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PubMed2001

The addition of morphine prolongs fentanyl-bupivacaine spinal analgesia for the relief of labor pain.

UNLABELLED: The combination intrathecal fentanyl (25 microg) and bupivacaine (2.5 mg) provides effective labor analgesia for approximately 90 minutes. The purpose of this prospective, randomized, double-blinded investigation was to determine if the addition of morphine (150 microg) to the intrathecal combination of fentanyl (25 microg) and bupivacaine (2.5 mg) would prolong labor analgesia. By using the combined spinal epidural technique, 95 healthy primiparous laboring women in early labor received 2 mL of one of the two intrathecal study solutions, either FB (n = 48): fentanyl (25 microg) and bupivacaine (2.5 mg); or FBM (n = 47): fentanyl (25 microg) and bupivacaine (2.5 mg) plus morphine (150 microg). The mean duration of labor analgesia was significantly longer in the FBM group than in the FB group (252 +/- 63 min vs 148 +/- 44 min, P < 0.01). There were no significant differences between the two groups regarding the sensory levels, the incidence of nausea, vomiting, pruritus, hypotension, or operative delivery. In conclusion, the addition of 150 microg of morphine to the intrathecal combination of fentanyl plus bupivacaine prolonged the duration of labor analgesia duration without increasing adverse effects. IMPLICATIONS: The addition of morphine (150 microg) to intrathecal fentanyl (25 microg) and bupivacaine (2.5 mg) prolongs the duration of labor analgesia duration without increasing adverse effects.

Analgesia, Epidural↗
PubMed2001

Prolonged epidural infusions of ropivacaine (2 mg/mL) after colonic surgery: the impact of adding fentanyl.

UNLABELLED: We evaluated the safety and efficacy of a 72-h epidural infusion of ropivacaine and measured the impact of adding fentanyl 2 microg/mL to the required infusion rate, on the quality of postoperative pain relief and the incidence of side effects, after colonic surgery. One hundred fifty-five patients scheduled for elective colonic surgery were randomized in this trial. Epidural infusions of ropivacaine 2 mg/mL with fentanyl 2 microg/mL (R + F) and without fentanyl (R) were commenced during surgery and continued for 72 h postoperatively. This was a prospective, randomized, double-blinded, multi-center trial. The median infusion rate required was less in the R + F group (9.3 vs 11.5 mL/h, P < 0.001). Median pain scores at rest and on coughing were lower in the R + F group (P < 0.0001). The incidence of hypotension was more in the R + F group (P = 0.01). Time to readiness for discharge was delayed in the R + F group (median 6.6 vs 5.5 days, P = 0.012). The addition of fentanyl to ropivacaine resulted in decreased infusion rates and enhanced pain control; however, adverse effects were increased and readiness to discharge was delayed. IMPLICATIONS: Epidural infusions of ropivacaine with and without fentanyl were administered to patients to control pain after colonic surgery. Patients who received ropivacaine with fentanyl had better pain control, increased side effects, and delayed readiness to discharge. This study questions the value of adding opioids to epidural infusions of local anesthetics.

Adult↗
PubMed2002

Epinephrine markedly improves thoracic epidural analgesia produced by a small-dose infusion of ropivacaine, fentanyl, and epinephrine after major thoracic or abdominal surgery: a randomized, double-blinded crossover study with and without epinephrine.

UNLABELLED: We have shown that epinephrine markedly improves the analgesic effect of a thoracic epidural infusion of bupivacaine and fentanyl. Ropivacaine has an intrinsic vasoconstrictive effect, and epinephrine may therefore not have the same pharmacokinetic interaction in a ropivacaine-fentanyl infusion; but a possible spinal cord alpha(2)-agonist effect of epinephrine would give the same positive pharmacodynamic interaction with ropivacaine and fentanyl during epidural analgesia. In a prospective, randomized, crossover study, a thoracic epidural infusion of ropivacaine 1 mg/mL and fentanyl 2 microg/mL with or without epinephrine 2 microg/mL was given to 12 patients in a double-blinded manner after major thoracic or upper abdominal surgery. Main outcome measures were pain intensity at rest and when coughing, evaluated on a visual analog scale. Extent of sensory blockade was evaluated by determining dermatomal hypoesthesia to cold. Pain increased (P < 0.001) and hypoesthetic dermatomal segments decreased (P < 0.001) when epinephrine was omitted from the triple epidural infusion. After 3 h without epinephrine, pain intensity when coughing was unacceptable despite rescue analgesia. After restarting the triple epidural mixture with epinephrine, pain was again reduced to mild pain when coughing, and the sensory blockade was restored. The mixture with epinephrine caused less nausea and facilitated mobilization. We conclude that epinephrine improves the pain relief and reduces the side effects of a thoracic epidural infusion of ropivacaine and fentanyl after major thoracic or upper abdominal surgery. IMPLICATIONS: Epidural epinephrine markedly improves the pain relief and sensory blockade of a small-dose thoracic epidural infusion of ropivacaine and fentanyl. Nausea was reduced, and mobilization of the patients was facilitated.

