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At least 19 recordsLinked to original sources
PubMed1977

Urine catecholamine excretion after large doses of fentanyl, fentanyl and diazepam and fentanyl, diazepam and pancuronium.

The effects of fentanyl (0.5 mg/kg iv), fentanyl with diazepam (1 mg/kg iv) and fentanyl, diazepam and pancuronium (0.1 mg/kg iv) on heart rate (HR), mean arterial blood pressure (BP), cardiac output (QT), urine flow rate and urine epinephrine and norepinephrine excretion were determined in nine dogs. Fentanyl did not significantly change QT or BP but did reduce HR and urine flow rate (P less than 0.05). Urine epinephrine and norepinephrine excretion rates were signicantly increased by fentanyl (P less than 0.05). Diazepam caused no significant further changes in QT, BP or HR 30 minutes after administration, but urine epinephrine and norepinephrine excretion rates were reduced to control (pre-fentanyl) levels. Addition of pancuronium after fentanyl and diazepam increased urine flow rate to pre-fentanyl levels and elevated QT, BP and HR above controls but produced no significant change in urine epinephrine or norepinephrine excretion. These data suggest that fentanyl increases catecholamine blood levels and imply that the latter may be one mechanism by which cardiovascular dynamics are maintained stable during fentanyl anaesthesia. Our findings also demonstrate that cardiovascular stimulation after pancuronium is not associated with increased urinary catecholamine excretion.

Animals↗
PubMed1976

The magnitude and duration of respiratory depression produced by fentanyl and fentanyl plus droperidol in man.

In 10 healthy male volunteers breathing 100% oxygen, we determined the effect of four intravenous dose levels of fentanyl (0.0015, 0.003, 0.006 and 0.009 mg/kg) and two of fentanyl plus droperidol (i.e., Innovar, 0.003 and 0.006 mg/kg of fentanyl with 2.5 mg of droperidol for each 0.05 mg of fentanyl) on PECO2 and the slope of the ventilatory response to imposed increases in PECO2. All doses of fentanyl and fentanyl plus droperidol depressed the slope and shifted the curve to the right. Depression was dose related and was maximum 5 minutes after administration. The slope returned to control by 2 hours postinjection even at the highest narcotic dose. However, the rightward shift of the CO2 response curve require 4 hours to return to control. Droperidol added to fentanyl did not increase or prolong the respiratory depression seen with fentanyl alone at equivalent dose levels. Nausea and emesis occurred more frequently with fentanyl alone and orthostatic hypotension occurred more frequently with droperidol plus fentanyl. Dysphoria was a prominent consequence of fentanyl plus droperidol administration.

Adult↗
PubMedDate not supplied

Fentanyl receptor assay. II. Utilization of a radioreceptor assay for the analysis of fentanyl analogs in urine.

A radioreceptor assay has been developed to measure fentanyl and fentanyl-like drugs in biological specimens. The assay is based on the competition of these drugs with [3H]fentanyl for opioid receptors. Rats were injected intravenously with fentanyl (15 micrograms/kg), alpha-methylfentanyl (15 micrograms/kg), (+/-)-cis-3-methylfentanyl (15 micrograms/kg), butyrylfentanyl (0.48 mg/kg), and benzylfentanyl (3.19 mg/kg). Urine samples were analyzed by radioreceptor assay (RRA), radioimmunoassay (RIA), and gas chromatography/mass spectrometry (GC/MS). The time-course of urinary analysis of fentanyl analogs showed some discrepancies. RRA measurement of urine concentrations of (+/-)-cis-3-methylfentanyl that were undetectable by RIA gave results 5-10 times higher than values obtained by GC/MS. Concentrations of alpha-methylfentanyl obtained by RRA and GC/MS were similar; however, these samples were negative by RIA. Following the administration of benzylfentanyl, urinary concentrations were not detected by RIA and only slightly detectable with RRA; however, high concentrations of benzylfentanyl were found by GC/MS in the same samples. Urine samples from animals injected with butyrylfentanyl showed high cross-reactivity with fentanyl antibody, giving values measured by radioimmunoassay about two times higher than those obtained by the other two methods. These findings suggest that this radioreceptor assay is well-suited as an initial assay for the detection of active analogs of fentanyl in urine and correlates well with other techniques in the analysis of fentanyl; however, there is substantial disagreement between techniques in the quantitation of fentanyl analogs.

