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At least 19 recordsLinked to original sources
PubMed1994

The effect of epidural administration of alfentanil on intra-operative intravenous alfentanil requirements during nitrous oxide-oxygen-alfentanil anaesthesia for lower abdominal surgery.

The effects of epidural administration of alfentanil on the intravenous alfentanil dose requirements and the plasma concentrations required to suppress responses to surgical stimulation during nitrous oxide-oxygen-alfentanil anaesthesia in 20 patients undergoing lower abdominal surgery were studied. Before induction of anaesthesia, patients in one group (E) received an epidural injection of 1 mg alfentanil, followed by an epidural infusion of alfentanil 0.2 mg.h-1 until skin closure, whilst patients in the other group (C, control) received a continuous infusion of sodium chloride via a sham catheter in order to blind the main investigator to the treatment. Anaesthesia was induced and maintained with nitrous oxide (66%) in oxygen and a 'target'-controlled intravenous infusion of alfentanil. During surgery, the 'target' alfentanil concentration was increased or decreased according to patients' responses. The number of responses to surgical stimulation was smaller in patients from group E (median 1, range 0-3) than in patients from group C (median 4, range 1-15; p < 0.005), even though the alfentanil intravenous infusion rates were smaller in group E [mean (SD): 1.6(0.5) micrograms.kg-1 min-1] than in group C [2.9(1.2) micrograms.kg-1 min-1, p < 0.02]. Both the lowest concentrations associated with no response [133(40) ng.ml-1] and the highest concentrations associated with a response [155(65) ng.ml-1] in group E were lower than those in group C [238(100) ng.ml-1, p < 0.01 and 334(163) ng.ml-1, p < 0.05, respectively]. We concluded that epidural administration of alfentanil reduces intravenous alfentanil requirements during nitrous oxide-oxygen-alfentanil anaesthesia for lower abdominal surgery. The results indicate a spinal mechanism of action of epidural alfentanil.

Abdomen↗
PubMed1993

Human alfentanil metabolism by cytochrome P450 3A3/4. An explanation for the interindividual variability in alfentanil clearance?

Alfentanil undergoes extensive hepatic metabolism and exhibits a high degree of interindividual variability in hepatic clearance. The purpose of this investigation was to determine the specific hepatic cytochrome P450 isozyme(s) that catalyzes alfentanil metabolism. Alfentanil metabolism by microsomes from rat and human livers was determined by using gas chromatography-mass spectrometry. Rat liver alfentanil oxidation was increased threefold by treatment with pregnenolone 16 alpha-carbonitrile, an inducer of cytochrome P450 3A, but not by treatment with phenobarbital, beta-naphthoflavone, or pyrazole (which induce P450s 2B, 1A, and 2E1, respectively). Human liver microsomal alfentanil metabolism was correlated strongly with the content of cytochrome P450 3A3/4 (r = 0.85, P < 0.005), measured by Western blot analysis with a rabbit anti-human P450 3A3/4 probe. Alfentanil metabolism was diminished by the P450 3A3/4 substrate and competitive inhibitor midazolam, and was abolished by the specific P450 3A3/4 inhibitor troleandomycin. No other selective inhibitor of P450 isozymes (P450s 1A2, 2A6, 2C9/10, 2D6, 2E1) diminished alfentanil metabolism. These results establish that human alfentanil metabolism is catalyzed predominantly, if not exclusively, by P450 3A3/4. Interindividual variability in human alfentanil disposition and alfentanil drug interactions may be attributable to individual differences in P450 3A3/4 activity.

Alfentanil↗
PubMed1986

The influence of hepatic plasma flow on alfentanil plasma concentration plateaus achieved with an infusion model in humans: measurement of alfentanil hepatic extraction coefficient.

