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Enhanced pain management for postgastrectomy patients with combined epidural morphine and fentanyl.

PURPOSE: To determine whether clinical advantages could be demonstrated by epidural fentanyl given in addition to epidural morphine for postgastrectomy analgesia. METHODS: One-hundred and twenty two patients undergoing elective gastrectomy were prospectively studied in a randomised, double-blind fashion. All patients received epidural lidocaine 1.5% with epinephrine (1:200,000) followed by light general anaesthesia for surgical anaesthesia. They were assigned to four groups according to the combinations of each epidural opioid: 2 mg morphine alone, 2 mg morphine + 100 micrograms fentanyl, 4 mg morphine alone, and 4 mg morphine + 100 micrograms fentanyl. Morphine and fentanyl were given epidurally approximately 60 and 15 min, respectively, before the completion of surgery. RESULTS: Addition of epidural fentanyl to both doses of morphine not only decreased intensity of pain associated with coughing during the early postoperative period, but also prolonged the time until the first analgesic request at each morphine dose studied. Of the combination doses, 4 mg morphine + 100 micrograms fentanyl provided the longest time to the first request for analgesic, and was associated with least amount of postoperative analgesic supplement and best patient satisfaction without increasing incidence of side effects. CONCLUSION: The addition of 100 micrograms fentanyl to 2 mg or 4 mg epidural morphine provides clinical advantages over morphine alone for post-gastrectomy analgesia.

Analgesia, Epidural↗

Patient anxiety scores after low-dose ketamine or fentanyl for epidural catheter placement.

PURPOSE: To compare the effect of low-dose ketamine with that of low-dose fentanyl on patient anxiety during the identification of the epidural space and catheterization. METHODS: Sixty patients were randomly assigned to one of three groups: saline group (n=20), saline 2 ml; ketamine group (n=20), 5 mg ketamine; or fentanyl group (n=20), 50 microg fentanyl. Each drug was administered intravenously (iv) five to ten minutes before the epidural procedures began. After epidural catheter placement had been accomplished, anxiety and pain were rated using a visual analog scale. RESULTS: The anxiety scores given for ketamine(20.2 +/- 18.5, mean +/- SD) and fentanyl (24.6 +/- 20.3) were similar, and both were lower than that for saline (44.1 +/- 32.7) (P=0.0034 and 0.0153 vs saline group, respectively). Pain scores were similar for all three groups. A decrease in hemoglobin oxygen saturation during the procedure was only observed in the fentanyl group, and two patients in fentanyl group had SpO2 <90%. CONCLUSION: Ketamine, 5 mg iv, is as effective as 50 microg fentanyl, iv, in alleviating patient anxiety and in providing adequate sedation during the procedures necessary for epidural catheter placement, without inducing severe complications.

Adult↗

Identification of independent risk factors for fentanyl-induced cough.

PURPOSE: To determine how the probability of fentanyl-induced cough is affected by patient characteristics and/or anesthetic technique. METHODS: We analyzed data from a cohort of 1,311 adult patients undergoing elective surgery under general anesthesia, accompanied by i.v. fentanyl. The following data were collected: patient demographics, history of cigarette smoking, presence of bronchial asthma or chronic obstructive pulmonary disease, administration of angiotensin converting enzyme inhibitors; and anesthetic technique, including: preanesthetic anxiolytic medication, prior use of atropine, epidural lidocaine, a priming dose of vecuronium, and the dose of i.v. fentanyl. Associations between individual variables in the clinical evaluation model and the likelihood of fentanyl-induced cough were characterized by calculating odds ratios. Multiple logistic regression analysis was used to examine the independent contribution of each variable while controlling for all variables. RESULTS: Fentanyl-induced cough was independently associated with the following: aging, cigarette smoking, a prior epidural injection of lidocaine, and a priming dose of vecuronium. Fentanyl-induced cough was unaffected by gender, the presence of either bronchial asthma or chronic obstructive pulmonary disease, or prior use of atropine. CONCLUSIONS: Fentanyl-induced cough may be suppressed by aging, cigarette smoking, prior epidural injection of lidocaine, or a priming dose of vecuronium. These findings may allow insights into the mechanism of this phenomenon, thereby leading to its prevention.