Adjuvants, Anesthesia↗
PubMed2002

Halothane, isoflurane, and fentanyl increase the minimally effective defibrillation threshold of an implantable cardioverter defibrillator: first report in humans.

UNLABELLED: Placing an implantable cardioverter defibrillator (ICD) involves the induction of ventricular fibrillation, whereupon the minimally effective defibrillation energy threshold (DFT) is determined. We evaluated the effects of 0.7% halothane, 1% isoflurane, or 1.5 micro g/kg of IV fentanyl during N(2)O/oxygen-based general anesthesia (GA) or those of subcutaneous 1.5% lidocaine plus IV 0.35 mg/kg of propofol on the DFT during ICD implantation in humans (n = 20 per group). Thirty minutes after the first set of DFT measurements under such conditions, the inhaled anesthetics were withdrawn, and all three GA groups received fentanyl 1 microg/kg IV (second set). A third set was taken 30 min later, before the GA patients awakened and when only N(2)O/oxygen was delivered for GA. The lidocaine plus propofol patients were given the same IV propofol bolus 1 min before each fibrillation/defibrillation trial and at the same time points as the three GA groups. The first DFTs were 16.1 +/- 2.2 J (halothane), 17.7 +/- 2.7 J (isoflurane), 16.4 +/- 2.9 J (fentanyl), and 12.9 +/- 3.8 J (lidocaine plus propofol) (P = 0.01). The second set of DFTs were significantly lower than the first sets for the halothane (P = 0.01) and isoflurane (P = 0.02), but not the fentanyl or lidocaine plus propofol, regimens. The third DFTs were significantly (P < 0.01) lower than the first ones for the three GA groups, but not for the lidocaine plus propofol patients. Thus, halothane, isoflurane, and fentanyl increased DFT values during ICD implantation in humans, whereas lidocaine plus intermittent small-dose IV propofol minimized these thresholds. IMPLICATIONS: Halothane, isoflurane, and IV fentanyl added to N(2)O/oxygen-based general anesthesia similarly increase minimal defibrillation threshold energy requirements (DFT) during cardioverter defibrillator implantation in humans. Subcutaneous lidocaine plus intermittent small-dose IV propofol minimizes DFT compared with these general anesthetics while providing equal patient satisfaction.

Aged↗
PubMed1976

Biphasic respiratory depression after fentanyldroperidol or fentanyl alone used to supplement nitrous oxide anesthesia.

Either fentanyl or Innovar (fentanyl, 0.05 mg/ml, and droperidol 2.5 mg/ml) was administered to supplement nitrous oxide anesthesia for operations on 29 patients. Both fentanyl and Innovar depressed the slope of the rebreathing CO2 response curve during operation to 42 per cent +/- 6 (mean of all intraoperative values, +/- SE) of the awake control value. Following the last injection of drug but with continuation of operation, the slope increased such that it was 77 per cent +/- 8 of control on the patients' arrival in the recovery room. The slope continued to increase to a peak of 103 per cent +/- 9 of control. Soon therafter respiratory depression recurred, as indicated by a decline in the slope to 55 per cent +/- 5 of control, with a subsequent gradual return to 85 per cent +/- 8 of control 230 minutes after the last injection. This biphasic response occurred in 90 per cent (26 of 29) of the patients treated either with fentanyl alone or with Innovar. Full recovery appeared to be more rapid with Innovar than with fentanyl alone. Droperidol did not augment and may have attenuated fentanyl-induced respiratory-depression.

