses of fentanyl, sufentanil, and alfentanil. 183 93

This report examines the relationship of plasma drug concentration to analgesic effect following bolus doses of alfentanil, fentanyl and morphine and assesses individual differences in analgesic response among volunteers. We predicted that the 3 opioids would yield disparate analgesic profiles because their physicochemical and pharmacokinetic characteristics differ. Ten healthy volunteers received intravenous bolus doses of either alfentanil, fentanyl, morphine or normal saline on different days. We stimulated their teeth electrically and measured brain evoked potential (EP) and pain report (PR) repeatedly over 2 h to assess analgesic effect. Concurrently, we drew 18 blood samples to assess opioid plasma concentrations during the test period. The relationship between opioid plasma concentration and analgesic effect was well defined for alfentanil but ambiguous for morphine. Fentanyl exhibited a marked hysteresis. We observed noteworthy individual differences in analgesic response with all 3 drugs but these differences were greatest for morphine and least for alfentanil. Inter- and intrasubject variability in analgesic response across drugs is related to the physicochemical properties of the drugs tested.
Pain 1990 Oct
PMID:Profiles of opioid analgesia in humans after intravenous bolus administration: alfentanil, fentanyl and morphine compared on experimental pain. 198 May 37

Three patients in a university hospital developed nosocomial infusion-related Pseudomonas pickettii bacteremia. Investigation identified six additional patients who had received intravenous fluid contaminated by P pickettii but did not become ill. All nine patients had had surgery, and each of these patients but only nine of 19 operated-on control patients had received intravenous fentanyl citrate in the operating room; the mean dose given to the nine case patients was far greater than that given to control patients. Fentanyl in 20 (40%) of 50 predrawn 30-mL syringes was shown to be contaminated by P pickettii. Contamination was caused by theft of fentanyl from predrawn synringes and replacement by distilled water contaminated by P pickettii. Narcotic theft by health care personnel may cause patients to suffer pain needlessly and can also result in dire unanticipated consequences, such as nosocomial bacteremia. Whereas drug testing in the workplace is highly controversial, we believe that testing of health care personnel is indicated when drug abuse or theft is suspected.
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PMID:Nosocomial Pseudomonas pickettii bacteremias traced to narcotic tampering. A case for selective drug screening of health care personnel. 199 96


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