Adult↗

Pharmacokinetics and transplacental distribution of fentanyl in epidural anesthesia for normal pregnant women.

BACKGROUND: Fentanyl is an opioid drug widely used as a co-adjuvant in abdominal delivery, a fact that justifies its pharmacokinetic study under these conditions. OBJECTIVE: Our objective was to investigate the pharmacokinetics and placental transfer of fentanyl in parturients whose pregnancies were resolved by cesarian section with epidural anesthesia. PATIENTS AND METHODS: Ten clinically normal parturients who delivered at term received 5 ml of 2% lidocaine hydrochloride without a vasoconstrictor for skin and subcutaneous blockade, followed by epidural injection of 2 ml fentanyl citrate (0.05 mg/ml), 15 ml 0.5% bupivacaine hydrochloride with 1:200,000 epinephrine, and 10 ml 2% lidocaine hydrochloride without a vasoconstrictor. Maternal blood samples were collected at various times after injection (1--840 min), and the fentanyl plasma concentrations were determined by gas chromatography-mass spectrometry. Pharmacokinetic analysis was performed using the bi- or tri-compartmental model. The fetal/maternal ratio of the plasma fentanyl was determined at birth. RESULTS: The values of the pharmacokinetic parameters were: t(1/2)alpha=13.5 min, t(1/2)beta=192.5 min, t(1/2)gamma=620 min, AUC(0-infinity)=137.404 ng.min per milliliter, C(l)/f=464.984 ml/min, V(d)/f=299.974 l, C(l)/f/kg=6.875 ml/min per kilogram, and V(d)/f/kg=4.441 l/kg. The latency between drug administration and birth was 28.5 min, with a maternal and fetal plasma concentration of 0.310 and 0.245 ng/ml, respectively, at a median fetal/maternal ratio of 0.892. CONCLUSION: The study demonstrated a rapid passage of fentanyl from the epidural space to maternal blood and a significant transplacental transfer of maternal fentanyl of about 90%, which should serve as an alert to obstetricians.

Analgesia, Epidural↗

Is the use of transdermal fentanyl inappropriate according to the WHO guidelines and the EAPC recommendations? A study of cancer patients in Italy.

BACKGROUND: World Health Organization (WHO) guidelines, Agency for Health Care Policy and Research (AHCPR) clinical practice guidelines, and EAPC recommendations indicate oral route of opioid administration as the preferred route. Transdermal administration of opioids is considered an alternative when patients cannot take medications orally. Moreover, WHO and EAPC indicate orally administered morphine as the first-choice drug for the treatment of moderate to severe cancer-related pain. However, we can see that in Italy there is an increasing use of transdermal fentanyl (TF) as first-choice strong opioid (and route) even when oral administration of opioids is possible. AIMS: The aims of this study are to describe the modality in the use of TF administration in two settings of care, taking into consideration (1) the drugs previously taken by the patients, (2) the reasons for switching from any drug to TF, (3) the conversion ratio used, and (4) the frequency of "inappropriate use of transdermal fentanyl according to the WHO guidelines and the EAPC recommendations", i.e., switching to fentanyl patch from any drug, even if there were no contraindications in using oral morphine. The settings of care considered were the out-patient palliative care unit (OP-PCU) and the oncological wards (OWs) of the National Cancer Institute (NCI) of Milan. PATIENTS AND METHODS: The clinical charts of 98 patients prescribed with and given fentanyl patch for the first time at the NCI of Milan in 2002 were reviewed and the data gathered were grouped according to the administration of fentanyl at the OP-PCU (63 out-patients) or at the OWs (35 in-patients). Summary descriptive statistics and bar and box plots have been used. Fisher two-tailed exact text was applied to test the differences between in- and out-patients. RESULTS: Before switching to TF, (1) in-patients were more frequently treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and weak opioids (mostly tramadol) in respect to the out-patients (44.1 vs 25.8%) who were mostly treated with oral morphine (48.4 vs 20.6%) (p=0.045), and (2) 88.7% of the out-patients were treated with oral opioids and only 1.6% with parenteral opioids in respect to OWs where 69.7% were on oral opioids and 18.2% on parenteral opioids (p=0.006). In 29% of out-patients and in 53% of in-patients, changing to fentanyl patch was considered as "inappropriate" (p=0.028) according to the WHO guidelines and the EAPC recommendations. No statistically significant differences between the two settings were observed regarding the reasons for switching and the conversion ratio used. CONCLUSIONS: There is a trend to use fentanyl patch as first-choice strong opioid in cancer patients in situations such as titration phase, in the presence of instable pain, and in the absence of dysphagia or gastrointestinal symptoms where the use of oral morphine is, however, not contraindicated.