Analgesics↗
PubMedDate not supplied

Cardiovascular dynamics after large doses of fentanyl and fentanyl plus N2O in the dog.

The effects of large doses of fentanyl (0.05 to 2 mg/kg) and fentanyl plus N2O on cardiovascular dynamics were determined in 10 unpremedicated dogs breathing 100% O2. Using computer analysis of the central aortic pulsepressure curve, stroke volume (SV), cardiac output, heart rate (HR), peripheral vascular resistance (PVR), and systolic, diastolic, and mean arterial blood pressures (BP) were determined while fentanyl was being given at a rate of 0.3 to 0.44 mg/min. Fentanyl caused a dose-related decrease in HR, which was significant at 0.05 mg/kg. Cardiac output, PVR, and systolic, diastolic, and mean arterial BP were also decreased and SV increased. The latter changes became significant at 0.1 mg/kg for diastolic BP; 0.15 mg/kg for cardiac output and mean BP; 0.25 mg/kg for sv and systolic BP; and at 1.25 mg/kg for peripheral vascular resistance. Addition of N2O after fentanyl did not significantly change any parameter, although SV, cardiac output, and HR were usually increased and PVR decreased. These data demonstrate that, while large doses of fentanyl or fentanyl plus N2O do alter cardiovascular dynamics in dogs, the changes appear to be less profound than those produced by equianalgesic doses of morphine. Our findings suggest that large doses of fentanyl-O2 may be an attractive alternative to morphine-O2 anethesia in critically ill patients.

Anesthesia, Inhalation↗
PubMed1975

Hemodynamic and ventilatory responses to fentanyl, fentanyl-droperidol, and nitrous oxide in patients with acquired valvular heart disease.

Fentanyl (10 mug/kh) or fentanyl (10 mug/kg) plus droperidol (100 mug/kg) administered intravenously during 20 minutes to adult patients with acquired valvular heart disease produced minimal circulatory changes. The trend during drug infusion was for mean arterial pressure and systemic vascular resistance to decrease, and for cardiac index and stroke volume index to increase without change in heart rate. Central venous pressure increased during drug infusion (P less than 0.05) but decreased to awake levels following controlled ventilation and skeletal-muscle paralysis, probably reflecting thoracoabdominal-muscle rigidity rather than a circulatory response. Hypoventilation during drug infusion necessitated assisted or controlled ventilation, with or without skeletal muscle paralysis, in 14 of 16 patients. Addition of 60 per cent nitrous oxide following fentanyl or fentanyl-droperidol infusion significantly decreased mean arterial pressure, heart rate, and cardiac index. All circulatory changes were similar in direction and extent to those previously found during morphine-nitrous oxide anesthesia. (Key words: Anesthetics, intravenous, fentanyl; Anesthetics, gases, nitrous oxide; Heart, effect of fentanyl, dorperidol, and nitrous oxide.).

Adult↗
PubMed1976

The effects of large doses of fentanyl and fentanyl with nitrous oxide on renal function in the dog.

Renal effects of large doses of fentanyl (1 mg/kg) were determined in 14 mongrel dogs before and after addition of 50 per cent nitrous oxide. Fentanyl significantly increased urine osmolarity and decreased urine output and free water clearance but did not change inulin or PAH clearances. The arterial blood pressure and cardiac output were significantly decreased after 0.1 mg/kg fentanyl and these changes were then maintained during the remainder of the study period. Addition of nitrous oxide produced no further changes in cardiac output and arterial blood pressure but did increase urine output, PAH, inulin and free water clearances and decreased urine osmolarity. These data demonstrate that high doses of fentanyl have significant antidiuretic properties in the dog and these probably are related to the release of antidiuretic hormone. Our results also indicate that addition of nitrous oxide reverses fentanyl induced antidiuresis.

Animals↗
PubMed2026

Partially countering the physiological effects of fentanyl with naloxone or d-cysteine ethyl ester in adult goats.

