Fentanyl reduces infarction but not stunning via delta-opioid receptors and protein kinase C in rats.
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Langendorff rat hearts were used (i) to examine whether fentanyl reduces stunning, infarction or both, and (ii) to investigate if this protection is mediated by delta-opioid receptors and/or protein kinase C (PKC). In the stunning study, hearts were subjected to global ischaemia (20 min) and reperfusion. This did not produce infarction. Postischaemic mechanical function was measured in hearts treated with or without fentanyl (740 nM). Fentanyl did not affect postischaemic mechanical function. In the infarction study, the left anterior descending coronary artery was occluded for 35 min and infarct size was assessed by triphenyltetrazolium chloride staining. Hearts in the control group exhibited an infarct zone/area at risk (I/R) of 39 (SEM 5)%, whereas the I/R for the fentanyl group was 13 (2)%. When the hearts were treated with a delta-opioid receptor antagonist (naltrindole 1 nM) or a PKC inhibitor (chelerythrine 2 microM), the effect of fentanyl was abolished, with I/R of 37 (1) and 36 (2)% respectively. In our model, we conclude that fentanyl protects against infarction but not against stunning, and that the limitation of ischaemic injury is mediated by both delta-opioid receptors and PKC. (+info)
Effect of anaesthesia on the cardiac response to intravenous adenosine.
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The cardiac response to intravenous adenosine 112 micrograms kg-1 was studied in 16 patients scheduled for coronary artery bypass surgery before and during anaesthesia with 1% end-tidal isoflurane and fentanyl 10 micrograms kg-1. Mean time from injection to onset of adenosine-induced PR prolongation was significantly greater during anaesthesia (12.8 (SD 5) vs 9.9 (3) s, P = 0.032). Atrioventricular block (assessed by the total number of non-conducted P waves) was significantly less during anaesthesia (12 vs 27, P = 0.016). We conclude that anaesthesia including 1% isoflurane and fentanyl 10 micrograms kg-1 delays the onset and reduces the magnitude of adenosine-induced atrioventricular block. (+info)
Supplemental intraoperative oxygen augments antimicrobial and proinflammatory responses of alveolar macrophages.
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BACKGROUND: The first goal was to test the hypothesis that 100% inspired oxygen maintained for approximately 8 h intraoperatively is not associated with impaired pulmonary oxygenation. The authors also tested the hypothesis that intraoperative inhalation of 100% oxygen augments proinflammatory and antimicrobial responses of alveolar macrophages during anesthesia and surgery. METHODS: The authors studied patients administered 100% oxygen (n = 30) and 30% oxygen (n = 30) during propofol-fentanyl general anesthesia. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, 2, 4, and 6 h after induction of anesthesia, and at the end of surgery. The authors measured "opsonized" and "unopsonized" phagocytosis and microbicidal activity. RNA was extracted from harvested cells and cDNA was synthesized. The expression of interleukin(IL)-1beta, IL-6, IL-8, interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) was measured by semiquantitative polymerase chain reaction. RESULTS: Gene expression of all proinflammatory cytokines except IL-6 increased fourfold to 20-fold over time in both groups. However, expression of TNF-alpha and IL-8, IFN-gamma, and IL-6 and IL-1beta was 2-20 times greater in patients administered 100% than in those administered 30% oxygen. Unopsonized and opsonized phagocytosis and microbicidal activity decreased progressively, with the decreases being nearly twice as great during inhalation of 30% oxygen versus 100% oxygen. CONCLUSION: Inhalation of 100% oxygen improved intraoperative decreases in phagocytic and microbicidal activity possibly because expression of proinflammatory cytokines was augmented. These data therefore suggest that intraoperative inhalation of 100% oxygen augments antimicrobial and proinflammatory responses in alveolar macrophages during anesthesia and surgery. (+info)
Effect of intravenous versus epidural fentanyl on the minimum local analgesic concentration of epidural bupivacaine in labor.
