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Subjective and behavioral responses to intravenous fentanyl in healthy volunteers.

Fentanyl is a mu opiate agonist which is occasionally abused by medical personnel who have ready access to the drug. We examined in healthy volunteers (N = 13) the subjective and psychomotor-impairing effects of intravenous fentanyl (0-100 micrograms/70 kg). A randomized, placebo-controlled, crossover design was used in which subjects were injected with 0, 25 (N = 6), 50 and 100 micrograms/70 kg fentanyl in a double-blind fashion. Subjects completed several questionnaires commonly used in abuse liability testing studies before drug injection and at periodic intervals for up to 3 h after drug injection. Subjects also completed several psychomotor tests at these times. Some aspects of psychomotor functioning (e.g., eye-hand coordination) were impaired by fentanyl. Fentanyl produced dose-related increases in ratings of "high" and "sedated," but also tended to produce dysphoria and somatic symptomatology. Most subjects reported liking the effects of the two higher doses of fentanyl for at least a brief time after injection, but they varied widely in their linking ratings across the 3-h post-drug injection period. Despite the transient increases in liking ratings, fentanyl did not increase scores on a widely-used measure of drug-induced euphoria (morphine-benzedrine group scale of the Addiction Research Center Inventory). The present results suggest that some medical personnel who experiment with fentanyl may like it, and thus be at increased risk for abusing the drug in the future.

Adult↗

Haemodynamic and biochemical variables after induction of anaesthesia with fentanyl and nitrous oxide in patients undergoing coronary artery by-pass surgery.

The effects on the haemodynamic and biochemical parameters of three different anaesthetic induction regimes, namely fentanyl (4.1 micrograms.kg-1 or 15 micrograms.kg-1) plus 60 per cent nitrous oxide with oxygen and fentanyl 15 micrograms.kg-1 plus 60 per cent nitrogen with oxygen, were studied in patients undergoing coronary artery surgery. Fentanyl 15 micrograms.kg-1 with nitrous oxide and oxygen produced simultaneous reductions in oxygen uptake, cardiac index and left ventricular stroke work with an unaltered oxygen extraction. Diastolic blood pressure (an index of coronary artery perfusion) was only slightly reduced, and there were no changes in arterial lactate, glucose and free fatty acids. The lower dose of fentanyl (4.1 micrograms.kg-1) with nitrous oxide produced no haemodynamic changes but decreased the oxygen uptake and extraction. The patients receiving fentanyl 15 micrograms.kg-1 with nitrogen and oxygen showed increases in heart rate, blood pressure, cardiac index and left ventricular stroke work, together with a significant fall in oxygen extraction. Moreover, in the patients who received fentanyl 4.1 micrograms.kg-1 with nitrous oxide and oxygen and fentanyl 15 micrograms.kg-1 with nitrogen and oxygen there were significant increases in blood lactate, glucose and free fatty acids, indicating increased sympathetic activity. We conclude that fentanyl 15 micrograms.kg-1, together with 60 per cent nitrous oxide with oxygen provides a satisfactory haemodynamic and biochemical state during induction of anaesthesia in patients with myocardial function prejudiced by coronary artery insufficiency.

Adult↗

Tussive effect of a fentanyl bolus.

The aim of this study was to investigate the incidence of pre-induction coughing, after an iv bolus of fentanyl. The study sample was 250 ASA physical status I-II patients, scheduled for various elective surgical procedures. The first 100 were randomly allocated to receive 1.5 micrograms.kg-1 fentanyl via a peripheral venous cannula (Group 1), or an equivalent volume of saline (Group 2). Twenty-eight per cent of patients who received fentanyl, but none given saline, coughed within one minute (P less than 0.0001). The second 150 patients were then randomly assigned to three equal pretreatment groups. Group 3 received 0.01 mg.kg-1 atropine iv one minute before fentanyl. Groups 4 and 5 received 0.2 mg.kg-1 morphine im, and 7.5 mg midazolam po, respectively, one hour before fentanyl. Thirty per cent of patients in Group 3, 6% in Group 4, and 40% in Group 5, had a cough response to fentanyl. Fentanyl, when given through a peripheral cannula, provoked cough in a considerable proportion of patients. This was not altered by premedication with atropine or midazolam, but was reduced after morphine (P less than 0.01). Coughing upon induction of anaesthesia is undesirable in some patients, and stimulation of cough by fentanyl in unpremedicated patients may be of clinical importance.

