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PubMed1989

A method to increase recovery of fentanyl from urine.

Fentanyl, a highly lipophilic drug (pk(a) 7.7), is a common drug of abuse. The current standard techniques to detect fentanyl in urine have low recovery rates and poor sensitivity. We report a modified solvent extraction technique that can recover between 63 and 86% of the drug with a detection limit of 0.2 ng/10 ml of urine. In addition, we report the duration of urinary fentanyl excretion in 11 adolescent patients administered either low (less than 10 mg/kg) or high (20-40 mg/kg) doses of fentanyl as part of anesthesia. The mean duration of urinary fentanyl excretion was similar in the two groups, with duration ranging from 1 to 5 days, and urine fentanyl concentration ranging from 0.1 ng to 10.3 ng/10 ml of urine.

Adolescent↗
PubMed1995

Fentanyl: a review for clinical and analytical toxicologists.

Fentanyl is a highly potent, short acting synthetic analgesic indicated as a preanesthetic medication. It is available for intravenous injection, as a transdermal patch and a lozenge dosage form. Fentanyl displays a large apparent volume of distribution, short plasma half life and extensive biotransformation. It is a popular drug of abuse among health care professionals. Diversion of pharmaceutical fentanyl preparations, as well as the availability of illicitly synthesized potent and highly toxic fentanyl analogs have resulted in numerous overdose deaths. Analysis of fentanyl and fentanyl analogs requires highly selective and sensitive methodologies. This review is intended as a quick reference source for clinical and analytical toxicologists.

Animals↗
PubMedDate not supplied

A study of the use of a transdermal fentanyl patch in cats.

A transdermal therapeutic system (TTS) has been developed for the continuous delivery of fentanyl citrate to provide ongoing analgesia in human patients with chronic pain. Several researchers believe that fentanyl transdermal patches have a place in postoperative pain control. The purpose of this study was to determine whether transdermal technology is an effective way of administering fentanyl to feline patients. Fentanyl patches were applied to the skin of six cats, and blood samples for fentanyl analysis were collected over 104 hours. This study establishes that the transdermal patch technology is an effective, long-lasting, cost-effective, noninvasive, and well-tolerated mode of deliverying fentanyl to cats.

Administration, Cutaneous↗
PubMedDate not supplied

A comparison of transdermal fentanyl versus epidural morphine for analgesia in dogs undergoing major orthopedic surgery.

Postoperative analgesia provided by transdermal fentanyl was compared with that provided by epidural morphine in dogs undergoing major orthopedic surgery. Dogs randomly were assigned to receive either a 100 microg per hour transdermal fentanyl patch 24 hours prior to surgery (n=8) or epidural morphine (0.1 mg/kg body weight) administered following induction of anesthesia (n=10). Temperature, heart rate, respiratory rate, and pain score were recorded prior to surgery and zero, six, 18, 30, and 42 hours after surgery. Blood samples were collected from the dogs in the transdermal fentanyl group beginning 24 hours preoperatively to 42 hours postoperatively. Fentanyl concentrations were determined by radioimmunoassay. When all time periods after surgery were combined, dogs in the transdermal fentanyl group were experiencing significantly less pain after surgery than dogs given epidural morphine. The transdermal fentanyl provided analgesia after major orthopedic surgery greater than or equivalent to that of epidural morphine.

Administration, Cutaneous↗
PubMed2006

Intrathecal fentanyl as adjunct to hyperbaric bupivacaine in spinal anesthesia for caesarean section.

