Stability of atracurium administered by infusion.
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Atracurium↗
Biomedical subjects
R D Miller
Publications and source records attributed to R D Miller.
Clinical pharmacology of edrophonium in infants and children.
The dose-response relationship, onset, duration of action, atropine requirement, and pharmacokinetic variables of edrophonium were determined in infants and children during N2O-halothane anesthesia. The technique of steady state infusion of d-tubocurarine anesthesia. The technique of steady state infusion of d-tubocurarine (dTc) was used to determine the ED50 for edrophonium (i.e., the dose producing 50% antagonism of 90% neuromuscular depression) in 4 infants (145 micrograms/kg) and 12 children (233 microgram/kg). The reported values for ED50 for edrophonium (obtained under similar anesthetic conditions) is 128 micrograms/kg for adults. These three dose-response curves do not differ statistically; however, there was greater variability among infants and children than adults. Time to peak antagonism was similar for all three age groups. Duration of antagonism was determined in six infants and six children and did not differ from the reported value for adults. The optimal dose and time of administration of atropine were established by administering edrophonium (1 mg/kg) and atropine (10-20 micrograms/kg) to 24 infants and children. The smallest changes in heart rate and systolic blood pressure occurred when atropine (10 micrograms/kg) was given 30 s before edrophonium. The pharmacokinetics of edrophonium (1 mg/kg) were studied in four infants and four children and were compared with published values for adults: distribution and elimination half-lives and distribution volumes were similar for the three groups. Total clearance (ml.kg-1.min-1) was greatest for infants (17.8 +/- 1.2) compared with children (14.2 +/- 7.3) and adults (8.3 +/- 2.9). The authors conclude that the dose of edrophonium required toantagonize dTc-induced neuromuscular blockade is similar or possibly greater for infants and children than for adults.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Clinical pharmacology of vecuronium and atracurium.
Vecuronium and atracurium provide addition flexibility to the clinician using neuromuscular blocking drugs. The shorter duration of action, lack of significant cardiovascular effects, and the lack of dependence on the kidney for elimination provide clinical advantages over, or alternatives to, currently available nondepolarizing neuromuscular blocking drugs.
Acid-Base Equilibrium↗
Metabolites of neostigmine and pyridostigmine do not contribute to antagonism of neuromuscular blockade in the dog.
The authors sought to determine whether the metabolites of neostigmine and pyridostigmine contribute to antagonism of neuromuscular blockade. Accordingly, the dose-response relationship, onset and duration of action (n = 60), and pharmacokinetics (n = 22) of neostigmine, pyridostigmine, their metabolites 3-hydroxyphenyltrimethylammonium (PTMA) and 3-hydroxy-N-methylpyridinium (MP), and edrophonium were determined in dogs anesthetized with sodium pentobarbital. The force of contraction of the anterior tibialis muscle was maintained at constant 90% depression by infusing pancuronium. Then, a single iv bolus dose of one of the drugs under study was injected while the pancuronium infusion was continued. Venous blood, urine, and bile were sampled for four hours. Concentrations were determined by liquid chromatographic techniques; a three-compartment pharmacokinetic model was fitted to the serum concentration data. The doses producing 50% antagonism were 6.5, 52, 69, and 40 micrograms/kg for neostigmine, pyridostigmine, edrophonium, and PTMA, respectively. MP was inactive as an antagonist. By comparing approximately equipotent doses, time to peak antagonism (onset) and until 30% of peak antagonism remained (duration) were shorter for both edrophonium and PTMA than for neostigmine and pyridostigmine. Slow distribution and elimination half-lives, volume of distribution at steady state (VDss), and total plasma clearance (Cl) were similar for the drugs except for a smaller Vdss and lower Cl for MP. More than 60% of the dose of each drug was recovered unchanged from urine; less than 1% was recovered from bile. Less than 10% of the dose of neostigmine was recovered as PTMA.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The pharmacokinetics and pharmacodynamics of atracurium in patients with and without renal failure.
To determine the influence of renal function on the pharmacology of atracurium, 10 patients with normal renal function and 10 with renal failure (scheduled for cadaver kidney transplant) were anesthetized with nitrous oxide and halothane. Atracurium besylate, 0.5 mg . kg-1, was given as an iv bolus and plasma samples were collected over a 4-h period. These samples were assayed for atracurium (all patients) and laudanosine, one of the principal metabolites (eight of the normal group), using an ion-exchange liquid chromatographic assay. The plasma concentrations of atracurium for each patient were fitted to a two-compartment pharmacokinetic model. The onset time, duration of action, and recovery time of atracurium neuromuscular blockade were measured. There were no differences found in the pharmacokinetics or pharmaco-dynamics of atracurium between patients with normal renal function and those with renal failure. There were measurable levels of laudanosine following atracurium administration with peak levels of 199 +/- 31 ng . ml-1 at 2 min. The authors conclude that the pharmacokinetics and pharmacodynamics of atracurium are not altered by renal failure.