Adult↗

Maternal and fetal effects of intravenous patient-controlled fentanyl analgesia during labour in a thrombocytopenic parturient.

The use of intravenous (i.v.) patient-controlled fentanyl analgesia during labour in a parturient with unexplained thrombocytopenia (70 x 10(3).ml-1) is described. The patient self-administered boluses of 25 micrograms of fentanyl with a lock-out interval of ten min. In addition, a concurrent fentanyl infusion of 25 micrograms.hr-1 was given. Effective analgesia was achieved during labour and a total of 1025 micrograms of fentanyl was infused over 11 hr 55 min until delivery of a vigorous infant with Apgar scores of 9 after one and five min. Respiratory depression or undue sedation were not observed in the mother either during labour or in the post-partum period. At birth, maternal total plasma fentanyl concentration was 1.11 ng.ml-1, whereas neonatal umbilical total plasma fentanyl concentration was 0.43 ng.ml-1. Newborn plasma protein binding of fentanyl was lower compared to the mother (63% vs 89%). Thus, free fentanyl concentrations (0.16 ng.ml-1) were identical in the mother and newborn at delivery.

Adult↗

Fentanyl increases catecholamine oxidation current measured by in vivo voltammetry in the rat striatum.

A proposed mechanism for fentanyl-induced muscular rigidity is the effect of opioids on dopaminergic transmission in the striatum. The objective of this study was to observe the effect of fentanyl on the rat striatal catechol oxidation current (CA.OC) which reflects extracellular DOPAC (3-4,dihydroxyphenylacetic acid) concentration (a major metabolite of dopamine), as measured by in vivo voltammetry. Male Sprague-Dawley rats, anaesthetized with halothane, were stereotaxically implanted with carbon fibre electrodes in the striatum and after an initial stabilization period of an hour were given a control saline IV injection followed 30 min later by fentanyl 10 micrograms.kg-1 IV over 10 min and at 70 min by the monoamine oxidase inhibitor pargyline 70 mg.kg-1 IP. Fentanyl produced a significant (P less than 0.05 Anova) increase in CA.OC in all animals. This reached a plateau 15 min following the administration of fentanyl and was at a maximum of 148 +/- 10.2 per cent of control 35 min after the administration of fentanyl. Pargyline produced a rapid decline in CA.OC peak height which went from 143 +/- 11.6 to 39 +/- 6.8 per cent of control over 30 min. There were no significant differences between the pH, PaO2 and PaCO2 during the saline and fentanyl injection periods and there was no significant variation of blood pressure throughout the experiment. This study shows that under stable physiological conditions, fentanyl produces a significant increase in CA.OC in the rat striatum.

Animals↗

Bupivacaine 0.125% produces motor block and weakness with fentanyl epidural analgesia in children.