Adult↗
PubMed1982

Myocardial blood flow and oxygen consumption during high-dose fentanyl anesthesia in patients with coronary artery disease.

The effects of high-dose fentanyl-oxygen anesthesia (100 micrograms/kg) on myocardial blood flow (argon washin), myocardial oxygen consumption, myocardial lactate balance, and cardiovascular dynamics were studied in nine patients undergoing three-vessel coronary artery bypass operations. All patients had been on maintenance doses of a beta-receptor blocker (pindolol). Except for pindolol all medication had been discontinued 48 hours prior to the study. Measurements were performed in the awake state, after 10 micrograms/kg fentanyl, after 100 micrograms/kg fentanyl, and during sternotomy. Moderate doses of fentanyl (10 micrograms/kg) produced minimal changes in myocardial blood flow, myocardial oxygen consumption, and cardiovascular dynamics; myocardial oxygen balance as well maintained. Large doses of fentanyl (100 micrograms/kg) produced a 16 per cent decrease in mean aortic pressure, cardiac index did not change significantly, while stroke volume index decreased by 23 per cent. Myocardial oxygen consumption decreased by 14 per cent and myocardial blood flow by 10 per cent. Myocardial lactate production was observed in five patients, indicating myocardial ischemia. During sternotomy arterial pressure and heart rate increased 8 per cent and 29 per cent, respectively, resulting in an increase in myocardial work, as reflected by a 38 per cent increase in myocardial oxygen consumption and by a 54 per cent increase in myocardial blood flow. Myocardial lactate production was observed in seven of nine patients. Our data demonstrate that in patients on maintenance doses of beta-receptor blockers, large doses of fentanyl as the sole "anesthetic" produce incomplete anesthesia and fail to protect the myocardium from ischemia due to noxious stimuli during coronary artery surgery.

Adult↗
PubMed1983

Effects of halothane anesthesia compared with fentanyl anesthesia and no anesthesia during coronary ligation in rats.

The effects of halothane and fentanyl anesthesia on responses to ligation of a coronary artery in chronically prepared rats were compared with responses in conscious animals. A total of 86 rats were used; 24 were ligated under halothane anesthesia, 18 under fentanyl, and 23 were left conscious. Three other groups (each of seven rats) were identically prepared but not ligated. Non-ligated rats were left conscious or anesthetized with halothane or fentanyl. Ligation was performed with the aid of a permanently implanted snare around the left anterior descending coronary artery. The responses to ligation that were measured were: arrhythmias, blood pressure changes, heart rate changes, ECG changes, mortality rate, occluded zone, and infarcted cardiac tissue mass. It was found that 1% halothane anesthesia starting 30 min before and continuing for 4 h after permanent ligation, had an overall beneficial effect, when compared with controls. Fentanyl (200-1,000 micrograms/kg, iv) had no overall beneficial effect, compared with conscious controls. Halothane reduced arrhythmias and mortality rates, when compared with controls, while fentanyl did not. Halothane produced lower blood pressures, fewer ECG changes, and lower heart rates than those seen in conscious or fentanyl anesthetized rats. The occluded and infarcted zones produced by ligation were not influenced by the two anesthetics.

Anesthesia, General↗
PubMed1987

Effects of fentanyl on peripheral and cerebral hemodynamics in neonatal lambs.

The effects of fentanyl or cardiovascular function, regional distribution of cardiac output, and the dose required for producing anesthesia were studied in ten previously catheterized, newborn lambs. In addition, the effects of fentanyl on cerebral blood flow and oxygen utilization were examined. Fentanyl in cumulative doses as high as 4.4 mg/kg (average plasma levels of 646 +/- 95 ng/ml, maximum plasma level of 862 ng/ml) did not reliably produce anesthesia as assessed by tail and foot clamping, although it did cause profound respiratory depression. With normocapnia maintained by mechanical ventilation, fentanyl did not alter cerebral oxygen delivery or consumption, and the two remained coupled. Fentanyl did not affect cardiac output, heart rate, or mean arterial blood pressure at the highest dose level, nor did it reduce blood flow to specific organ beds, other than the kidney. Thus, the hemodynamic stability seen with fentanyl in the lamb does not occur at the expense of reduced blood flow to organs, such as the gastrointestinal tract or brain, that are particularly vulnerable in the neonate.

