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PubMed2006

The effect of acutely induced hepatic failure on remifentanil and fentanyl blood levels in a pig model.

BACKGROUND AND OBJECTIVE: Opioids and especially fentanyl are widely used during the intensive care unit management of intracranial pressure in fulminant hepatic failure patients as well as during and after liver transplantation. The newer synthetic opioid remifentanil is also increasingly being used in critical care patients. Due to a lack of data relating to the influence of acute hepatic failure on remifentanil and fentanyl pharmacokinetics, this study was designed in order to determine the impact of this condition on the blood levels of these opioids using a pig model. METHODS: Twenty pigs were randomly assigned to one of two groups: A group with surgically induced acute hepatic failure by hepatic devascularization (acute hepatic failure, n=10) and a control group (SHAM, n=10), subjected to a SHAM operation. Postoperatively, five animals in each group were administered remifentanil (1 microg kg-1 min-1) or fentanyl (0.2 microg kg-1 min-1) by continuous intravenous infusion. Blood samples for determination of drug concentrations were withdrawn at 0 h and 0.5, 1, 5, 7, 9 h after initiation of dosing. RESULTS: Significantly higher blood concentrations were found in animals with acute hepatic failure compared to SHAM-operated animals receiving remifentanil at 5 h (P=0.003), 7 h (P=0.007) and 9 h (P=0.004) and fentanyl at 7 h (P<0.0005) and 9 h (P=0.05). The small number and the great variability in drug concentrations did not allow a detailed kinetic analysis to be performed. Approximate clearance values were found to be greater for the SHAM compared with the acute hepatic failure animals for both fentanyl and remifentanil. CONCLUSIONS: Hepatic devascularization in our porcine acute hepatic failure model, appears to have significantly altered the disposition of fentanyl and unexpectedly remifentanil. These changes were thought to be brought about by severe disruption of blood flow and biotransformation in the liver, as well as by haemodynamic changes in the acute hepatic failure animals.

Acute Disease↗
PubMed1998

Clonidine prolongs fentanyl-induced ventilatory depression.

The aim of the present study was to investigate the effect of intravenously (i.v.) administered fentanyl and clonidine on ventilation in 12 healthy male volunteers (age 30.8 +/- 4.9 years) who either received fentanyl alone (1.5 > or = micrograms kg-1) or fentanyl (1.5 > or = micrograms kg-1) in combination with clonidine (3 > or = micrograms kg-1). The effect on ventilation was measured with a CO2 rebreathing system. The respiratory depression caused by fentanyl disappeared 120 min after injection. The corresponding slopes were 7430 +/- 2075 mL kPa-1 prior to (t0) and 6263 +/- 1864 mL kPa-1 120 min post-application (base-line vs. t120; P = 0.106). An impaired ventilatory response was observed during CO2 rebreathing at t120 after the injection of fentanyl and clonidine. Before drug administration, the slope of the response curves was 7700 +/- 2800 mL kPa-1, which was reduced to 5480 +/- 2135 mL kPa-1 (P < 0.035) at t120. These data suggest a prolongation of a fentanyl-induced ventilatory depression when used in combination with clonidine.

Adrenergic alpha-Agonists↗
PubMed2006

Use of lidocaine and fentanyl premedication for neuroprotective rapid sequence intubation in the emergency department.