OBJECTIVE: To compare the effect of adding fentanyl to intrathecal bupivacaine on the onset, duration and quality of spinal anesthesia and its effect of mother and neonate. DESIGN: Single blind randomized controlled clinical trial. PLACE AND DURATION OF STUDY: Department of Anesthesiology, Surgical Intensive Care Unit and Pain Management, Dow University of Health Sciences and Civil Hospital, Karachi, from January 2003 to June 2004. PATIENTS AND METHODS: Sixty young adult females, ASA physical status I and II, with singleton pregnancy undergoing elective or emergency cesarean section under spinal anesthesia were randomly allocated to receive spinal anesthesia either by using 0.75% hyperbaric bupivacaine 1.5 ml with 0.25 ml normal saline or 0.75% hyperbaric bupivacaine 1.5 ml with 0.25 ml fentanyl (12.5 microg). Blood pressure, heart rate, respiratory rate, oxygen saturation, sensory level, motor block, pain score and side effects were observed every 2 minutes for first 20 minutes, then at-5 minute interval throughout the surgery, thereafter at 30 minutes interval until the patient complained of pain. RESULTS: Comparing the bupivacaine group, time to achieve highest sensory level was significantly shorter in fentanyl group (*p < 0.05), while the duration of complete analgesia (time from injection to first report of pain) lasted significantly more longer in fentanyl group (184+/-20 minutes) than bupivacaine group (126+/-10 minutes). Duration of effective analgesia was also significantly more prolonged in fentanyl group (p < 0.05). There was no significant difference in the incidence of side effects between the two groups. CONCLUSION: Addition of fentanyl to intrathecal bupivacaine results in faster onset with improved peri-operative anesthesia without increasing the side effects.

Adjuvants, Anesthesia↗
PubMed1999

[Epidural analgesia in total gastrectomy--combination of bupivacaine with ketamine or fentanyl].

The effects of intraoperative epidural administration of ketamine added to bupivacaine were compared with fentanyl added to bupivacaine in patients undergoing total gastrectomy. Prospective, randomized, double blind study was designed to compare: group F: 20 patients (pts) receiving 20 ml of 0.125% bupivacaine and 50 ug of fentanyl and group K: 20 pts in whom 20 ml of 0.125% bupivacaine was combined with 50 mg of ketamine. Pts received an epidural injection through peridural catheter introduced through either T7-8 or T8-9 interspinous space. Non invasive arterial blood pressure, heart rate and ECG were recorded every 5 mins. We measured supplementary fentanyl requirement, ephedrine consumption, first postoperative complain on pain, tracheal extubation time. The groups were comparable with regard to patients characteristics, operation and anaesthesia related factors. There were no difference between groups in mean intraoperative fentanyl requirements (F vs. K = 118.5 (122.5) ug vs. 122.5(122.5)ug) (p n > 0.05), in the duration of epidural pain relief (F vs. K = 393.72 (98.75)min vs.403.63 (111.41)min, in the tracheal extubation time (F vs.K = 52.31 (50.4) vs.46.75 (48.35) min), postoperative sedation score (F vs.K = 1.26 (0.73) vs.1.11 (0.32)) (p > 0.05). Significantly higher systolic blood pressure was measured in group K comparing with group F in 20, 75, 105, 120, 150 min (p > 0.05). Statistically significant more ephedrine was applied in F group (F vs.K = 0.88(1.76)ml vs.0.05(0.23)ml) (p > 0.05). There were no statistically significant differences between groups in heart rate during the operation. None of the pts complained of bad dreams or awakeness during operation. Both fentanyl and ketamine added to bupivacaine and given as a bolus provided good intraoperative analgesia in combination with general anaesthesia, minimal sensorimotor disturbance and early tracheal extubation. In our study fentanyl added to bupivacaine caused higher incidence of hypotension than ketamine added to bupivacaine.

Adult↗
PubMed2000

[The effects of remifentanil on hemodynamic response to intubation. A comparative study with fentanyl] .

BACKGROUND: The aim of this study was to evaluate the effects of remifentanil in comparison with those of fentanyl on the hemodynamic response to orotracheal intubation. METHODS EXPERIMENTAL DESIGN: prospective comparative and randomized study. SETTING: operating room in a neurosurgery department at University. PATIENTS: 50 patients, ASA I or II with age ranging from 32 to 64 years were divided in two groups randomly. INTERVENTIONS: 25 patients received fentanyl as single bolus dose of 2.0 micrograms/kg and atropine 0.01 mg/kg i.v. as premedication while the remainders received atropine 0.01 mg/kg i.v. and remifentanil 0.2 microgram/kg/min as infusion. All patients were induced with propofol 2.0 mg/kg and cisatracurium 0.15 mg/kg for muscle relaxation and were intubated 4 min after induction of anesthesia. MEASUREMENTS: Heart rate, SAP, DAP, MAP and RPP were recorded at different times: baseline, induction, intubation, 1, 2, 3 and 4 min after intubation; ECG and pulsoximetry were monitored continuously. Statistical analysis was carried out using ANOVA for repeated measures and Bonferroni t-test a value of p < 0.05 was considered to be significant. RESULTS: Significant increases in PAS were recorded, at intubation and at 1 min after in patients treated with fentanyl; in the remifentanil group significant decreases in SAP at induction and at 4 min after intubation were recorded. HR increased significantly at intubation and at 1, 2 and 3 min after in the fentanyl group. RPP showed a significant decrease at induction in the remifentanil group and significant increases at intubation and at 1, 2 and 3 min after in patients treated with fentanyl. CONCLUSION: In conclusion remifentanil was found to properly control the hemodynamic response to intubation in comparison with fentanyl.