Administration, Cutaneous↗

Antifibrillatory action of the narcotic agonist fentanyl.

Morphine, an opiate alkaloid with mixed mu- and delta-agonist properties, raises the ventricular fibrillation threshold in anesthetized dogs by altering autonomic tone. To elucidate further underlying structure-activity relationships, the effect of fentanyl, a nonalkaloid, mu-selective agonist in wide clinical use, was studied. Fentanyl (30 micrograms/kg) was given intravenously to 27 chloralose-anesthetized dogs, and ventricular fibrillation threshold was measured by means of the single-stimulus technique. In the baseline state fentanyl raised the ventricular fibrillation threshold by 14%. When the dogs were subjected to hemorrhagic stress, this effect was amplified to 29% (p less than 0.0001). Bilateral cervical vagotomy abolished fentanyl's antifibrillatory effect, but neither atropine sulfate (0.4 mg/kg/hr) nor atropine methylnitrate (0.5 mg/kg/hr) did so. Fentanyl's influence on the fibrillation threshold during hemorrhage was significantly reduced by bilateral stellate ganglionectomy (p less than 0.005). It is concluded that fentanyl raises the ventricular fibrillation threshold by its known sympathoinhibitory action rather than by its vagal efferent activating effect. The facts that an intact vagus is required and that hemorrhage amplifies the effect suggest that the antifibrillatory effect of fentanyl is mediated through the afferent component of the baroreflex arc.

Animals↗

The maternal and fetal cardiovascular effects of epidural fentanyl in the sheep model.

Since the demonstration of opiate receptors in the spinal cord in the mid-1970s, investigators have been looking for the most effective epidural narcotic. With the use of the chronically catheterized maternal sheep model, we injected two different doses of preservative-free fentanyl (50 and 100 micrograms) into the epidural space. No statistically significant changes were observed, either in maternal or fetal arterial pressure and acid-base status or in maternal central venous pressure, systemic and pulmonary vascular resistance, cardiac output, and intrauterine pressure (p greater than 0.05). With a dose of 50 micrograms of fentanyl, maternal levels of fentanyl peaked at 60 minutes (50 pg/ml) and the fetal levels of fentanyl peaked at 45 minutes (20 pg/ml). With the 100 micrograms dose of fentanyl, maternal levels of fentanyl peaked at 45 minutes (230 pg/ml) and the fetal levels peaked at 15 minutes (110 pg/ml). We conclude that the injection of 50 and 100 micrograms of fentanyl into the maternal epidural space has no adverse effects on mother or fetus in the sheep model.

Anesthesia, Epidural↗

Action of the morphinometic agent, fentanyl, on the nucleas tractus solitarii and the nucleus ambiguus cardiovascular neurons.