INTRODUCTION: Autoregulation is dysfunctional in the injured brain. Increases in intracranial and arterial pressure may therefore result in extension of the primary injury. Rapid sequence intubation (RSI) is a well-known cause of surges in both arterial pressure and intracranial pressure. Neuroprotective agents, namely lidocaine and fentanyl, have the potential to minimize the pressure surges implicated in secondary brain injury. The purpose of this study was to determine the frequency with which neuroprotective agents were used for neuroprotective RSI in the emergency department. METHODS: We conducted a retrospective chart review of all 139 patients intubated in the emergency department of Vancouver General Hospital between March and October 2003. Patients were eligible if there was an indication for neuroprotective agents defined as presumed intracranial pathology and a mean arterial pressure (MAP) > 85 mm Hg. Contraindications to fentanyl included MAP < 85 mm Hg or allergy to fentanyl. RESULTS: Seventy-seven patients were intubated for primary neurological indications. Indication for intubation included non-traumatic causes (n = 37) (including cerebrovascular accident or intracranial hemorrhage) and closed head injury (n = 40). The mean age (+/- standard deviation) was 52.3+/-20.4 years, and 31.4% were female. Fifty-seven (74.0%) patients had indications for neuroprotective agents, without contraindications. When neuroprotective agents were indicated, lidocaine was used in 84.2% (95% confidence interval [CI] 72.6%-91.5%) of patients while fentanyl was used in 33.3% (95%CI 22.4%-46.3%) of patients. Eleven percent of the intubations were performed with a fentanyl dose of delta 2 mcg/kg, which is the lower limit considered effective. CONCLUSIONS: Despite the potential benefit of using lidocaine and fentanyl in appropriate patients undergoing neuroprotective RSI in the emergency department, our study identified a significant underutilization of optimal premedication. The identification of barriers to use and the implementation of strategies to optimize use are necessary.

British Columbia↗
PubMed1981

Opiate receptor interaction of compounds derived from or structurally related to fentanyl.

The opiate receptor affinity of compounds derived from or structurally related to fentanyl (1) was determined by in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2-CH3, 2-OCH3, or a 2-Cl substituent into the anilino phenyl and was moderately reduced by 2-C2H5, 2-OC2H5, and 2,6-(CH3)2 substitution in this ring. Removal of the n-propionyl g in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2-CH3, 2-OCH3, or a 2-Cl substituent into the anilino phenyl and was moderately reduced by 2-C2H5, 2-OC2H5, and 2,6-(CH3)2 substitution in this ring. Removal of the n-propionyl g in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2-CH3, 2-OCH3, or a 2-Cl substituent into the anilino phenyl and was moderately reduced by 2-C2H5, 2-OC2H5, and 2,6-(CH3)2 substitution in this ring. Removal of the n-propionyl group of the 2-OCH3 derivative, fixation of the anilino phenyl in fentanyl to the propionyl group or the piperidine ring, and replacement of the amide N by C all caused a sharp decline of receptor affinity. Examination of molecular models seemed to indicate that optimal opiate receptor interaction of fentanyl and its derivatives requires a virtually perpendicular position of the anilino phenyl with respect to the amide function.

Animals↗
PubMed2000

Molecular docking reveals a novel binding site model for fentanyl at the mu-opioid receptor.

The ligand binding modes of a series of fentanyl derivatives are examined using a combination of conformational analysis and molecular docking to the mu-opioid receptor. Condensed-phase molecular dynamics simulations are applied to evaluate potential relationships between ligand conformation and fentanyl substitution and to generate probable "bioactive" structures for the ligand series. Automated docking of the largely populated solution conformers identified a common binding site orientation that places the N-phenethyl group of fentanyl deep in a crevice between transmembrane (TM) helices II and III while the N-phenylpropanamide group projected toward a pocket formed by TM-III, -VI, and -VII domains. An analysis of the binding modes indicates the most potent fentanyl derivatives adopt an extended conformation both in solution and in the bound state, suggesting binding affinity may depend on the conformational preferences of the ligands. The results are consistent with ligand binding data derived from chimeric and mutant receptor studies as well as structure-activity relationship data reported on a wide range of fentanyl analogues. The binding site model is also compared to that of N-phenethylnormorphine. An overlay of the bound conformation of the opiate and cis-3-methylfentanyl shows the N-phenethyl groups occupy equivalent binding domains in the receptor. While the cationic amines of both ligand classes were found docked to an established anchor site (D149 in TM-III), no overlap was observed between the N-phenylpropanamide group and the remaining components of the opiate scaffold. The unique binding mode(s) proposed for the fentanyl series may, in part, explain the difficulties encountered in defining models of recognition at the mu-receptor and suggest opioid receptors may display multiple binding epitopes. Furthermore, the results provide new insight to the design of experiments aimed at understanding the structural basis to the differential selectivities of ligands at the mu-, delta-, and kappa-opioid receptors.

