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PubMed2000

Intrathecal fentanyl is superior to intravenous ondansetron for the prevention of perioperative nausea during cesarean delivery with spinal anesthesia.

This study compares intrathecal (IT) fentanyl with IV ondansetron for preventing intraoperative nausea and vomiting during cesarean deliveries performed with spinal anesthesia. Thirty healthy parturients presenting for elective cesarean delivery with standardized bupivacaine spinal anesthesia were randomized to receive 20 microg IT fentanyl (Group F) or 4 mg IV ondansetron (Group O) by using double-blinded methodology. At eight specific intervals during the surgery, a blinded observer questioned the patient about nausea (1 = nausea, 0 = no nausea), observed for the presence of retching or vomiting (1 = vomiting or retching, 0 = no vomiting or retching), and recorded a verbal pain score (0-10, 0 = no pain, 10 = worst pain imaginable). Cumulative nausea, vomiting, and pain scores were calculated as the sum of the eight measurements. Intraoperative nausea was decreased in the IT fentanyl group compared with the IV ondansetron group: the median (interquartile range) difference in nausea scores was 1 (1, 2), P = 0.03. The incidence of vomiting and treatment for vomiting was not different (P = 0.7). The IT fentanyl group had a lower cumulative perioperative pain score than the IV ondansetron group; the median difference in the cumulative pain score was 12 (8, 16) (P = 0.0007). The IT fentanyl group required less supplementary intraoperative analgesia. The median difference in the cumulative fentanyl dose was 100 (75, 100) microg fentanyl, (P = 0.0002).

Adjuvants, Anesthesia↗
PubMed2001

The effect of intranasal fentanyl on the emergence characteristics after sevoflurane anesthesia in children undergoing surgery for bilateral myringotomy tube placement.

UNLABELLED: Children undergoing placement of bilateral myringotomy tubes (BMT) often exhibit pain-related behavior (agitation) in the postanesthesia care unit. We compared the emergence and recovery profiles of pediatric patients who received sevoflurane with or without supplementary intranasal fentanyl for BMT surgery. By using a prospective, double-blinded design, 150 children 6 mo to 5 yr of age, scheduled for routine BMT surgery, were anesthetized with sevoflurane (2%-3%) in a 60% N(2)O/O(2) gas mixture. Patients were randomized to receive equal volumes of intranasal saline (Control), 1 microg/kg fentanyl or 2 microg/kg fentanyl. A blinded observer evaluated each patient using a previously described 4-point agitation scale and the Steward recovery scale. Response to parental presence was observed after a score of six (full recovery) was achieved on the Steward recovery scale. There were no significant differences among the three groups regarding age, weight, surgeon, duration of anesthesia, or ear condition. Recovery times and emergence characteristic scores were not statistically different. Agitation scores were significantly reduced in the 2-microg/kg Fentanyl group as compared with the Control group (P = 0.012). Fentanyl 2 microg/kg is recommended to reduce the incidence of agitation seen in these patients. IMPLICATIONS: We examined the use of nasally administered fentanyl for the relief of agitation or discomfort after placement of bilateral myringotomy tubes in 150 children ages 6 mo to 5 yr using a prospective, double-blinded design. Fentanyl 2 microg/kg was found to reduce the incidence of agitation in these patients.

Administration, Intranasal↗
PubMed2001

The concentration-effect relationship of the respiratory depressant effects of alfentanil and fentanyl.

