Tumour cell killing using chemically engineered antibody constructs specific for tumour cells and the complement inhibitor CD59

BACKGROUND: Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses, the sedative properties of these compounds might decrease anesthetic requirements. This study was designed to determine whether esmolol, a short-acting beta 1-receptor antagonist, could reduce the propofol concentration required to prevent movement at skin incision. METHODS: Sixty consenting patients were premedicated with morphine, and then propofol was delivered by computer-assisted continuous infusion along with 60% nitrous oxide. Patients were randomly divided into three groups, propofol alone, propofol plus low-dose esmolol (bolus of 0.5 mg/kg, then 50 micrograms.kg-1.min-1), and propofol plus high-dose esmolol (bolus of 1 mg/kg, then 250 micrograms.kg-1.min-1). Two venous blood samples were drawn at equilibrium. The serum propofol concentration that prevented movement to incision in 50% of patients (Cp50) was calculated by logistic regression. RESULTS: The propofol Cp50 with nitrous oxide was 3.85 micrograms/ ml. High-dose esmolol infusion was associated with a significant reduction in the Cp50 to 2.80 micrograms/ml (P < 0.04). Propofol computer-assisted continuous infusion produced stable serum concentrations with a slight positive blas. Esmolol did not alter the serum propofol concentration. No intergroup differences in heart rate or blood pressure response to intubation or incision were found. CONCLUSIONS: Esmolol significantly decreased the anesthetic requirement for skin incision. The components and mechanism of this interaction remain unclear. A simple pharmacokinetic interaction between esmolol and propofol does not explain the Cp50 reduction. These results demonstrate an anesthetic-sparing effect of a beta-adrenergic antagonist in humans under clinically relevant conditions.     

Anesthetic depth defined using multiple noxious stimuli during isoflurane/oxygen anesthesia. I. Motor reactions

BACKGROUND: Potency of inhaled anesthetics usually is defined by determining the minimal alveolar concentration (MAC) that prevents movement in 50% of patients in response to skin incision. Skin incision, however, is usually only a single event and, thus, determination of potency cannot be repeated in one patient. Traditional MACskin incision cannot be used to predict response to other noxious stimuli. The aim of this study was to investigate the effects of other noxious stimulation patterns and then compare these to MACskin incision measuring the end-tidal isoflurane concentrations with the corresponding arterial concentrations. METHODS: In 26 patients, the end-tidal and corresponding arterial isoflurane concentrations needed to suppress eye opening to verbal command and motor response after trapezius squeeze, 50 Hz electric tetanic stimulation, laryngoscopy, skin incision, and tracheal intubation in 50% of all patients were determined. RESULTS: The end-tidal (equivalent arterial) isoflurane concentrations (mean +/- SE, adjusted to sea level) expressed in vol% (to allow comparison) increased in the following order (mean +/- SE): vocal command 0.37 +/- 0.09 (0.36 +/- 0.09); trapezius squeeze 0.84 +/- 0.07 (0.65 +/- 0.07); laryngoscopy 1.00 +/- 0.12 (0.78 +/- 0.09); tetanic stimulation 1.03 +/- 0.09 (0.80 +/- 0.06); skin incision 1.16 +/- 0.10 (0.97 +/- 0.17); and intubation 1.76 +/- 0.13 (1.32 +/- 0.11). CONCLUSIONS: Different stimuli require different isoflurane concentrations to suppress motor responses. Tetanic stimulation and, to some extent, trapezius squeeze are reproducible and noninvasive stimulation patterns that can be used as an alternative to skin incision when evaluating potency of an anesthetic agent. In contrast to skin incision, they can be repeated.     

Concentration-response relationships for fentanyl and sufentanil in patients undergoing coronary artery bypass grafting