Using extracellular recordings, the discharges of blood pressure dependent neurons were detected in the nucleus tractus solitarii (NTS) and in the nucleus ambiguus (NA) of anesthetized dogs. Type A blood pressure dependent neurons (sympathoinhibitory or vagoexcitatory neurons) were detected when their firing rates were increased during i.v. noradrenaline and when their firing rates were reduced or abolished during bilateral carotid occlusion. Type B blood pressure dependent neurons (sympathoexcitatory neurons or vagoinhibitory neurons) were identified when their firing rates were reduced or when firing was abolished during the rise in blood pressure induced by noradrenaline and when their firing rates were increased during bilateral carotid occlusion. Baroreceptor neurons were identified when neuronal activity with cardiac rhythm, was detected in the NTS. Fentanyl (20 micrograms/kg i.v.) decreased the spontaneous firing rate of type A neurons found in the NTS. In contrast, fentanyl altered in two opposite ways the firing rate of neurons classified as type A and found in the NA. In the first group of type A neurons, fentanyl induced a marked increase in firing rates. A second group of type A neurons in the NA responded to fentanyl by a reduction in firing rates. Fentanyl reduced the firing rate of type B neurons detected in the NTS and the NA. Fentanyl (20 micrograms/kg i.v.) induced biphasic changes in the firing rate of baroreceptor neurons detected in the NTS. The effects of fentanyl on blood pressure, heart rate and firing rate of all types of cardiovascular neurons were antagonized by naloxone.

Animals↗

Evidence for mu1-opioid receptor involvement in fentanyl-mediated respiratory depression.

Several fentanyl analogs (Bagley et al., 1989, J. Med. Chem. 32, 663) were compared to fentanyl and morphine for their effects on respiratory depression as determined by arterial blood gas (pH, pCO2 and pO2) measurements. Fentanyl (0.1 mg/kg), morphine (10 mg/kg), #16 (1-phenethyl-4-[N-(pyridin-2-yl)-N-(methoxymethylcarbonyl)amino] piperidine, 1 mg/kg), #17 (1-phenethyl-4-[N-(pyridin-2-yl) -N-(2-furoyl)amino]piperidine, 0.5 mg/kg) and #29 (1-phenethyl-4-[N- (pyrimidin-2-yl)-N-(methoxy-methylcarbonyl) amino]piperidine, 10 mg/kg) produced significant respiratory depression in rats. Pretreatment with the mu1-opioid receptor selective antagonist, naloxonazine (10 mg/kg), blocked the respiratory effect of fentanyl and its analogs, but not that of morphine. The results suggest that the mu1-opioid receptor plays an important role in the respiratory effects of fentanyl and its analogs. Hence, the mechanism of fentanyl-induced respiratory depression appears to be distinct from that produced by morphine. The most likely explanation for this difference is the possible contribution of muscle rigidity and catalepsy to the observed changes in blood gas parameters caused by the fentanyl analogs, while the respiratory depression of morphine, measured by these same parameters, appears to be independent of its effect on muscle rigidity.

Animals↗

Effect of fentanyl and naloxone on the P300 auditory potential.

The effect of fentanyl (opioid agonist) and naloxone (morphine antagonist) on the amplitude, area and latency of the P300 auditory potential was studied in patients undergoing minor surgical procedures. Fentanyl (5.0 micrograms/kg), naloxone (3.0 micrograms/kg) and isotonic saline (for control) were injected intravenously through a catheter just before surgery, and following a single-blind procedure and three different pharmacological paradigms with three consecutive conditions each: (1) initial baseline (C), saline (S) and late baseline (C'); (2) C, fentanyl (F) and C'; (3) C, naloxone (N) and C'. Fentanyl significantly reduced the amplitude and area with no changes in the latency of small (S) and large (L) P300 potentials. Concomitantly, fentanyl increased the number of omitted counts of the target tones of the "odd ball" P300 test and the spatial threshold of the two point discrimination test in patients with small and large P300 potentials. Naloxone significantly increased the amplitude and area and decreased the latency of the small P300 potential and decreased the amplitude and area with no changes in latency of the large P300 potentials. Concomitantly, naloxone decreased the number of omitted counts of the patients with small but not large P300 potentials and decreased the spatial threshold in patients with both small and large P300 potentials. Neither fentanyl nor naloxone produced systematic changes in the evaluation of pain and hearing of patients with small and large P300 potentials. Although dramatic changes in pulse, blood pressure, respiration and EEG were found in some cases immediately after the administration of fentanyl and naloxone, these changes were not consistent and were not present at the time other tests were performed.