Animals↗
PubMed1988

Effects of fentanyl on baroreceptor reflex control of heart rate in newborn infants.

Baroreceptor reflex control of heart rate was studied in ten neonates and young infants before and after intravenous fentanyl (10 micrograms/kg). All infants were in stable condition while being mechanically ventilated. Mean (+/- SD) corrected gestational age was 40.1 +/- 3.7 weeks, mean weight 3120 +/- 700 g. The pressor response was tested using phenylephrine and the depressor response using nitroglycerin. Changes in heart rate (R-R interval) were plotted against changes in systolic arterial pressure, and the slope of the linear portion of this relationship expresses the baroreflex sensitivity. No significant changes in systolic arterial pressure, heart rate, and blood gas values were observed after fentanyl injection when compared to control values. Mean (+/- SEM) control phenylephrine slope was 8.44 +/- 2.05 msec/mmHg, and mean nitroglycerin slope was 2.54 +/- 0.37 msec/mmHg. Both slopes decreased significantly by 48% and 42%, respectively, after fentanyl injection (P less than 0.02). Mean plasma fentanyl concentrations measured at the end of each test were not statistically different (5.11 +/- 0.65 ng/ml and 4.28 +/- 0.58 ng/ml, respectively). This suggests that the baroreflex control of heart rate is present in term neonates and markedly depressed during fentanyl anesthesia. Changes in blood pressure occurring during fentanyl anesthesia have to be carefully considered, because cardiac output is principally rate-dependent in newborns.

Fentanyl↗
PubMed1989

Fentanyl-induced ventilatory depression: effects of age.

To determine whether infants are more sensitive than older patients to the ventilatory-depressant effects of fentanyl, patients were anesthetized with fentanyl and nitrous oxide (N2O) and ventilatory depression was assessed following elimination of N2O and in the immediate postoperative period. Three groups of patients were studied: infants (1-12 mo old, n = 14), children (1-5 yr old, n = 14), and adults (23-38 yr old, n = 13). Skin-surface PCO2 was measured to determine the peak PCO2 occurring at the end of anesthesia when end-tidal N2O concentration was less than 6%. Naloxone was administered if PCO2 exceeded 70 mmHg. During recovery from anesthesia, ventilatory pattern was recorded using impedance pneumography to determine the longest breath-to-breath interval and the number of episodes of central apnea (defined as breath-to-breath intervals greater than or equal to 10 s in infants and children and greater than or equal to 20 s in adults). Elevation of PCO2 correlated with increasing plasma fentanyl concentrations but did not differ between groups. Four patients (two infants, one child, and one adult) required naloxone. The only subject who had a low plasma fentanyl concentration but required naloxone was a 6-wk-old infant; this was the only subject younger than 3 mo. For each range of fentanyl concentrations, the incidence of apnea increased with age, as did the number of episodes of apnea per subject. Fentanyl-induced ventilatory depression, as assessed by elevation of resting PCO2 during emergence from anesthesia and disruption of ventilatory pattern during recovery from anesthesia, is not greater in infants older than 3 mo than in children and adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Absence of agonistic or antagonistic effect of flumazenil (Ro 15-1788) in dogs anesthetized with enflurane, isoflurane, or fentanyl-enflurane.

This study determined the effects of flumazenil on the anesthetic requirements (MAC) of the dog for isoflurane (group 1; n = 6), enflurane (group 2; n = 7), and a combination of fentanyl-enflurane (group 3; n = 6). Control MAC in each group was determined by the tail-clamp method. Each animal in groups 1 and 2 received four iv incremental doses of flumazenil: 0.5, 1.0, 1.5, and 4.5 mg/kg, and isoflurane MAC or enflurane MAC was determined after each dose. The animals in group 3 received a loading dose and a continuous infusion of fentanyl 0.8 micrograms.kg-1.min-1 over 8 h, and enflurane MAC was determined four times during this experimental period. After the fourth enflurane MAC determination in each animal of group 3, a single iv dose of flumazenil 1.5 mg/kg was injected and enflurane MAC was then determined for the last time. In the incremental doses administered, flumazenil did not demonstrate any agonistic or antagonistic interaction with isoflurane, enflurane, or the fentanyl-enflurane combination. In group 3, plasma fentanyl concentrations remained stable at 12.5 +/- 3.0 ng/ml (mean +/- SD) throughout the experiment and reduced enflurane MAC by 60 +/- 8%. The addition of flumazenil changed neither the fentanyl concentration in plasma (12.2 +/- 3.8 ng/ml) nor its reduction of enflurane MAC (61 +/- 7%). In conclusion, the absence of effect of flumazenil on the MAC of enflurane, isoflurane, or a fentanyl-enflurane combination suggests that they do not interact with the benzodiazepine receptor.

