ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

BackgroundSuccinylcholine‐induced masseter muscle rigidity (MMR) is a potentially life‐threatening complication of anesthesia and is closely correlated with the heterogeneous disorder malignant hyperthermia (MH) susceptibility. MMR also is identified with a variety of neuromuscular disorders, including the myotonias, that are associated with abnormal in vitro contracture test (IVCT) results. Recently, mutations in the adult skeletal muscle sodium channel alpha‐subunit gene (SCN4A) have been shown to cause generalized nondystrophic myotonias, some of which are associated with mild nonspecific symptoms. The purpose of the current investigation was to begin to evaluate the molecular genetic relationship between known mutations in the SCN4A gene, MMR, and the results of the IVCT used to diagnose MH‐susceptibility.MethodsA single extended pedigree of 16 individuals was ascertained through a proband who experienced MMR and whole‐body rigidity after succinylcholine administration. Subsequently, four individuals were shown to have a mild form of myotonia on clinical and laboratory examination. IVCT was carried out according to standardized protocols. Mutations in the SCN4A gene were sought in exons 22 and 24 using single‐strand conformational analyses. Variability in the SCN4A gene sequence was confirmed by direct DNA sequence analyses.ResultsFour individuals with myotonia were shown to carry a guanine‐to‐cytosine mutation at nucleotide position 3917 of the reported SCN4A sequence. This DNA mutation was coinherited with MMR and an abnormal IVCT result in this family. Previous studies have demonstrated that the glycine1306‐to‐alanine substitution is associated with a mild clinical syndrome referred to as myotonia fluctuans.ConclusionsThe current report provides direct evidence that succinylcholine‐induced MMR, whole‐body rigidity, and an abnormal IVCT result are associated with a mutation in the SCN4A gene.

ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

BackgroundRocuronium is a new nondepolarizing muscle relaxant with a rapid onset and intermediate duration of action. Although the pharmacokinetics of rocuronium have been determined in adults and the elderly, similar data are lacking in children. Accordingly, rocuronium's pharmacokinetics were determined in children aged 4–11 yr.MethodsRocuronium (600 micro gram/kg) was administered to 20 children aged 4–11 yr anesthetized with nitrous oxide and less or equal to 1% halothane, and four plasma samples were obtained over 4 h to determine rocuronium concentrations. The pharmacokinetics of rocuronium were determined using two sparse‐sampling population approaches, mixed‐ effects modeling, and naive pooled data analysis.ResultsWith mixed‐effects modeling, weight‐normalized plasma clearance varied with weight (P < 0.01), being 79.4 ml *symbol* min sup ‐1 + 3.13 ml *symbol* kg sup ‐1 *symbol* min sup ‐1. Neither weight‐ normalized distributional clearance (2.67 ml *symbol* kg sup ‐1 *symbol* min sup ‐1), weight‐normalized central compartment volume (106 ml/kg), nor weight‐normalized volume of distribution at steady‐state (224 ml/kg) varied with weight, height, or age. Similar results were obtained with the naive pooled data approach.ConclusionsMaturational changes were observed in rocuronium's weight‐normalized clearance but not in its weight‐normalized distributional clearance or volume of distribution. Assuming that the duration of rocuronium's neuromuscular effects is influenced by its pharmacokinetics, repeated administration or continuous infusion of rocuronium should result in larger dose requirements and more rapid recovery in younger, compared to older, children.

ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

BackgroundPatients with asthma who require general anesthesia and tracheal intubation are at increased risk for the development of bronchospasm during induction. The incidence of wheezing during induction with different intravenously administered agents is unknown. A randomized, double‐blinded prospective study was undertaken to evaluate the incidence of wheezing in asymptomatic asthmatic and nonasthmatic patients receiving three commonly used intravenous anesthetic agents for induction of anesthesia.MethodsFifty‐nine asymptomatic asthmatic and 96 nonasthmatic patients of ASA physical status 1 and 2 were studied. All patients received 1.5 micro gram/kg fentanyl, oxygen, followed by either 5 mg/kg thiopental or thiamylal, 1.75 mg/kg methohexital or 2.5 mg/kg propofol, 1.5 mg/kg succinylcholine, tracheal intubation, and inhalational anesthesia. Wheezing was assessed by an independent blinded observer auscultating the lungs at 2 and 5 min postintubation. Data were analyzed by Pearson's chi‐squared, Fisher's exact test, and multiple logistic regression with significance set at P < 0.05.ResultsBoth asthmatic and nonasthmatic patients who received a thiobarbiturate for induction had a greater incidence of wheezing than did patients receiving propofol. In asthmatic patients, 45% (23, 67) (mean and 95% confidence interval) who received a thiobarbiturate, 26% (8, 44) who received an oxybarbiturate, and none (0, 17) who received propofol wheezed after intubation. In nonasthmatic patients, 16% (3, 28) who received thiobarbiturate and 3% (0, 9) who received propofol wheezed.ConclusionsThis study suggests that propofol should be considered for induction of anesthesia in patients, particularly those with asthma, who require timely intubation.

ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

BackgroundDexmedetomidine is a new potent and highly selective alpha2‐adrenoceptor agonist with sedative‐hypnotic and anesthetic sparing properties. Because of its sympathoinhibitory activity, it may prove useful in balancing the cardiostimulalory effects and attenuating the adverse central nervous system effects of ketamine.MethodsA double‐blind, randomized and comparative parallel‐group study design was employed in 40 volunteers with ASA physical status 1 who were scheduled for elective superficial surgery under ketamine anesthesia. Dexmedetomidine (2.5 micro gram/kg, n = 20) or midazolam (0.07 mg/kg, n = 20) was administered intramuscularly 45 min before induction of anesthesia. Anesthesia was induced with 2 mg/kg ketamine intravenously, and muscle relaxation was achieved with vecuronium. After tracheal intubation, anesthesia was maintained with nitrous oxide/oxygen (2:1) and additional 1 mg/kg intravenous ketamine boluses according t clinical and cardiovascular criteria. Hypotension and bradycardia were treated by increasing the intravenous infusion rate of crystalloids and intravenous atropine, respectively. Sedative and anxiolytic properties, intra‐ and postoperative drug requirements, psychomotor and cognitive impairments, and cardiovascular effects were compared between the two groups.ResultsDexmedetomidine and midazolam proved to have equal sedative and anxiolytic effects after intramuscular administration, but dexmedetomidine induced significantly less preoperative psychomotor impairment and less anterograde amnesia than did midazolam. Compared to midazolam, dexmedetomidine decreased the need for intraoperative ketamine and was more effective in reducing ketamine‐induced adverse central nervous system effects. Dexmedetomidine also was superior to midazolam in attenuating the hemodynamic responses to intubation and the cardiostimulatory effects of ketamine in general, but it increased the incidence of intra and postoperative bradycardia.ConclusionsThese results suggest that premeditation with 2.5 micro gram/kg dexmedetomidine is effective in attenuating the cardiostimulatory and postanesthetic delirium effects of ketamine. However, because of its propensity to cause bradycardia, routine use of an anticholinergic drug should be considered.

ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

BackgroundClonidine, which is known to have analgesic and sedative properties, has recently been shown to be an effective preanesthetic medication in children. The drug may cause side effects, including bradycardia and hypotension. This study was conducted to evaluate the ability of intravenous atropine to increase the heart rate (HR) in awake children receiving clonidine preanesthetic medication.MethodsWe studied 96 otherwise healthy children, 8–13 yr old, undergoing minor surgery. They received, at random, oral clonidine 2 or 4 micro gram *symbol* kg sup ‐1 or placebo 105 min before scheduled induction of anesthesia. Part I (n = 48, 16 per group): When hemodynamic parameters after insertion of a venous catheter had been confirmed to be stable, atropine was administered in incremental doses of 2.5, 2.5, and 5 micro gram *symbol* kg sup ‐1 every 2 min. The HR and blond pressure were recorded at 1‐min intervals. Part II (n = 48, 16 per group): After the recording of baseline hemodynamic values, successive doses of atropine (5 micro gram *symbol* kg sup ‐1 every 2 min, to 40 micro gram *symbol* kg sup ‐1), were administered until HR increased by 20 beats *symbol* min sup ‐1. The HR and blood pressure were recorded at 1‐min intervals.ResultsPart I: The increases in HR in response to a cumulative dose of atropine 10 micro gram *symbol* kg sup ‐1 were 33 plus/minus 3%, 16 plus/minus 3%, and 8 plus/minus 2% (mean plus/minus SEM) in children receiving placebo, clonidine 2 micro gram *symbol* kg sup ‐1, and clonidine 4 micro gram *symbol* kg sup ‐1, respectively (P < 0.05). Part II: The HR in the control group increased by more than 20 beats *symbol* min sup ‐1 in response to atropine 20 micro gram *symbol* kg sup ‐1 or less. In two patients in the clonidine 4 micro gram *symbol* kg sup ‐1 group, HR did not increase by 20 beats *symbol* min sup ‐1 even after 40 micro gram *symbol* kg sup ‐1 of atropine.ConclusionsOral clonidine premedication (4 micro gram *symbol* kg sup ‐1) blunted the increase in HR after intravenous atropine in awake children, although clonidine 2 micro gram *symbol* kg sup ‐1 did not. A larger dose of atropine was required to increase the HR by 20 beats *symbol* min sup ‐1 in children receiving the premedicant in the larger dose.

ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

BackgroundAtracurium consists of a mixture of ten stereoisomers. One of these isomers, 51W89, is a potent intermediate‐acting nondepolarizing neuromuscular blocking agent. Its ED95is 0.05 mg *symbol* kg1in patients receiving nitrous oxide/opioid anesthesia. In preclinical trials, 51W89 did not show evidence of histamine release in cats at doses up to 80 times the human ED95. This study was undertaken to determine the cardiovascular effects and histamine‐ releasing properties of 51W89 in patients undergoing elective surgical procedures.MethodsSixty patients, ASA physical status 1 or 2, anesthetized with nitrous oxide/fentanyl/thiopental were studied. Patients received either 2 times the ED95of atracurium or 51W89 or 4 or 8 times the ED95of 51W89 as a rapid intravenous bolus under stable anesthesia, before surgical stimulation. Blood pressure and heart rate were measured by oscillometry and the electrocardiogram in patients receiving 2 times the ED95of 51W89 or atracurium and by an intraarterial catheter and a tachograph triggered by the arterial pulse waveform in patients receiving 4 or 8 times the ED95of 51W89. Maximal blood pressure and heart rate changes during the 5 min after administration of the muscle relaxant were recorded. Venous blood samples were obtained before the administration of relaxant and at 2 and 5 min after the administration of relaxant for determination of plasma histamine concentrations by radioenzymatic assay.ResultsMaximal blood pressure and heart rate changes in all groups of patients receiving 51W89 were small and similar to those observed in patients receiving 2 times the ED95of atracurium. The mean maximum percent changes (plus/minus SE) in heart rate and mean arterial pressure were ‐0.6 plus/minus 1.5 and 0.4 plus/minus 2.5, respectively, in the group receiving 2 times the ED95atracurium; ‐ 1.3 plus/minus 3.3 and 2.3 plus/minus 4.4, respectively, in the group receiving 2 times the ED9551W89; ‐2.6 plus/minus 1.0 and 2.6 plus/minus 1.5, respectively, in the group receiving 4 times the ED9551W89; and 2.4 plus/minus 1.5 and 1.0 plus/minus 1.3, respectively, in the group receiving 8 times the ED9551W89. No patient developed a decrease in blood pressure greater or equal to 20% or an increase in heart rate greater or equal to 20% that was attributable to muscle relaxant administration. There was no dose‐related change in plasma histamine concentration associated with the administration of 51W89. One patient in the study developed transient facial flushing after the administration of atracurium.Conclusions51W89 is a benzylisoquinolinium‐type, nondepolarizing muscle relaxant that does not affect plasma histamine concentrations. No cutaneous flushing or clinically important cardiovascular effects were noted after rapid injection of doses up to and including 8 times its ED sub 95 (0.4 mg *symbol* kg1) in healthy patients undergoing elective surgical procedures.

ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

BackgroundAtracurium is a mixture of ten stereoisomers. 51W89, one of these isomers, is a potent nondepolarizing intermediate‐duration neuromuscular blocking agent. Preclinical studies have shown 51W89 to be significantly more potent than atracurium but with a similar neuromuscular blocking profile. This study was undertaken to establish the neuromuscular blocking potency and pharmacodynamics of 51W89 in patients undergoing elective surgical procedures.MethodsNinety‐nine ASA physical status 1 or 2 patients undergoing elective surgical procedures under nitrous oxide/opioid/barbiturate anesthesia were studied. The neuromuscular blocking effect of 51W89 was assessed after administration of bolus doses from 0.015 to 0.4 mg/kg, as well as during and after continuous infusions from 11 to 249 min in length.ResultsThe calculated ED95for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.048 mg/kg. At 0.10 mg/kg, maximum block developed within 5.2 plus/minus 0.3 min, and recovery to 95% twitch height occurred 64.4 plus/minus 3.9 min after injection. At 0.4 mg/kg, onset was 1.9 plus/minus 0.1 min, and 95% recovery developed within 121.0 plus/minus 5.9 min. Comparative recovery indexes from 5% to 95% or from 25% to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.4 mg/kg (means ranged from 29.6 to 32.3 min and from 12.6 to 14.3 min, respectively). The average infusion rate necessary to maintain approximately 95% twitch suppression was 1.35 micro gram/kg/min. Recovery indexes from infusions were 5–95% 33.2 plus/minus 1.8 min and 25–75% 15.0 plus/minus 0.6 min, not differing significantly from recovery indexes from single bolus doses. Twenty‐ five patients received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at twitch height recovery of between 6% and 21%. Antagonism to 95% control twitch height developed within 6.8 plus/minus 0.3 min, and the neostigmine‐accelerated 25–75% recovery index was 2.8 plus/minus 0.2 min.Conclusions51W89 is a potent nondepolarizing neuromuscular blocking agent that shows noncumulative intermediate‐duration neuromuscular blocking pharmacodynamics.

ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

BackgroundIontophoresis is a method of transdermal administration of ionizable drugs in which the electrically charged components are propelled through the skin by an external electric field. This study was designed to determine whether iontophoresis could be used to deliver clinically significant doses of fentanyl in humans and whether there is a charge‐dose relation in the delivery of fentanyl by iontophoresis.MethodsFive adult volunteers were tested three times on separate days, once receiving passive treatment of 0.0 mA for 2 h (0 mA *symbol* min), iontophoresis 1.0 mA for 2 h (120 mA *symbol* min), and iontophoresis 2.0 mA for 2 h (240 mA *symbol* min) in an open, randomized, crossover design. Respiratory rate, heart rate, blood pressure, and hemoglobin oxygen saturation were monitored throughout the study. Plasma fentanyl concentrations were measured several times before, during, and after iontophoresis. Plasma fentanyl concentrations were measured by radioimmunoassay.ResultsNo fentanyl was detected after passive (0.0‐mA) fentanyl delivery. The following results were obtained for the 1.0 and 2.0‐mA deliveries, respectively. Mean times to detectable concentrations of plasma fentanyl were 33 and 19 min; mean times to maximum concentration were 122 and 199 min; maximum concentrations were 0.76 and 1.59 ng/ml (P = 0.010); mean areas under the curve of the plasma fentanyl concentration versus time relation were 233 and 474 ng *symbol* ml sup ‐ 1 *symbol* min (P = 0.003); and mean elimination half‐lives were 354 and 413 min (P = 0.326). Only minor adverse side effects related to iontophoresis occurred. However, typical opioid‐related effects occurred frequently in the 1.0‐ and 2.0‐mA administration groups.ConclusionsClinically significant doses of fentanyl can be administered by iontophoresis for delivery periods of 2 h. A charge‐ dose relation exists after administration with currents of 1.0 and 2.0 mA. Future research into the iontophoresis of fentanyl as a method of potent opioid administration is indicated.

ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

BackgroundIt should be possible to avoid variations in plasma glucose concentration during anesthesia by adjusting glucose infusion rate to whole‐body glucose uptake. To study this hypothesis, we measured glucose utilization and production, before and during halothane anesthesia.MethodsAfter an overnight fast, six adolescents between 12 and 17 yr of age were infused with tracer doses of [6,6‐sup 2 H2]glucose for 2 h before undergoing anesthesia, and the infusion was continued after induction, until the beginning of surgery. Plasma glucose concentration was monitored throughout, and free fatty acids, lactate, insulin, and glucagon concentrations were measured before and during anesthesia.ResultsDespite the use of a glucose‐free maintenance solution, plasma glucose concentration increased slightly but significantly 5 min after induction (5.3 plus/minus 0.4 vs. 4.5 plus/minus 0.4 mmol *symbol* 1 sup ‐1, P < 0.05). This early increase corresponded to a significant increase in endogenous glucose production over basal conditions (4.1 plus/minus 0.4 vs. 3.6 plus/minus 0.2 mg *symbol* kg sup ‐1 *symbol* min sup ‐1, P < 0.05), with no concomitant change in peripheral glucose utilization. Fifteen minutes after induction, both glucose utilization and production rates decreased steadily and were 20% less than basal values by 35 min after induction (2.9 plus/minus 0.3 vs. 3.6 plus/minus 0.2 mg *symbol* kg sup ‐1 *symbol* min sup ‐1, P < 0.05). Similarly, glucose metabolic clearance rate decreased by 25% after 35 min. Despite the increase in blood glucose concentration, anesthesia resulted in a significant decrease in plasma insulin concentration.ConclusionsThese data suggest that halothane anesthesia per se affects glucose metabolism. The decrease in peripheral glucose utilization and metabolic clearance rates and the blunted insulin release question the relevance of glucose infusion in these clinical settings.

ISSN:0003-3022    

出版商:OVID    

年代:1995

数据来源: OVID