BACKGROUND: Concentration-response relationships for sufentanil and fentanyl are undefined in patients undergoing coronary artery bypass grafting. METHODS: Separate studies of sufentanil and fentanyl were performed in lorazepam-premedicated patients undergoing coronary artery bypass grafting. Patients were assigned randomly to groups with different prebypass effect-site opioid concentrations targeted by computer-assisted infusion. The target sufentanil concentrations were 0.4 ng/ml (group LS, n = 11), 0.8 ng/ml (group MS, n = 10), and 1.2 ng/ml (group HS, n = 11); the target fentanyl concentrations were 5 ng/ml (group LF, n = 7), 10 ng/ml (group MF, n = 7), and 15 ng/ml (group HF, n = 6). Propofol at a dose of 1 mg/kg was administered at induction of anesthesia and isoflurane was used for hemodynamic control Hemodynamics, end-tidal isoflurane concentration, and opioid concentration in arterial blood were measured at specific intervals. RESULTS: Intraoperative opioid concentrations were constant, averaging 0.71 +/- 0.13, 1.25 +/- 0.21, and 2.03 +/- 0.46 ng/ml for groups LS, MS, and HS, respectively, and 7.3 +/- 1.1, 13.2 +/- 2.2, and 24.4 +/- 5.8 ng/ml for groups LF, MF, and HF, respectively (all mean +/- SD). Isoflurane requirements were significantly greater in group LS than in groups MS and HS and greater in group LF than in groups MF and HF. The serum opioid and end-tidal isoflurane concentrations were correlated significantly. There were no intergroup differences in hemodynamics. CONCLUSIONS: Serum sufentanil and fentanyl concentrations of 0.71 +/- 0.13 ng/ml and 7.3 +/- 1.3 ng/ml, respectively, are on the steep parts of the concentration-response relationships and facilitate prebypass hemodynamic control in patients undergoing coronary artery bypass grafting with opioid-isoflurane anesthesia. Concentrations of sufentanil > or = 1.25 +/- 0.21 ng/ml and of fentanyl > or = 13.3 +/- 2.2 ng/ml minimize isoflurane requirements but do not improve hemodynamic control.     

Determination of propofol in rat whole blood and plasma by high-performance liquid chromatography

A simple, accurate and sensitive high-performance liquid chromatographic method was developed for the determination of propofol, an intravenous anaesthetic agent, in rat whole blood or plasma samples. The method is based on precipitation of the protein in the biological fluid sample and direct injection of the supernatant into an HPLC system involving a C18 reversed-phase column using a methanol-water (70:30) mobile phase delivered at 1 ml/min. Propofol and the internal standard (4-tert.-octylphenol) were quantified using a fluorescence detector set at 276 nm (excitation) and 310 nm (emission). The analyte and internal standard had retention times of 6.3 and 10.5 min, respectively. The limit of quantification for propofol was 50 ng/ml using 100 microl of whole blood or plasma sample. Calibration curves were linear (r2=0.99) over a 1-10 microg/ml concentration range and intra- and inter-day precision were between 4-11%. The assay was applied to the determination of propofol whole blood pharmacokinetics and propofol whole blood to plasma distribution ratios in rats.     

Hemodynamic response to induction and intubation. Propofol/fentanyl interaction

BACKGROUND: When given as an intravenous bolus for induction of anesthesia, propofol can decrease postintubation hypertension but can also create moderate to severe postinduction, preintubation hypotension. The addition of fentanyl usually decreases the postintubation hypertension but can increase the propofol-induced preintubation hypotension. The goal of the study was to determine the relation between propofol and fentanyl doses and the hemodynamic changes post-induction, preintubation and postintubation. METHODS: Twelve groups of 10 patients, ASA physical status 1 or 2, first received fentanyl 0, 2, or 4 micrograms.kg-1 and then 5 min later received propofol 2.0, 2.5, 3.0, or 3.5 mg.kg-1 as an intravenous bolus for induction of anesthesia. Arterial blood pressure was continuously monitored. The trachea was intubated 4 min after propofol administration. RESULTS: The mean decrease in systolic blood pressure after propofol was 28 mmHg when no fentanyl was given, 53 mmHg after 2 microgram.kg-1 of fentanyl (P < 0.05 vs. no fentanyl), and 50 mmHg after 4 micrograms.kg-1 (P < 0.05 vs. no fentanyl; no statistically significant difference 4 vs. 2 micrograms.kg-1). There was no statistically significant difference in hemodynamic response to intubation relative to propofol dose. Hemodynamic response to intubation was decreased by the administration of fentanyl; the mean increase of systolic blood pressure after intubation was 65 mmHg from preintubation value without fentanyl, 50 mmHg after 2 micrograms.kg-1, and 37 mmHg after 4 micrograms.kg-1 (P < 0.05 for 2 and 4 micrograms.kg-1 vs. no fentanyl and for 4 vs. 2 micrograms.kg-1). Hemodynamic changes postintubation were not statistically different with increasing doses of propofol. CONCLUSIONS: Hemodynamic changes after induction with propofol or propofol/fentanyl, pre- or postintubation, are not modified when the propofol dose is increased from 2 to 3.5 mg.kg-1. Maximal hypotension preintubation occurs with a fentanyl dose of 2 micrograms.kg-1, whereas the magnitude of postintubation hypertension is significantly decreased with an increase in the fentanyl dose to 4 micrograms.kg-1.     

Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea

BACKGROUND: Subhypnotic doses of propofol possess direct antiemetic properties. The authors sought to determine the plasma concentration of propofol needed to effectively manage postoperative nausea and vomiting. METHODS: Patients aged 18-70 yr who were classified as American Society of Anesthesiologists physical status 1 or 2 and had surgery during general anesthesia were approached for the study. Only patients who had nausea (verbal rating score > 5 on a 0- to 10-point scale), retching, or vomiting in the postanesthetic care unit participated. Propofol was administered to these patients to achieve target plasma concentrations of 100, 200, 400, and 800 ng/ml using a computer-assisted continuous infusion device. Target concentrations were increased every 15 min until patients described at least a 50% reduction in symptoms on the verbal rating score. An arterial blood sample was obtained at each step. The measured plasma propofol concentrations were used to analyze data. Blood pressure, heart and respiratory rates, arterial blood saturation, sedation score, and overall satisfaction with treatment were recorded. RESULTS: Of the 89 patients who consented to the study, 15 patients met entry criteria and were enrolled. Five of these patients also had retching or vomiting when they entered the study. Fourteen patients responded successfully to treatment. One patient did not achieve the required response at plasma concentrations of 830 ng/ml. Hence the success rate for the treatment of postoperative nausea and vomiting was 93%. Among patients who responded, the median plasma concentration associated with an antiemetic response was 343 ng/ml. There was no difference in sedation scores from baseline and no episodes of desaturation. Hemodynamic parameters were stable during the study. CONCLUSIONS: Propofol is generally efficacious in treating postoperative nausea and vomiting at plasma concentrations that do not produce increased sedation. Simulations indicate that to achieve antiemetic plasma propofol concentrations of 343 ng/ml, a bolus dose of 10 mg followed by an infusion of approximately 10 microg x kg(-1) x min(-1) are necessary.     

Pentaerithrityl tetranitrate and its phase I metabolites are potent activators of cellular cyclic GMP accumulation

This study was designed to examine the optimal time of injection of a small dose of fentanyl during anesthetic induction to attenuate circulatory responses to laryngoscopy and tracheal intubation. One hundred seventy patients were randomly assigned to one of five groups. In Groups II, III, IV, and V, patients received fentanyl (2 microg/kg) 1, 3, 5, or 10 min before tracheal intubation, respectively. Group I patients did not receive fentanyl and served as the control group. In Groups III and IV, blood pressures were not increased, except diastolic pressure in Group III, significantly postintubation compared with preinduction values; but Groups I, II, and V showed a significant increase (P < 0.05). The 1-min postintubation values of systolic, diastolic, and mean arterial pressure in Groups III and IV were less than those in the control group (P < 0.05). Increases of heart rate in Group IV were less (P < 0.05) than those in the control group, but significant differences were not observed in Groups II, III, and V. The number of patients with tachycardia and dysrhythmia was significantly smaller in Group IV than in the control group (P < 0.05). We conclude that the most effective time to administer fentanyl to protect circulatory responses to laryngoscopy and tracheal intubation is 5 min before tracheal intubation. IMPLICATIONS: Fentanyl is often used to reduce the hemodynamic response to tracheal intubation. However, large doses may cause unwanted side effects. Administration of fentanyl at the optimal time reduces the dose required. Our results indicate that optimal injection time of fentanyl for intubation is 5 min before intubation.     

In vivo and in vitro studies of the inhibitory effect of propofol on human platelet aggregation

BACKGROUND: The inhibitory effects of propofol on platelet aggregation are controversial because the fat emulsion used as the solvent for propofol may affect platelet function. The effects of propofol on platelet intracellular calcium ion concentration and on aggregation were investigated. METHODS: Platelet aggregation was measured in 10 patients who received an intravenous infusion of propofol. Intralipos, the propofol solvent, was infused in 10 healthy volunteers and platelet aggregation were measured. The in vitro effects of propofol and Intralipos on platelets were also investigated. The inhibitory effects of various concentrations of propofol were studied. The effects of propofol on the changes in intracellular calcium level using a fluorescent dye, fura-2, were also observed. Template bleeding time was measured to determine the effect of propofol in clinical use. RESULTS: Platelet aggregation was significantly inhibited by infusion of propofol, although bleeding time was not prolonged. Intralipos did not inhibit platelets either in vivo or in vitro. Propofol significantly inhibited platelet aggregation in vitro and at 5.81 +/- 2.73 microg/ml but not at 2.08 +/- 1.14 microg/ml. The increase of intracellular calcium concentration was inhibited both in influx and discharge of calcium. CONCLUSIONS: Propofol inhibited platelet aggregation both in vivo and in vitro. Inhibition of platelet aggregation appeared to be caused by propofol itself and not by the fat emulsion. This inhibitory effect was also supported by the suppressed influx and discharge of calcium. No change in the bleeding time suggests that this inhibitory effect does not impair hemostasis clinically.     

