In rabbits, landiolol, a new ultra-short-acting beta-blocker, exerts a more potent negative chronotropic effect and less effect on blood pressure than esmolol.

PURPOSE: To compare the cardiovascular and sympathetic effects of a new ultra-short-acting, highly cardioselective beta- blocker, landiolol, with esmolol, using an in vivo rabbit model. METHODS: Different bolus doses of landiolol (0.3, 1.0, 3.0 and 10.0 mg*kg(-1)) or esmolol (0.5, 1.5 and 5.0 mg*kg(-1)) were given intravenously, and the effects on heart rate (HR) mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were compared. RESULTS: Both landiolol and esmolol produced a dose-dependent decrease in HR. The maximum percent reductions of HR were similar with landiolol 3 mg*kg(-1) and esmolol 5 mg*kg(-1) (-14.0 +/- 0.9% and -13.9 +/- 1.4%, mean +/- SE, respectively). HR decreased more rapidly with landiolol than with esmolol. Esmolol produced a dose-dependent decrease in MAP that was not observed with landiolol. The percent maximum reduction of MAP was -38.2 +/- 3.2% with esmolol 5 mg*kg(-1). RSNA increased in a dose-dependent fashion with esmolol, but no changes were noted with landiolol. CONCLUSION: These results suggest that, in rabbits, landiolol has slightly more potent negative chronotropic action than esmolol with significantly less effects on blood pressure.

Stress responses in three different anesthetic techniques for carbon dioxide laparoscopic cholecystectomy.

STUDY OBJECTIVE: To evaluate and compare the stress hormone responses during laparoscopic cholecystectomy during general anesthesia, general anesthesia supplemented by fentanyl, and general anesthesia combined with epidural anesthesia. DESIGN: Prospective, randomized clinical study. SETTING: Operating rooms at a municipal hospital. PATIENTS: 52 ASA physical status I and II patients. INTERVENTIONS: Anesthesia was induced slowly with sevoflurane and nitrous oxide (N2O) in oxygen (O2) by mask. Endotracheal intubation was facilitated with intravenous (i.v.) vecuronium 0.1 mg/kg. In 17 patients, anesthesia was maintained with sevoflurane and 50% N2O in O2. For another 18 patients, fentanyl 4 micrograms/kg was administered after endotracheal intubation, and anesthesia was maintained with sevoflurane and 50% N2O in O2. The remaining 17 patients received thoracic epidural anesthesia (1% mepivacaine in an 8 ml bolus followed by a continuous infusion of 1% mepivacaine, 3 ml/hr) after endotracheal inturbation, and general anesthesia was maintained with sevoflurane and 50% N2O in O2. End-tidal sevoflurane concentrations were adjusted to maintain mean arterial pressure between 70% and 100% of preinduction values. MEASUREMENTS AND MAIN RESULTS: Venous blood was sampled for measurements of cortisol and catecholamines (epinephrine and norepinephrine) immediately before and 30 minutes after surgical incision. Cortisol levels increased in all three anesthesia techniques. Both catecholamines increased in patients receiving general anesthesia only; catecholamines did not increase significantly in patients receiving general anesthesia combined with epidural anesthesia; in patients receiving general anesthesia supplemented with fentanyl, both catecholamines increased significantly, but the degree of increase in norepinephrine was less than that in the general anesthesia only group. CONCLUSIONS: The fentanyl supplemented group received relatively small doses insufficient to inhibit an increase in catecholamines. Thoracic epidural anesthesia depressed the sympathetic response presumably by blocking afferent sympathetic pathways under the conditions of this study. However, it did not attenuate an increase in cortisol, one of the hypothalamic-pituitary-adrenal stress hormones, during carbon dioxide laparoscopic cholecystectomy in our study. This action may be due to the inability of epidural anesthesia to block phrenic nerves that can convey noxious surgical stimulation to the central nervous system.

Fentanyl-induced rigidity and unconsciousness in human volunteers. Incidence, duration, and plasma concentrations.