Adult↗
PubMedDate not supplied

From codeine to transdermal fentanyl for cancer pain control: a safety and efficacy clinical trial.

BACKGROUND: Fentanyl is a synthetic opioid, suitable for transdermal delivery, offering an interesting solution as a step 3 opioid in cancer pain treatment. The purpose of the study was to carefully investigate: 1) the feasibility of the direct conversion from codeine to TTS fentanyl, in patients already receiving codeine and requiring strong opioids for their analgesia; 2) the safety of 25 microg/hour incremental steps and at shorter than 72-hour intervals, if clinically required. PATIENTS AND METHODS: 130 patients were judged eligible for the study. All the patients were receiving 280-360 mg or more of codeine and required strong opioid for their analgesia. The study lasted 56 days. The initial dose was 25 microg/hour. TTS fentanyl for all patients. Data assessments were made on baseline, day 1, day 2, day 3, in the hospital and thereafter on days 7, 14, 21, 28, 42 and 56. After the patch application, all the patients were given an immediate release oral morphine (5 mg) every 4-6 hours for the first 12 hours and then if needed only as rescue doses. The patients remained in the hospital for the first three days of the study where follow-up (pain score, satisfaction, side effects etc.). was recorded by the palliative care team and by daily cards. RESULTS: The itnitial dose of fentanyl was 25 microg/hour while the mean dose on day 3 was 45.9 microg/hour. All the patients required upward titration of the study medication during follow-up visits. On day 56 the mean dose of fentanyl was 87.4 microg/hour. Mean pain intensity decreased from an initial 5.96 on the baseline to 0.83 on day 3. Karnofsky scale measurements between treatment phases revealed non-significant changes. The rate of overall satisfaction was quite high. Nine patients discontinued the study due to inadequate pain relief or side effects between day 7 and day 28, while five patients died between day 28 and day 56. Constipation, nausea and vomiting were the most common side effects. Skin reaction was relatively mild and acceptable during the study. CONCLUSION: Under controlled conditions, TTS fentanyl seems to be feasible for direct conversion from mild to strong opioids and additionally, 25 microg/hour incremental steps day by day can be made by palliative care specialists, if clinically required for cancer pain management.

Administration, Cutaneous↗
PubMed2001

[Influence of bispectral index monitoring on fentanyl requirements during total intravenous anesthesia for major gynecological surgery].

OBJECTIVE: To determine the influence that bispectral index (BIS) monitoring of hypnosis might have on need for analgesia during surgery under total intravenous anesthesia provided by bolus administration of fentanyl. PATIENTS AND METHOD: Prospective, randomized and partially double-blind study of 40 patients undergoing major gynecological surgery under total intravenous anesthesia with propofol and fentanyl. In the BIS group (n = 20) propofol administration was adjusted to maintain BIS between 40 and 60. In the control group (n = 20) standard doses were given: 10 mg/kg-1/h-1 after anesthetic induction and for 5 minutes, 8 mg/kg-1/h-1 over the next 5 minutes and 6 mg/kg-1/h-1 throughout the rest of the operation. All patients received intravenous bolus administration of 150 or 75 microg of fentanyl to maintain analgesia whenever systolic blood pressure and heart rate increased 20% over baseline. We compared propofol and fentanyl requirements, intraoperative changes in BIS, and awakening from anesthesia. RESULTS: Patient and surgical characteristics were similar in both groups. BIS monitoring allowed propofol administration to be decreased a mean 24% during maintenance of anesthesia, and this in turn was associated with a significant increase in mean dose of fentanyl (415 microg versus 253 microg in the BIS and control groups, respectively; p = 0.01). Mean values of BIS were higher in the BIS group (46.4 versus 42.2; p = 0.04) and patients in the BIS group awoke sooner (in 7.7 min versus 11.1 min; p = 0.01) and tended to report less pain upon arrival at the postanesthetic recovery room, although the difference was not statistically significant. CONCLUSIONS: BIS monitoring of depth of hypnosis can influence requirements for fentanyl during total intravenous anesthesia by bolus dosing for maintenance of analgesia. This is probably due to changes in the administration of propofol made possible by BIS monitoring.