Fentanyl is the leading contributor to opioid-involved overdose (OD) mortality in the United States. Despite the demonstrated efficacy, safety, and wide availability of naloxone (NAL), opioid-involved OD fatalities remain high. This suggests our understanding of the negative integrated physiological effects of fentanyl remains incomplete, and highlights the need to develop additional novel countermeasures. Here we tested whether the physiological and behavioral effects of intravenous fentanyl in adult female goats (n = 12) could be mitigated with NAL or the potential countermeasure d-cysteine ethyl ester (d-CYSee). As hypothesized, intravenous injections of high doses (HD) fentanyl caused immediate ventilatory suppression via reduced breathing frequency leading to hypoventilation and hypoxemia (≥10 min). HD fentanyl elicited immediate and sustained (≥90 min) increases in diaphragm, intercostal, abdominal, and laryngeal constrictor muscle activity along with an increased alveolar to arterial oxygen (A-a O2) gradient and hypertension. Intravenous NAL administered immediately following HD fentanyl mitigated most of these effects except the increased activation of respiratory pump and airway muscles. In contrast, d-CYSee administration immediately following HD fentanyl countered the initial hypoventilation but did not mitigate the increases in muscle activation and persistent hypoxemia. Neither treatment prevented acute withdrawal-like behaviors emerging >90 min after fentanyl administration. The data suggest that there are physiological effects of HD fentanyl that are NAL-insensitive, and d-CYSee can transiently normalize blood gases and counter opioid-induced respiratory depression (OIRD) in adult goats.NEW & NOTEWORTHY Here we determined whether any of the deleterious physiological effects of high-dose fentanyl could be countered by naloxone and/or d-cysteine ethyl ester (d-CYSee) in adult goats. Fentanyl induced hypoventilation and sustained increases in respiratory and airway muscle activity and hypoxemia. Naloxone reversed all fentanyl effects except tonic muscle activation, and d-CYSee reversed fentanyl-induced hypoventilation. These data suggest some effects of fentanyl are naloxone-insensitive and that d-CYSee may be a valuable countermeasure for OIRD.

Animals↗
PubMed1979

Fentanyl concentrations in brain and serum during respiratory acid--base changes in the dog.

It is a clinical impression that less fentanyl is needed for anesthesia during hyperventilation and hypocarbia. If true, it might be due to both increased penetration of fentanyl, a highly lipid-soluble agent, into the brain and increased brain tissue binding. Serum and brain concentrations of fentanyl were determined in dogs anesthetized with halothane during normocarbia, hypocarbia by hyperventilation, and hypercarbia by addition of CO2 to the inspired mixture. Fentanyl, 12.5 micrograms/kg, was injected iv, and serum and brain samples were taken for fentanyl analysis by radioimmunoassay. Brain fentanyl values peaked latest (15--20 min) and were highest during hypocarbia; brain fentanyl values peaked earliest (0--5 min) and were lowest during hypercarbia; values during normocarbia were intermediate in time to peak (10--15 min) and concentration. Thereafter, brain levels declined, but during hypocarbia were significantly higher and during hypercarbia were significantly lower than during normocarbia. Interestingly, serum fentanyl levels were also significantly higher during hypocarbia. The brain--blood fentanyl ratios for each of the three CO2 levels increased for 30 min and thereafter stayed relatively constant. The brain--blood ratios were highest with hypocarbia and lowest with hypercarbia. At 35 min, when clinical analgesia may be considered terminated, hypocarbic brain levels were double those of normocarbia. The authors feel this reflects, to a large extent, higher serum fentanyl concentrations and delayed cerebral wash-out because of decreased blood flow. To a small but unknown extent the higher brain fentanyl levels result from increased brain--blood penetration due to increased lipid solubility, and increased brain tissue binding of fentanyl during respiratory alkalosis.

Alkalosis, Respiratory↗
PubMed1979

Pharmacokinetics of 3H-fentanyl in the dog anesthetized with enflurane.

Fentanyl is often used as an anesthetic supplement for short procedures because it has a rapid onset and brief duration of action. However, persistence of ventilatory depression several hours following the last dose has been seen. The authors studied the pharmacokinetics of fentanyl in the dog to find an explanation for the occasionally prolonged duration of action. 3H-fentanyl citrate, 10 or 100 microgram/kg, was injected intravenously in dogs anesthetized with enflurane-O2. Arterial plasma and urine were analyzed for unchanged 3H-fentanyl and for total 3H radioactivity. Kinetic indices were derived by nonlinear least-squares analysis of log concentration (ng/ml) vs. time relationships. Initially, the elimination of fentanyl from plasma was very rapid, and 98 per cent of the amount administered was removed from plasma in the first 5 min after an intravenous injection. However, the terminal elimination phase was prolonged (t1/2 = 199 +/- 17 min). The apparent volume of distribution was large (9.81/kg) and independent of dose. Repetitive doses produced an accumulation of fentanyl. 3H-labelled metabolites of fentanyl were present in the earliest samples of plasma, and accounted for the major portion of the total 3H radioactivity in both plasma and urine. Urine collected for six hours contained 36 per cent of the total 3H radioactivity administered, but only 4 per cent of fentanyl administered was excreted as unchanged fentanyl. The authors conclude that most of a single dose of fentanyl is rapidly eliminated from the body by biotransformation and leads to accumulation of the drug when administered in very large or repeated doses. Under these circumstances the slow release of drug from tissues results in persistent plasma levels of fentanyl and a prolonged duration of action.