UNLABELLED: The relative potencies of fentanyl and alfentanil for respiratory depression were determined in eight healthy male volunteers in a double-blinded, randomized study with a cross-over design. The drugs were delivered by computer-driven infusion with logarithmically ascending plasma concentrations until the respiratory rate reached 2/min and/or oxygen saturation decreased below 85% with subjects breathing room air. Ventilation was measured with respiratory inductive plethysmography, indirect calorimetry, and arterial blood gas analysis, and plasma drug concentrations were determined. Pharmacodynamic modeling was performed using a fractional E(max) model for minute volume and respiratory rate and the concentrations producing 50% depression (i.e., apparent 50% effective concentration [EC(50)] values) were determined. Both drugs decreased ventilation in a similar manner, and drug infusions were terminated at mean +/- SD measured plasma concentrations of 254 +/- 88 ng/mL and 5.1 +/- 1.7 ng/mL for alfentanil and fentanyl, respectively. Alfentanil decreased minute volume from baseline by 54% +/- 19% and respiratory rate by 40% +/- 11% with EC(50) values of 234 +/- 57 ng/mL and 195 +/- 101 ng/mL. The respective decreases for fentanyl were 50% +/- 11%, 41% +/- 15%, and the estimated EC(50) values were 6.1 +/- 1.4 ng/mL and 3.5 +/- 1.4 ng/mL, respectively. Using the apparent EC(50) values, the calculated potency ratio for alfentanil:fentanyl was (mean and 95% confidence interval) 1:39 (1:31-1:46) for minute volume and 1:51 (1:34-1:68) for respiratory rate. This is analogous to the analgesic effect studied earlier. The findings support the notion of parallel analgesic and respiratory depressant effects of alfentanil and fentanyl. Therefore equianalgesic concentrations of both drugs will lead to equally pronounced respiratory depression. IMPLICATIONS: This double-blinded, randomized study evaluated the potency ratio of alfentanil and fentanyl-induced respiratory depression. The findings support the notion of parallel analgesic and respiratory depressant effects of alfentanil and fentanyl. Therefore equianalgesic concentrations of both drugs will lead to equally pronounced respiratory depression.

Adult↗
PubMed2002

The prevention of pain from injection of rocuronium by ondansetron, lidocaine, tramadol, and fentanyl.

UNLABELLED: We compared the efficacy of ondansetron, lidocaine, tramadol, and fentanyl in minimizing pain caused by the injection of rocuronium in 250 patients. After tourniquet application on the forearm, the patients were given saline (3 mL) (Group 1, n = 50), ondansetron (4 mg) (Group 2, n = 50), lidocaine (30 mg) (Group 3, n = 50), tramadol (50 mg) (Group 4, n = 50), or fentanyl (100 microg) (Group 5, n = 50) diluted into a 3-mL solution. The occlusion was released after 20 s and rocuronium was injected over 10-15 s. The patients were observed and asked immediately if they had pain in the arm, and the response was assessed. Reactions such as discomfort and pain, withdrawal of the hand, and so on after the administration of rocuronium were recorded as side effects for 24 h. Ten patients in Group 1, 28 patients in Group 2, 37 patients in Group 3, 30 patients in Group 4, and 15 patients in Group 5 reported no pain. Light pain was seen in 11 patients in Group 1, 14 patients in Group 2, 11 patients in Group 3, 12 patients in Group 4, and 20 patients in Group 5. Moderate pain was seen in 15 patients in Group 1, 6 patients in Group 2, 2 patients in Group 3, 8 patients in Group 4, and 10 patients in Group 5. Severe pain was seen in 14 patients in Group 1, 2 patients in Group 2, 0 patients in Group 3, 0 patients in Group 4, and 5 patients in Group 5. Correlation determined with log-linear analysis found in Group 1 pain score 0 (P < 0.001), Group 1 pain score 1 (P < 0.001), and Group 3 pain score 0 (P < 0.001). We conclude that ondansetron, lidocaine, tramadol, and fentanyl decrease the level of rocuronium injection pain. Among these drugs, lidocaine is the most effective, whereas fentanyl is the least effective. IMPLICATIONS: We compared the efficacy of ondansetron, lidocaine, tramadol, and fentanyl in minimizing the pain on injection of rocuronium in 250 patients. Ondansetron, lidocaine, tramadol, and fentanyl were effective in preventing and decreasing the level of rocuronium injection pain. Among these drugs, lidocaine was the most effective, and fentanyl was the least effective.

Adult↗
PubMed1984

Fentanyl and cerebral vascular responsivity in dogs.

