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PubMed1991

Comparison of continuous epidural bupivacaine infusion plus either continuous epidural infusion or patient-controlled epidural injection of fentanyl for postoperative analgesia.

We compared the postoperative epidural analgesia provided by the continuous epidural infusion of bupivacaine supplemented with patient-controlled injection (PCA) of epidural fentanyl with that provided by a continuous infusion of bupivacaine supplemented with a continuous epidural infusion of fentanyl. Our patient population comprised 16 ASA physical status I or II patients undergoing laparotomy with a midline incision under general anesthesia combined with bupivacaine epidural analgesia. Post-operatively, a continuous epidural infusion of bupivacaine (0.1 mg.kg-1.h-1) was combined with epidural fentanyl given by either (a) PCA (15-micrograms bolus with a lockout interval of 12 min, n = 8) or (b) continuous infusion (1 microgram.kg-1.h-1, n = 8). In the case of inadequate pain relief in the latter group, the fentanyl infusion rate was increased by 10 micrograms/h. Analgesia evaluated by a visual analogue pain score and by a verbal pain score was similarly effective in both groups. The sedation score was also similar in both groups. The total dose of epidural fentanyl administered during the first 24 h was significantly lower in the PCA group than in the continuous infusion group (405 +/- 110 micrograms vs 1600 +/- 245 micrograms, P less than 0.001). The dose of fentanyl given during each 4-h interval ranged between 40 and 160 micrograms in the PCA group and 251 and 292 micrograms in the continuous infusion group. Clinically detectable respiratory depression was not observed in either group. In conclusion, epidural administration of 0.1 mg.kg-1.h-1 bupivacaine combined with fentanyl provides effective postoperative analgesia with a total dose of fentanyl required that is lower when fentanyl is administered by epidural PCA rather than by continuous epidural infusion.

Adult↗
PubMed1993

An analysis of the duration of fentanyl and its metabolites in urine and saliva.

This study was undertaken to determine if metabolites of fentanyl might be useful in the detection and monitoring of substance abuse. The presence of fentanyl and two of its metabolites in the urine and saliva of seven female patients receiving small doses (110 +/- 56 micrograms) of fentanyl was studied up to 96 h from the time of administration. Fentanyl and its two metabolites (norfentanyl and despropionylfentanyl) were extracted from samples and analyzed by gas chromatography/mass spectrometry. Unchanged fentanyl was detectable in urine in all patients immediately postoperatively and in 3 of 7 patients at 24 h. By 72 h, fentanyl was undetectable. Norfentanyl was present in larger quantities than fentanyl immediately postoperatively and was detected in all patients at 48 h and in 4 of 7 patients at 96 h. Despropionylfentanyl was not detected in any of the urine specimens tested. Neither fentanyl nor its metabolites could be detected consistently at any time in saliva. Saliva testing does not appear to be a viable alternative to urine testing based on this study. Urinary norfentanyl might be considered as the substance of choice when testing for fentanyl abuse.

Adult↗
PubMed1993

Fentanyl plasma concentrations maintained by a simple infusion scheme in patients undergoing cardiac surgery.