Anesthesia, Intravenous↗
PubMed1989

Cardiac electrophysiologic effects of fentanyl and sufentanil in canine cardiac Purkinje fibers.

The electrophysiologic effects of high concentrations of the opioid agonists, fentanyl and sufentanil, on isolated canine cardiac Purkinje fibers were studied. Changes in action potential parameters were examined at the following concentrations: fentanyl 94.6 nM, 0.19 microM, and 0.95 microM; sufentanil 8.6 nM, 86.4 nM, 0.17 microM, and 0.26 microM. Naloxone 5.5 microM was administered after maximal changes were induced by fentanyl in order to explore the possibility of an opioid receptor interaction. Action potential parameters measured were Vmax of phase 0, amplitude, overshoot, maximum diastolic potential, action potential duration at 50%, and 90% repolarization and membrane responsiveness. Fentanyl 0.19 microM and sufentanil-0.17 microM caused a significant lengthening of action potential duration at 50 and 90% repolarization, 6.4% and 7.3%, and 10.2% and 12.4%, respectively, P less than 0.05. Other action potential parameters were not significantly affected by the opioids. Naloxone 5.5 microM alone did not alter action potential characteristics and failed to reverse action potential prolongation produced by fentanyl. The authors suggest that fentanyl and sufentanil prolong action potential duration in canine cardiac Purkinje fibers via direct membrane actions.

Action Potentials↗
PubMed1990

Continuous epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor.

A randomized, double-blind, placebo-controlled study was performed to evaluate the analgesic efficacy and influence of continuing an epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor in nulliparous women. When the cervix was fully dilated, coded study solution was substituted for the known bupivacaine-fentanyl solution. The study solution for 29 patients was 0.0625% bupivacaine-0.0002% fentanyl; 34 patients received saline placebo. The two groups had similar pain scores during the first stage of labor. During the second stage, pain scores were significantly higher in the saline-placebo group at each 30-min interval between 60 and 150 min after the diagnosis of full cervical dilation. Similarly, there was a significant difference between the two groups in global assessment of analgesia quality during the second stage, but the difference occurred in those patients with a second-stage duration of greater than or equal to 60 min. Among the women who delivered vaginally, eleven of 28 (39%) women in the bupivacaine-fentanyl group, versus five of 34 (15%) in the saline-placebo group, had surgical perineal anesthesia for vaginal delivery (P less than .05). Six of 28 (21%) women in the bupivacaine-fentanyl group, and five of 34 (15%) in the saline-placebo group, underwent instrumental vaginal delivery (P = NS). The median duration of the second stage of labor was 53 min (range = 5-283) in the bupivacaine-fentanyl group, and 63 min (range = 16-181) in the saline-placebo group (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1990

Comparative tissue concentration profiles of fentanyl and alfentanil in humans predicted from tissue/blood partition data obtained in rats.

The steady-state tissue/blood partition coefficients of fentanyl and alfentanil were determined in 13 organs and tissues in the rat. A 6-h infusion of both drugs was used in order to achieve steady-state. Blood and tissue concentrations of drugs were measured by gas-liquid chromatography. The partition coefficients of fentanyl were two- to 30-fold higher than those of alfentanil. These data were then used in a physiologic pharmacokinetic model describing the disposition of the two opioids in humans. The model predicted the plasma pharmacokinetics of these drugs in humans reasonably well. However, simulation beyond 24 h after a bolus administration showed a terminal half-life of 20 h for fentanyl, i.e., an elimination phase that has not yet been described in actual pharmacokinetic studies. In keeping with this, the volume of distribution of fentanyl in the model was also larger than expected. The simulated tissue concentration curves of fentanyl and alfentanil in humans could be used to explain the propensity of fentanyl to give secondary peaks in plasma concentration curves and the difference in effect kinetics between the two opioids. Physiologic pharmacokinetic modeling, based on measured data in small animals, can generate information that is not obtainable by empirical methods in humans.