Effectiveness of polyclonal and monoclonal antibodies prepared for an immunoassay of the etofenprox insecticide

The aim of this study was to compare hemodynamic responses to intubation and pin head-holder application in two groups of neurosurgical patients given oral clonidine (3 microg/kg) or oral temazepam (10-20 mg) 90 min before the induction of anesthesia. Fifty patients undergoing elective craniotomy were randomized to either group. Anesthesia was induced with i.v. propofol 1500 mg/h, fentanyl 4 microg/kg, vecuronium 0.15 mg/kg, and lidocaine 1.5 mg/kg and was maintained with propofol 6 mg x kg(-1) x h(-1). Mean arterial blood pressure (MAP) and heart rate were recorded before the induction of anesthesia and before and after intubation and application of the pin head holder. Interventions required to maintain hemodynamic stability were compared between groups. Preinduction sedation scores and MAP values were similar between groups. MAP was significantly lower (P = 0.031) in the clonidine group after pin head-holder application. Interventions to stabilize MAP were not significantly different between groups (P = 0.11). We conclude that clonidine is effective in reducing the MAP increase with pin head-holder application in patients undergoing craniotomy. Implications: In this study, we investigated an approach to the prevention of increased blood pressure often seen during the early part of anesthesia for brain surgery. Oral clonidine was effective in reducing the mean arterial blood pressure increase resulting from pin head-holder application. Clonidine, a blood pressure-reducing drug, was given to 25 patients before anesthesia. Their blood pressure measurements were then compared with those of 25 patients not given clonidine.     

Antiemetic activity of propofol after sevoflurane and desflurane anesthesia for outpatient laparoscopic cholecystectomy

BACKGROUND: Controversy exists regarding the effectiveness of propofol to prevent postoperative nausea and vomiting. This prospective, randomized, single-blinded study was designed to evaluate the antiemetic effectiveness of 0.5 mg/kg propofol when administered intravenously after sevoflurane- compared with desflurane-based anesthesia. METHODS: Two hundred fifty female outpatients undergoing laparoscopic cholecystectomy were assigned randomly to one of four treatment groups. All patients were induced with intravenous doses of 2 mg midazolam, 2 microg/kg fentanyl, and 2 mg/kg propofol and maintained with either 1-4% sevoflurane (groups 1 and 2) or 2-8% desflurane (groups 3 and 4) in combination with 65% nitrous oxide in oxygen. At skin closure, patients in groups 1 and 3 were administered 5 ml intravenous saline, and patients in groups 2 and 4 were administered 0.5 mg/kg propofol intravenously. Recovery times were recorded from discontinuation of anesthesia to awakening, orientation, and readiness to be released home. Postoperative nausea and vomiting and requests for antiemetic rescue medication were evaluated during the first 24 h after surgery. RESULTS: Propofol, in an intravenous dose of 0.5 mg/kg, administered at the end of a sevoflurane-nitrous oxide or desflurane-nitrous oxide anesthetic prolonged the times to awakening and orientation by 40-80% and 25-30%, respectively. In group 2 (compared with groups 1, 3, and 4), the incidences of emesis (22% compared with 47%, 53%, and 47%) and requests for antiemetic rescue medication (19% compared with 42%, 50%, and 47%) within the first 6 h after surgery were significantly lower, and the time to home-readiness was significantly shorter in duration (216 +/- 50 min vs. 249 +/- 49 min, 260 +/- 88 min, and 254 +/- 72 min, respectively). CONCLUSIONS: A subhypnotic intravenous dose of propofol (0.5 mg/kg) administered at the end of outpatient laparoscopic cholecystectomy procedures was more effective in preventing postoperative nausea and vomiting after a sevoflurane-based (compared with a desflurane-based) anesthetic.     

Endocrine stress reaction, hemodynamics and recovery in total intravenous and inhalation anesthesia. Propofol versus isoflurane