Adult↗
PubMed2002

[Effects of fentanyl on acetylcholine release from hippocampus and righting reflex in rat: an in vivo brain microdialysis study].

Fentanyl, a synthetic mu-opioid agonist, is one of the most popular opioids in clinical anesthesia. It is well-known that memory is affected by opioids and opioid antagonists in animals. Cholinergic neurones releasing acetylcholine (ACh) particularly in the hippocampus have been shown to be related to memory. This study, therefore, was conducted to examine the effects of fentanyl on hippocampal ACh release in rats. The experiments were performed on male SD rats under freely moving condition by in vivo brain microdialysis technique. After taking initial three samples, test drugs were administered. The ACh release was determined by HPLC-ECD method. Effect on behavior was determined as loss of righting reflex (LRR). Fentanyl 50, 100 and 200 micrograms.kg-1 i.p. significantly decreased the ACh release from the rat hippocampus. Naloxone, a mu-antagonist, 100 micrograms.kg-1 i.p. antagonized the inhibitory effect of fentanyl 100 micrograms.kg-1 i.p. on the ACh release in the hippocampus. Only fentanyl 200 micrograms.kg-1 i.p. produced LRR. The effects of fentanyl, the dose of which is so little that it does not produce LRR, on the rat hippocampal ACh release may be controlled by the inhibitory actions of mu-opioid receptors.

Acetylcholine↗
PubMed2002

Oral transmucosal fentanyl: new preparation. For breakthrough cancer pain when morphine fails.

(1) Some cancer patients suffer occasional breakthrough pain despite well-conducted opiate treatment, warranting the use of immediate-release oral morphine. (2) A fentanyl preparation for oral transmucosal administration has just been granted this indication in France. (3) The evaluation file mainly contains results from a randomised double-blind cross-over trial comparing transmucosal fentanyl with oral morphine tablets in cancer patients. It showed a small gain in terms of rapidity and efficacy of pain relief with fentanyl relative to morphine, but this was of dubious clinical relevance. (4) The adverse effects of oral transmucosal fentanyl are those of all opiates, such as drowsiness, dizziness, nausea, vomiting and confusion. (5) The oral transmucosal fentanyl preparation has the taste and appearance of a lollipop, and may therefore be attractive to children. The packaging seems to take this risk into account, but precautions must be taken to keep this treatment away from children, especially after opening. (6) Immediate-release oral morphine remains the standard treatment for breakthrough pain in patients receiving opiate therapy. If it is inadequate, oral transmucosal fentanyl may sometimes be slightly better.

Administration, Buccal↗
PubMedDate not supplied

Urodynamic changes following intrathecal administration of morphine and fentanyl to dogs.

The effect of intrathecal (i.t.) injection of morphine and fentanyl on the urinary bladder was studied by ascending cystogram in 18 anaesthetized dogs. Examinations were performed before and 60 and 120 minutes after i.t. injection of saline (group I), 0.03 mg/kg morphine (group II) and 1.5 microg/kg fentanyl (group III). A significant increase in maximal volume and compliance and a decrease in voiding pressure were observed, indicating relaxation of the detrusor muscle after i.t. administration of morphine or fentanyl. I.t. morphine produced greater and more prolonged bladder relaxation than i.t. fentanyl. We conclude that i.t. morphine and fentanyl cause variable degrees of urinary retention. As fentanyl produced milder and shorter bladder relaxation than morphine, it may be useful in patients with urinary disturbances.

Analgesics, Opioid↗
PubMed2003

[The effect of intrathecal fentanyl added to hyperbaric bupivacaine for caesarean section].