The effect of high-dose fentanyl on the cerebral vascular response to alterations in mean arterial blood pressure, arterial O2 tension (PaO2), and arterial CO2 tension (PaCO2) was studied in 28 mongrel dogs using the cerebral venous outflow technique. In 13 animals anesthetized with sodium pentobarbital (30 mg/kg, iv), bolus injection of fentanyl (25 micrograms/kg, iv) decreased mean arterial blood pressure (MABP) without a change in cerebral blood flow (CBF). In these animals, the response of the cerebral circulation to changes in PaO2, PaCO2, and MABP was determined before and after fentanyl administration. Fentanyl did not alter the increase in CBF caused by hypoxic hypoxia or hypercapnia. The lower and upper limit of cerebral autoregulation determined by hypovolemic hypotension and norepinephrine infusion, respectively, also were unaltered by fentanyl administration. The CBF response to alterations of MABP, PaO2, and PaCO2 were studied in another group of 15 dogs anesthetized with fentanyl (100 micrograms/kg) plus small doses (3-5 mg/kg) of pentobarbital. The CBF response to PaO2, and PaCO2 in these animals was not different from that observed in animals anesthetized with barbiturates only. The lower and upper limit of cerebral autoregulation also were not different from that observed in animals anesthetized with barbiturates only. These data suggest that fentanyl in doses sufficient to cause profound analgesia and anesthesia did not alter cerebral responsivity to changes in PaO2, and PaCO2, and MABP.

Animals↗
PubMed1984

Optimization of the radioimmunoassays for measuring fentanyl and alfentanil in human serum.

Measurement of serum fentanyl and alfentanil concentrations by radioimmunoassay (RIA) may result in significant errors and high variability when the technique described in the available fentanyl and alfentanil RIA kits is used. The authors found a 29-94% overestimation of measured fentanyl and alfentanil serum levels when 3H-fentanyl or 3H-alfentanil was added lastly to the mixture of antiserum and sample. This finding is related to a reduction in binding sites for the labeled compounds after preincubation of sample and antiserum. If this sequence is used, it becomes necessary to extend the incubation period up to 6 h for fentanyl and up to 10 h for alfentanil in order to achieve equilibration between unlabeled and labeled drug with respect to antiserum binding. However, when antiserum is added lastly to the mixture of sample and labeled drug, measurement accuracy and precision for fentanyl and alfentanil serum concentrations are enhanced markedly. In addition, it is important to perform the calibration curves and sample measurements using the same medium (i.e., serum alone or a serum/buffer dilution). In summary, to optimize the RIA for fentanyl and alfentanil, the authors recommend the following: 1) adding the antiserum lastly to the mixture of sample and labeled drug; 2) performing calibration curves using patient's blank serum when possible; 3) carefully examining and standardizing each step of the RIA procedure to reduce variability, and, finally; 4) comparing results with those of other established RIA laboratories.

Alfentanil↗
PubMed1989

Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane, and halothane anesthesia in adults and children.

To determine in adults and children the dose-response relationship and the duration of action of pipecuronium bromide during fentanyl-nitrous oxide (N2O), isoflurane, and halothane anesthesia, the authors studied 30 ASA Physical Status 1-2 adults (age: 16-55 yr) and 30 ASA Physical Status 1-2 children (age: 1.7-11.5 yr) during minor elective surgery. Patients were anesthetized with N2O/O2 (60:40) supplemented with either fentanyl (4 micrograms/kg), or isoflurane (adults, 0.9%; children, 1.2%), or halothane (adults, 0.6%; children, 0.7%). Neuromuscular (NM) blockade was measured by electromyography. Incremental iv doses of pipecuronium were administered to determine the cumulative dose-response relationship of pipecuronium until a 95% twitch depression (ED95) had been obtained. In adults, ED50 was 31.7 +/- 2.9 micrograms/kg (mean +/- SE) during fentanyl-N2O/O2, reduced by isoflurane (18.0 +/- 4.8 micrograms/kg, P less than 0.05) but not by halothane (25.0 +/- 2.6 micrograms/kg, NS). ED95 was 59.4 +/- 5.4 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (42.3 +/- 2.5 micrograms/kg, P less than 0.05), but not by halothane (49.7 +/- 3.1 micrograms/kg, NS). In children, ED50 was 43.9 +/- 4.7 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (23.1 +/- 1.6 micrograms/kg, P less than 0.05), and halothane (33.2 +/- 3.2 micrograms/kg, P less than 0.05). ED95 was 79.3 +/- 9.8 micrograms/kg during fentanyl-N2O/O2, and reduced by isoflurane (49.1 +/- 3.1 micrograms/kg, P less than 0.05), but not by halothane (62.5 +/- 7.3 micrograms/kg, NS). Comparison between adults and children reveals no statistically significant differences, except for ED50 during fentanyl-N2O/O2 anesthesia which was increased in children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Pharmacokinetic model-driven infusion of fentanyl: assessment of accuracy.