Amino Acid Sequence↗
PubMed2002

Biasing effect of the electromyogram on BIS: a controlled study during high-dose fentanyl induction.

OBJECTIVE: A biasing effect of the electromyogram (EMG) on the Bispectral Index (BIS) may explain discrepancies in previous studies assessing BIS in the presence of neuromuscular activity. Our aims were: to evaluate variations of BIS in the presence of high EMG activity associated with muscular rigidity after administration of high-dose fentanyl; to compare muscular rigidity, as measured by the EMG variable of the BIS monitor, in patients who were administered two different dosages of fentanyl at induction of cardiac anaesthesia. METHODS: 26 patients undergoing CABG surgery, after premedication with morphine 0.15 mg/kg, were randomized to receive either fentanyl 50 mcg/kg (group F) or fentanyl 10 mcg/kg plus etomidate 0.2 mg/kg (group EF). The induction dose was administered over 2 minutes. Patients were manually ventilated with O2 via face mask. Five minutes after induction was complete, patients were clinically assessed using the Responsiveness portion of the Observer's Assessment of Alertness/Sedation scale (OAAS). Haemodynamic data were recorded and arterial blood samples obtained at the time of OAAS observation. Patients were administered a neuromuscular blocking agent only after the OAAS assessment. BIS (3.4) was recorded from an A-2000 EEG monitor (Aspect Medical Systems) using disposable sensors (BIS Sensor, Aspect Medical Systems) applied per manufacturer's instructions. Data were recorded on a PC for off-line analysis. RESULTS: At the time of OAAS observation, mean (95% CI) BIS in group F was 85 (77-92) compared to 67 (56-79) in group EF (p = 0.01). Similarly, mean (95% CI) EMG was 50 dB (45-56) in F and 41 dB (35-47) in EF (p = 0.01). Correlation between BIS and EMG was very high (r2 = 0.88). OAAS scores were significantly higher in group F (p = 0.03). Non significant correlation was observed between BIS and OAAS scores (r2 = 0.32, p = 0.1). Backward stepwise multiple regression analysis including EMG, pH, CO2, O2 and OASS scores showed EMG as strong predictor of BIS (p < 0.0001, r2 = 0.7). Regression of EMG against BIS yielded the equation: BIS = 3.7 + (1.6 x EMG). CONCLUSION: During fentanyl-induced muscular rigidity BIS recordings reflect EMG variations. When assessing BIS in the absence of neuromuscular blockade, it is necessary to evaluate the effect of EMG on BIS before making conclusions about depth of sedation. Fentanyl-induced rigidity appears to be a dose-related phenomenon which the EMG variable of BIS 3.4 is able to quantify.

Aged↗
PubMed2001

Fentanyl does not improve the nerve block characteristics of axillary brachial plexus anaesthesia performed with ropivacaine.

BACKGROUND: The aim of this prospective, randomized, double-blind study was to evaluate the effects of adding 1 microg. kg-1 fentanyl to ropivacaine 7.5 mg. ml-1 for axillary brachial plexus anaesthesia. METHODS: With Ethics Committee approval and written consent, 30 ASA physical status I-II in-patients, scheduled for orthopaedic hand procedures were randomly allocated to receive axillary brachial plexus block with 20 ml of either ropivacaine 7.5 mg. ml-1 (n=15) or ropivacaine 7.5 mg. ml-1+1 microg. ml-1 fentanyl (n=15). Nerve blocks were placed using a nerve stimulator with the multiple injection technique. A blinded observer recorded the time to onset of surgical block (loss of pinprick sensation in the innervation areas of the hand (C6-C8) with concomitant inability to flex the wrist against gravity and move the fingers when squeezing the hand) and first request for pain medication after surgery. RESULTS: No differences in demography, degree of sedation or peripheral oxygen saturation were observed between the two groups. Median (range) time required to achieve readiness for surgery was 15 min (5-36 min) with ropivacaine alone and 15 min (5-40 min) with the ropivacaine-fentanyl mixture. No differences in the intraoperative quality of nerve block were reported between the two groups. Four patients receiving ropivacaine plain and two patients receiving the ropivacaine-fentanyl mixture did not require analgesics during the first 24 h after surgery (P=0.62). The degree of pain experienced at first analgesic request in those patients asking for pain medication, as well as median consumption of postoperative analgesics, were similar in the two groups. First postoperative analgesic request was made at 11 h (25th-75th percentiles: 9.1-14 h) in patients receiving ropivacaine alone and at 11.8 h (25th-75th percentiles: 9.8-15 h) in patients receiving the ropivacaine-fentanyl mixture (P=0.99). CONCLUSION: The addition of fentanyl 1 microg. ml-1 to ropivacaine 7.5 mg. ml-1 does not improve the nerve block characteristics of axillary brachial plexus anaesthesia for orthopaedic procedures involving the hand.