Anesthesia, General↗
The Newcastle Endogenous Depression Diagnostic Index: validity and reliability.
The newcastle Endogenous Depression Diagnostic Index of Carney et al. was studied for reliability and validity. Good inter-rater reliability was obtained for diagnostic category and for item scores in 36 patients. The scale showed construct validity with reference to the Hamilton and Montgomery-Asberg rating scales. Concurrent validity was shown relative to other diagnostic scales of endogenous depression. Predictive validity was demonstrated in that endogenous and nonendogenous depressive responded differently to isocarboxazid. The continued use of 5 as the point of separation between endogenous and nonendogenous depression is questionable.
Depressive Disorder↗
Different effects of RAD genes of Saccharomyces cerevisiae on incisions of interstrand crosslinks and monoadducts in DNA induced by psoralen plus near UV light treatment.
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DNA, Fungal↗
Outpatient commitment: treatment in the least restrictive environment?
Despite the growing emphasis on treatment in the least restrictive environment, states rarely use commitment to outpatient treatment as an alternative to involuntary hospitalization. The authors studied the effects of changes in North Carolina commitment laws that were made in 1979 and designed to facilitate the appropriate use of outpatient commitment. The changes resulted in some increase in the appropriate use of outpatient commitment; nevertheless, clinicians who work at hospitals and community treatment facilities continue to doubt its efficacy. The authors discuss possible reasons for the clinicians' reluctance to use outpatient commitment and attitudinal shifts needed on the part of the general public, professionals, and the judiciary if outpatient commitment is to become a viable alternative.
Ambulatory Care↗
Public mental hospital work: pros and cons for psychiatrists.
The extensive literature concerning public mental hospitals has largely been written from the perspective of administrators and systems analysts; most of the reports emphasize the frustrations and problems of working in public mental hospitals and the continued exodus of psychiatrists from these facilities. The author addresses the pros and cons of such a career choice from the viewpoint of one who has been an "Indian" rather than a "chief" for a decade. He suggests that the current financial situation in both private practice and academia makes work in public mental hospitals increasingly attractive.
Career Choice↗
Hypocarbia and spontaneous recovery from vecuronium neuromuscular blockade in anesthetized patients.
The effect of hypocarbia on the recovery from the neuromuscular blockade produced by vecuronium was studied in 20 anesthetized patients. Vecuronium was administered until twitch tension was reduced to between 0-15% of control. Neuromuscular function was then allowed to spontaneously recover during continued normocarbia (end-tidal PCO2 5.5 kPa [41 mm Hg]) in half the patients, and in the other half of the patients hyperventilation producing hypocarbia (mean end-tidal PCO2 of 3.1 +/- 0.4 kPa SD [23 +/- 3 mm Hg] at the completion of twitch force recovery) was initiated at the beginning of spontaneous recovery from neuromuscular blockade. The mean vecuronium recovery index (time for spontaneous recovery from 25-75% of control twitch tension) was slightly but not significantly shorter in the hyperventilated patients (8.4 +/- 1.8 min SD) than in the normally ventilated patients (10.4 +/- 3.4 min SD). We conclude the vecuronium recovery index in anesthetized patients is not significantly changed by hyperventilation with hypocarbia when induced at the beginning of recovery from neuromuscular blockade.
Adult↗
Depressed mononuclear cell phagocytic activity associated with menstruation.
The peak of the normal distribution curve for pelvic inflammatory disease occurs near the onset of menses. This study was undertaken to determine if there were changes in the cell-mediated immunity of normal menstruating women which could explain the increase in inflammatory disease. The cellular immune response of 8 normal women, measured by number of T- and B-cells and response of mononuclear cells to stimulation with mitogen, was not dependent on the menstrual cycle. However, there was a significant decrease in phagocytic activity of mononuclear cells early in the cycle. The depressed phagocytic activity was not altered by treating the subjects with ibuprofen.
Female↗
The treating psychiatrist as forensic evaluator.
Much has been made in the literature of the importance of "objective" or "impartial" expert psychiatric testimony in forensic psychiatric cases; one result of this emphasis is a strong feeling that a treating physician cannot present unbiased testimony in court on issues such as competency to stand trial and especially criminal responsibility. Many states have explicit regulations designed to ensure that expert psychiatric witnesses who testify in criminal cases are not contaminated by past (or even the potential of future) treatment relationships with defendants. The author argues that such policies often prevent mentally ill defendants from receiving treatment from psychiatrists with the most experience in working with forensic psychiatric patients; and that the opportunity to treat as well as to evaluate such patients might well attract more treating psychiatrists to the forensic science field.
Expert Testimony↗
Transposable element IS50 improves growth rate of E. coli cells without transposition.