Computer-assisted continuous infusion (CACI) is a pharmacokinetic model-driven infusion device that enables physicians to administer intravenous (iv) drugs in a quantitative fashion, specifying a theoretical blood or plasma concentration. This study evaluated the accuracy of CACI administration of fentanyl using a newly developed CACI device programmed with a well-known set of pharmacokinetic parameters for fentanyl. Patients received diazepam 1 or 2 h before surgery. Anesthesia was induced by a combination of 70% N2O and fentanyl administered by CACI to a predicted concentration of 15-25 ng.ml-1. After neuromuscular blockade and tracheal intubation, the desired plasma fentanyl concentration (setpoint) entered into CACI was 3-6 ng.ml-1, and then the setpoint fentanyl concentration was titrated according to strict criteria of adequate or inadequate anesthesia. Plasma samples for subsequent assay of fentanyl concentration then were taken: at predefined stimuli, when inadequate anesthesia occurred, or 5 min before an anticipated decrease in the fentanyl setpoint. The predictive accuracy of CACI was assessed by calculating for each patient the tenth, 50th, and 90th percentile of the performance error and absolute performance error from each measured and predicted plasma sample pair. Cumulative probability functions for each of these were then plotted. Precision was defined as the dispersion of the tenth to 90th percentile of the median percent performance error for the population and was found to be -31-26%. The median population performance error was -4%, and the median population absolute performance error was 21%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of fentanyl versus sufentanil in equianesthetic doses on middle cerebral artery blood flow velocity.

BACKGROUND: Sufentanil has been reported to increase cerebral blood flow in comparison with fentanyl. However, because of the use of animal models, supraclinical doses and/or background anesthetic agents, the clinical applicability of these studies remains difficult to assess. Therefore, transcranial Doppler ultrasonography was used to determine the cerebral hemodynamic effects of equianesthetic doses of fentanyl and sufentanil on middle cerebral artery (MCA) blood flow velocity in patients without intracranial pathologic conditions. METHODS: Twenty-four unpremedicated American Society of Anesthesiologists physical status 1 and 2 patients undergoing elective nonintracranial neurosurgery were assigned randomly to receive equipotent blinded infusions of either sufentanil (15 micrograms/min) or fentanyl (150 micrograms/min) for anesthetic induction during spontaneous ventilation of 100% oxygen. Normocapnia, as measured by infrared capnography, was maintained by manually assisting ventilation, as necessary. The cerebral opioid effect was quantified using the spectral edge frequency parameter. The infusion was continued until either 1) spectral edge frequency decreased below 10 Hz or 2) 150 micrograms of sufentanil or 1,500 micrograms of fentanyl was infused, whichever occurred first. On average, the patients received 1.7 +/- 0.55 micrograms/kg or 16 +/- 4 micrograms/kg of sufentanil or fentanyl, respectively. The right MCA mean, peak systolic, and peak diastolic velocities and pulsatility index were measured continuously by transcranial Doppler ultrasonography. RESULTS: The mean arterial pressure decreased slightly in both groups, but only in the fentanyl group were the changes significant. The MCA velocity increased by approximately 25% in both groups. However, the relative changes in MCA velocity were not different between groups. The pulsatility indexes were unchanged in both groups. CONCLUSIONS: These data suggest that, at clinically relevant doses in the absence of other drugs, cerebral blood flow velocity is increased by both fentanyl and sufentanil. Furthermore, there appears to be no significant differences in the cerebral hemodynamic profiles of the two drugs, as assessed by transcranial Doppler ultrasonography.