The ability of a simple infusion scheme for fentanyl to achieve and maintain one of two target concentrations of fentanyl in plasma was studied in 17 patients having cardiac surgery that required the use of moderate hypothermic cardiopulmonary bypass (CPB). All patients received preanesthetic medication including morphine, a benzodiazepine, and/or scopolamine. Anesthesia was induced and maintained by one of two fentanyl infusion regimens: HIGH-FEN (n = 6), a priming infusion of 2.4 micrograms.kg-1 x min-1 for 20 min in combination with a continuous infusion of 0.3 microgram.kg-1.min-1 for the duration of the operation to produce a plasma fentanyl concentration of 20-25 ng/mL; or LOW-FEN (n = 11), priming and maintenance infusions of 2.4 and 0.15 micrograms.kg-1 x min-1 designed to produce a fentanyl concentration of 12-15 ng/mL of plasma. The six patients receiving HIGH-FEN had plasma fentanyl concentrations maintained between 20 and 27 ng/mL and none required anesthetic supplementation before CPB; one patient required a single dose of thiopental 50 mg after the termination of CPB. The total fentanyl dose for the operation (3.2 +/- 0.1 h) averaged 107 +/- 2 micrograms/kg (range 100.5-115.5 micrograms/kg). The 11 patients receiving LOW-FEN had a plasma fentanyl concentration maintained below 20 ng/mL (range 13-17 ng/mL). Eight patients before and 10 patients after CPB required anesthetic supplementation for adverse hemodynamic or somatic responses. For comparison purposes, another eight patients received a single 75 micrograms/kg dose of fentanyl during 20 min for induction of anesthesia, and 7 of the 8 required supplemental anesthetic agents before and after CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1993

Effects of fentanyl, diazepam, and the combination of both on arterial baroreflex and sympathetic nerve activity in intact and baro-denervated dogs.

The combination of fentanyl and diazepam significantly decreases systemic vascular resistance and blood pressure. We attempted to elucidate the reason the combination of these drugs can reduce blood pressure. In alpha-chloralose-anesthetized dogs, we investigated the effects of fentanyl and diazepam on mean arterial pressure (MAP) and arterial baroreflex control of renal sympathetic nerve activity (RSNA) in both intact (Study 1) and baroreflex-denervated dogs (Study 2). Study 1 included five dogs that received fentanyl 10 micrograms/kg followed by diazepam 0.4 mg/kg after a 10-min interval. Five more received both drugs in reversed sequence. The arterial baroreflex depressor test was performed with sodium nitroprusside before and after administration of each drug. Sensitivity of arterial baroreflex was examined by using the ratio of maximum increase of RSNA to maximum decrease of MAP (delta RSNA/delta MAP). RSNA and MAP significantly decreased only after both drugs had been administered (P < 0.05). Fentanyl alone did not attenuate arterial baroreflex sensitivity. Diazepam after fentanyl and diazepam alone attenuated baroreflex sensitivity to the same extent (P < 0.05). Study 2 comprised 14 dogs that underwent further surgical preparation of bilateral carotid sinus, aortic, and vagal nerve denervations. Seven received fentanyl, 5 and 10 micrograms/kg, and the other seven received diazepam, a total of 0.4 mg/kg. Fentanyl decreased both RSNA and MAP. Diazepam decreased only MAP significantly. The results indicate that fentanyl decreases mainly sympathetic outflow, whereas diazepam attenuates arterial baroreflex. We conclude that these combined effects of fentanyl and diazepam significantly decrease arterial blood pressure.

Animals↗
PubMed1994

Balanced postoperative analgesia: effect of intravenous clonidine on blood gases and pharmacokinetics of intravenous fentanyl.

Agonist interactions in antinociceptive effects between clonidine and opioids can be used to reduce opioid requirements in surgical patients. However, clonidine can cause marked sedation and associated respiratory dysfunction. Thus, the benefit of using clonidine to reduce opioid use on respiration is questionable. This double-blind randomized study compared the analgesic efficacy, arterial blood gases, and pharmacokinetics of an intravenous (IV) infusion of fentanyl 75 micrograms/h and a mixture of fentanyl 25 micrograms/h plus clonidine 0.3 micrograms.kg-1.h-1 in 32 healthy young adults after surgery for scoliosis correction. Oxygen saturation (FIO2: 0.21) and respiratory rate were monitored as well as supplemental analgesia demands (IV ketoprofen via a patient-controlled device), pain, sedation, and hemodynamics. Oxygen and naloxone (5 micrograms.kg-1.min-1) were administered, respectively, if more than three episodes of oxygen saturation less than 90% were observed within 10 min and if PaCO2 was higher than 50 mm Hg. Pain relief, sedation, and ketoprofen requirements were similar in both groups. The number of episodes of arterial desaturation less than 90% (> 20 s) was 106 for four patients in the fentanyl group (versus none in the clonidine-fentanyl group). Naloxone was required in six patients and oxygen in two patients of the fentanyl group (versus none in the group receiving clonidine). Dopamine, 10 micrograms.kg-1.min-1, was required in one patient of the clonidine-fentanyl group to correct hypotension. Mean arterial blood pressure, plasma clearance, and the elimination rate constant of fentanyl were lower in the clonidine-fentanyl group than in the fentanyl group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