Adolescent↗
PubMed2003

Which administration route of fentanyl better enhances the spread of spinal anaesthesia: intravenous, intrathecal or both?

BACKGROUND: To enhance the spread of spinal anaesthesia, fentanyl may be administered intrathecally (i.t.) or intravenously (i.v.). The purpose of this prospective study was to investigate the effects of fentanyl administered i.v., i.t. or concurrently by both i.v. and spinal routes on the spread of spinal anaesthesia. METHODS: Sixty patients were randomly assigned to one of three groups. In Groups I and II, spinal anaesthesia was performed with plain bupivacaine 10 mg plus 20 micro g fentanyl and in Group III with 10 mg of plain bupivacaine. The level of first peak sensory block was marked. In addition, fentanyl 50 micro g was administered i.v. in Groups II and III or by saline in Group I after the sensory blockade reached the highest dermatomal level. Ten minutes after i.v. administration, the level of the second peak sensory block was marked. The distance between the first- and second-highest levels of sensory block was measured. RESULTS: The distance between the first- and second-highest level of sensory block was significantly different for the three groups: Group II (5.8 +/- 2.6 cm) > Group III (2.9 +/- 2.1 cm) > Group I (-0.15 +/- 1.7 cm). The peak dermatomal level of spinal block was significantly higher in Group II [T4 (T3-T7)] than in Group I [T6 (T4-T9)] and Group III [T6 (T4-T8)]. In Groups I and II the sensory block regressed to S2 for a longer period of time than it did in Group III. CONCLUSION: Both the spinal and systemic administration of fentanyl enhanced the spread of spinal anaesthesia. The co-administration of spinal and i.v. fentanyl produced a greater increase in the cephalad spread of spinal block.

Adult↗
PubMed1997

Sex differences in effects of predictable and unpredictable footshock on fentanyl self-administration in rats.

An operant conditioning paradigm was used to examine effects of predictable and unpredictable footshock on oral fentanyl (50 micrograms/ml self-administration (SA) in 12 female and 12 male Wistar rats (Rattus norvegicus). Rats were tested for drug SA under a progressive ratio schedule with and without repeated predictable or unpredictable footshock over 8 weeks. Female rats consumed greater amounts of fentanyl than did male rats. Male rats exhibited greater withdrawal behaviors following naloxone challenge. Predictable footshock with repeated exposure (i.e., chronic stress) was accompanied by greater fentanyl SA than was unpredictable footshock, particularly for female rats. Corticosterone levels were positively correlated with fentanyl SA. Predictability of the stressor also had a greater effect on maintenance of fentanyl SA than it did on relapse to fentanyl SA. Results suggest that sex plays an important role in drug-taking behavior by rats.

Analgesics, Opioid↗
PubMed2006

Genetic polymorphisms in the ABCB1 gene and the effects of fentanyl in Koreans.