In a group of seven patients undergoing intracranial surgery under neurolept anesthesia, an alfentanil infusion was initiated with a loading dose of 235 micrograms/kg over 5 min, followed by a maintenance infusion rate of 1.8 microgram X kg-1 X min-1 in order to obtain a steady state plasma concentration (Css) of 400 ng/ml-1 according to an infusion model. The mean values of Css (446 +/- 209 ng/ml) were close to the predicted ones. Nevertheless, an important intersubject variability in Css values was observed. A positive linear correlation existed between alfentanil steady state clearance and indocyanine green clearance (r = 0.88) and between alfentanil steady state clearance and cardiac index (r = 0.93). In three patients, a catheter was inserted into an hepatic vein to determine the alfentanil hepatic extraction coefficient. Alfentanil plasma clearance did not differ from alfentanil hepatic clearance and alfentanil hepatic extraction coefficient values ranged from 0.32-0.53. We conclude that alfentanil is a drug with an intermediate hepatic extraction coefficient and that alfentanil plasma clearance depends on hepatic plasma flow, which is thus one of the factors accounting for individual variability in plasma concentration plateaus achieved with an infusion model.

Adult↗
PubMed2006

Pharmacokinetics and pharmacodynamics of alfentanil in P-glycoprotein-competent and P-glycoprotein-deficient mice: P-glycoprotein efflux alters alfentanil brain disposition and antinociception.

Previous studies have indicated that P-glycoprotein (P-gp) attenuates the central nervous system penetration and central activity of some opioids. The impact of P-gp-mediated efflux on the disposition and efficacy of the synthetic opioid alfentanil currently is unknown. In this study, P-gp-competent [mdr1a(+/+)] and P-gp-deficient [mdr1a(-/-)] mice were used to investigate the impact of P-gp-mediated efflux on the systemic pharmacokinetics, brain disposition, and central activity of alfentanil. Equipotent doses of alfentanil were administered to mdr1a(+/+) and mdr1a(-/-) mice (0.2 and 0.067 mg/kg, respectively), and the time course of brain and serum concentrations as well as antinociception were determined. A pharmacokinetic-pharmacodynamic (PK-PD) model was fit to the data and used to assess the impact of P-gp on parameters associated with alfentanil disposition and action. The mdr1a(+/+) mice were less sensitive to alfentanil than mdr1a(-/-) mice, requiring a 3-fold higher dose to produce similar antinociception. PK-PD modeling revealed no differences in alfentanil systemic pharmacokinetics between P-gp expressers and nonexpressers. However, the steady-state brain-to-serum concentration ratio (K(p,brain,ss)) was approximately 3-fold lower in mdr1a(+/+) mice compared with mdr1a(-/-) mice (0.19 +/- 0.01 versus 0.54 +/- 0.04, respectively). Consistent with the approximately 3-fold lower K(p,brain,ss), the antinociception versus serum concentration relationship in mdr1a(+/+) mice was shifted approximately 3-fold rightward compared with mdr1a(-/-) mice. However, there was no difference in the antinociception versus brain concentration relationship, or in the brain tissue EC(50) (11 +/- 1.8 versus 9.2 +/- 1.7 ng/g), between mdr1a(+/+) and mdr1a(-/-) mice. These results indicate that alfentanil is an in vivo P-gp substrate and are consistent with the hypothesis that P-gp-mediated efflux attenuates antinociception by reducing alfentanil K(p,brain,ss).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Gas chromatographic-mass spectrometric analysis of alfentanil metabolites. Application to human liver microsomal alfentanil biotransformation.

The short-acting synthetic opioid alfentanil undergoes extensive biotransformation to several metabolites. A gas chromatographic-mass spectrometric assay, using selected-ion monitoring and deuterated internal standards, was developed for quantitating the predominant metabolites of alfentanil. Optimal extraction and derivatization conditions are described. The assay was applied to the analysis of metabolites formed during alfentanil metabolism in vitro by human liver microsomes. Formation of known alfentanil metabolites was confirmed, and formation of a metabolite, not previously detected in vitro, is described. The assay represents a significant improvement over existing methods of alfentanil metabolite analysis, which use HPLC and radiochemical detection.

Alfentanil↗
PubMed1993

Closed-loop feedback controlled administration of alfentanil during alfentanil-nitrous oxide anaesthesia.