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BACKGROUND: The minimum local analgesic concentration (MLAC) has been defined as the median effective local analgesic concentration (EC50) in a 20-ml volume for epidural analgesia in the first stage of labor. The aim of this study was to determine the relative local anesthetic sparing efficacies of intravenous and epidural fentanyl by comparison of their effects on the MLAC of bupivacaine. METHODS: In this double-blind, randomized, prospective study, 84 parturients at < or = 7-cm cervical dilation who requested epidural analgesia were allocated to one of two groups. After lumbar epidural catheter placement, 20 ml bupivacaine (n = 44) or bupivacaine with 3 microg/ml (60 microg) fentanyl (n = 40) was administered. The plain bupivacaine group then received 60 microg intravenous fentanyl. The bupivacaine-fentanyl group received intravenous saline. The concentration of bupivacaine was determined by the response of the previous patient in that group to a higher or lower concentration using up-down sequential allocation. Analgesic efficacy was assessed using 100-mm visual analog pain scores, with < or = 10 mm within 30 min define as effective. RESULTS: The MLAC of bupivacaine-intravenous fentanyl was 0.064% wt/vol (95% confidence interval, 0.049-0.080), and the MLAC of bupivacaine-epidural fentanyl was 0.034% wt/vol (95% confidence interval, 0.017-0.050). Epidural fentanyl significantly increased the analgesic potency of bupivacaine by a factor of 1.88 (95% confidence interval, 1.09-3.67) compared with intravenous fentanyl. The epidural fentanyl group demonstrated significantly higher dermatomal spread (P = 0.0064) and increased pruritus (P = 0. 01). CONCLUSIONS: Epidural fentanyl significantly reduced the MLAC of bupivacaine when compared with intravenous fentanyl for the parturients in this study. The significantly enhanced local anesthetic sparing, dermatomal level, and pruritus with epidural fentanyl suggest a primarily spinal site of action. (+info)
Anaesthetic agents inhibit gastrin-stimulated but not basal histamine release from rat stomach ECL cells.
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By mobilizing histamine in response to gastrin, the ECL cells in the oxyntic mucosa play a key role in the control of the parietal cells and hence of gastric acid secretion. General anaesthesia suppresses basal and gastrin- and histamine-stimulated acid secretion. The present study examines if the effect of anaesthesia on basal and gastrin-stimulated acid secretion is associated with suppressed ECL-cell histamine secretion. A microdialysis probe was implanted in the submucosa of the ventral aspect of the acid-producing part of the stomach (32 rats). Three days later, ECL-cell histamine mobilization was monitored 2 h before and 4 h after the start of intravenous infusion of gastrin (5 nmol kg(-1) h(-1)). The rats were either conscious or anaesthetized. Four commonly used anaesthetic agents were given 1 h before the start of the experiments by intraperitoneal injection: chloral hydrate (300 mg kg(-1)), pentobarbitone (40 mg kg(-1)), urethane (1.5 g kg(-1)) and a mixture of fluanisone/fentanyl/midazolam (15/0.5/7.5 mg kg(-1)). In a parallel series of experiments, basal- and gastrin-induced acid secretion was monitored in six conscious and 25 anaesthetized (see above) chronic gastric fistula rats. All anaesthetic agents lowered gastrin-stimulated acid secretion; also the basal acid output was reduced (fluanisone/fentanyl/midazolam was an exception). Anaesthesia reduced gastrin-stimulated but not basal histamine release by 55 - 80%. The reduction in gastrin-induced acid response (70 - 95%) was strongly correlated to the reduction in gastrin-induced histamine mobilization. The correlation is in line with the view that the reduced acid response to gastrin reflects impaired histamine mobilization. Rat stomach ECL cells were purified by counter-flow elutriation. Gastrin-evoked histamine mobilization from the isolated ECL cells was determined in the absence or presence of anaesthetic agents in the medium. With the exception of urethane, they inhibited gastrin-evoked histamine secretion dose-dependently, indicating a direct effect on the ECL cells. Anaesthetized rats are widely used to study acid secretion and ECL-cell histamine release. The present results illustrate the short-comings of such an approach in that a number of anaesthetic agents were found to impair not only acid secretion but also the secretion of ECL-cell histamine - some acting in a direct manner. (+info)
Epidural ropivacaine with fentanyl following major gynaecological surgery: the effect of volume and concentration on pain relief and motor impairment.