The effect of different isoflurane-fentanyl dose combinations on early recovery from anesthesia and postoperative adverse effects.

UNLABELLED: We evaluated the effect of different combinations of fentanyl-isoflurane on early recovery from anesthesia in 80 adult patients undergoing laparoscopic cholecystectomy. Anesthesia was induced with fentanyl 2 microg/kg and thiopental 5 mg/kg. Nitrous oxide was not used and patients were randomly assigned to one of four groups: Group 1 (n = 20) received 0.6% end-tidal isoflurane plus fentanyl, Group 2 (n = 20) received 1.2% end-tidal isoflurane plus fentanyl, Group 3 (n = 20) received 1.8% end-tidal isoflurane plus fentanyl, and Group 4 (n = 20) received only isoflurane. In Groups 1, 2 and 3 isoflurane concentration was kept constant and fentanyl was given as necessary to maintain the mean arterial blood pressure within +/- 10% of the minimum mean arterial blood pressure measured in the ward. In Group 4, isoflurane concentration was adjusted to maintain mean arterial blood pressure as above. At the end of skin closure isoflurane was discontinued and the time to spontaneous breathing (TSB), time to extubation (TE) and time to eye opening (TEO) were recorded. In the postanesthesia care unit, the degree of sedation, respiratory rate, Spo(2), emesis, pain, and morphine consumption were evaluated every 15 min for 1 h, and thereafter every 30 min until discharge. Fentanyl requirements were 8.3 +/- 4.5 microg/kg (mean +/- sd) in Group 1, 3.8 +/- 1.3 microg/kg in Group 2, and 3.0 +/- 0.7 microg/kg in Group 3 (P < 0.001), whereas in Group 4 the mean end-tidal concentration of isoflurane was 2.0% +/- 0.4%. Although the mean TSB was <5.5 min in all groups, TE increased from 7.3 +/- 5.1 min in Group 1 to 20.6 +/- 10.7 min in Group 4 (P < 0.001), and TEO increased from 7.4 +/- 5.1 min in Group 1 to 25.8 +/- 9.4 min in Group 4 (P < 0.001). There were no differences among the groups in any of the variables measured in the postanesthesia care unit. This study shows that the combination of a small concentration of isoflurane and a relatively larger dose of fentanyl results in a faster recovery from anesthesia than the inverse combination of doses. IMPLICATIONS: A fast recovery from anesthesia increases patient safety. This study shows that the combination of a small concentration of isoflurane and a relatively larger dose of fentanyl results in a faster recovery from anesthesia than the inverse combination of doses.

Adjuvants, Anesthesia↗
PubMed2002

Fentanyl-associated syndrome of inappropriate antidiuretic hormone secretion.