Adult↗

Sensitive gas liquid chromatography method for the determination of fentanyl concentrations in blood.

A method for the determination of fentanyl blood concentrations using gas liquid chromatography coupled to a nitrogen phosphorus detector (NPD) is presented. A highly inert fused-silica, megabore column coated with a methyl silicone stationary phase was used for the analysis. The mean coefficient of variation for the range of fentanyl concentrations tested (0.25-10 ng/ml) was 4.65%, ranging from 0.85% at 10 ng/ml to 10.8% at 0.25 ng/ml. The assay was used to quantify blood fentanyl concentrations collected from a 56-year-old woman who was administered fentanyl postoperatively via a patient-controlled on-demand analgesic computer (ODAC). The mean hourly fentanyl dose rate over the 44 hr study period was 41.8 micrograms/hr (range 20-120). The sixfold variation in hourly dose rate was not mirrored by similar fluctuations in the fentanyl blood concentration (mean 0.45 ng/ml, range 0.3-0.7 ng/ml). The patient thus titrated herself to a perceived minimum effective concentration (MEC) of fentanyl.

Cholecystectomy↗

Transdermal fentanyl: suggested recommendations for clinical use.

Transdermal fentanyl offers the advantage of providing continuous administration of a potent opioid in the absence of needles and expensive drug-infusion pumps for the treatment of cancer pain. When transdermal fentanyl is initiated, it may be necessary to change the dose every 24-48 hr until an appropriate dose is titrated to the needs of the patient. This should be done by providing short-acting opioids as rescue analgesics for breakthrough pain. Well-accepted principles established for chronic opioid use in cancer pain management should apply to the administration of transdermal fentanyl as well. These include dose titration, the coadministration of adjuvant drugs to counteract opioid side effects and enhance analgesia, and the need to reassess the patient continuously for recurrent tumor and other new sources of pain. Further clinically relevant studies are needed and include 1) the determination of the relative potency of transdermal fentanyl, especially in comparison with oral and parenteral morphine; 2) a prospective study of the side-effect profile of transdermal fentanyl in relationship to oral morphine; and 3) the role of oral transmucosal administration of fentanyl in selection of starting doses of transdermal fentanyl and as a means to provide rescue doses for breakthrough pain.

Administration, Cutaneous↗

Prebypass hemodynamic stability of sufentanil-O2, fentanyl-O2, and morphine-O2 anesthesia during cardiac surgery: a comparison of cardiovascular profiles.

Cardiovascular responses and the need for intervention with vasoactive agents were measured prospectively in a randomized study of 50 adult patients receiving sufentanil (n = 20), fentanyl (n = 20), or morphine (n = 10) anesthesia for cardiac surgery. Measurements were recorded and compared during induction and prebypass at intervals during which airway or surgically induced stress responses were likely to be greatest. Randomized, double-blinded doses of opioids were administered slowly and titrated according to clinical responses (hemodynamics) and the electroencephalogram. Mean doses were as follows: from induction until time of incision, sufentanil, 9.1 microg/kg; fentanyl, 58 microg/kg; and morphine, 2.5 mg/kg; and total dose for surgery; sufentanil, 18.9 microg/kg; fentanyl, 95.4 microg/kg; and morphine, 4.4 mg/kg. Equi-anesthetic depth in patients receiving sufentanil or fentanyl was confirmed by continuous electroencephalographic monitoring. Patients anesthetized with sufentanil and fentanyl showed marked cardiovascular stability and rarely responded to stimuli. Systolic arterial pressure, mean arterial pressure, heart rate, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, stroke volume index, and stroke work index values were similar in the two groups. Patients receiving morphine experienced large changes in several variables. Pharmacologic intervention was made when systolic arterial pressure deviated more than 30% from pre-event values and was uncontrolled by additional opioids. Interventions were necessary more often in patients receiving morphine (nine of ten) or fentanyl (12 of 20) than in patients receiving sufentanil (six of 20), P < 0.05. Results from this study suggest that morphine is a relatively unsatisfactory anesthetic, while sufentanil and fentanyl, at equi-anesthetic depths, provide stable and satisfactory hemodynamics.