This prospective, randomised study compared total intravenous anaesthesia (TIVA) and inhalation anaesthesia with respect to endocrine stress response, haemodynamic reactions, and recovery. METHODS. The investigation included two groups of 20 ASA I-II patients 18-60 years of age scheduled for orthopaedic surgery. For premedication of both groups, 0.1 mg/kg midazolam was injected IM. Patients in the propofol group received TIVA (CPPV, PEEP 5 mbar, air with oxygen FiO2 33%) with propofol (2 mg/kg for induction followed by an infusion of 12-6 mg/kg.h) and fentanyl (0.1 mg before intubation, total dose 0.005 mg/kg before surgery, repetition doses 0.1 mg). For induction of patients in the isoflurane-group, 5 mg/kg thiopentone and 0.1 mg fentanyl was administered. Inhalation anaesthesia was maintained with 1.2-2.4 vol.% isoflurane in nitrous oxide and oxygen at a ratio of 2:1 (CPPV, PEEP 5 mbar). For intubation of both groups, 2 mg vecuronium and 1.5 mg/kg suxamethonium were injected, followed by a total dose of 0.1 mg/kg vecuronium. Blood samples were taken through a central venous line at eight time points from before induction until 60 min after extubation for analysis of adrenaline, noradrenaline (by HPLC/ECD), antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH), and cortisol (by RIA). In addition, systolic arterial pressure (SAP) heart rate (HR), arterial oxygen saturation (SpO2), and recovery from anaesthesia were observed. RESULTS. Group mean values are reported; biometric data from both collectives were comparable (Table 1). Plasma levels of adrenaline (52 vs. 79 pg/ml), noradrenaline 146 vs. 217 pg/ml), and cortisol (82 vs. 165 ng/ml) were significantly lower in the propofol group (Table 2, Figs. 1 and 3). Plasma levels of ADH (4.8 vs. 6.1 pg/ml) and ACTH (20 vs. 28 pg/ml) did not differ between the groups (Table 2, Figs 2 and 3). SAP (128 vs. 131 mmHg) was comparable in both groups, HR (68/min vs. 83/min) was significantly lower in the propofol group, and SpO2 (97.1 vs 97.4%) showed no significant difference (Table 3). Recovery from anaesthesia was slightly faster in the propofol group (following of simple orders 1.9 vs. 2.4 min, orientation with respect to person 2.4 vs. 3.4 min, orientation with respect to time and space 2.8 vs. 3.7 min), but differences failed to reach statistical significance. CONCLUSIONS. When compared with isoflurane inhalation anaesthesia, moderation of the endocrine stress response was significantly improved during and after TIVA with propofol and fentanyl. Slightly shorter recovery times did not lead to an increased stress response. With respect to intra- and postoperative stress reduction, significant attenuation of sympatho-adrenergic reaction comparable SAP and reduced HR, sympatholytic and hypodynamic anaesthesia with propofol and fentanyl seems to be advantageous for patients with cardiovascular and metabolic disorders. For this aim, careful induction and application of individual doses is essential.     

Pharmacokinetics of propofol after a single dose in children aged 1-3 years with minor burns. Comparison of three data analysis approaches

BACKGROUND: No complete pharmacokinetic profile of propofol is yet available in children younger than 3 yr, whereas clinical studies have demonstrated that both induction and maintenance doses of propofol are increased with respect to body weight in this age group compared to older children and adults. This study was therefore undertaken to determine the pharmacokinetics of propofol after administration of a single dose in aged children 1-3 yr requiring anesthesia for dressing change. METHODS: This study was performed in 12 children admitted to the burn unit and in whom burn surface area was less than or equal to 12% of total body surface area. Exclusion criteria were: unstable hemodynamic condition, inappropriate fluid loading, associated pulmonary injury, or burn injury older than 2 days. Propofol (4 mg.kg(-1))plus fentanyl (2.5 microg.kg(-1)) was administered while the children were bathed and the burn area cleaned during which the children breathed spontaneously a mixture of oxygen and nitrous oxide (50:50). Venous blood samples of 300 microl were obtained at 5, 15, 30, 60, 90, and 120 min, and 3, 4, 8, and 12 thereafter injection; an earlier sample was obtained from 8 of 12 children. The blood concentration curves obtained for individual children were analyzed by three different methods: noncompartmental analysis, mixed effects population model, and standard two-stage analysis. RESULTS: Using noncompartmental analysis, total clearance of propofol (+/-SD) was 0.053+/-0.013l.kg(-1).min(-1), volume of distribution at steady state9.5 +/- 3.7l.kg(-1),and residence time 188 +/- 85 min. Propofol pharmacokinetics were best described by a weight-proportional three-compartmental model in both population and two-stage analysis. Estimated and derived pharmacokinetic parameters were similar using these two pharmacokinetic approaches. Results of population versus two-stage analysis are as follow: systemic clearance 0.049 versus 0.048 l.kg(-).min(-1), volume of central compartment 1.03 versus 0.95 l.kg(-1), volume of steady state 8.09 versus 8.17 l.kg(-1). CONCLUSIONS: The volume of the central compartment and the systemic clearance were both greater than all values reported in older children and adults. This is consistent with the increased propofol requirements for both induction and maintenance of anesthesia in children 1-3 yr. (Key words: Anesthesia: pediatric. Pharmacokinetics: propofol.)     