A 43-year-old woman with advanced pulmonary blastoma was admitted for worsening back pain. Her drug regimen included hydromorphone and benazepril. On admission, hydromorphone patient-controlled analgesia (PCA) was started for acute pain control and dexamethasone for possible cord compression. Baseline laboratory tests were unremarkable, but magnetic resonance imaging revealed T3 and L3 lesions. Irradiation was started with improvement in her pain. In anticipation of discharge, a fentanyl transdermal patch was given, and PCA was tapered. Two days later, the patient became progressively confused and fell. Neurologic examination and computed brain tomography were normal. Her serum sodium was 119 mEq/L (normal 136-144 mEq/L) and was confirmed on repeat testing, urine sodium was 194 mEq/L, and urine and serum osmolalities were 554 mOsm/kg (normal 300-900 mOsm/kg) and 245 mOsm/kg (normal 280-300 mOsm/kg), respectively, consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluids were restricted, hydromorphone PCA was started again, and fentanyl was discontinued. After 36 hours, her serum sodium increased to 136 mEq/L. Because we were unsure whether the fentanyl or her cancer was causative and were unable to find any published reports of fentanyl-associated SIADH, we readministered the fentanyl patch 2 days later. Within 48 hours, serum sodium dropped to 123 mEq/L. Fentanyl was discontinued, fluids were restricted, and 3% saline was started. Her serum sodium increased to 132 mEq/L in 48 hours. The patient was prescribed oral hydromorphone and benazepril and was discharged. The repeated temporal relationship between the administration of fentanyl and the onset of SIADH strongly implicates fentanyl as the causative agent in this case. To our knowledge, this is the first report of fentanyl-associated SIADH.

Administration, Cutaneous↗
PubMed2005

Pharmacokinetics and dose proportionality of fentanyl effervescent buccal tablets in healthy volunteers.

BACKGROUND AND OBJECTIVES: Fentanyl effervescent buccal tablets (FEBT) are designed to enhance the rate and efficiency of fentanyl absorption through the buccal mucosa. This study was undertaken to characterise the pharmacokinetics and assess the dose proportionality of FEBT in healthy volunteers within the potential therapeutic dose range. METHODS: Twenty-five healthy adults (mean age 33 years) completed a single-dose, randomised, open-label, four-dose, four-period, crossover study of FEBT. They were administered FEBT 200, 500, 810 or 1080microg. The subjects in this study were not opioid tolerant; therefore, naltrexone was administered to block any opioid receptor-mediated effects of fentanyl. Venous blood samples for measurement of serum fentanyl concentrations were obtained over 36 hours following dosing. Adverse events were recorded throughout the study. RESULTS: The pharmacokinetics of FEBT were characterised by an absorption phase with a median time to reach maximum serum concentration (tmax) of 0.75-0.99 hours that was consistent irrespective of dose. Mean serum fentanyl concentrations exhibited a biexponential decline from peak after FEBT 200 and 500microg doses and a triexponential decline after FEBT 810 and 1080microg doses. The maximum serum concentration (Cmax) of fentanyl was proportional up to and including the 810microg dose. The increase in Cmax was 20% less than proportional at the 1080microg dose. Systemic exposure to fentanyl, as measured by the area under the serum concentration-time curve from time zero to infinity (AUCinfinity), increased proportionally with increasing doses of FEBT (200-1080microg). No serious adverse events were reported during the study. CONCLUSION: The pharmacokinetics of FEBT were characterised by a high early fentanyl concentration as a result of absorption across the buccal mucosa of the oral cavity, which results in bypassing first-pass metabolism. This high early tmax contributed to enhanced early systemic fentanyl exposure. Maximum concentration and AUCinfinity of FEBT increased in a dose-proportional manner from 200 to 810microg. This study provides preliminary pharmacokinetic data for FEBT across the potential therapeutic dose range.

Administration, Buccal↗
PubMed2000

Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats.

OBJECTIVE: To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats. ANIMALS: 6 healthy adult cats with a mean weight of 3.78 kg. PROCEDURE: Each cat was given fentanyl IV (25 mg/cat; mean +/- SD dosage, 7.19 +/- 1.17 mg/kg of body weight) and via a transdermal patch (25 microg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curve-stripping process followed by nonlinear, least-squares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data. RESULTS: Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 +/- 0.57 hours). Mean +/- SEM calculated rate of transdermal delivery of fentanyl was 8.48 +/- 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steady-state concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5-day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer.