Anesthesia, Inhalation↗
PubMed1978

Pharmacokinetics of fentanyl as determined by radioimmunoassay.

The pharmacokinetics of fentanyl were determined in human surgical patients using radioimmunoassay. Fentanyl was measured in the serum, cerebrospinal fluid (CSF), and urine of patients receiving 0.1, 0.5, or 1.0 mg/m2 of fentanyl intravenously. The kinetics of the disappearance of fentanyl from the serum were very similar at the three administered doses. At all doses, levels fell rapidly in the first five minutes to approximately 20% of the peak value. Thereafter, serum levels fell more slowly with an observed half-life (t 1/2) of approximately 10 to 20 min. depending on dose. By 2 hr serum levels had stabilized at low values (1, 5, and 8 ng/ml) and continued to decrease very slowly thereafter, with an observed t 1/2 of 1 to 2 hr at the low dose (0.1 mg/m2) and greater than 4 hr at 0.5 and 1.0 mg/m2. The serum elimination curves were dissected and described mathematically in terms of a three-compartment model. Urinary excretion of fentanyl accounted for 15% to 20% of the administered dose. Urinary excretion was very low during the first 2 hr, suggesting that this route of elimination is not important in terminating the actions of fentanyl in man. Fentanyl levels in the CSF of patients given terminating the actions of fentanyl in man. Fentanyl levels in the CSF of patients given the high dose (1 mg/m2) were low, and never exceeded 4 ng/ml. Peak levels of fentanyl in the CSF were not seen until at least 15 min after administration.

Adult↗
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↗
PubMedDate not supplied

Cardiovascular effects of fentanyl during enflurane anesthesia in man.

The cardiovascular effects of three doses of intravenous fentanyl (50, 100, and 200 microgram) were determined in 42 adult patients undergoing intraabdominal surgical procedures with enflurane (2--3%) and nitrous oxide (50%) in oxygen. Fentanyl was administered a minimum of 40 minutes after induction of anesthesia and 30 minutes after initiation of the surgical procedure. Stroke volume, heart rate, cardiac output, mean arterial and central venous blood pressures, and peripheral arterial resistance were determined by computer analysis of the central aortic pulse-pressure curve according to the method of Warner. Measurements were made before and 2, 4, 6, 8, and 10 minutes after fentanyl. Fentanyl (50 microgram) produced increases in stroke volume and cardiac output as well as a decrease in peripheral arterial resistance but did not alter heart rate or mean arterial blood pressure. Fentanyl (100 microgram) did not significantly change any variable at any time. Fentanyl (1l (200 microgram) produced sustained decreases in stroke volume, cardiac output and mean arterial blood pressure and increased central venous pressure but did not alter heart rate or peripheral arterial resistance. The data indicate that fentanyl (50--100 microgram) stimulates or has no effect on cardiovascular dynamics during enflurane-nitrous oxide anesthesia but fentanyl (200 microgram) produces significant cardiovascular depression. Our findings suggest that small doses of intravenous fentanyl may be of benefit during enflurane-nitrous oxide but larger doses should probably be avoided.

Adult↗
PubMed1977

Alpha-adrenergic blocking action of fentanyl on the isolated aorta of the rabbit.

The contractile response of helically-cut strips of rabbit ascending aorta to transmural electrical stimulation was attenuated in a dose-dependent manner by treatment for 20 min with fentanyl, 10(-6) to 10(-5) M. Fentanyl also shifted the dose-response curve of the contractile response of aorta to norepinephrine to the right. The response to transmural stimulation was more resistant to fentanyl than was the response to an equipotent dose of norepinephrine. The inhibitory effect of fentanyl was neither prevented nor reversed by naloxone, but was partially reversed by repeated washing of the preparations. The contractile responses to histamine and serotonin were not significantly altered by fentanyl. Treatment with fentanyl as well as phentolamine protected alpha-adrenergic receptors from persistent blockade by phenoxybenzamine. Morphine to 10(-3) M failed to influence the dose-response curve of norepinephrine significantly. It may be concluded that fentanyl reversibly blocks alpha-adrenergic receptors in a competitive manner in vascular smooth muscle, and the potency of fentanyl is approximately 1/30 that of phentolamine.