BACKGROUND: Muscle rigidity frequently accompanies induction of anesthesia with opioids. The authors sought to determine whether unconsciousness and amnesia occur when humans develop rigidity and apnea after intravenous fentanyl (without other concomitant anesthetics). METHODS: The incidence and duration of rigidity and level of consciousness were evaluated and associated plasma concentrations of fentanyl were measured in 12 healthy adult male volunteers given only intravenous fentanyl. Fentanyl was infused at a rate of 150 micrograms/min until a total of 15 micrograms/kg had been administered. Arterial blood samples for fentanyl assay were drawn and responsiveness, heart rate (HR), and systolic and diastolic arterial blood pressures were determined at frequent intervals during and after infusion. If rigidity was accompanied by an Spo2 < 90%, positive pressure ventilation with 100% O2 with a mask was instituted until spontaneous ventilation resumed. RESULTS: The incidence of muscular rigidity was 50% (6/12). All subjects who developed rigidity were apneic, unresponsive, and had no recall of commands to breathe or of positive pressure ventilation. Subjects not developing rigidity remained awake and responsive. No subject developing rigidity required neuromuscular blockade to allow positive pressure ventilation and adequate oxygenation (Spo2 > 90%). When rigidity occurred, it started 3 +/- 0.9 (range 1-4) min after the peak plasma fentanyl concentration and lasted for 11.5 +/- 5.8 (range 7-23) min. Rigidity started at a plasma fentanyl concentration of 21.5 +/- 4.4 (range 16-28) ng/ml and ended at 6.9 +/- 1.5 (range 5.2-8.7) ng/ml. Baseline HR was less in the subjects who subsequently developed rigidity (56.7 +/- 7.8 vs. 67.2 +/- 7.8 P = 0.04). No differences in fentanyl plasma concentrations or predicted effect site concentrations for rigidity were detected between subjects who developed rigidity and those who did not. CONCLUSIONS: These findings support the hypothesis that unconsciousness occurs in the unstimulated subject during fentanyl-induced apnea and rigidity.

Absorption and bioavailability of oral transmucosal fentanyl citrate.

Oral transmucosal fentanyl citrate (OTFC) is a novel, noninvasive dosage form of fentanyl used to provide children and adults with sedation, anxiolysis, and analgesia. In order to determine the bioavailability and absorption of fentanyl from OTFC, 12 volunteers were given intravenous fentanyl citrate or OTFC 15 micrograms/kg on each of two occasions. On a third occasion, the authors assessed oral administration (gastrointestinal absorption) by giving eight of the same volunteers the same dose of a solution of fentanyl citrate to swallow. In each study, arterial blood samples were taken over 24 h for analysis of plasma fentanyl. After intravenous (iv) administration of fentanyl, clearance (mean +/- standard deviation) was 0.67 +/- 0.15 l/min; volume of distribution at steady state was 287 +/- 79 l; and the terminal elimination half-life was 425 +/- 102 min. Peak plasma concentrations of fentanyl were higher (3.0 +/- 1.0 vs. 1.6 +/- 0.6 ng/ml, P = 0.01) and occurred sooner (22 +/- 2.5 vs. 101 +/- 48.8 min, P = 0.003) after OTFC than after oral solution administration. Plasma concentrations of fentanyl after OTFC decreased rapidly, to less than 1.0 ng/ml within 75-135 min after the beginning of administration. Peak absorption rate was greater (11.1 +/- 4.3 vs. 3.6 +/- 2.1 micrograms/min, P = 0.004) and occurred much sooner after OTFC than after oral solution administration (19 +/- 2.6 vs. 87.5 +/- 38.1 min, P = 0.001). Systemic bioavailability was greater after OTFC administration than after the oral solution (0.52 +/- 0.1 vs. 0.32 +/- 0.1, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Oral transmucosal fentanyl citrate for premedication in paediatric outpatients.

Two doses (10-15 micrograms.kg-1, Group I, and 15-20 micrograms.kg-1, Group II) of oral transmucosal fentanyl citrate (OTFC) plus a placebo (Group III) were evaluated for premedication in 105 healthy children, aged 2 to 13 yr, undergoing short (less than 1 hr) operations in the hospital short-stay unit. The study was randomized and double-blinded and 91 of the 105 children also received droperidol, 25 micrograms.kg-1 IV, after induction of anaesthesia with halothane and N2O in oxygen. Both doses of OTFC produced significantly greater sedation (first present at 20 min) and anxiolysis (first present in Group I at 40 min) than the placebo. Recovery times were similar in the three groups and analgesic requirements in the recovery room were significantly lower in Group I than Group III. Both OTFC groups took longer to tolerate oral fluids in the postoperative discharge unit than the placebo group and this caused patients in Group I to have a delayed discharge from the hospital compared to Group III. Preoperative pruritus occurred significantly more frequently in Groups I and II (58 and 76 per cent, respectively) than Group III (23 per cent). Although the incidences of nausea and vomiting tended to be slightly higher in the OTFC groups in the preoperative holding and postoperative discharge units, the differences among the groups were not statistically significant. Likewise droperidol did not reduce the incidence of postoperative nausea or vomiting. The data indicate that OTFC may be a safe and effective premedicant in paediatric patients having short operations but delays discharge from the hospital (by 30-50 min) by delaying the time patients tolerate fluids early after operation.