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In a prospective, randomized, double-blind study, 40 patients undergoing gynaecological oncology surgery received either 0.1% ropivacaine with fentanyl 1 microgram ml-1 or 0.2% ropivacaine with fentanyl 2 micrograms ml-1. A PCEA pump was set to deliver ropivacaine 8 mg with fentanyl 8 micrograms with each successful demand and a lockout period of 15 min without background infusion. Patients were observed for rest and activity pain VAS, side effect incidence, peak expiratory flow rate (PEFR), leg strength, sensory block to cold and pinprick, and PCEA usage into the second postoperative day. Passive and active pain scores for both groups were both satisfactory and comparable for the duration of the study. There were no differences between groups with regard to side effects. There was a 24% increase in total drug used in the high-concentration/low-volume group (P < 0.05). The study demonstrated that PCEA ropivacaine with fentanyl is an effective means of postoperative analgesia for this patient population. Reduced drug consumption with high-volume/low-concentration solution confirms similar findings by other investigators using alternate local anaesthetic agents, and suggests that the therapeutic ratio of ropivacaine is widened if a low-concentration/high-volume solution is used. (+info)
Breath interval as a measure of dynamic opioid effect.
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We measured breath interval to characterize the time course of opioid effect in anaesthetized patients breathing spontaneously during knee replacement surgery with concurrent regional nerve blockade. Breath interval was recorded before and after a single dose of fentanyl 0.75 microgram kg-1 i.v. Breath interval was measured between the start of successive inspirations, identified by a decrease in carbon dioxide concentration, sampled at the laryngeal mask connection. Nineteen patients were admitted to the study, of whom nine were withdrawn (there was a recording failure for one patient, five patients had inadequate block and three were excessively depressed by the fentanyl). Using MKMODEL software, the mean (SD) dynamic elimination half-life and dynamic mean brain residence time of fentanyl were 15.3 (7.8) and 24.1 (8.1) min, respectively. The times to detection of change from baseline, and peak effect of fentanyl on breath interval were 0.9 (0.6) and 5.2 (1.4) min, respectively. Breath interval increased from 2.9 (1.0) s to a maximum of 9.0 (5.7) s. There were no differences between the time course of changes in breath interval and end-tidal carbon dioxide concentrations. End-tidal carbon dioxide concentrations increased from a baseline of 6.6 (0.9)% to a peak of 8.2 (0.8)%. Breath interval was a useful and reproducible method of monitoring the duration of opioid effect in anaesthetized patients breathing spontaneously when surgical stimulation was not affecting the CNS. The data provide information on the duration of action of fentanyl and could guide dosage. (+info)
Fentanyl and midazolam anaesthesia for coronary bypass surgery: a clinical study of bispectral electroencephalogram analysis, drug concentrations and recall.
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Bispectral index (BIS) was assessed as a monitor of depth of anaesthesia during fentanyl and midazolam anaesthesia for coronary bypass surgery. In 10 patients given morphine premedication, anaesthesia was induced with a combination of midazolam and fentanyl and thereafter maintained with a continuous infusion of a mixture of midazolam and fentanyl 5 and 50 micrograms kg-1 h-1, respectively. BIS was recorded continuously but not shown to the attending anaesthetist. Plasma concentrations of midazolam and fentanyl were measured five times during the procedure. An auditory stimulus was given during bypass. All patients were interviewed twice after operation for explicit and implicit recall. No patient had any anaesthetic complications. BIS decreased during anaesthesia, but varied considerably during surgery (range 36-91) with eight patients having values > 60. Midazolam and fentanyl drug concentrations did not correlate with BIS. No patient reported explicit or implicit recall. During clinically adequate anaesthesia with midazolam and fentanyl BIS varies considerably. The most likely reason is that BIS is not an accurate measure of the depth of anaesthesia when using this combination of agents. (+info)