Treatment failure and methadone dose in a public methadone maintenance treatment programme in Geneva

PURPOSE: To determine the effect of an anaesthetic with antioxidant potential, propofol, on red blood cell (RBC) antioxidant enzyme activities and RBC susceptibility to peroxidative challenge. METHODS: Propofol was administered by intravenous bolus (2.5 mg.kg-1) and continuous infusion (36 and 72 ml.hr-1 in nine swine; 216 ml.hr-1 in two swine), to achieve serum concentrations between 5 and 30 micrograms.ml-1 for two hours at each rate. Arterial blood sampling was at 0, 10, 30, 60, and 120 min for each rate of infusion, for measurement of plasma propofol concentration, activities of plasma and RBC superoxide dismutase, glutathione peroxidase, glutathione reductase, RBC catalase, and RBC malondialdehyde (MDA) formation in response to ex vivo oxidative challenge with t-butyl hydrogen peroxide (tBHP; 1.5 mM). Antioxidant mechanisms were determined by in vitro study of MDA formation, GSH depletion, and oxidation of haemoglobin to methaemoglobin in human erythrocytes exposed to propofol 0-75 microM. The antioxidant potential of propofol was compared with that of alpha-tocopherol utilising the reaction with 2,4,6-tripyridyl-s-triazine (TPTZ). RESULTS: Propofol had no effect on plasma or RBC antioxidant enzyme activities. It inhibited RBC MDA production over the range of 0-20 micrograms.ml-1 (y = -18.683x + 85.431; R2 = 0.8174). Effective propofol concentrations for 25% and 50% reductions in MDA levels were 7-12 and 12-20 micrograms.ml-1, respectively. Propofol has a similar effect on human erythrocytes in vitro (R2 = 0.98). CONCLUSION: Propofol antagonises the effects of forced peroxidation of red cells at anaesthetic and sub-anaesthetic concentrations in swine. Its actions include scavenging of oxygen derived free radicals in a tocopherol-like manner.     

The intubating laryngeal mask airway (ILMA): initial experience in Singapore

We have evaluated the intubating laryngeal mask airway (ILMA) for ventilation and for blind tracheal intubation. After induction of anaesthesia with fentanyl 1 microgram kg-1 and propofol 3 ml kg-1, the ILMA was placed successfully on the first attempt in all 100 patients. After administration of atracurium 0.5 mg kg-1, blind tracheal intubation was successful in 97% of patients--50% on the first attempt, 42% on the second and 5% on the third. Success was improved by pulling the metal handle of the ILMA towards the intubator in an "extension" manoeuvre, if intubation was not possible on the first attempt. These findings confirm the effectiveness of the ILMA in an Asian population.     

Upper airway reflexes during a combination of propofol and fentanyl anesthesia

BACKGROUND: The effects of intravenous anesthetics on airway protective reflexes have not been fully explored. The purpose of the present study was to characterize respiratory and laryngeal responses to laryngeal irritation during increasing doses of fentanyl under propofol anesthesia. METHODS: Twenty-two female patients anesthetized with propofol and breathing through the laryngeal mask airway were randomly allocated to three groups: (1) eight patients who received cumulative total doses of 200 microg fentanyl given in the form of two doses of 50 microg and one dose of 100 microg spaced 6 min under mechanical controlled ventilation while end-tidal carbon dioxide tension (PCO2) was maintained at 38 mmHg (fentanyl-controlled ventilation group), (2) eight patients who received cumulative total doses of 200 microg fentanyl while breathing spontaneously while end-tidal PCO2 was allowed to increase spontaneously (fentanyl-spontaneous ventilation group), and (3) six spontaneously breathing patients who were anesthetized with propofol alone (propofol group). The laryngeal mucosa of each patient was stimulated by spraying the cord with distilled water, and the evoked responses were assessed by analyzing the respiratory variables and endoscopic images. RESULTS: Before administration of fentanyl, laryngeal stimulation caused vigorous reflex responses, such as expiration reflex spasmodic panting, cough reflex, and apnea with laryngospasm. Increasing doses of fentanyl reduced the incidences of all these responses, except for apnea with laryngospasm, in a dose-related manner in both the fentanyl-controlled ventilation and the fentanyl-spontaneous ventilation groups. Detailed analysis of endoscopic images revealed several characteristics of laryngeal behavior during the airway reflex responses. CONCLUSION: Incremental doses of fentanyl depress airway reflex responses in a dose-related manner, except for apnea with laryngospasm.     