P-glycoprotein (PGP) is a polymorphic transporter encoded by the ABCB1 gene that contributes to the access of xenobiotics into the brain. There is no report on associations between genetic polymorphisms in ABCB1 and the clinical effects of fentanyl, although fentanyl may be a substrate of PGP. One hundred and twenty-six (126) unrelated Korean patients under spinal anesthesia with intravenous fentanyl (2.5 microg/kg) were recruited. Clinical effects (bispectral index, respiration rate, and need for oxygen supplementation) were monitored and these were compared between genotypes for three single nucleotide polymorphisms in ABCB1 (1236C>T, 2677G>T/A, and 3435C>T). The allele and genotype frequencies were similar to previous data from Asians; the three major haplotypes, TTT (30%), TGC (24%), and CGC (24%) were expected among nine known haplotypes. During the initial 10 min, there were differences in suppression of respiration rate by fentanyl among the three genotypes (P=0.0933 for 1236C>T; P=0.0941 for 2677G>A/T; P=0.0013 for 3435C>T, repeated-measures analysis of variance), but the differences in bispectral index among genotypes were not observed. Furthermore, patients carrying the linked 3435T and 2677T alleles showed a significant difference in the level of respiratory suppression (P=0.0056); those with genotypes susceptible to fentanyl (1236TT, 2677TT, and 3435TT) showed early (2-3 min) and profound suppression of respiration (65-73% of initial respiration rate) compared with other resistant genotypes (83-85% of initial respiration rate in 1236CC, 2677GG, and 3435CC). Although the need to supply oxygen was not significantly different between genotypes, there was a trend for increased demand by patients carrying both 1236T and 3435T alleles (P=0.0847). In conclusion, our results confirm ABCB1 genotype data for Koreans and suggest that analysis of ABCB1 polymorphisms may have clinical relevance to prevent respiratory suppression by intravenous fentanyl or to anticipate its clinical effects.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1998

The influence of intrathecal fentanyl on the characteristics of subarachnoid block for caesarean section.

Forty healthy parturients scheduled for elective Caesarean section were randomly allocated to receive either 0.3 ml 0.9% saline (control group, n = 20), or 15 micrograms (0.3 ml) fentanyl (treatment group, n = 20) added to 2.5 ml 0.5% hyperbaric bupivacaine given intrathecally in the sitting position. A sensory block to T4 was achieved after 6.5 min in those who received fentanyl compared to 8.0 min in the control group; this was not significantly different. The highest level of sensory block achieved in both groups was similar. Ephedrine was required earlier (p < 0.05) in those who received fentanyl but the total requirement of ephedrine intra-operatively was similar. Fentanyl significantly improved the quality of intra-operative surgical anaesthesia as none of the patients in the treatment group complained of discomfort compared with seven in the control group (p < 0.05). Similarly those in the treatment group had better comfort scores as evaluated by visual analogue score (p < 0.01). Regression of anaesthesia to T12 took longer (184 vs 156 min, p < 0.05) in those who received fentanyl but this did not affect the total requirement of morphine in the first 24 h after operation. There was no difference in the incidence of side effects in the mother and no adverse effects were detected in the baby. The results indicate that adding 15 micrograms fentanyl to hyperbaric bupivacaine for spinal anaesthesia markedly improves intra-operative anaesthesia for Caesarean section.

Adult↗
PubMed1999

Hypnotic endpoints vs. the bispectral index, 95% spectral edge frequency and median frequency during propofol infusion with or without fentanyl.