Aged↗

Comparison of sufentanil-oxygen and fentanyl-oxygen anesthesia for mitral and aortic valvular surgery.

The cardiovascular responses, speed of anesthetic induction, incidence of chest wall rigidity, need for anesthetic supplements (phentolamine, N2O, and nitroprusside) to control intraoperative hypertension, and speed of postoperative recovery were measured and compared in 44 patients undergoing aortic and mitral valvular replacement with fentanyl-O2 or sufentanil-O2 anesthesia. After a lorazepamatropine premedication and pancuronium pretreatment, fentanyl was administered intravenously at a rate of 400 micrograms/min and sufentanil at 200 micrograms/min until patients were unconscious; at this time they were given succinylcholine and their tracheas were intubated. After intubation, an amount of fentanyl or sufentanil equal to the dose producing unconsciousness was infused over the next 30 minutes, at which time the operation began. Additional fentanyl or sufentanil was given whenever systolic arterial blood pressure (SBP) increased more than 15% over preanesthetic values. When three successive supplemental doses of the narcotic failed to effectively decrease SBP, phentolamine was used to control pressure before and during bypass; after bypass, N2O (25% to 50%) or, if N2O was ineffective, nitroprusside was used. Average time of induction was 3.4 +/- 0.3 for fentanyl and 1.0 +/- 0.2 min (mean +/- SD) for sufentanil. Chest wall rigidity occurred in 36% of patients in both groups. Total doses of fentanyl and sufentanil required for the entire operation were 113 +/- 11 and 9.0 +/- 0.4 micrograms/kg (mean +/- SD), respectively. Heart rate, cardiac output, and mean right atrial pressure remained unchanged throughout the study in both groups. Mean arterial blood pressure (MBP) and SBP were significantly decreased during induction and after intubation in patients receiving sufentanil, but not fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

Hemodynamic effects of a lorazepam-fentanyl anesthetic induction for coronary artery bypass surgery.

Previous anesthetic induction techniques using the combination of a benzodiazepine (midazolam or diazepam) and fentanyl have been reported to produce marked hypotension. In this study, anesthesia was induced with a combination of lorazepam and fentanyl in patients undergoing coronary artery bypass graft surgery. In 10 patients, anesthesia was induced using an exponentially declining continuous infusion of lorazepam equivalent to a total infused dose of 0.1 mg/kg over 15 minutes, which was supplemented at 10 minutes by fentanyl, 75 micrograms/kg, given as an infusion over 5 minutes. In 8 additional patients, anesthesia was induced with an exponentially declining infusion of fentanyl to a total dose of 75 micrograms/kg over 15 minutes, which was supplemented at 10 minutes by lorazepam, 0.1 mg/kg, given as an infusion over 5 minutes. Hemodynamics were recorded during a 20-minute observation period. One patient in each group required treatment for bradycardia during the initial drug infusion (before the second drug was added). Four additional patients in the group receiving lorazepam followed by fentanyl required treatment for bradycardia or hypotension within 10 minutes of the beginning of the fentanyl infusion. When an infusion of lorazepam was added to the fentanyl infusion, hemodynamics remained stable; however, the reverse order produced a high level of bradycardia and hypotension.

Anesthesia, Intravenous↗

Evaluation of pain following electrocautery tubal ligation and effect of intraoperative fentanyl.