Administration, Topical↗
PubMed2007

Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses.

REASONS FOR PERFORMING STUDY: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. OBJECTIVES: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. METHODS: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry. RESULTS: Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.

Anesthesia, General↗
PubMed1999

Pharmacokinetics of fentanyl after intravenous and transdermal administration in goats.

OBJECTIVE: To evaluate disposition of fentanyl in goats after IV and transdermal administration. ANIMALS: 8 healthy 2-year-old goats weighing 31.8 to 53.6 kg (mean+/-SD, 40.4+/-7.5 kg). PROCEDURE: Each goat was given 2 treatments consisting of fentanyl administered IV (2.5 microg/kg of body weight) and via a transdermal patch (50 microg/h). There was a 2-month interval between treatments. Blood samples were collected at specified times and analyzed in duplicate to determine plasma fentanyl concentrations. Pharmacokinetic values were calculated, using a computerized modeling program. RESULTS: Administration of fentanyl was tolerated by all goats. Intravenous administration of fentanyl resulted in a transitory increase in rectal temperature that was not clinically important. Terminal elimination half-life after IV administration was 1.20+/-0.78 h, volume of distribution at steady state was 1.51+/-0.39 L/kg, and systemic clearance was 2.09+/-0.62 L/kg/h. Transdermal administration of fentanyl resulted in variable plasma concentrations, with peak plasma concentrations ranging from 1.12 to 16.69 ng/ml (mean+/-SD, 6.99+/-6.03 ng/ml) and time to peak concentration ranging from 8 to 18 hours (mean+/-SD, 13+/-4.5 hours). After removal of the transdermal patch, mean+/-SD terminal elimination half-life was 5.34+/-5.34 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of fentanyl (2.5 microg/kg) in goats results in a relatively short half-life that will limit its use for management of pain. Transdermal administration of fentanyl (50 microg/h) in goats results in variable plasma concentrations that may exceed those anticipated on the basis of a theoretical delivery rate, but stable plasma concentrations of fentanyl may not be achieved.

Administration, Cutaneous↗
PubMed2001

[Tracheal intubation without muscle relaxants using propofol and varying doses of fentanyl].

This study was designed to evaluate airway and intubating conditions without muscle relaxants after administration of fentanyl and propofol in 55 patients aged 20-60 years for elective surgery. Patients were randomly assigned to one of four groups to receive fentanyl 0, 2, 3, or 4 micrograms.kg-1, respectively. Three minutes after the administration of fentanyl, propofol (2 mg.kg-1) was given for induction of anesthesia. After the loss of consciousness, laryngoscopy and tracheal intubation, supplemented with topical anesthesia of lidocaine (2 mg.kg-1), were attempted. In control group, without administration of fentanyl, all patients were judged to provide poor intubating conditions. Increasing doses of fentanyl reduced the incidences of movement and persistent coughing on laryngoscopy and intubation in a dose-related manner. However, visualization of the vocal cord was significantly. (P < 0.05) more likely to be impossible in patients in 4 micrograms.kg-1 fentanyl group (40%) compared with patients in 2 micrograms.kg-1 fentanyl group (7%). There were no significant differences among groups receiving fentanyl with respect to vocal cord position. The vocal cords were closed in 26% of patients receiving fentanyl and propofol for intubation. Tracheal intubation without muscle relaxants is not recommended because of the potential unacceptable intubating conditions.