PURPOSE: Epidural infusions of fentanyl (2 micrograms.ml-1) alone or combined with bupivacaine 0.125% were compared for perioperative analgesia, motor block and other side-effects in children who underwent urological surgery. METHODS: In a prospective, double-blind study, 42 children, ASA I-II, 1-16 yr, were randomly allocated to receive either epidural F (fentanyl bolus 2 micrograms.kg-1 in 0.5 ml.kg-1 saline followed by 2 micrograms.ml-1 fentanyl infusion) or epidural F-B (fentanyl bolus 2 micrograms.kg-1 in 0.5 ml.kg-1 bupivacaine 0.25% followed by 2 micrograms.ml-1 fentanyl infusion in bupivacaine 0.125%) after induction of general anaesthesia. Adequacy of analgesia, lower limb motor block and side-effects were assessed four hourly postoperatively. RESULTS: Both infusion regimens provided excellent analgesia (median objective pain scores = 0). Epidural infusion rates were similar in the F (0.29 +/- 0.07 ml.kg-1.hr-1) and F-B (0.26 +/- 0.05 ml.kg-1.hr-1) groups. Three children in the F group and all children in the F-B group developed lower limb weakness. (P < 0.05) Bromage scores were different in the F group (median 0, range 0-0.66) compared with the F-B group (median 0.33, range 0-1) (P < 0.001). Other side-effects did not differ. CONCLUSION: Postoperative epidural fentanyl infusion provides equipotent analgesia to administration of a solution including both fentanyl and bupivacaine 0.125% and causes less lower limb weakness. No reduction in the fentanyl requirement resulted from the addition of bupivacaine 0.125%.

Adolescent↗

Intravenous fentanyl PCA during labour.

PURPOSE: To evaluate the usefulness of intravenous patient-controlled analgesia (PCA) fentanyl for labour analgesia, its effectiveness for maternal pain and safety for the fetus and newborn. METHODS: Twenty primigravidas were randomised to receive intravenous PCA fentanyl or epidural analgesia for labour pain. Maternal pain, heart rate and arterial oxyhaemoglobin saturation (SpO2) were monitored. Fetal and neonatal monitoring included cardiotocogram (CTG), APGAR, neurological scoring and static-charge-sensitive bed (SCSB) recording for 12 hr postnatally with ECG and SpO2. Fentanyl concentrations and pH of umbilical artery and vein were analysed. RESULTS: Initially, epidural analgesia was more effective (P = 0.01), and three patients in the fentanyl group were given epidural due to unsatisfactory pain relief. Overall satisfaction for analgesia did not differ between the groups. Maternal side-effects were more frequent in the fentanyl group (dizziness and tiredness most often, P = 0.0001). Severe side-effects were not reported. In CTG there were no differences between groups. All the newborns were healthy, APGAR and pH were normal. Naloxone was not used. Neurological scoring was similar in both groups. In 12 hr monitoring heart rate, breathing frequency and movement time were similar in both groups, but SpO2 was lower in the fentanyl group (P < 0.001). Umbilical cord fentanyl concentrations were low or beyond the detection limit. CONCLUSION: Intravenous fentanyl can be used for labour analgesia with the doses reported here as an alternative to epidural analgesia. However, the fetus and neonate must be appropriately monitored. Naloxone and oxygen should be available if neonatal distress occurs.

Adult↗

Patient-controlled analgesia with fentanyl provides effective analgesia for second trimester labour: a randomized controlled study.

PURPOSE: To examine dose and lockout intervals for effective fentanyl patient-controlled analgesia (PCA) in second trimester genetic termination of pregnancy, and compare three different fentanyl PCA regimes with morphine PCA. METHODS: In a double-blind randomized study, 60 ASA physical status I-II patients received one of three fentanyl PCAs or morphine PCA. Labour was induced with prostaglandins and PCA use continued until delivery. Within two hours following delivery, four visual analogue scales (VAS) were administered measuring anticipated pain, pain relief in labour and delivery, and overall satisfaction. The drug delivery/demand ratio for two hours preceding delivery was obtained from the PCA pump. The outcome variables were analyzed using the Chi square test and analysis of variance as appropriate. RESULTS: The delivery/demand ratio was 0.71 +/- 0.27 (mean +/- standard deviation) for morphine; 0.67 +/- 0.21 for fentanyl 50 micro g, lockout six-minute; 0.63 +/- 0.21 for fentanyl 25 micro g, lockout three-minute; and 0.81 +/- 0.17 for fentanyl 50 micro g, lockout three-minute groups. We found no significant differences among the four groups with respect to using delivery/demand ratio as a measure of pain relief. Morphine had the highest rate of side effects compared to fentanyl. There was strong evidence of differences among groups with regard to patient satisfaction and expected pain, and moderate evidence of differences in the delivery and labour pain scores. CONCLUSION: This study found PCA fentanyl 50 micro g with a lockout period of six minutes provided satisfactory analgesia for second trimester labour.