We have studied the automatic administration of alfentanil during alfentanil-nitrous oxide anaesthesia in 11 patients using a closed-loop feedback control system based on EEG analysis. We chose a median EEG frequency of 2-4 Hz as the EEG set point. The slope of the asymptote to the cumulative dose requirement was used to define an effective therapeutic infusion of alfentanil. Median EEG frequency (mean (SD)) during the feedback period was 3.03 (0.45) Hz. The average effective therapeutic infusion of alfentanil was 0.140 (0.032) mg min-1. We conclude that EEG feedback control may be useful in assessing and defining the dose requirements of alfentanil.

Adult↗
PubMed1986

Alfentanil supplemented anaesthesia for short procedures. A double-blind study of alfentanil used with etomidate and enflurane for day cases.

Thirty-nine unpremedicated patients who presented for cystoscopy were given either alfentanil or saline in a random double-blind fashion immediately before anaesthesia with etomidate, nitrous oxide and enflurane. Alfentanil significantly reduced myoclonus associated with etomidate. During anaesthesia, patients who received alfentanil had smaller minute volumes, lower respiratory frequencies, and smaller increases in heart rate. The incidence of apnoea was not significantly increased. After operation, patients who received alfentanil were prescribed significantly more analgesia, possibly because of their reduced uptake of volatile anaesthetic agent. It is concluded that supplementation with alfentanil improves the quality of anaesthesia induced with etomidate.

Adjuvants, Anesthesia↗
PubMed1988

Alfentanil infusion in the elderly. Prolonged computer-assisted infusion of alfentanil in the elderly surgical patient.

The use of a computer-assisted infusion of alfentanil, combined with 66% nitrous oxide in oxygen, for induction and maintenance of anaesthesia was evaluated in 18 elderly patients. The target alfentanil concentration for induction was varied between 300 and 475 ng/ml, to be achieved in 2 minutes. During maintenance, the alfentanil concentration was increased or decreased according to each patient's responses. Arterial blood samples were taken for measurement of alfentanil concentration. There were high incidences of muscle rigidity, bradycardia and hypotension during induction. Hypotension was dose- and concentration-dependent. Signs of light anaesthesia during maintenance were controlled rapidly by increasing the target plasma concentration. Nine patients required naloxone at the end of surgery. Ventilatory depression recurred in three of these. The use of published alfentanil pharmacokinetic data from elderly patients to predict plasma concentrations during prolonged infusion resulted in significant prediction errors, notably in the higher concentration range.

Aged↗
PubMed1994

Oral transmucosal back permeation of alfentanil in dogs--a novel method to determine blood alfentanil concentration.

This study explores a novel noninvasive method for monitoring blood alfentanil concentrations using a dog model. Alfentanil which "back" permeated across the oral mucosa from the systemic circulation was collected from the oral mucosal surface and quantitated. The levels of the "back" permeated alfentanil were found to closely reflect real time serum alfentanil concentrations. With further work, this finding may lead to a novel noninvasive method for monitoring real time serum alfentanil concentrations in its clinical applications.

Alfentanil↗
PubMed2002

The comparison of caudal ketamine, alfentanil and ketamine plus alfentanil administration for postoperative analgesia in children.

BACKGROUND: Our aim was to compare the effect of single dose caudal ketamine, alfentanil or a mixture of both drugs in the treatment of pain after hypospadias repair surgery in children. METHODS: The group comprised 109 boys, ASA I-II, aged 1-9 years, who were undergoing hypospadias repair surgery as day cases. The children were randomly divided into three groups for postoperative analgesia: group 1, only alfentanil (20 microg x kg(-10) was given caudally; group 2, ketamine (0.5 mg x kg(-1)) alone; and group 3, alfentanil (20 microg x kg(-1))-ketamine (0.5 mg x kg(-1)) was given caudally. The analgesic effect of caudal block was evaluated using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and sedation was assessed using a five-point sedation score. The first analgesic requirement time and the number of supplementary analgesics required by each child in a 24-h period were also recorded. RESULTS: No statistical differences were found in demographic characteristics, haemodynamic and respiratory parameters, objective pain scores, postoperative sedation scores and duration of surgery among the groups. The median time to first analgesia was significantly shorter in group 1 than in groups 2 and 3 (P=0.009, P=0.001). Significantly more patients in group 1 required additional postoperative analgesia (paracetamol 15 mg x kg(-1)) compared with groups 2 and 3 (P < 0.001). CONCLUSIONS: Caudal administration of ketamine 0.5 mg.kg-1 with or without alfentanil in children produced satisfactory postoperative analgesia without respiratory depression or other side-effects.