Adolescent↗
PubMed1997

Involvement of cerulospinal glutamatergic neurotransmission in fentanyl-induced muscular rigidity in the rat.

BACKGROUND: Investigators in the authors' laboratory previously established the critical participation of the cerulospinal noradrenergic pathway in muscular rigidity elicited by fentanyl. The identification of colocalization of glutamate with tyrosine hydroxylase in most locus ceruleus neurons suggests a role for cerulospinal glutamatergic neurotransmission in fentanyl-induced muscular rigidity. This suggestion and the subtype(s) of glutamate receptors involved were investigated here. METHODS: Electromyographic signals activated by bilateral microinjection of 2.5 microg fentanyl into the locus ceruleus were recorded differentially from the left sacrococcygeus dorsi lateralis muscle of adult male Sprague-Dawley rats. The effect of intrathecal administration at the lower lumbar spinal cord of various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists or agonists on this index of muscular rigidity was studied. Rats were under mechanical ventilation, and intravenous infusion of ketamine (30 mg x kg(-1) x h(-1)) was maintained until 10 min before fentanyl was administered. RESULTS: Microinjection of fentanyl bilaterally into the locus ceruleus increased the root mean square and decreased the mean power frequency values of electromyographic signals. The efficacy of fentanyl to elicit muscular rigidity in this manner was significantly reduced by previous intrathecal administration of either 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), D-(-)-2-amino-5-phosphonovaleric acid (AP5), or (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). Intrathecal administration of kainic acid or NMDA also resulted in significant electromyographic activation. CONCLUSIONS: In addition to the cerulospinal noradrenergic mechanism, the cerulospinal glutamatergic pathway and both NMDA and non-NMDA receptors in the spinal cord may mediate fentanyl-induced muscular rigidity in the rat.

Analgesics, Opioid↗
PubMed1998

The pharmacodynamic interaction between propofol and fentanyl with respect to the suppression of somatic or hemodynamic responses to skin incision, peritoneum incision, and abdominal wall retraction.

BACKGROUND: Sufficient propofol or fentanyl doses necessary to prevent the response to skin incision do not necessarily attenuate hemodynamic responses during surgery. The goal of this study was to characterize the pharmacodynamic interaction between propofol and fentanyl with respect to the suppression of somatic or hemodynamic responses after three stimuli: skin incision, peritoneum incision, and abdominal wall retraction. METHODS: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide equilibration between plasma-blood and biophase concentrations. Patients were randomized to nine groups that received predetermined concentrations of fentanyl (from 0 to 9 ng/ml). Each patient was administered different target concentrations of propofol. Somatic and hemodynamic responses were measured before and after each of three different stimulations: skin incision (si), peritoneum incision (pi), and abdominal wall retraction (ret). The propofol plasma concentrations at which 50% of the patients did not respond to each type of stimulation (Cp50si, Cp50pi, and Cp50ret) were calculated by fitting the Loewe synergistic model. RESULTS: For propofol alone, Cp50si, Cp50pi, and Cp50ret were 12.9, 17.1, and 19.4 microg/ml, respectively. Increasing the fentanyl concentration markedly reduced propofol Cp50si, Cp50pi, and Cp50ret for somatic response, indicating the potential synergistic interaction of both drugs. During the prestimulation period, fentanyl did not decrease systolic blood pressure; however, propofol specifically decreased systolic blood pressure. Both drugs had a synergistic drug interaction on the systolic blood pressure increase after various surgical stimulations. Fentanyl and propofol concentrations that suppressed both the 50% probability of somatic response and the 50% probability of moderate hemodynamic change defined by the 15% systolic blood pressure increase over the prestimulation value were 3.6 ng/ml and 2.5 microg/ml for skin incision, 8.4 ng/ml and 1.6 microg/ml for peritoneum incision, and 5.9 ng/ml and 5.1 microg/ml for wall retraction, respectively. CONCLUSIONS: The anesthesia requirements for stimuli that are more intense than skin incision should be considered during abdominal surgery. Somatic and hemodynamic responses varied depending on the type of surgical stimuli.