STUDY OBJECTIVE: To evaluate pain following laparoscopic tubal sterilization (LTS) and the effects of supplemental intraoperative fentanyl. DESIGN: Open evaluation of pain intensity and opioid requirements with double-blind, randomized evaluation of intraoperative fentanyl. SETTING: Outpatient center of a university-affiliated teaching hospital. PATIENTS: 44 ASA status I patients who underwent LTS by electrocautery. INTERVENTIONS: Patients received either intravenous fentanyl (F) 1 microgram/kg or saline (S) at induction. MEASUREMENTS AND MAIN RESULTS: Pain intensity was measured with patient assessments of visual analog scales (VAS) and cumulative opioid requirements. The group that received intraoperative fentanyl received 70.2 +/- 3.7 micrograms at induction. VAS on postanesthesia care unit arrival was 4.9 +/- 0.5 (F) and 5.9 +/- 0.5 (S) (means +/- SEM). VAS after one hour was 2.1 +/- 0.2 in both groups. During that hour, the F group consumed 107.5 +/- 14.7 micrograms and the S group consumed 140.5 +/- 15.7 micrograms fentanyl. The range of fentanyl consumed by each group in the postoperative period was 0 to 250 micrograms. There were no statistically significant differences between the F and S groups. CONCLUSIONS: Pain following LTS by electrocautery is of significant magnitude and may require relatively large doses of opioids for adequate management. Supplemental intraoperative fentanyl 1 microgram/kg did not produce a clinically significant reduction in either pain scores or opioid requirements.

Adult↗

Thoracic epidural analgesia with bupivacaine and fentanyl for postoperative thoracotomy pain.

This study was designed to evaluate the potential fentanyl-sparing effect of a dilute local anesthetic, bupivacaine, administered in fixed combinations with fentanyl for post-thoracotomy analgesia via a continuous thoracic epidural infusion. Forty adult patients scheduled for thoracotomy were randomly allocated in a double-blind fashion to receive an epidural infusion containing 0, 0.03, 0.06, or 0.125% bupivacaine in combination with fentanyl (4 micrograms/mL). The epidural infusions were initiated in the operating room at 10 mL/hr. During the first 24 hours, there were no between-group differences in pain scores. Total fentanyl use was significantly decreased 24% to 33% in all bupivacaine treatment groups. However, fentanyl plasma levels at 24 hours were not significantly different between groups. Arterial blood gas measurements performed on the morning after surgery revealed significant reductions in PaCO2 values, 38 +/- 4, 36 +/- 4, 37 +/- 4 mmHg for 0.03, 0.06, and 0.125% bupivacaine groups respectively, versus 44 +/- 6 for the plain fentanyl group. Arterial pH values were significantly higher in all bupivacaine treatment groups. These findings suggest that the combination of dilute bupivacaine with fentanyl for thoracic epidural analgesia for post-thoracotomy pain may have beneficial effects on pulmonary gas exchange.

Adult↗

Severe deficit in brain reward function associated with fentanyl withdrawal in rats.

BACKGROUND: During the last decade, there has been a strong increase in the use of the mu-opioid receptor agonist fentanyl. The aim of these studies was to investigate the effects of fentanyl withdrawal on brain reward function and somatic withdrawal signs. METHODS: Fentanyl and saline were chronically administered via minipumps. An intracranial self-stimulation procedure was used to provide a measure of brain reward function. Somatic signs were recorded from a checklist of opioid abstinence signs. RESULTS: The opioid receptor antagonist naloxone induced a dose-dependent elevation in brain reward thresholds and somatic withdrawal signs in fentanyl-treated rats. Discontinuation of fentanyl administration resulted in a time-dependent elevation of brain reward thresholds and somatic withdrawal signs. CONCLUSIONS: These findings indicate that fentanyl withdrawal is associated with affective and somatic withdrawal signs. The severity of the deficit in brain reward function in this animal model suggests that affective fentanyl withdrawal symptoms may be a strong deterrent to abstinence.

Affect↗