Hypnotic endpoints and/or EEG variables, e.g. bispectral index, 95% spectral edge frequency and median frequency, have been studied to monitor anaesthetic (hypnotic) depth during total intravenous anaesthesia. In this study, the relation between the hypnotic endpoints of unresponsiveness to verbal commands, loss of eyelash reflex and body movement response to mechanical nasal membrane stimulation vs. bispectral index, 95% spectral edge frequency and median frequency during propofol anaesthesia with or without fentanyl is presented. Forty-two patients were randomly assigned to receive either propofol infusion, 30 mg kg-1 h-1 (n = 22), or propofol infusion, 30 mg kg-1 h-1 + fentanyl bolus, 2 micrograms kg-1 i.v. (n = 20). Bispectral index, 95% spectral edge frequency and median frequency and propofol doses were monitored and recorded at unresponsiveness to verbal commands, loss of eyelash reflex and inhibition of nasal body movement response. The bispectral index values were significantly higher in the propofol + fentanyl compared with the propofol group, i.e. 74.7 +/- 10.9, 73.1 +/- 10.5 and 47.1 +/- 9.2 vs. 65.8 +/- 9.8, 59.6 +/- 10 and 33.8 +/- 5.7 at unresponsiveness to verbal commands, loss of eyelash reflex and inhibition of nasal body movement response respectively. Doses of propofol for achieving the hypnotic endpoints were significantly lower in the propofol + fentanyl compared with the propofol group. Plasma propofol concentrations at inhibition of nasal body movement response were lower in the propofol + fentanyl compared with the propofol group (9.2 +/- 2.0 micrograms mL-1 vs. 14.1 +/- 4.2 micrograms mL-1). Our results suggest that fentanyl pretreatment potentiates the effects of propofol and achieves the hypnotic endpoints at higher bispectral index values and lower propofol doses and concentrations (measured at inhibition of nasal body movement response).

Adjuvants, Anesthesia↗
PubMed2000

Combined sciatic-femoral nerve block with 0.75% ropivacaine: effects of adding a systemically inactive dose of fentanyl.

To evaluate the effects of adding low-dose fentanyl to 0.75% ropivacaine during peripheral nerve blocks, 30 ASA physical status I-II patients undergoing hallux valgus repair under combined sciatic-femoral nerve block were randomly allocated in a double-blind fashion to receive nerve block placement with 30 mL of either 0.75% ropivacaine alone (group: ropivacaine, n = 15) or 0.75% ropivacaine plus fentanyl 1 microg kg(-1) (group: ropivacaine-fentanyl, n = 15). A blinded observer recorded haemodynamic variables and sedation, as well as the time required to achieve surgical block and the first request for analgesia. Readiness to surgery required 10 min (5-20 min) with 0.75% ropivacaine and 10 min (3-20 min) with the ropivacaine-fentanyl mixture. No differences in the degree of sedation, peripheral oxygen saturation, and haemodynamic variables were observed between the two groups. The degree of pain measured at first analgesic request, and the consumption of postoperative analgesics, was similar in the two groups, while the mean time from block placement to the first request for pain medication was 13.7 h (25-75th percentiles: 11.8-14.5 h) in the ropivacaine group and 13.9 h (25-75th percentiles: 10.5-14.5 h) in the ropivacaine-fentanyl group (P = not significant). We conclude that adding fentanyl 1 microg kg(-1) to 0.75% ropivacaine did not provide clinically relevant advantages in terms of onset time, quality and duration of combined sciatic-femoral nerve block in patients undergoing elective hallux valgus repair.

Adjuvants, Anesthesia↗
PubMed1996

Comparison of diclofenac and tenoxicam for postoperative analgesia with and without fentanyl in children undergoing adenotonsillectomy or tonsillectomy.

127 children scheduled for elective tonsillectomy or adenotonsillectomy were studied. Anaesthesia was induced with propofol and maintained with a volatile agent. At induction the child received either rectal diclofenac 1 mg.kg-1 with or without fentanyl 0.75 microgram.kg-1 i.v., or intravenous tenoxicam 0.4 mg.kg-1 with or without fentanyl 0.75 microgram.kg-1 i.v. Blood loss was measured peroperatively. Nausea and vomiting scores, sedation scores and pain scores were recorded in the recovery room, at one, two, four and eight h postoperatively and at discharge. There were no significant differences in blood loss between the groups or between nausea and vomiting scores. Pain scores in the tenoxicam without fentanyl group were significantly higher in recovery (P < 0.05) than the diclofenac group without fentanyl and both fentanyl groups. This group required supplemental analgesia earlier although this was not significant. The pain scores in the diclofenac with fentanyl group were significantly lower at one h and four h than the group receiving diclofenac alone (P = 0.008 and 0.02 respectively).