Abdominal Muscles↗
PubMed1998

Differential effects of fentanyl and morphine on intracellular Ca2+ transients and contraction in rat ventricular myocytes.

BACKGROUND: Our objective was to elucidate the direct effects of fentanyl and morphine on cardiac excitation-contraction coupling using individual, field-stimulated rat ventricular myocytes. METHODS: Freshly isolated myocytes were loaded with fura-2 and field stimulated (0.3 Hz) at 28 degrees C. Amplitude and timing of intracellular Ca2+ concentration (at a 340:380 ratio) and myocyte shortening (video edge detection) were monitored simultaneously in individual cells. Real time Ca2+ uptake into isolated sarcoplasmic reticulum vesicles was measured using fura-2 free acid in the extravesicular compartment. RESULTS: The authors studied 120 cells from 30 rat hearts. Fentanyl (30-1,000 nM) caused dose-dependent decreases in peak intracellular Ca2+ concentration and shortening, whereas morphine (3-100 microM) decreased shortening without a concomitant decrease in the Ca2+ transient. Fentanyl prolonged the time to peak and to 50% recovery for shortening and the Ca2+ transient, whereas morphine only prolonged the timing parameters for shortening. Morphine (100 microM), but not fentanyl (1 microM), decreased the amount of Ca2+ released from intracellular stores in response to caffeine in intact cells, and it inhibited the rate of Ca2+ uptake in isolated sarcoplasmic reticulum vesicles. Fentanyl and morphine both caused a downward shift in the dose-response curve to extracellular Ca2+ for shortening, with no concomitant effect on the Ca2+ transient. CONCLUSIONS: Fentanyl and morphine directly depress cardiac excitation-contraction coupling at the cellular level. Fentanyl depresses myocardial contractility by decreasing the availability of intracellular Ca2+ and myofilament Ca2+ sensitivity. In contrast, morphine depresses myocardial contractility primarily by decreasing myofilament Ca2+ sensitivity.

Actin Cytoskeleton↗
PubMed2000

Long-lasting hyperalgesia induced by fentanyl in rats: preventive effect of ketamine.

BACKGROUND: It has been reported that mu-opioid receptor activation leads to a sustained increase in glutamate synaptic effectiveness at the N-methyl-D-aspartate (NMDA) receptor level, a system associated with central hypersensitivity to pain. One hypothesis is that postoperative pain may result partly from the activation of NMDA pain facilitatory processes induced by opiate treatment per se. The authors tested here the effectiveness of the opiate analgesic fentanyl for eliciting a delayed enhancement in pain sensitivity. METHODS: The consequences of four bolus injections (every 15 min) of fentanyl (20-100 microg/kg per injection, subcutaneously) on immediate (for several hours) and long-term (for several days) sensitivity to nociceptive stimuli in the rat (paw-pressure vocalization test) were evaluated. The effects of the combination of the NMDA-receptor antagonist ketamine (10 mg/kg, subcutaneously) with fentanyl also were assessed. RESULTS: Fentanyl administration exhibited a biphasic time-dependent effect: first, an early response (for 2-5 h) associated with a marked increase in nociceptive threshold (analgesia), and second, a later response associated with sustained lowering of the nociceptive threshold (5 days for the longest effect) below the basal value (30% of decrease for the maximal effect) indicative of hyperalgesia. The higher the fentanyl dose used, the more pronounced was the fentanyl-induced hyperalgesia. Ketamine pretreatment, which had no analgesic effect on its own, enhanced the earlier response (analgesia) and prevented the development of long-lasting hyperalgesia. CONCLUSIONS: Fentanyl activates NMDA pain facilitatory processes, which oppose analgesia and lead to long-lasting enhancement in pain sensitivity.

Analgesics, Opioid↗
PubMed2000

Plasma concentration of fentanyl with xenon to block somatic and hemodynamic responses to surgical incision.