Alfentanil↗
PubMed1991

Electroencephalographic quantitation of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil.

The authors compared the pharmacodynamics of sufentanil with those of fentanyl using the electroencephalogram (EEG) as a measure of opioid drug effect. Sixteen patients were given a rapid infusion of sufentanil (18.75 micrograms/min) during EEG recording. To quantitate the opioid-induced slowing of the EEG, the authors analyzed its power spectrum and calculated the spectral edge. An inhibitory sigmoid Emax model of the maximal decrease in spectral edge produced by the opioid related spectral edge values to serum concentrations of sufentanil. The resulting data for the pharmacodynamic parameters of sufentanil were compared with fentanyl parameters that were obtained by reanalysis from an identically conducted, previously published study. The half-time of blood-brain equilibration (T1/2Keo) was not statistically different between sufentanil and fentanyl (6.2 +/- 2.8 vs. 6.6 +/- 1.7 min, mean +/- SD, respectively). The intrinsic potency of sufentanil, as measured by the serum concentration needed to cause half the maximal EEG slowing (IC50), was 12-fold greater (0.68 +/- 0.31 ng/ml) than that of fentanyl (8.1 +/- 2.2 ng/ml). The second part of the study verified the hypothesis that administration of equipotent bolus doses would produce equal onset times. Bolus injections of either 125 micrograms of sufentanil or 1,250 micrograms of fentanyl were given during EEG recording. The time from injection to 50% maximal EEG slowing (T50) was calculated for each patient. The values for T50 for the two groups did not differ. The authors conclude that fentanyl and sufentanil have similar pharmacodynamic profiles, the former being 12 times more potent than the latter.

Adolescent↗
PubMed1991

Effect of epidural clonidine on analgesia and pharmacokinetics of epidural fentanyl in postoperative patients.

Epidural clonidine produces postoperative analgesia in patients and potentiates opioid analgesia in animals. The aim of the current study was to assess the effect of epidural clonidine on the plasma concentrations and analgesic effect of fentanyl after epidural administration. Twenty ASA physical status 2 or 3 patients recovering from abdominal surgery were allocated randomly to receive either epidural fentanyl (100 micrograms in 10 ml isotonic saline; EF group) or epidural fentanyl (same dose) plus epidural clonidine (150 micrograms; EF + C group) in isotonic saline solution. Analgesia was assessed over a period of 12 h after epidural injection. Venous samples were obtained until 360 min after epidural injection for radioimmunoassay determination of plasma fentanyl concentration. Onset of analgesia was similar in the two groups of patients (13 +/- 6 and 13 +/- 3 min, respectively, after injection), but duration was more than doubled in the patients receiving clonidine (543 +/- 183 vs. 250 +/- 64 min). Peak plasma fentanyl concentrations (Fmax) and the time to reach Cmax (Tmax) were comparable in the two groups (0.29 +/- 0.15 ng.ml-1 at 16.2 +/- 14.8 min in the EF group and 0.27 +/- 0.11 ng.ml-1 at 8.3 +/- 5.5 min in the EF + C group), as were plasma concentrations at each definite time of measurement. Drowsiness and hypotension were noticed in the EF + C group. Thus, epidural clonidine appears to prolong epidural fentanyl analgesia without affecting its plasma concentration.

Aged↗
PubMed1994

Potentiation of the analgesic properties of fentanyl-like opioids with alpha 2-adrenoceptor agonists in rats.