Alfentanil↗
PubMed1989

Alfentanil requirement in Crohn's disease. Increased alfentanil dose requirement in patients with Crohn's disease.

The dose requirement of alfentanil as a supplement to nitrous oxide anaesthesia was studied in 13 patients with Crohn's disease and seven control patients all of whom underwent laparotomy. Alfentanil was administered as a variable rate infusion with supplemental bolus injections titrated to the patient's needs. The alfentanil requirement was independent of the duration of surgery and was significantly higher in patients with Crohn's disease than in control patients. The results indicate that Crohn's disease alters the dose requirement of alfentanil.

Adjuvants, Anesthesia↗
PubMed1986

A comparison of the effects of alfentanil applied to the spinal cord and intravenous alfentanil on noxiously evoked activity of dorsal horn neurons in the cat spinal cord.

The purpose of this study was to examine the effects of alfentanil applied to the surface of the spinal cord and the effects of intravenously administered alfentanil on noxiously evoked activity of dorsal horn neurons. Extracellular single neuron recordings were obtained from wide dynamic range neurons in 26 decerebrate cats with transected spinal cords. Spinally administered alfentanil, 25 micrograms or 50 micrograms, caused 36 and 86% suppression of noxiously evoked activity, respectively. Maximum mean suppression was achieved at 24 and 21 min after 25 micrograms, and 50 micrograms, respectively. Intravenous naloxone, 0.1 mg, when tested, completely reversed the suppression. Spontaneous recovery to control values occurred within 2 hr. Intravenously administered alfentanil, 12.5 micrograms/kg or 25 micrograms/kg, produced suppression of 43 and 89%, respectively, with maximum mean suppression observed at the 6- and 3-min time points, respectively. Complete recovery after intravenous administration was seen within 30 min. This study, using a sensitive neurophysiologic assay, demonstrates the important differences in onset and duration of drug effects that must be considered when comparing the responses of spinal cord neurons to intravenously administered narcotics and narcotics applied directly to the surface of the spinal cord.

Alfentanil↗
PubMedDate not supplied

Plasma concentration profile of epidural alfentanil. Bolus followed by continuous infusion technique in the parturient: effect of epidural alfentanil and fentanyl on fetal heart rate.

BACKGROUND AND OBJECTIVES: A combined bolus and continuous epidural infusion technique of opioid and bupivacaine mixture has been described, although no pharmacokinetic data for this technique exists. The study documents the plasma concentration profile of epidural alfentanil in parturients using this technique, and evaluates the fetal heart rate tracing for associated changes following opioid administration. METHODS: Twenty-four subjects were randomized to receive epidural alfentanil 500 micrograms in 10 mL 0.125% bupivacaine, group A, or fentanyl 50 micrograms in 10 mL 0.125% bupivacaine, group B, as a bolus dose, followed by continuous infusions of alfentanil 20 micrograms/mL in 0.125% bupivacaine (group A) or fentanyl 2 micrograms/mL in 0.125% bupivacaine (group B) for labor analgesia. Plasma drug levels for each group were examined using repeated measures analysis of covariance. RESULTS: Fetal heart rate tracings were recorded throughout the study and were retrospectively analyzed by a "blinded" perinatologist. Data from fetal heart rate tracings were examined by repeated measures analysis of variance. Mean infusion rates were 9.3 +/- 2.1 mL/hour and 9.6 +/- 1.7 mL/hour for groups A and B, respectively. Mean study duration was 3.7 hours in group A, and 3.0 hours in group B. Low plasma levels precluded analysis of fentanyl data. Group A subjects exhibited stability of drug levels over time. Fetal heart rate tracings in 21 patients demonstrated no changes associated with epidural opioid infusion in either group. CONCLUSIONS: With the dosage regimen used in this study, an initial epidural bolus with continuous infusion technique generates a steady state plasma concentration of alfentanil that is below levels associated with direct respiratory depression.