BACKGROUND: Although anesthesia with xenon has been supplemented with fentanyl, its requirement has not been established. This study was conducted to determine the plasma concentrations of fentanyl necessary to suppress somatic and hemodynamic responses to surgical incision in 50% patients in the presence of 0.7 minimum alveolar concentration (MAC) xenon. METHODS: Twenty-five patients were allocated randomly to predetermined fentanyl concentration between 0.5 and 4.0 ng/ml during 0.7 MAC xenon anesthesia. Fentanyl was administered using a pharmacokinetic model-driven computer-assisted continuous infusion device. At surgical incision each patient was monitored for somatic and hemodynamic responses. A somatic response was defined as any purposeful bodily movement. A positive hemodynamic response was defined as a more than 15% increase in heart rate or mean arterial pressure more than the preincision value. The concentrations of fentanyl to prevent somatic and hemodynamic responses in 50% of patients were calculated using logistic regression. RESULTS: The concentration of fentanyl to prevent a somatic response to skin incision in 50% of patients in the presence of 0.7 MAC xenon was 0.72 +/- 0.07 ng/ml and to prevent a hemodynamic response was 0.94 +/- 0.06 ng/ml. CONCLUSIONS: Comparing these results with previously published results in the presence of 70% nitrous oxide, the fentanyl requirement in xenon anesthesia is smaller than that in the equianesthetic nitrous oxide anesthesia.

Abdomen↗
PubMed2001

Minimum local analgesic dose of intrathecal bupivacaine in labor and the effect of intrathecal fentanyl.

BACKGROUND: Combining bupivacaine with fentanyl for intrathecal analgesia in labor is well recognized, but dosages commonly used are arbitrarily chosen and may be excessive. This study aimed to determine the median effective dose (ED50) of intrathecal bupivacaine, defined as the minimum local analgesic dose (MLAD), and then use this to assess the effect of different doses of fentanyl. METHODS: In this double-blind, randomized, prospective study, 124 parturients receiving combined spinal epidural analgesia at 2-6-cm cervical dilatation were allocated to one of four groups to receive bupivacaine alone or with 5, 15, or 25 microg fentanyl, using the technique of up-down sequential allocation. Analgesic effectiveness was assessed using 100-mm visual analog pain scores, with less than or equal to 10 mm within 15 min defined as effective. MLAD was calculated using the formula of Dixon and Massey. Pruritus and duration of spinal analgesia were also recorded. RESULTS: Minimum local analgesic dose of intrathecal bupivacaine was 1.99 mg (95% confidence interval, 1.71, 2.27). There were similar significant reductions in MLAD (P < 0.001) for all bupivacaine-fentanyl groups compared with bupivacaine control. There was a dose-dependent increase in both pruritus and duration of spinal analgesia with increasing fentanyl (P < 0.0001). CONCLUSION: Under the conditions of this study, the addition of intrathecal fentanyl 5 microg offers a similar significant bupivacaine dose-sparing effect as 15 and 25 microg. Analgesia in the first stage of labor can be achieved using lower doses of fentanyl, resulting in less pruritus but with a shortening of duration of action.

Adult↗
PubMed2003

Cephalad movement of morphine and fentanyl in humans after intrathecal injection.

BACKGROUND: Despite decades of use, controversy remains regarding the extent and time course of cephalad spread of opioids in cerebrospinal fluid (CSF) after intrathecal injection. The purpose of this study was to examine differences between two often used opioids, morphine and fentanyl, in distribution in the CSF after intrathecal injection. METHODS: Eight healthy volunteers received intrathecal injection of morphine (50 microg) plus fentanyl (50 microg) at a lower lumbar interspace. CSF was sampled through a needle in an upper lumbar interspace for 60-120 min. At the end of this time, a sample was taken from the lower lumbar needle, and both needles were withdrawn. CSF volume was determined by magnetic resonance imaging. Pharmacokinetic modeling was performed with NONMEM. RESULTS: Morphine and fentanyl peaked in CSF at the cephalad needle at similar times (41 +/- 13 min for fentanyl, 57 +/- 12 min for morphine). The ratio of morphine to fentanyl in CSF at the cephalad needle increased with time, surpassing 2:1 by 36 min and 4:1 by 103 min. CSF concentrations did not correlate with weight, height, or lumbosacral CSF volume. The concentrations of morphine and fentanyl at both sampling sites were well described by a simple pharmacokinetic model. The individual model parameters did not correlate with the distance between the needles, CSF volume, patient height, or patient weight. CONCLUSIONS: Fentanyl is cleared more rapidly from CSF than morphine, although their initial distribution in the first hour after injection does not differ greatly. The pharmacokinetic model demonstrates that mixing is the primary determinant of early concentrations and is highly variable among individuals.