Perseverance of viruses]

The effects of intravenous administration of variable-dose midazolam (0, 0.05, 0.075, 0.1, 0.3 and 0.5 mg/kg) and ketamine (3 mg/kg) were studied in twenty-four healthy unmedicated cats from time of administration until full recovery. End-points were chosen to determine the optimal dose to allow a short period of restraint without noxious stimuli, a short period of restraint with noxious stimuli and endotracheal intubation. Recovery characteristics, as well as undesirable behaviours observed during recovery, were also recorded. The dose of midazolam to achieve lateral recumbency with head down was found to be 0.016 mg/kg in 50% of the population (ED50) and 0.054 mg/kg in 95% (ED95) of the population. A midazolam dose of 0.286 mg/kg was required to prevent conscious perception of a stimulus to the ulnar nerve in 50% of the population and 0.652 mg/kg in 95% of the population. The ED50 and ED95 of midazolam required to prevent swallowing in response to a laryngoscope placed on the back of the tongue were found to be 0.265 mg/kg and 0.583 mg/kg, respectively. The ED50 doses of 0.265 mg/kg for intubation and 0.286 mg/kg for restraint with noxious stimulation were close to the tested dose of 0.3 mg/kg. At that dose, the lack of responses lasted 3.67 +/- 2.27 min for laryngoscope and 2.50 +/- 2.20 min for ulnar nerve stimulation, with recovery to walking with ataxia taking 41.50 +/- 15.18 min and complete recovery taking 3.6 +/- 1.3 h. The predominant behavioural pattern during recovery was found to be normal, but some cats also exhibited abnormal behavioural patterns. Nine of the twelve cats exhibited an abnormal arousal state, with 4 being restless and 5 being sedated. Seven of the twelve cats exhibited an abnormal behaviour when approached, with three of the cats being more difficult to approach and four of the cats being easier to approach. Eight of the twelve cats exhibited an abnormal behavioural pattern when restrained, with the cats equally divided between more difficult and easier to restrain. Five of the twelve cats vocalized more during the recovery. The ED50 of 0.042 mg/kg to induce chemical restraint without a noxious stimulus is close to the tested dose of 0.05 mg/kg. At that dose, cats remained lateral with head down for 5.49 +/- 4.02 min, took 25.96 +/- 5.77 min to walk with ataxia and 1.7 +/- 0.4 h for complete recovery. The predominant behavioural patterns during recovery were normal, with several cats exhibiting some abnormal patterns. Two cats were sedated, one cat was more difficult to approach, one cat was easier to restrain and three cats were more vocal.     

JC virus detection in the cerebrospinal fluid of AIDS patients with progressive multifocal leucoencephalopathy and monitoring of the antiviral treatment by a PCR method

Data from two published and one new meta-analysis were reviewed to compare the antiemetic efficacy of three different anaesthetic regimens: (i) propofol anaesthesia compared with another anaesthetic (control); (ii) anaesthesia without nitrous oxide compared with the same anaesthetic with nitrous oxide (control); (iii) propofol anaesthesia without nitrous oxide (TIVA) compared with another anaesthetic with nitrous oxide (control). Efficacy (prevention of postoperative nausea and vomiting compared with control) was estimated using odds ratio and number-needed-to-treat methods, and compared within a range of 20-60% control event rates for early efficacy (0-6 h) and 40-80% for late efficacy (0-48 h). Propofol anaesthesia or omitting nitrous oxide had similar effects on vomiting, both early and late. Propofol (but not omitting nitrous oxide) decreased the incidence of nausea. TIVA studies were documented poorly; appropriate comparison with other interventions were not possible. Efficacy of treatments should be compared within a setting-specific range of control event rates. There is insufficient evidence that TIVA with propofol is an anaesthetic technique with a low emetogenic potency.     

Cultured human airway smooth muscle cells stimulated by interleukin-1beta enhance eosinophil survival

Airway smooth muscle may be an important cellular source of proinflammatory mediators and cytokines and may participate directly in airway inflammation. In this study we have examined whether airway smooth muscle cells could contribute to mechanisms of eosinophil accumulation by prolonging their survival. To investigate this possibility, conditioned medium from human airway smooth muscle cells stimulated with interleukin (IL)-1beta was examined on the in vitro survival of highly purified human peripheral blood eosinophils. After 7 d, when cultured in control medium, less than 1 +/- 0.2% of the initial eosinophil population remained viable. In contrast, culture in medium conditioned for 96 h by human airway smooth muscle cells stimulated with IL-1beta (1 pg-100 ng/ml) resulted in a concentration-dependent increase in eosinophil survival. (The concentration that produced 50% of this effect was 0.03 ng/ml IL-1beta.) Maximum eosinophil survival occurred at 1 to 3 ng/ml IL-1beta. This effect was also time-dependent and was readily detected in airway smooth muscle cell-conditioned medium after just 3 h of stimulation with IL-1beta (1 ng/ml). It continued to increase before reaching a plateau around 24 h, with no decrease in activity for up to 120 h of stimulation. Conditioned medium from unstimulated airway smooth muscle cells did not enhance eosinophil survival. The survival-enhancing activity was completely inhibited (the concentration that inhibited 50% [IC50] was 6.9 microg/ml) by a polyclonal goat antihuman antibody to granulocyte-macrophage colony stimulating factor (GM-CSF) (0.3-100 microg/ml), but antibodies (10-100 microg/ml) to IL-3 and IL-5, and a normal goat immunoglobulin G control had no effect on the eosinophil survival-enhancing activity. GM-CSF levels in culture medium from smooth muscle cells were markedly increased by IL-1beta and were maximum at 30 ng/ml (0.037 ng/ml/10(6) cells versus 3.561 ng/ml/10(6) cells, unstimulated versus 30 ng/ml IL-1beta). The IL-1 receptor antagonist inhibited both the production of GM-CSF (IC50 19. 1 ng/ml) and the eosinophil survival-enhancing (IC50 53.7 ng/ml) activity stimulated by IL-1beta. Release of GM-CSF elicited by IL-1beta was inhibited by dexamethasone but not by indomethacin. These data indicate that cultured human airway smooth muscle cells stimulated with IL-1beta support eosinophil survival through production of GM-CSF and thus may contribute to the local control of inflammatory cell accumulation in the airways.     