Adult↗
PubMed1994

[Total intravenous anesthesia with methohexital-alfentanil or propofol-alfentanil in hypogastric laparotomy. Clinical aspects and the effects of stress reaction].

Total intravenous anaesthesia (TIVA) using a combination of a hypnotic and an analgesic agent is gaining increasing popularity as an alternative to balanced anaesthesia with volatile anaesthetics for abdominal surgery. Among the required characteristics of the drugs used in this technique are a good correlation between dose, plasma concentrations, and effect as well as rapid elimination from the circulation, allowing close control of anaesthetic depth. Two hypnotic drugs with similar pharmacokinetic and pharmacodynamic profiles are propofol and methohexitone, both of which can be employed as a component of a TIVA technique. Two TIVA combinations utilising either of these drugs with alfentanil were tested against isoflurane-nitrous oxide in a balanced regimen. METHODS. Twenty-seven healthy women undergoing hysterectomy for non-malignant diseases participated in the study after having given written consent. They were randomly allocated to receive either isoflurane (Iso), methohexital-alfentanil (M-A), or propofol-alfentanil (P-A). Blood samples for determination of cortisol, prolactin, catecholamines, glucose, lactate, non-esterified fatty acids, and pharmacon concentrations were drawn repeatedly from before induction until 360 min after surgery. Anaesthesia was induced in group Iso with fentanyl 0.1 mg and M 1.5 mg.kg-1 and maintained with Iso-N2O. In the TIVA groups M or P was given in a two-step infusion to load peripheral compartments and then maintain plasma concentrations within the hypnotic range. A was given as a continuous infusion in an identical dose (0.1 mg.kg-1 initial, 0.125 mg.kg-1.h-1 maintenance) in both groups. If signs of insufficient depth of anaesthesia occurred (heart rate or systolic blood pressure > 25% above baseline), then first A (0.5-1 mg), and if that was ineffective, then 50 mg hypnotic was administered. The A infusion was stopped 30 min before the end of surgery, and Iso or the hypnotic was stopped at skin closure. Recovery time was the time until the patients were able to give their birth date after stopping the Iso or hypnotic. RESULTS. The three groups were comparable with regard to age, weight, and duration of surgery. The total doses of M and P were 1,357 +/- 125 mg (mean +/- SEM) and 1,315 +/- 121 mg, respectively, and the total A doses were 20.7 +/- 2.5 mg (M-A) and 23.4 +/- 3.5 (P-A). The peak plasma concentrations were P 10.6 +/- 1.5 micrograms.ml-1 and M 12.4 +/- 2.6 micrograms.ml-1. At the end of surgery the P concentrations were in the projected range while those of M were somewhat lower than expected (P 3.7 +/- 0.4 microgram.ml-1; M 3.5 +/- 0.6 microgram.ml-1). Three patients each in the P-A and M-A groups required supplementary A injections. Five patients in the P-A group required additional bolus injections of the hypnotic as compared to 2 in the M-A group. The median recovery times were Iso 15 min, M-A 50 min, and P-A 25 min (P < 0.05). The incidence of shivering was Iso 3/9, M-A 5/9, and P-A 0/9 (P < 0.05); vomiting occurred with equal frequency in all groups (Iso 33%, M-A 33%, P-A 22%). The patients were somewhat more restless in group M-A. Systolic blood pressure dropped in a similar manner in all groups after induction of anaesthesia (Iso -31%, M-A -37%, P-A -36%) but recovered during surgery. The intraoperative response of cortisol (Iso + 216%, M-A +92%, P-A +43%) and catecholamines (noradrenaline Iso +56%, M-A +30%, P-A -21%) was lower in the TIVA groups, whereas prolactin increased after induction in all groups. Plasma concentrations of glucose, lactate, and fatty acids were lower in the TIVA groups than in the Iso group intraoperatively, but increased to comparable postoperative levels. CONCLUSIONS. Both TIVA regimens are acceptable alternatives to balanced anaesthesia with Iso N2O. (ABSTRACT TRUNCATED)

Adult↗
PubMed1985

Patient-controlled postoperative analgesia with alfentanil. Adaptive, on-demand intravenous alfentanil or pethidine compared double-blind for postoperative pain.