Adult↗
PubMed2002

Effects of intravenous ketorolac and fentanyl combined with midazolam on analgesia and side effects during extracorporeal shock wave lithotripsy.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) is usually carried out on ambulatory or outpatient basis, and thus an appropriate anesthesia with minimal side effects is required. This study was to compare the analgesic and side effects of intravenous ketorolac with that of intravenous fentanyl, in combination with midazolam in ESWL. METHODS: Sixty patients were randomly divided into two groups; group K (n = 30) received 60 mg ketorolac i.v. 30 min before ESWL and group F (n = 30) received 100 micrograms fentanyl i.v. 3 min before ESWL. All patients received 2.5 mg midazolam i.v. 3 min before ESWL for intraoperative sedation. The pain intensity was evaluated by a numeric rating scale (NRS). A supplemental analgesia with intravenous fentanyl 25 micrograms was given when inadequate analgesia occurred (NRS > 3). Oxygen supplement through a face mask was given when the SpO2 fell below 94%. Side effects (nausea, vomiting, dizziness) and the time of discharge from post-anesthesia room (PAR) were recorded. The criterion of discharge from PAR was absence of any discomfort especially when the patient held upright. RESULTS: There was no difference between two groups in the demographic data, number of shock waves, duration of ESWL procedure, and fentanyl supplement. The incidence of oxygen supplement was lower in ketorolac group (1/30) compared with that of fentanyl group (20/30), P < 0.01. The frequency of dizziness was lower in ketorolac group (1/30) than that in fentanyl group (25/30), P < 0.01. Three patients in fentanyl group complained of nausea, but none did in ketorolac group. The discharge time from PAR was significantly shorter in ketorolac group (14.7 +/- 8.4 min) than that in fentanyl group (49.5 +/- 14.6 min), P < 0.01. CONCLUSIONS: Both intravenous ketorolac and fentanyl in combination with midazolam could provide good anesthesia for ESWL. However, ketorolac plus midazolam had less side effects and allowed shorter discharge time from PAR. We suggest that intravenous ketorolac combined with midazolam is a safe and effective anesthetic regiment for ESWL, particularly on ambulatory basis.

Adult↗
PubMed2002

Effect of fentanyl on TNF-alpha and IL-1beta levels during global ischemia/reperfusion in rats.

To reduce surgical stress, fentanyl is frequently used for neurosurgical procedures in which focal and/or global ischemia may occur. However, the effect of fentanyl on cytokine levels during ischemia/reperfusion is still uncertain. The goal of this study was to evaluate the effect of fentanyl infusion on levels of the proinflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, during global cerebral ischemia/reperfusion in rats using the intracerebral microdialysis technique. Forty male Sprague-Dawley rats weighing 280-320 g were randomly assigned to each of four groups: group 1 (no fentanyl infusion and only ischemia/reperfusion); group 2 (1.5 ng/ml of fentanyl infusion during ischemia/reperfusion) and group 3 (3 ng/ml of fentanyl infusion during ischemia/reperfusion) (n=5 in each group). The rats were anesthetized with an intraperitoneal injection of pentobarbital (50 mg/kg). They were then intubated and ventilated with room air using an animal ventilator. A CMA-12 probe was inserted into the left hippocampal CA-1 region according to the guidelines. Artificial cerebrospinal fluid was run from the inserted microdialysis probe and infused with or without fentanyl at 3 microl/min using a microinjection syringe pump during ischemia/reperfusion. Ischemia was induced by clamping the carotid arteries. Hemorrhagic hypotension was induced for 17 min via the femoral artery, and reperfusion was accomplished by unclamping the sling and reinfusing the blood via the femoral artery. After 2 h of stabilization, the microdialysate was collected 10 times every 17 min, just before ischemia (control), after ischemia (I) and after reperfusion (R1-R8), and stored at -80 degrees C until analysis using high-performance liquid chromatography During global ischemia/reperfusion, TNF-alpha and IL-1beta significantly increased at reperfusion (R5) compared with the control value (p < 0.05). However, in both cases of fentanyl infusion, TNF-alpha and IL-1beta showed no increase compared with the control value. Fentanyl inhibited an increase of the proinflammatory cytokines, TNF-alpha and IL-1beta levels, during global cerebral ischemia/reperfusion in rats.

Anesthetics, Intravenous↗
PubMed2002

Comparison of sufentanil and fentanyl for surgical repair of congenital cardiac defects.