Adolescent↗
PubMed2004

Accuracy of pharmacokinetic models for predicting plasma fentanyl concentrations in lean and obese surgical patients: derivation of dosing weight ("pharmacokinetic mass").

BACKGROUND: The currently available pharmacokinetic models for fentanyl were derived from normal weight patients and were not scaled to body weight. Their application to obese patients may cause overprediction of the plasma concentration of fentanyl. This study examined the influence of body weight on the predictive accuracy of two models (Anesthesiology 1990; 73:1091-102 and J Pharmacol Exp Ther 1987; 240:159-66). Further, we attempted to derive suggested dosing mass weights for fentanyl that improved predicted accuracy. METHOD: Seventy patients undergoing major elective surgery with total body weight (TBW) <85 kg and body mass index <30 (Group L) and 39 patients with TBW >/=85 kg and body mass index >30 (Group O) were studied. In Group L and Group O, the mean TBW was 69 kg, and 125 kg, respectively and the mean body mass index in Group L and Group O was 24 and 44, respectively. Fentanyl infusion was used during surgery and postoperatively for analgesia. Plasma fentanyl concentrations were measured and predicted concentrations were obtained by computer simulation; 465 pairs of measured and predicted values were obtained. RESULTS: The influence of TBW on the performance errors of the original two models was examined with nonlinear regression analysis. Shafer error versus TBW showed a highly significant negative relationship (R squared = 0.689, P < 0.001); i.e., the Shafer model systematically overestimated fentanyl concentration as weight increased. The Scott and Stanski model showed greater variation (R squared = 0.303). We used the exponential equation for Shafer performance error versus TBW to derive suggested dosing weights ("pharmacokinetic mass") for obese patients. The pharmacokinetic mass versus TBW curve was essentially linear below 100 kg (with slope of 0.65) and approached a plateau above 140 kg. For patients weighing 140 to 200 kg, dosing weights of 100-108 kg are projected. Total body clearance (ml/min) showed a strong linear correlation with pharmacokinetic mass (r = 0.793; P < 0.001), whereas the relationship with TBW was nonlinear. CONCLUSION: Actual body weight overestimates fentanyl dose requirements in obese patients. Dosing weight (pharmacokinetic mass) derived from the nonlinear relationship between prediction error and TBW proved to have a linear relationship with clearance.

Aged↗
PubMed1988

Delayed respiratory depression following fentanyl anesthesia for cardiac surgery.

High-dose fentanyl anesthesia is widely used in cardiac surgery. Its immediate side-effects are well known. However, its late adverse effect manifested by extreme truncal rigidity, decreased chest wall compliance, hypoventilation, respiratory acidosis and hemodynamic instability is not sufficiently appreciated. Of 380 patients who underwent aortocoronary artery bypass under high-dose (100 micrograms/kg) fentanyl anesthesia, 29 (7.6%) developed the sudden onset of extreme thoracic and abdominal rigidity, leading to respiratory depression 2 to 6 h postoperative, after an apparently normal recovery from the anesthesia. In 15 patients, a high plasma level of fentanyl (5.2 to 7.8 ng/ml) correlated with the clinical events. Administration of naloxone or a muscle relaxant rapidly reversed this late complication of fentanyl, thought to be due to re-entry of fentanyl into plasma from deposits in adipose tissue, muscle and the GI tract, leading to a secondary peak in plasma fentanyl. It is more likely to be encountered when hypothermia, rewarming, and acidosis occur in the postoperative period. Awareness of this life-threatening complication is critical in patients undergoing surgery with fentanyl anesthesia.

Aged↗