A double-blind study comparing alfentanil and pethidine given intravenously by an adaptive, patient-controlled on-demand analgesic system is described. It was demonstrated that, despite its well-known rapid onset of effect, alfentanil took several hours to achieve good quality analgesia. Nevertheless, it had a much more predictable consumption pattern than pethidine. Alfentanil was associated with significantly less sedation during the postoperative period than pethidine, and was also associated with a significantly greater urine output during the 24-hour period of study. There was no evidence of tolerance or accumulation with either of the two drugs.

Adult↗
PubMed1992

Alfentanil infusion in total intravenous anaesthesia (TIVA). Population pharmacokinetics fails to predict plasma concentration of alfentanil.

In order to evaluate the ability to predict plasma concentrations from population-corrected pharmacokinetics, a prospective study comprising 14 women admitted for elective hysterectomy was done. Alfentanil was given in combination with propofol in a total intravenous anaesthesia technique. The predicted median alfentanil concentration (289(256-363) ng ml-1) was significantly lower than the measured median plasma concentration of 368(168-666) ng ml-1). In conclusion, population-based pharmacokinetics were found not to be accurate as they underestimate plasma concentrations of alfentanil.

Alfentanil↗
PubMed1991

[Comparison of the incidence of bleeding of 2 anesthetic technics midazolam-alfentanil versus propofol-alfentanil during treatment of otospongiosis].

This study was performed to compare the incidence of bleeding associated with two anaesthetic techniques during otolaryngological microsurgery. Twenty-eight venous interpositions for otospongiosis have been carried out at random either under local anaesthesia combined with light sedation (midazolam 0.1 mg.kg-1 and alfentanil 0 micrograms.kg-1) or using general anaesthesia (propofol 2.5 mg.kg-1, then 9 mg.kg-1.hr-1 and alfentanil 30 micrograms.kg-1, then 15 micrograms.kg-1). The patients' lungs were mechanically ventilated. Every ten minutes, heart rate, arterial blood pressure and FETCO2 were observed. Bleeding was assessed on a four-point scale and evaluated according to its duration and the annoyance that it caused. General anaesthesia was clinically better tolerated. Heart rate and arterial blood pressure were lower than with general anaesthesia. The end-expiratory CO2 was 4.7 +/- 0.2 per cent. Bleeding was less frequent, lasted less time, but when it occurred the surgical disturbance was identical in the two groups. General anaesthesia produced a less bloody operating field and local anaesthesia required the cooperation of the patient.

Adult↗
PubMed1998

An open, randomized comparison of alfentanil, remifentanil and alfentanil followed by remifentanil in anaesthesia for craniotomy.

We studied 52 adults undergoing elective craniotomy, allocated randomly to one of three opioid treatments: alfentanil 50 micrograms kg-1 followed by 0.833 microgram kg-1 min-1 until dural closure (group Alf.); alfentanil 50 micrograms kg-1 followed by 0.833 microgram kg-1 min-1 for 2 h, then remifentanil 0.25 microgram kg-1 min-1 (group Alf.-Remi.); or remifentanil 1 microgram kg-1 followed by 0.5 microgram kg-1 min-1 reducing to 0.25 microgram kg-1 min-1 after craniotomy (group Remi.). Anaesthesia was maintained with infusion of propofol and 66% nitrous oxide in oxygen. Infusions of propofol and remifentanil were stopped at head bandaging. Group Remi. had the least intraoperative haemodynamic responses and group Alf. the most (P < 0.05). Times to tracheal extubation and obey commands were similar in all groups. In all patients in group Alf.-Remi. and group Remi., the trachea was extubated 27 min from the end of anaesthesia; three patients in group Alf. were slower to recover. Use of analgesia in the recovery room and time to transfer to the neurosurgical unit were similar in the three groups.

Adult↗