Abortion, Induced↗

[Does fentanyl or midazolam improve patient's comfort and cooperation when given for regional catheter placement? A randomized, controlled and double-blind trial].

BACKGROUND: The procedure of placing a catheter for continuous regional anaesthesia is often associated with fear and pain in the patient. Thus, we evaluated the use of midazolam and fentanyl to improve patient's comfort and cooperation. METHODS: After an oral dose of 20 mg clorazepate, 174 patients receiving peripheral nerve catheters for regional anaesthesia where randomized into 3 groups to receive either intravenous placebo, 3 mg midazolam or 0.1 mg fentanyl immediately before catheter placement in a double-blind manner. Stepwise regression analysis was used to identify factors associated with patient's assessment of subjective discomfort (measured using a VAS 0-10) during the procedure. Amnesia was evaluated 24 h later. The anaesthetist rated patient's cooperation during catheter placement. RESULTS: Female sex and longer duration of catheter placement had significant negative impact on patient's comfort, whereas fentanyl showed an improvement. Age, body mass index, midazolam and the type of catheter had no influence. The following day 27% of the midazolam group, 6% of the placebo group and 9% of the fentanyl patients did not remember catheter placement. Patient's cooperation was poor in 26% of the midazolam patients but only in 9% of the placebo and 3% of the patients receiving fentanyl. Of the placebo patients 18.4% had to be supplemented with fentanyl because they found the procedure of catheter placement unbearable. No side effects occurred in either group. CONCLUSION: As patient's comfort and cooperation were significantly improved by fentanyl, we recommend fentanyl to facilitate catheter placement for regional anaesthesia.

Aged↗

[Addition of fentanyl to bupivacaine--peridural analgesia in cesarean section].

UNLABELLED: Epidural anaesthesia for elective caesarean section can have advantages over general anaesthesia. The anaesthesiologist can avoid endotracheal intubation as well as fetal depression following placental transfer of systemic anaesthetics. However, despite reaching an effective blockade preoperatively, intraoperative discomfort and pain may occur during epidural anaesthesia with local anaesthetics alone, necessitating supplemental systemic analgesics or even conversion to general anaesthesia [21]. Addition of epidural fentanyl has been shown to improve onset and quality of perioperative analgesia without evident side effects for mother or newborn [24]. Nevertheless, administration of epidural opioids before cord clamping is still hotly debated, some fearing maternal and or neonatal depression [6, 26]. The aim of the present study was to investigate the quality of analgesia, associated side effects and the resulting maternal and neonatal plasma opiate concentrations after a single preoperative addition of 0.1 mg fentanyl to epidural bupivacaine analgesia in comparison to epidural bupivacaine analgesia alone. METHODS: Following governmental and ethics committee approval, 43 elective consenting patients for caesarean section were randomized to receive double-blind injections of either 8 ml 0.5% bupivacaine(+)0.1 mg fentanyl (B+F group, n = 22) or 8 ml 0.5% bupivacaine +2 ml saline (Bup group, n = 21) into an epidural catheter. In both groups additional injections of bupivacaine were given to achieve sensory blockade up to T4. Systolic blood pressure, heart and respiratory rates were measured regularly. Quality of intraoperative pain relief was assessed at delivery, uterine eventration, and during uterine and abdominal closure using a visual analogue scale (VAS). The duration of postoperative analgesia was compared between groups, as well as the incidence of nausea, itching or sedation. Similarly, Apgar scores and umbilical arterial and venous blood gas analyses were compared. Fentanyl concentrations were determined in maternal venous blood sampled before and 20 and 40 min after epidural injection and at birth, and in umbilical venous and arterial blood sampled after delivery. Radioimmunoassay analysis was performed from plasma specimens centrifuged and frozen at -20 degrees C [19]. The statistical level of significance was defined as P < 0.05. RESULTS: Groups were comparable regarding age, weight and time of gestation. Total bupivacaine doses and injection to delivery times were similar in both groups. Figure 1 shows that there were 40% more pain-free (VAS = 0) patients in the B+F group during uterine eventration and wound closure (P < 0.05). Mean postoperative duration of analgesia was significantly longer in the B+F group (382 vs 236 min). The rate of nausea and mild itching was significantly higher in the B+F group. Respiratory depression was never detected in patients or newborns. Small group differences in blood pressure or respiratory rate were inconstant and clinically irrelevant, as were differences in umbilical venous pCO2. One hundred and twenty-five blood samples were analysed for fentanyl concentrations. The mean fentanyl concentration before epidural injection was not zero, but 0.25 ng/mg (range 0.02-0.32). Maternal concentrations at 20 and 40 min after injection were 0.55 ng/ml (0.12-1.14) and 0.52 ng/ ml (0.26-1.04) (Fig. 3). At delivery, mean maternal fentanyl concentration was 0.58 ng/ml (0.14-1.18); mean umbilical arterial and venous concentrations were 0.51 ng/ml (0.04-1.8) and 0.41 ng/ml (0.18- 1.2), respectively. Rare results of fentanyl concentrations > 1.0 ng/ml correlated neither with sedation, maternal respiratory rate and side effects, nor with Apgar scores and umbilical blood gas values. No Apgar score at 5 min was below 9, and no umbilical pH was below 7.20. (ABSTRACT TRUNCATED)