Adenoidectomy↗
PubMed1997

Evaluation of awakening and recovery characteristics following anaesthesia with nitrous oxide and halothane fentanyl or both for brief outpatient procedures in infants.

This study compared recovery characteristics and postoperative ventilatory function when halothane, fentanyl or combination of halothane and fentanyl in addition to N2O were used for intraoperative anaesthesia in term infants undergoing hernia repair as outpatients. Sixty-six full term ASA PS I infants ages 1-12 months were studied. All received inhalation induction with N2O, O2 and halothane, followed by intravenous atropine and atracurium, tracheal intubation, and controlled ventilation. For anaesthesia maintenance, patients were randomized into one of three groups. Group I received 70% N2O, 30% O2 and halothane. Group II received 70% N2O, 30% O2, halothane and 2 micrograms.kg-1 fentanyl. Group III received 70% N2O, 30% O2 and 10 micrograms.kg-1 fentanyl. Awakening times were similar in all three groups, however, Group I patients had significantly shorter recovery and discharge times than those of Group II and III. None of the patients experienced postoperative apnoea or periodic breathing. One patient in Group III experienced two brief episodes of bradycardia not associated with apnoea or arterial desaturation (SpO2 > 90% for greater than 30 s). Decreased SpO2 occurred less frequently in Group I (5.9%) compared to Group II (22.7%) and Group III (19.0%) patients, however, the group differences were not significant. Transcutaneous CO2 (TcCO2) values were not statistically different among the three groups. Pain scores were initially lower in Groups II and III, but at 120 min the differences were not significant. Postoperative apnoea was not observed in this study. SpO2 < 90% and TcCO2 > 9 kPa (70 mmHg) was more common in infants receiving 2 and 10 micrograms.kg-1 fentanyl than in infants receiving halothane and nitrous oxide anaesthesia. Infants < 3 months old did not have a higher incidence of SpO2 < 90% or significantly higher TcCO2 values when compared to infants > 3 months old. Fentanyl in doses used in this study did not prolong awakening time but did prolong recovery and discharge times in outpatient infants.

Ambulatory Surgical Procedures↗
PubMed2003

Increased incidence of postoperative nausea and vomiting without additional analgesic effects when a low dose of intravenous fentanyl is combined with a caudal block.

BACKGROUND: The use of opioids is known to increase the incidence of postoperative nausea and vomiting (PONV). In spite of this, administration of low doses of an opioid during anaesthesia is common practice, even if a regional anaesthetic technique is used. This study was designed to estimate the effects of intraoperative intravenous administration of fentanyl on PONV in paediatric daycase surgery. METHODS: PONV and pain were evaluated in 29 boys during the first 24 h after daycase penile surgery. Anaesthesia was standardized. The patients were allocated to two groups. Fentanyl 1 micro g.kg-1 i.v. or placebo was administered in a randomized, double-blind design. A caudal block with ropivacaine 2 mg.ml-1, 0.5 ml.kg-1 was performed preoperatively and topical lidocaine gel 20 mg.ml-1 was applied over the wound area immediately after surgery. RESULTS: The total incidence of PONV in hospital and at home during the first 24 h was 36% (5/14) when fentanyl was used, whereas no PONV was reported when placebo was given (P < 0.05). The median time to first administration of analgesics after the caudal block was approximately 6 h. It did not differ between groups. Intraoperative fentanyl did not result in any reduction in pain scores nor the incidence of pain. Fentanyl caused apnoea in one-half of the cases and decreased the breathing rates during the first 10 min of surgery. CONCLUSIONS: Intraoperative use of i.v. fentanyl 1 micro g.kg-1 combined with a regional anaesthetic block is associated with an increased incidence of PONV without any significant contribution to the postoperative pain relief.

Adolescent↗
PubMed2003

Reduction of isoflurane MAC by fentanyl or remifentanil in rats.