Adrenergic alpha-Antagonists↗
PubMed1978

[Plasma concentration of fentanyl during and after its administration at constant flow].

Using the technique of the radio-immunological estimation with fentanyl-H3, a study was made in sixteen adults anaesthetised by the administration at a constant rate of alfadione and fentanyl, of plasma concentrations of fentanyl during and after anaesthesia. Anaesthesia was induced by the administration of 4.2ml of alfadione and 0.084mg of fentanyl. The maintenance dose was 0.147 ml/kg/hour of alfadione and 2.95 microgram/hg/hour of fentanyl. Five minutes after induction, the concentration of fentanyl was 2.7 microgram/l. The level fell significantly to 2.56 microgram/l at the 45th minute. From this point onwards, it increased regularly up to the 120th minute, when it reached a level of 3.7 microgram/l. When the infusion was stopped, the level first decreased rapidly, the excretion curve then becoming flattened out. At the 120th minute, a level of 1 microgram/l persisted. This study indicates that the administration of fentanyl at a constant rate is not accompanied by a constant blood concentration up to the 120th minute, the point at which the study was terminated. The residual level found after administration and in the absence of any clinical effect implies the need for a reduction in dose at the time of any complementary administration of fentanyl during the postoperative period.

Adult↗
PubMed1978

[Respiratory depression after fentanyl and antagonism by naloxone (author's transl)].

The postoperative respiratory depressant effect of fentanyl in combination with flunitrazepam (Rohypnol) was assessed in awake and in unconscious patients. In awake patients respiratory function was measured with blood-gas analyses. For measurements in unconscious patients the administration of nitrous oxide/oxygen was continued postoperatively and the respiratory depression was judged from the increase in respiratory minute volume after the i.v. administration of 0.05 mg naloxone (Narcan). In the group of awake patients blood-gasvalues were within the normal range after anaesthesia with flunitrazepam (1 mg) and fentanyl (0.80 mcg/kg body weight/10 min anaesthesia; last fentanyl given 40 min before the end of the operation), and the administration of naloxone was without any effect. If, however, naloxone was given while the patients were kept under light nitrous oxide/oxygen anaesthesia, the effect was different. The respiratory minute volume was considerably less than its predicted value in all groups of patients having received fentanyl, and naloxone caused a marked increase in respiratory minute volume and in respiratory rate. In a group of patients which have received no opiate but enflurane, naloxone showed no effect. After premedication with pethidine as compared with flunitrazepam the effect of naloxone on ventilation was more pronounced. This marked difference in the postoperative effect of fentanyl on ventilation depending on the state of consciousness has to be attributed to an interaction between a residual respiratory depressant effect of fentanyl and the effect of unconsciousness. Since after the combined use of flunitrazepam and fentanyl deep postoperative sleep occurs quite frequent, a residual effect of fentanyl should always be antagonized with naloxone to protect the patients from a possible hazardous effect of this interaction.

Adolescent↗
PubMed1976

Fentanyl and tooth pulp evoked responses in the spinal trigeminal nucleus caudalis region.

Electrical activities evoked by tooth pulp stimulation were recorded in the subnucleus caudalis region of the spinal trigeminal nucleus, and the action of fentanyl, a short-acting narcotic, on these activities was investigated in the alpha-cholinergic anesthetized cat. Fentanyl (20 to 40 mug/kg i.v.) depressed the first peak and potentiated the second one of negative potentials evoked by pulp stimulation in the border area betaeen the nucleus proprius (Pr) and the lateral reticular formation (LRF). Neurons, whose responses to pulp stimulation were depressed by fentanyl, were also predominantly localized in this region. Pulp-induced monophasic negative potential and spike discharges in the more ventro-medial portion of the LRF were not affected by fentanyl. The effect of fentanyl on cells in the marginal zone varied from unit to unit. The selective action of fentanyl on neurons in the border area between the Pr and the LRF may partially explain the analgesic action of fentanyl.

Animals↗