Adjuvants, Anesthesia↗

The rate-decreasing effects of fentanyl derivatives in pigeons before, during and after chronic morphine treatment.

Mirfentanil is a fentanyl derivative with non-opioid actions, including non-opioid antinociceptive effects in rhesus monkeys. The current study examined the rate-altering effects of mirfentanil and several other compounds in pigeons to assess: 1) the opioid and non-opioid actions of acutely-administered fentanyl derivatives; and 2) the development of cross-tolerance between each of these compounds and morphine. Seven pigeons responded under a fixed-ratio 20 (FR20) schedule of food delivery. In untreated pigeons, fentanyl, morphine, naltrexone, ketamine and three fentanyl derivatives (mirfentanil, OHM3463 and OHM3295) decreased rates of key pecking in a dose-related manner. Naltrexone (0.1-1.0 mg/kg) attenuated the effects of OHM3463 and not mirfentanil or OHM3295, suggesting non-opioid mediation of the rate-decreasing effects for the latter two fentanyl derivatives. Subjects were treated daily with morphine for 9 weeks, up to a dose of 100 mg/kg per day, during which time the dose-effect curves for morphine, fentanyl and OHM3463 shifted rightward 6-, 10- and 2-fold, respectively, indicating the development of tolerance to morphine and cross-tolerance to fentanyl and OHM3463. Dose-effect curves for ketamine, OHM3295 and mirfentanil were not shifted to the right during morphine treatment, and the dose-effect curve for naltrexone was shifted leftward 180-fold. To the extent that rate-decreasing effects are predictive of antinociceptive effects, these data suggest that some fentanyl derivatives might be useful therapeutics under conditions where tolerance develops to morphine-like opioids.

Analgesics↗

OHM3295: a fentanyl-related 4-heteroanilido piperidine with analgesic effects but not suppressive effects on splenic NK activity in mice.