Insertion sequence IS50R, which encodes the transposase and an inhibitor of transposition of the kanamycin-resistance transposon Tn5, increases the growth rate of E. coli K12 cells relative to that of their otherwise isogenic counterparts during competition in continuous culture. Most clones isolated from chemostats in which selection had occurred retain their original number of copies of IS50R at their original genomic locations, implying that the increased growth rate is not mediated by transposition. The selective advantage due to a single IS50R element averages about 5% per hour. When the number of copies of IS50R is small, the growth-rate advantage is approximately proportional to the number of copies of IS50R. These results imply that IS50R has effects on cells that are independent of both position and transposition and may be important in the initial selection leading to the appearance of such elements in bacterial populations.
Chromosomes, Bacterial↗
Pharmacokinetics and pharmacodynamics of vecuronium (ORG NC45) and pancuronium in anesthetized humans.
The pharmacokinetics and pharmacodynamics of vecuronium (25-50 micrograms/kg) and pancuronium (25-50 micrograms/kg) were determined in nine ASA class I or II patients anesthetized with nitrous oxide and halothane. Force of thumb adduction in response to supramaximal stimulation of the ulnar nerve was quantified and recorded. Serum concentrations of the muscle relaxants were determined for eight hours after their administration using a mass spectrometry assay. Data were analyzed by nonlinear regression and fit to a three-compartment pharmacokinetic model and a four-compartment pharmacodynamic model. Vecuronium had a more rapid clearance (5.2 +/- 0.7 ml X kg-1 X min-1; mean +/- SD) and a shorter elimination half-life (71 +/- 20 min) as compared with pancuronium (1.8 +/- 0.4 ml X kg-1 X min-1; 140 +/- 25 min). No other pharmacokinetic differences were found between the drugs. Pharmacodynamic analysis showed that the plasma concentration at steady state which produced a 50% neuromuscular blockade (Cpss 50) was similar for vecuronium and pancuronium. The authors conclude that the drugs are equivalent in their onset and potency; however, the more rapid clearance and shorter elimination half-life for vecuronium provides a kinetic basis for its shorter duration of neuromuscular blockade as compared with pancuronium.
Adult↗
The cardiovascular effects of vecuronium (ORG NC45) and pancuronium in patients undergoing coronary artery bypass grafting.
Vecuronium is a new nondepolarizing muscle relaxant which has been shown to cause no significant cardiovascular effects. Utilizing invasive monitoring in patients undergoing coronary artery bypass grafting, the authors compared the cardiovascular effects of vecuronium (0.28 mg/kg) in seven anesthetized patients with those of pancuronium (0.1 mg/kg) in five anesthetized patients. This dose of pancuronium represents three times its ED90 (dose producing a 90% depression of evoked twitch tension), while the vecuronium dose represents twelve times its ED90. This relatively large dose of vecuronium was chosen deliberately in an attempt to manifest any possible cardiovascular effects. Following administration of vecuronium, cardiac output increased 9% and systemic vascular resistance decreased 12%, while pancuronium produced a significantly greater 17% increase in cardiac output without change in systemic vascular resistance. Heart rate and systemic mean arterial pressure did not change following vecuronium, while increasing 22% and 24%, respectively, following pancuronium. The authors conclude that large doses of vecuronium have minimal cardiovascular effects and thus offer an advantage over pancuronium in patients anesthetized for coronary artery surgery.
Adrenergic beta-Antagonists↗
Acquired immunodeficiency syndrome (AIDS) and blood products.
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Acquired Immunodeficiency Syndrome↗
Neuromuscular effects of vecuronium (ORG NC45) in infants and children during N2O, halothane anesthesia.
The authors determined the neuromuscular effects of vecuronium (ORG NC45, Norcuron) during anesthesia with nitrous oxide and 0.9 MAC halothane. To determine potency, they administered vecuronium (15, 20, or 25 micrograms/kg) to 18 infants (less than 1 year old) and 18 children (1-8 years old). They then compared these dose-response relationships with values obtained for adults (greater than 18 years old) under comparable anesthetic conditions. The ED50S (dose producing 50% depression of adductor pollicis twitch tension) of 16.5, 19.0, and 15.0 micrograms/kg for infants, children, and adults, respectively, did not differ significantly. To determine the time course of neuromuscular blockade, the authors administered vecuronium, 70 micrograms/kg, to six infants, six children, and six adults. Onset time (time to maximal effect) was shortest for infants (1.5 +/- 0.6 min, mean +/- SD) compared with that for children (2.4 +/- 1.4 min) and adults (2.9 +/- 0.2 min). Duration (time from injection to 90% recovery) was longest for infants (73 +/- 27 min) compared with that for children (35 +/- 6 min) and adults (53 +/- 21 min). The authors conclude that vecuronium can be used in infants and children in doses similar to those recommended for adults. The time interval for supplemental doses will be longest in infants and shortest in children.
Adolescent↗