BACKGROUND: Data on the analgesic properties of alpha 2 agonists and their interactions with opioids are conflicting. Experiments were conducted in rats to evaluate whether various available alpha 2 agonists can potentiate the analgesic properties of opioids and to determine the route of administration needed for optimal interaction. METHODS: The tail-withdrawal reaction test was used as an analgesia assay. In separate experiments, the interactions between systemic (subcutaneous, intravenous, and intraperitoneal) and spinally (epidural and intrathecal) administered alpha 2 agonists and opioids were evaluated. The antagonism of medetomidine plus fentanyl with naloxone and/or idazoxan also was studied. RESULTS: All alpha 2 agonists tested, when injected subcutaneously with fentanyl, potentiated the opioid-induced analgesia. In terms of a reduction of the amount of fentanyl needed to produce a deep surgical analgesia (tail-withdrawal reaction latency > or = 10 s) over more than 2 h, the relative order of potency of the alpha 2 agonists tested was: medetomidine > dexmedetomidine > xylazine > clonidine > detomidine. For some of these alpha 2 agonists there was a biphasic effect: at the larger doses tested, a reduction in the fentanyl potentiation was present. The potentiation of the opioid activity with alpha 2 agonists was also demonstrated in terms of a longer duration of analgesia after combined treatment with fixed doses of opioids. The interaction between the alpha 2 agonists and the opioids remained present when a more profound criterion of analgesia (tail-withdrawal reaction latency > or = 30 s) was used. Furthermore, the interactions between the alpha 2 agonists tested and fentanyl or sufentanil appeared to be independent of the route of administration. Potentiations were observed after simultaneous subcutaneous injections of both groups of compounds, after the combination of intraperitoneal (alpha 2 agonist) plus subcutaneous (opioid), intravenous (alpha 2 agonist) plus epidural (opioid) and simultaneous epidural or intrathecal administrations. With regard to antagonism of the analgesic activity of combined treatment with alpha 2 agonists plus opioids, naloxone provided total antagonism, whereas the alpha 2 antagonist idazoxan overcame only the alpha 2 agonist-induced potentiation of fentanyl. CONCLUSIONS: The tested alpha 2 agonists can potentiate the analgesic properties of opioids, but they have no intrinsic antinociceptive effects on spinal reflexes on their own. The potentiating activities of the alpha 2 agonists could be measured both in terms of a reduction of the amount of opioid needed to reach a particular level of analgesia and in terms of a longer duration of analgesia with a fixed dose of the opioid. The potentiations were observed with various alpha 2 agonists and opioids and appeared independent of the routes of administration.

Adrenergic alpha-Agonists↗
PubMed1997

The comparative amnestic effects of midazolam, propofol, thiopental, and fentanyl at equisedative concentrations.

BACKGROUND: The authors evaluated the effects of midazolam, propofol, thiopental, and fentanyl on volunteer participants' memory for words and pictures at equisedative concentrations. METHODS: Sixty-seven healthy volunteers were randomized to receive intravenous infusions of midazolam (n = 11), propofol (n = 11), thiopental (n = 10), fentanyl with ondansetron pretreatment (n = 11), ondansetron alone (n = 8), or placebo (n = 16) in a double-blind design. Three increasing and then two decreasing sedative concentrations were achieved by computer-controlled infusion in each volunteer. Measures of sedation, memory, and drug concentration were obtained at each target concentration. Drug concentrations were normalized to equisedative effects using both Emax and logistic regression methods of pharmacodynamic modeling. The serum concentrations at 50% memory effect (Cp50s) were determined using four different memory end points. The relative potencies compared with midazolam for memory impairment were determined. RESULTS: Equisedative concentrations were midazolam, 64.5 +/- 9.4 ng/ml; propofol, 0.7 +/- 0.2 microg/ml; thiopental, 2.9 /- 1.0 microg/ml; and fentanyl, 0.9 +/- 0.2 ng/ml. The Cp50s for 50% loss of memory for words were midazolam, 56 +/- 4 ng/ml; propofol, 0.62 +/- 0.04 microg/ml; thiopental, 4.5 +/- 0.3 microg/ml; and fentanyl, 3.2 +/- 0.4 ng/ml. Compared with midazolam, relative potencies (with 95% confidence intervals) were propofol, 0.96 (0.44-1.78); thiopental, 0.76 (0.52-0.94); and fentanyl, 0.34 (0.05-0.76). Large effects on memory were only produced by propofol and midazolam. CONCLUSIONS: At equal sedation, propofol produces the same degree of memory impairment as midazolam. Thiopental has mild memory effects whereas fentanyl has none. Ondansetron alone has no sedative or amnesic effects.

Adult↗