The immunoregulatory effects of fentanyl and a fentanyl-related compound, OHM3295, were studied in mice. Male CD1 mice treated with a range of fentanyl doses (0.1-1.0 mg/kg, subcutaneously) showed suppression of splenic natural killer (NK) activity following 0.25-0.50 mg/kg fentanyl dose but not higher (0.75-1.0 mg/kg) or lower (0.1 mg/kg) doses. Fentanyl (0.01-32.0 mg/kg) also induced dose-related analgesia as measured by an increase in tail flick latency; these analgesic effects were antagonized by naltrexone (1.0-10.0 mg/kg). Pretreatment with naltrexone (1.0-3.2 mg/kg) resulted in significant suppression of splenic NK activity following fentanyl (10.0-32.0 mg/kg) administration. In comparison to fentanyl, OHM3295 (3.2-25.0 mg/kg) augmented splenic NK activity in a naltrexone-reversible manner. Similar to fentanyl, OHM3295 (1.0-32.0 mg/kg) also induced a naltrexone-sensitive, dose-related analgesia as measured by an increase in tail flick latency. These results with OHM3295 demonstrate a novel profile of effects which includes naltrexone-sensitive analgesic effects in the absence of immunosuppressive effects. In addition, this is the first reported case in which a compound with opioid analgesic effects has been shown to potentiate natural killer cytolytic activity following in vivo administration.

Analgesics↗

Transdermal fentanyl and initial dose-finding with patient-controlled analgesia in cancer pain. A pilot study with 20 terminally ill cancer patients.

This pilot study evaluated the efficacy and side effects of a combination of initial patient-controlled analgesia (PCA) for dose-finding with transdermal fentanyl administration. Twenty inpatients, requiring strong opioids for severe cancer pain, received intravenous fentanyl on an on-demand basis over a 24-h period. The amount of fentanyl administered was then used as a guideline for selecting a suitable transdermal therapeutic system (TTS) on the 2nd day, which remained in place for 3 days. The size of a 2nd TTS, being used from day 5 to 7, was adjusted according to the amount of supplementary intravenous fentanyl doses on day 3. From day 4 to 7 intravenous fentanyl was stopped, and subcutaneous morphine was made available as a rescue medication. A standardized adjuvant medication was allowed. Pain intensity, pain relief, quality of sleep, mood, general state of health, activity, mobility, rescue morphine consumption and side effects were assessed using a diary after baseline pain and symptoms were recorded. Vital functions were monitored and fentanyl plasma levels were measured daily in 15 patients. The use of TTS fentanyl in combination with initial dose titration using PCA gave rapid and statistically significant pain relief. Patient compliance and acceptance were excellent. In the absence of severe side effects the main complaints were dryness of the mouth and constipation. Increasing pain intensity and increasing supplementary morphine requirements as well as decreasing plasma fentanyl levels on day 7 may indicate that conversion ratios from intravenous to transdermal administration should be increased or that TTS should be changed earlier.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Fentanyl: clinical use as postoperative analgesic--epidural/intrathecal route.

The administration of epidural and intrathecal opioids for the management of postoperative pain is well established. Fentanyl, because of its greater lipophilicity, offers a number of advantages over morphine for epidural analgesia, including a lower incidence of side effects and reduced risk of delayed-onset respiratory depression. The relatively short duration of action of epidural fentanyl makes this agent more ideally suited for continuous infusion or patient-controlled epidural analgesia (PCEA). The effective doses and adverse effects profile of epidural fentanyl are reasonably well understood. Because of the lack of spread through the cerebrospinal fluid (CSF) and hence the segmental nature of the analgesia achieved, location of epidural catheter placement is of paramount importance when this agent is used. Prolonged epidural infusion of fentanyl may result in high systemic concentrations not dissimilar to IV infusion, and, therefore, the greatest efficacy of epidural fentanyl administration may be in combination with low concentrations of bupivacaine, an approach that achieves a synergistic effect. 2-Chloroprocaine has been shown to antagonize epidural fentanyl analgesia. Intrathecal fentanyl for postoperative analgesia is limited by its short duration of action with single-bolus administration. The widespread international increase in the use of epidural fentanyl for postoperative analgesia promises further improvements and refinement in techniques.

Analgesia, Epidural↗

Anesthetic induction with fentanyl and intravenous lidocaine for coronary artery surgery.