In the present study, the authors compared sufentanil to fentanyl in pediatric patients undergoing congenital cardiac repair. The purpose of the study was to evaluate the hemodynamic variables, time of awakening and successful extubation of the two groups. A prospective, randomized study of 60 children scheduled for elective surgery of congenital cardiac defects was made. Patients were randomly divided into two groups: Group I; sufentanil and Group II; fentanyl (mean body weight, 16.02 +/- 6.67 kg; range 4 to 35 kg; mean age, 5.22 +/- 3.55 years; range 4 months to 1 year). All were premedicated with oral chloralhydrate 50 mg/kg, one hour preoperatively. Anesthesia was induced with sufentanil 1 microg/kg (Group I) or fentanyl 2 microg/kg (Group II) and thiopenthal 2 mg/kg, followed by atracurium 0.6 mg/kg. All patients were intubated with atracurium 0.6 mg/kg. Anesthesia was maintained using isoflurane in oxygen, nitrous oxide (in non-cyanotic patients). In Group I, sufentanil 0.5 microg/kg was administered intravenously prior to skin incision, median sternotomy, cardiopulmonary bypass (CPB) and after coming off CPB. In Group II, fentanyl 1 mg/kg was administered at the same time periods. Hemodynamic parameters, heart rate (HR), systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP), central venous pressure (CVP) were recorded. The administration of pain therapy was determined postoperatively. There was no statistical difference in the demographic data between the patients in the two groups. Following induction of anesthesia, the systolic, diastolic and mean arterial pressures and heart rate decreased. Following tracheal intubation, all hemodynamic parameters in the sufentanil group remained below the baseline values, while the fentanyl group showed an increase above baseline values. An increase above control values of all hemodynamic variables was detected in both groups following skin incision and sternotomy, except that the mean systolic blood pressure and heart rate in the sufentanil group was less than the baseline values. No differences in hemodynamic variables were detected between the two groups following median sternotomy and skin closure. There were significant differences in mean arterial pressure at the time of intubation and skin incision between the two groups. No significant changes in CVP occurred. There were no significant differences in the average time of awakening from anesthesia. The average time before postoperative tracheal extubation was 171.38 +/- 112.74 and 113.72 +/- 67.83 minutes in the sufentanil group and fentanyl group respectively, which was statistically significant. There was no difference in the requirements for morphine (pain relief) and sedation with chlolorahydrate between the groups. Bradycardia was found in 7 and 3 patients receiving sufentanil and fentanyl respectively which was not statistically significantly different. The bradycardia recovered in a few minutes, following intravenous injection of atropine. Slow injection of the anesthetic drugs can protect patients against serious bradycardia. In conclusion, the safety and efficacy of sufentanil in patients undergoing repair of complex congenital heart defects was the same as fentanyl. There were no significant differences in times of awakening in the two groups. The patients in sufentanyl group had a longer time to extubate than the fentanyl group. The need of postoperative sedation and analgesia was the same in both groups.

Analysis of Variance↗
PubMed2002

Fentanyl-induced coughing and airway hyperresponsiveness.

BACKGROUND: The tussive effect of fentanyl, in sharp contrast to the antitussive effect that common opioids have, is not rarely seen in clinical anesthesia. Pretreatment with beta 2 agonist inhalation could dramatically suppress fentanyl-induced coughing. We hypothesized that airway hyperresponsiveness might exist in large proportion of the subjects who had experienced fentanyl-induced coughing during previous anesthesia. METHODS: We designed a case-controlled matching study to investigate the correlation between fentanyl-induced coughing and airway hyperresponsiveness. Twenty-six consecutive subjects (ASA I-III), who experienced fentanyl-induced coughing during anesthesia in our hospital from 1999 to 2000, were enrolled in this study as the fentanyl-cough group. In all the subjects baseline spirometry was first obtained. Airway responsiveness was evaluated with either PC20 of methacholine challenge test or bronchodilator test. After matching age and sex, another 26 subjects without history of fentanyl-induced coughing during previous anesthesia were also enrolled in the study as the control group. RESULTS: The proportion of airway hyperresponsiveness in fentanyl-cough group and control group was 30.77% and 19.23% respectively. After pairing of these two groups, McNemar test revealed no significant difference in the proportion of airway hyperresponsiveness between these two groups (P = 0.257). CONCLUSIONS: From the analysis of the present study, we cannot prove that there is a direct correlation between fentanyl-induced coughing and airway hyperresponsiveness.