Rate of cerebrospinal fluid formation, resistance to reabsorption of cerebrospinal fluid, brain tissue water content, and electroencephalogram during desflurane anesthesia in dogs

Propofol decreases intraocular pressure (IOP) and the IOP response to laryngoscopy and intubation, but the mechanisms responsible for this effect have not been reported. The present study examined the effect of propofol on IOP, intraocular fluid formation and outflow facility, and intraocular compliance. Twenty-two white New Zealand rabbits were anesthetized with halothane (0.8%-1.0% inspired concentration) in nitrous oxide (2 L/min) and oxygen (1 L/min). Muscle paralysis was established with pancuronium, and the lungs were mechanically ventilated through a tracheal tube. Twelve rabbits examined under these conditions served as controls. In the treatment group (n = 10), 6 mg/kg propofol followed by 18 mg.kg-1 x h-1 propofol intravenously was added to halothane/nitrous oxide/oxygen anesthesia. In both groups, a series of intraocular infusions was made via a 30-gauge needle in the anterior chamber, and IOP, the rate of aqueous humor formation (Fa), and trabecular outflow facility (Ctr) were determined using conventional analysis. These same measures, as well as intraocular compliance, were determined using a new method of analysis adapted from the manometric technique for determining cerebrospinal fluid dynamics. IOP was 11.3 +/- 1.8 mm Hg (mean +/- SD) in halothane-anesthetized controls and decreased to 9.4 +/- 2.2 mm Hg when propofol was added to halothane anesthesia (P < 0.05). By conventional analysis, Fa was 2.82 +/- 0.94 microL/min and Ctr was 0.121 +/- 0.044 microL.min-1 x mm Hg-1 in controls. After addition of propofol, Fa decreased by 24% to 2.15 +/- 0.62 microL/min (P < 0.05) and Ctr decreased by 18% to 0.099 +/- 0.034 microL.min-1 x mm Hg-1 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of fentanyl on sevoflurane requirements for somatic and sympathetic responses to surgical incision

BACKGROUND: Fentanyl produces a reduction in the minimum alveolar concentration (MAC) of isoflurane and desflurane needed to blockade adrenergic response (BAR) to surgical incision in 50% of patients (MAC-BAR). MAC-BAR of sevoflurane and the reduction in MAC-BAR of sevoflurane by fentanyl have not been described previously. The purpose of this study was to determine the MAC and MAC-BAR reduction of sevoflurane by fentanyl with and without nitrous oxide (N2O). METHODS: Two hundred twenty-six patients were randomly assigned to one of two groups: a sevoflurane group and a sevoflurane/N2O group. Patients in each group were randomly assigned to one of five different fentanyl concentration subgroups. Patients were anesthetized with sevoflurane and fentanyl in the sevoflurane group and with sevoflurane, fentanyl, and N2O (66 vol%) in the sevoflurane/N2O group. Somatic and sympathetic responses to surgical incision were observed for MAC and MAC-BAR assessment at predetermined concentrations of sevoflurane. RESULTS: Fentanyl produced an initial steep reduction in the MAC and MAC-BAR of sevoflurane, with 3 ng/ml resulting in a 61% reduction in MAC and an 83% reduction in MAC-BAR. A ceiling effect was observed for MAC and MAC-BAR, with 6 ng/ml fentanyl providing only an additional 13% and 9% reduction in MAC and MAC-BAR, respectively. In the presence of 66 vol% N2O, MAC and MAC-BAR of sevoflurane were reduced with increasing concentrations of fentanyL A ceiling effect was not observed for reduction in MAC and MAC-BAR in the presence of N2O. CONCLUSIONS: MAC and MAC-BAR decreased similarly with increasing concentrations of fentanyl in plasma, showing an initial steep reduction followed by a ceiling effect. In the presence of N2O, MAC and MAC-BAR decreased similarly but did not exhibit a ceiling effect.