In a randomized, double-blind trial, 59 patients undergoing coronary artery surgery received fentanyl 10, 15, or 25 microg/kg infused over 5 minutes for anesthetic induction. Half of the patients received intravenous lidocaine, 1.5 mg/kg, 1 minute before laryngoscopy. Efficacy of induction as judged by loss of consciousness was evaluated, and hemodynamic values during induction, laryngoscopy, and tracheal intubation were recorded each minute for 10 minutes. Plasma fentanyl concentrations were determined after termination of the fentanyl infusion. Opioid induction with fentanyl was successful in 90% (18 of 20) of patients receiving 25 microg/kg, 89% (17 of 19) of patients receiving 15 microg/kg, but only 55% (11 of 20) of patients receiving 10 microg/kg (P < .01). While plasma fentanyl concentrations were proportional to the dose infused (25 ng/mL, 18 ng/mL, and 14 ng/mL in the 25, 15. and 10 microg/kg fentanyl groups, respectively), there was no relationship between plasma fentanyl concentration and hemodynamic response to laryngoscopy or intubation. Opioid induction caused a gradual decrease in blood pressure that was restored with intubation. Lidocaine partially blocked this restoration (systolic blood pressure 122 +/- 5 v 138 +/- 5 mmHg, lidocaine v placebo, 1 minute after laryngoscopy, P < .05). Fentanyl, 15 or 25 microg/kg, intravenously, is an effective induction agent for patients with coronary artery disease. Supplementation with intravenous lidocaine, 1.5 mg/kg, will obtund the increase in blood pressure that occurs with laryngoscopy and intubation and help prevent infrequent hypertensive responses seen with this opioid technique.

Adjuvants, Anesthesia↗

The effects of thiopental sodium on fentanyl-induced muscle rigidity in a human model.

STUDY OBJECTIVE: To describe a safe human model in which to study the treatment of fentanyl-induced muscle rigidity and report on the efficacy of thiopental sodium for this purpose. DESIGN: Randomized, observer-blinded comparison of regimens. SETTING: Inpatient surgery at a university-affiliated teaching hospital. PATIENTS: Thirty patients scheduled for elective surgery in whom the administration of high-dose fentanyl was felt to be appropriate and who experienced severe muscle rigidity in the chest, abdomen, and upper extremities after the fentanyl was administered. INTERVENTIONS: One arm was isolated from circulation with a blood pressure (BP) cuff inflated to 100 mmHg above systolic blood pressure (SBP), after which fentanyl 25 to 50 micrograms/kg was administered intravenously (IV) at a rate of 1 mg/min in the contralateral arm. If severe muscle rigidity became apparent in three muscle groups (the chest, abdomen, and arms), patients were either (1) observed for 3.5 minutes without further intervention, (2) given thiopental sodium 1.5 mg/kg IV, followed 120 seconds later by succinylcholine 1 mg/kg IV, or (3) given succinylcholine 1 mg/kg IV, followed 120 seconds later by thiopental sodium 1.5 mg/kg IV. MEASUREMENTS AND MAIN RESULTS: A single observer, blinded to the technique, evaluated and recorded the degree of muscle rigidity present in the chest wall, abdomen, and upper extremities (one isolated from the circulation by a tourniquet) 90 seconds and 3.5 minutes after the onset of muscle rigidity in the control group and 90 seconds after the administration of either thiopental sodium or succinylcholine in the two experimental groups. The observer was the same individual in all instances. The muscle rigidity associated with the administration of high-dose fentanyl was clinically attenuated by the administration of thiopental sodium, especially in the extremities. Succinylcholine was more effective than thiopental sodium in producing muscle flaccidity in all muscle groups not isolated by a tourniquet. In no case did the muscle rigidity compromise our ability to oxygenate the patient adequately. CONCLUSIONS: Thiopental sodium does blunt the degree of muscle rigidity induced by high-dose fentanyl, though not as effectively as does succinylcholine. One can safely isolate an extremity prior to the administration of high-dose fentanyl and a muscle relaxant, intubate the trachea, and ventilate a patient, while retaining the ability to study the effect of centrally acting drugs on fentanyl-induced rigidity in the isolated extremity.

Fentanyl↗

Use of analgesics during propofol sedation: a comparison of ketorolac, dezocine, and fentanyl.