BACKGROUND: Management of cesarean section with spinal anesthesia is often accompanied with intraoperative nausea and pain. In a randomized controlled study, we explored the effect of intrathecal fentanyl on the characteristics of subarachnoid block in patients undergoing cesarean section. METHODS: Twenty-four healthy parturients scheduled for elective Cesarean section were allocated to receive either fentanyl 0.3 ml (15 micrograms) or 0.9% saline 0.3 ml added to 0.5% hyperbaric bupivacaine 2.0 ml given intrathecally in the right decubitus position (n = 12 in each group). Level of sensory blockade was evaluated with cold test and intraoperative use of antiemetics and analgesics was recorded. RESULTS: The maximum level of sensory blockade was significantly higher in the fentanyl group as compared with the control group (P = 0.019). Use of intraoperative antiemetics was significantly less often in the fentanyl group (P = 0.007). The required amount of intraoperative analgesics was smaller in the fentanyl group, although the difference was not significant (P = 0.11). No remarkable side effects, such as respiratory depression and hypoxia were observed. Apgar scores in the newborn were similar. CONCLUSION: Addition of intrathecal fentanyl to hyperbaric bupivacaine in parturients undergoing cesarean section improved quality of anesthesia without producing significant side effects.

Adjuvants, Anesthesia↗
PubMed2003

Postoperative pain management using fentanyl patches in dogs.

To the ability of the fentanyl patch to control pain in a postoperative canine model, we provided two male beagles with 25-mg/h patches and two with 50-mg/h patches 24 h prior to surgery. Each animal underwent a major abdominal surgical procedure to place three separate catheters with associated vascular access ports. Serum plasma levels of fentanyl were analyzed at multiple time points throughout the study period. Animals were subjectively assessed for postoperative pain by using a Simple Descriptive Scale at regular intervals postoperatively. Other parameters observed and recorded included heart and respiration rates, rectal temperature, appetite, and activity. The fentanyl patch appeared to adequately control postoperative pain in our canine abdominal surgical model. Three animals demonstrated mild pain 1 to 2 h postoperatively. Two animals, one from each dose group, showed mild pain 8 h postoperatively. Mild pain is commensurate with USDA category C, which encompasses procedures that do not result in more than momentary or slight pain or distress and do not require intervention. At no other time points were any of the animals considered to be in pain. Our study also suggested that increased subcutaneous fat delayed the rate of absorption of fentanyl. The lower body-weight beagles, which had the 25-mg/h patches, reached reported human serum analgesic levels within 8 h after placement, whereas the heavier beagles with the 50-mg/h patches reached human serum analgesic levels 12 h after placement. Fentanyl concentrations remained at the reported human analgesic levels in all animals between 2 to 4 h after the patches were removed. Regardless of the dose, decreases in heart rate, respiration rate, and temperature were observed in all four animals 12 h after placing the patches. Issues regarding the regulatory requirements to prevent drug abuse, the side effects and potency of fentanyl, and the prolonged duration of action as a transdermal system should be addressed by the veterinarian when considering usage of this analgesic method.

Administration, Cutaneous↗
PubMed2003

[Influence of different doses of fentanyl on T-lymphocyte subpopulations and natural killer cells of patients with esophageal tumor during preoperation and postoperation].

BACKGROUND & OBJECTIVE: Morphine has been proved to inhibit human immune system, and large dose of fentanyl also decrease the activation of natural killer cells. This study was designed to investigate the effects of different doses of fentanyl on T-lymphocyte subpopulations and natural killer cells during esophageal cancer surgery under general anesthesia. METHODS: Forty-five patients with esophageal cancer were randomly divided into 3 groups (I, II,III) with 15 cases in each group respectively. The doses of fentanyl in three groups were 5, 10, and 20 microg/kg, respectively. Central venous blood samples (6 ml) were collected before anesthesia, 24 hours and 48 hours after the operation, respectively. Monoclonal antibodies assay was used to identify T cells and NK cells. RESULTS: The counts of CD3(+) (T%) (Group I 50.30+/-8.42, Group II 48.53+/-9.62, GroupIII 46.58+/-8.56), CD4(+) (T%) (Group I 30.04+/-7.24, Group II 28.67+/-7.52, Group III 26.65+/-6.55),and NK cells (Group I 3.26+/-1.62, Group II 3.01+1.56, GroupIII 3.01+/-1.54) in three groups decreased significantly at 24 hours after surgery (P< 0.01). The decrease at 48 hours after surgery were more significant in groupIII (CD3(+) 48.89+/-9.82, CD4(+) 22.64+/-6.02, NK Cells 3.41+/-1.88) than in group I(CD3(+) 57.32+/-9.13, CD4(+) 35.62+/-5.98, NK cells 5.96+/-1.08) and group II(CD3(+) 55.62+/-10.21, CD4(+) 34.24+/-6.85, NK cells 6.04+/-1.09) (P< 0.05). There was no statistical significance in the counts of CD3(+), CD4(+), and NK cells between the time of 48 hours after the operation and preoperation in group I and group II. CONCLUSION: Fentanyl, as a kind of opiate drug, could contribute to the immunosuppression, and large-dose fentanyl administration would be more effective in suppression of immunity function than small dose fentanyl.