Adolescent↗
PubMed1992

[Cardiovascular effects of, and catecholamine response to, high dose fentanyl or NLA in patients for valve replacement].

We measured the cardiovascular effect of, and catecholamine and other hormonal responses to, anesthetic doses of fentanyl and original NLA in 25 patients for open heart surgery. The patients were randomly divided into three groups (group N, F30, F75). During induction, in group N; droperidol 0.25 mg.kg-1 and fentanyl 5 micrograms.kg-1, in group F30; fentanyl 30 micrograms.kg-1, and in group F75; fentanyl 75 micrograms.kg-1 were administered intravenously. Additional fentanyl was administered at a rate of 100 to 200 micrograms.h-1. Droperidol 0.25 mg.kg-1 was administered in group N when cardiopulmonary bypass (CPB) was disconnected. Plasma samples were assayed for norepinephrine, epinephrine, ACTH and cortisol before and after induction, during sternotomy, 60 minutes after institution of CPB, after weaning from CPB, and before as well as after extubation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and rate pressure product (RPP) were calculated simultaneously at the blood samplings. In all groups, no remarkable change in cardiovascular dynamics was observed. CPB was associated with marked increases in catecholamines, but high dose fentanyl in dose of 75 micrograms.kg-1 was able to suppress epinephrine level more than in group N. In high dose fentanyl group (F30, F75) ACTH was within normal ranges, even during CPB. The results suggest that high dose fentanyl is a complete anesthetic in patients for cardiac surgery. But a large dose of fentanyl causes small decreases in heart rate and arterial blood pressure. Our data indicate that group F30 is an attractive anesthetic technique for patients with valvular disease.

Adrenocorticotropic Hormone↗
PubMed2003

Comparison of remifentanil and fentanyl in patients undergoing modified radical mastectomy or total hysterectomy.

OBJECTIVE: To compare the efficacy and safety of remifentanil and fentanyl in patients undergoing a modified radical mastectomy or total hysterectomy. METHODS: Fifty-four patients were evenly randomised into remifentanil group and fentanyl group. Anesthesia was induced by propofol (1 - 2 mg/kg) and either remifentanil (2 microg/kg) or fentanyl (2.5 microg/kg), and was maintained with inhalation of nitrous oxide in oxygen (2:1) and continuous infusion of either remifentanil (0.2 microg.kg(-1).min(-1)) or fentanyl (0.03 microg.kg(-1).min(-1)). RESULTS: The number of patients exhibiting light anesthesia responses in the remifentanil group during intubation and the maintenance of anesthesia was significantly less than that in the fentanyl group. Both systolic and diastolic blood pressures in the fentanyl group were significantly higher than those in the remifentanil group during intubation, skin incision, maintenance of anesthesia and extubation. The time to opening eyes on command and the time for extubation after surgery was comparable between the two groups. More patients in the remifentanil group (25 patients) required bolus injection of morphine for postoperative pain relief than those in the fentanyl group (5 patients, P < 0.05). There was no significant difference between the two groups in terms of side effects. CONCLUSIONS: Under the condition of this study protocol, the anesthetic and analgesic effects of remifentanil are more potent than those of fentanyl. Remifentanil can offer superior intraoperative hemodynamic stability in comparison with fentanyl, and has no compromising recovery from anesthesia.

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