STUDY OBJECTIVE: To evaluate the comparative efficacy and side effect profile of ketorolac 60 mg, dezocine 6 mg, and fentanyl 100 micrograms when used as analgesic supplements to a propofol infusion during monitored anesthesia care (MAC). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Ambulatory surgery facility at a university medical center. PATIENTS: 80 outpatients undergoing breast biopsy or inguinal herniorraphy procedures under MAC. INTERVENTIONS: All patients received midazolam 2 mg intravenously (IV) followed by 1 ml of the study medication containing either dezocine 3 mg IV, ketorolac 30 mg IV, fentanyl 50 micrograms IV, or normal saline. A propofol infusion was initiated at 75 micrograms/kg/min and then varied to maintain a stable level of sedation (i.e., Observer Assessment of Alertness/Sedation scale score of 3). An additional 1 ml of the same study medication was administered IV 2 to 3 minutes prior to infiltration of the local anesthetic solution. During the operation, supplemental (rescue) medication consisted of fentanyl 25 micrograms IV, bolus injections in all four treatment groups. MEASUREMENTS AND MAIN RESULTS: Propofol infusion and supplemental fentanyl dosage requirements, oxygen saturation values, respiratory rates, recovery times, and postoperative side effects were recorded. Visual analog scales were used to assess sedation, anxiety, pain, and nausea preoperatively (baseline), upon entry into the postanesthesia care unit, and at 30-minute intervals until discharge. The fentanyl and dezocine groups required lower average infusion rates of propofol to maintain a stable level of sedation than the control (saline) group. The saline and ketorolac groups required rescue analgesic medication more frequently and/or larger supplemental dosages of fentanyl than the two opioid analgesic treatment groups. Compared with the three analgesic treatment groups, postoperative pain scores were only marginally higher in the control group. Ketorolac-treated patients had consistently (but not significantly) shorter recovery times to oral intake, ambulation, and discharge than those in the dezocine or fentanyl groups. No postoperative nausea, vomiting, or pruritus was reported in the ketorolac group. CONCLUSION: Compared with ketorolac 60 mg, fentanyl 100 micrograms and dezocine 6 mg produced a greater decrease in the propofol sedation requirement during MAC. However, the use of ketorolac in combination with propofol for MAC was associated with an improved recovery profile.

Adult↗

Midazolam and fentanyl continuous infusion anesthesia for cardiac surgery: a comparison of computer-assisted versus manual infusion systems.

Continuous infusion of intravenous anesthetics can be achieved either by a manually controlled infusion (MCI) pump, or by a computer-assisted continuous infusion (CACI) pharmacokinetic model-driven infusion system. Randomized double-blind comparisons of the two infusion systems for general anesthesia were performed in 24 patients undergoing coronary artery bypass grafting. Patients were allocated to receive continuous infusions of midazolam and fentanyl by either a MCI device or CACI. Midazolam and fentanyl infusions were independently titrated to maintain hemodynamic stability, defined as mean arterial pressure (MAP) and heart rate (HR) within 20% of baseline values. As directed by the study design, comparable hemodynamic control was achieved in both groups. Mean plasma fentanyl concentrations measured at specific timepoints were similar between groups. The plasma midazolam level for induction was 196 +/- 139 ng/mL in the CACI group and 300 +/- 128 ng/mL in the MCI group, and the fentanyl level was similar in both groups, 6.7 +/- 1.9 ng/mL in CACI and 6.3 +/- 4.6 ng/mL in the MCI group. The drug levels were lower (P < or = .05) for midazolam during maintenance of anesthesia and similar for fentanyl during the maintenance of anesthesia. In the MCI group, the average duration of anesthesia was 246.5 +/- 35.0 minutes, with a mean total fentanyl dose of 30.27 +/- 11.14 micrograms/kg. In the CACI group, the average duration of anesthesia was 230.8 +/- 44.1 minutes, with a mean total fentanyl dose of 34.61 +/- 5.40 micrograms/kg (P > 0.05 for comparisons between groups for duration of anesthesia and total fentanyl dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