Adult↗
PubMed1992

[Rapid induction with vecuronium/fentanyl combinations for coronary artery surgery: influence on cardiovascular responses and plasma fentanyl concentrations].

Cardiovascular effects of fentanyl (60 micrograms.kg-1.min-1)/vecuronium combination for rapid induction were studied in fifty five patients for coronary artery bypass grafts. Cardiovascular and cerebral profiles of patients who had rapid fentanyl administration (39 patients) or slow fentanyl administration (15 patients) were compared with base line values and between each group. Plasma samples were assayed for epinephrine, norepinephrine, growth hormone, anti diuretic hormone and fentanyl. There were no differences in all hemodynamic parameters between each group. However, in the rapid administration group, statistically significant changes were detected in the heart rate, cardiac index, stroke volume index and left ventricular stroke work index. The changes in the heart rate were small and returned to the baseline value after sternotomy. A decrease in cardiac index after induction depends on a decrease in stroke volume index rather than in the heart rate. In rapid administration group, the EEG showed low frequency activity within a minute. The hormonal stress responses were significantly attenuated in both groups. High plasma concentrations of fentanyl could be achieved at the intubation. The data demonstrate that rapid induction by fentanyl is safe and convenient.

Anesthesia↗
PubMed1992

[Effects of high-dose fentanyl anesthesia on auditory brain stem responses].

It was previously reported that high-dose (50 micrograms.kg-1) fentanyl anesthesia had no effect on auditory brainstem response (ABR). However, the effect of the dose of 100 micrograms.kg-1 of fentanyl is unknown. We examined the effects of the dose of 50 micrograms.kg-1 and 100 micrograms.kg-1 of fentanyl on ABRs in 10 patients scheduled for cardiovascular surgery. No significant change was observed immediately after infusion of 50 micrograms.kg-1 of fentanyl, but peak latencies of waves I, III and V were significantly prolonged and the amplitude of wave V was significantly decreased immediately after infusion of 100 micrograms.kg-1 of fentanyl. The interpeak latencies of I-III and I-V were not affected. Therefore, prolongations of latencies of waves III and V were due to the change of latency of wave I. These results demonstrate that high-dose (100 micrograms.kg-1) fentanyl anesthesia depresses the peripheral auditory perception but dose not depress the central conduction.

Adult↗
PubMed2003

[Simulation analysis of estimated effect-site concentrations of propofol and fentanyl administered by a TCI system for other drugs].

BACKGROUND: We experienced a case of inadequate sedation because of inappropriate use of TCI system for fentanyl. METHODS: We evaluated the blood and effect-site concentrations of propofol and fentanyl calculated by a pharmacokinetic simulation model in which the administration of one drug was managed with target-controlled infusion pump set for another drug. RESULTS: In case propofol was administered with an effect-site-steering TCI system for fentanyl, the blood concentration of propofol increased within the first few minutes, especially immediately after starting the infusion, decreased for the next 10 minutes, and then was stabilized at a level of 0.7 times the target concentration. When fentanyl was administered with a blood-steering TCI for propofol, the calculated blood concentration of fentanyl was almost equal to the target concentration in the first few minutes, and then gradually increased until reaching 2.21 times the target concentration, at 240 minutes. Furthermore, the propofol concentration and the fentanyl concentration showed small differences between the target and calculated concentrations when the infusion time was not so long. CONCLUSIONS: When the administration time is short, the anesthesiologist must be aware of the difficulty in distinguishing the human error of choosing one drug for the TCI system for another drug.

Anesthesia, Intravenous↗