OBJECTIVE: The main objective of the study was to determine the effects of three different infusion rates of fentanyl and remifentanil on the minimum alveolar concentration (MAC) of isoflurane in the rat. A secondary objective was to assess the cardiovascular and respiratory effects of the two opioid drugs. ANIMAL POPULATION: Thirty-seven male Wistar rats were randomly allocated to one of six treatment groups. MATERIAL AND METHODS: For all treatment groups anaesthesia was induced with 5% isoflurane in oxygen using an induction chamber. A 14-gauge catheter was used for endotracheal intubation, and anaesthesia was maintained with isoflurane delivered in oxygen via a T-piece breathing system. A baseline determination of the minimum alveolar concentration of isoflurane (MACISO) was made for each animal. Fentanyl (15, 30, 60 micro g kg-1 hour-1) or remifentanil (60, 120, 240 micro g kg-1 hour-1) were infused intravenously into a previously cannulated tail vein. Thirty minutes after the infusion started, a second MACISO (MACISO+drug) was determined. The carotid artery was cannulated to monitor the arterial pressure and to take samples for arterial gas measurements. Cardiovascular (heart rate and arterial pressure) and respiratory (respiratory rate and presence/absence of apnoea) effects after opioid infusion were also recorded. RESULTS: Fentanyl (15, 30, 60 micro g kg-1 hour-1) and remifentanil (60, 120, 240 micro g kg-1 hour-1) similarly reduced isoflurane MAC in a dose-dependent fashion: by 10% at lower doses, 25% at medium doses and by 60% at higher doses of both the drugs. Both opioids reduced the respiratory rate in a similar way for all doses tested. No episodes of apnoea were recorded in the remifentanil groups, while administration of fentanyl resulted in apnoea in three animals (one at each dose level). The effects on the cardiovascular system were similar with both drugs. CONCLUSIONS: We conclude that the intraoperative use of remifentanil in the rat reduces the MAC of isoflurane, and that this anaesthetic sparing effect is dose-dependent and similar to that produced by fentanyl at the doses tested. CLINICAL RELEVANCE: The use of remifentanil during inhalant anaesthesia in the rat can be considered an intravenous alternative to fentanyl, providing similar reduction in isoflurane requirements. Due to its rapid offset, it is recommended that alternative pain relief be instituted before it is discontinued.

Analgesics, Opioid↗
PubMed2004

Comparison of bolus remifentanil versus bolus fentanyl for induction of anesthesia and tracheal intubation in patients with cardiac disease.

OBJECTIVE: Large bolus-dose remifentanil may be advantageous for use during induction of anesthesia because of its short duration of effect. Currently, there are little data on the use of large bolus-dose remifentanil because of reports of severe bradycardia and hypotension. The purpose of this study is to compare the hemodynamic effects of bolus remifentanil versus fentanyl with glycopyrrolate for induction of anesthesia in patients with heart disease. DESIGN: A randomized, double-blinded study. SETTING: A tertiary-care academic medical center. PARTICIPANTS: One hundred patients for coronary artery bypass or valvular surgery. INTERVENTION: Subjects received either (1) remifentanil, 5 microg/kg, with glycopyrrolate, 0.2 mg, or (2) fentanyl, 20 microg/kg, with 0.2 mg of glycopyrrolate, and both groups also received midazolam, 70 microg/kg, for induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Heart rate, mean arterial pressure, systemic vascular resistance, and cardiac output were similar between the 2 groups during induction of anesthesia and tracheal intubation. The incidence of adverse events such as bradycardia (remifentanil 10%, fentanyl 10%), hypotension (remifentanil 16%, fentanyl 10%), and ischemia (remifentanil 0%, fentanyl 2%) were also similar. A greater percentage of patients in the remifentanil group lost consciousness within 1 minute of opioid administration (86% v 66%, p = 0.034). CONCLUSION: Remifentanil with glycopyrrolate is associated with rapid and predictable clinical anesthetic effect, cardiac stability, and the ability to blunt the hemodynamic responses to tracheal intubation. Bolus remifentanil may be a feasible alternative to bolus fentanyl for induction of anesthesia in patients with heart disease because of its short duration of action and its ability to blunt the hemodynamic responses to tracheal intubation.

Adjuvants, Anesthesia↗