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Biomedical subjects

D M Fisher

Publications and source records attributed to D M Fisher.

At least 109 records · Page 6Linked to original sources
PubMed1987

Effects of fentanyl on vasopressin secretion in human subjects.

To test the influence of an opioid on vasopressin (AVP) secretion, plasma AVP concentration was measured in five semirecumbent unmedicated volunteers before and during two continuous i.v. infusions of fentanyl. Infusion rates were adjusted to produce steady-state plasma fentanyl concentrations of 2.0 +/- 0.4 and 4.1 +/- 0.6 ng/ml; mild to moderate hypercarbia was induced during the control and infusion periods. Fentanyl increased plasma AVP concentration in a dose-dependent manner to 559 +/- 215 and 929 +/- 199% of the basal level of 1.9 +/- 0.7 pg/ml. Neither mild hypercarbia (PCO2 = 50 +/- 1 mm Hg) in the absence of fentanyl nor moderate hypercarbia (PCO2 = 66 +/- 3 mm Hg) in the presence of fentanyl changed plasma AVP concentration. Neither fentanyl nor hypercarbia, nor the combination of the two, altered plasma renin activity.

Adult↗
PubMed1986

A pharmacokinetic explanation for increasing recovery time following larger or repeated doses of nondepolarizing muscle relaxants.

The authors used pharmacokinetic and pharmacodynamic modeling to explain the time course of neuromuscular blockade following single or multiple doses of three nondepolarizing muscle relaxants. Published and unpublished pharmacokinetic and pharmacodynamic data for 13 normal subjects were used to simulate the duration of neuromuscular blockade (time from administration of the muscle relaxant to 25% recovery of control twitch tension) following six successive doses of atracurium (150-400 micrograms/kg initially, followed by 100 micrograms/kg), vecuronium, or pancuronium (30-80 micrograms/kg initially, followed by 20 micrograms/kg). With atracurium, duration of action was similar for the second and sixth doses, regardless of the initial dose. With vecuronium (initial doses of 30-80 micrograms/kg) and pancuronium (initial doses of 30-60 micrograms/kg), duration of action was longer after the sixth dose than after the second; with larger initial doses of pancuronium (70 and 80 micrograms/kg), duration of action was similar following the second and sixth doses. The authors also determined two recovery times (time for twitch tension to recover from 5-25% and from 25-75% of control value) for varying single doses of atracurium, vecuronium, or pancuronium. When the dose of atracurium was increased from 200 to 400 micrograms/kg, neither recovery time increased. When the dose of vecuronium was increased from 40 to 80 micrograms/kg, 5-25% recovery time increased from 6.0 +/- 2.5 min to 8.8 +/- 4.0 min (mean +/- SD) and 25-75% recovery time increased from 8.7 +/- 4.3 min to 12.6 +/- 4.4 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Elimination of atracurium in humans: contribution of Hofmann elimination and ester hydrolysis versus organ-based elimination.

Atracurium, a nondepolarizing muscle relaxant, is eliminated through several pathways, including Hofmann elimination (spontaneous degradation in plasma and tissue at normal body pH and temperature) and ester hydrolysis (catalysis by nonspecific esterases). Because elimination of atracurium occurs in both tissue and plasma, traditional pharmacokinetic models assuming elimination from a single central compartment are inaccurate for atracurium. The authors developed a two-compartment pharmacokinetic model in which hepatic and/or renal elimination occurs from the central compartment (Cl organ), and Hofmann elimination and ester hydrolysis occur from both central and peripheral compartments (Cl nonorgan). To determine the in vitro rate constant for Hofmann elimination and ester hydrolysis, atracurium was added to whole blood kept at each patient's pH and temperature. The values for this rate constant ranged from 0.0193 to 0.0238 per min. When these values were applied to the pharmacokinetic model, Cl total, Cl organ, and Cl nonorgan were 4.8 +/- 1.1, 3.0 +/- 0.9, and 1.9 +/- 0.6 ml . kg-1 . min-1, respectively. The authors conclude that more than one-half of the clearance of atracurium occurs via pathways other than Hofmann elimination and ester hydrolysis.

Adult↗
PubMed1985

Descriptive anatomy of fibrocartilaginous menisci in the finger joints of the hand.

Observations were made from the dissection of 156 digital joints (thumbs excluded). In all joints fibrocollagenous menisci projected into the articular cavity from a ring-like structure based on the joint capsule. These meniscal structures separated the articulating cartilage surfaces at the margins of the joint. Histological examination confirmed a fibrocartilaginous nature of the tissue which demonstrated positive staining for proteoglycans and collagen fibers. Although generally similar in form, these meniscal structures varied in extent when compared between joint groups. The greatest amount and articular contribution was noted in metacarpophalangeal joints with least being found distally.

Aged↗
PubMed1985

Major childhood tumor resection using normovolemic hemodilution anesthesia and hetastarch.

Acute normovolemic hemodilution is a safe technique for minimizing operative blood loss during major tumor resection in children. Based on our experience using hemodilution anesthesia in 14 successful extensive tumor resections, we conclude the following: (1) this is an effective means of reducing use of bank blood and thus avoiding the risks of multiple transfusions; (2) it facilitates surgical dissection due to increased visibility with dilute blood, and decreased bleeding due to controlled hypotension; (3) this technique is acceptable for Jehovah's Witnesses; (4) hetastarch is an effective, inexpensive colloid hemodiluent which minimized perioperative edema compared to crystalloid hemodilution.

Adolescent↗
PubMed1985

Vecuronium kinetics and dynamics in anesthetized infants and children.

Vecuronium kinetics and dynamics were determined in five infants (3 to 11 months old) and five children (1 to 5 years old) during anesthesia with 70% nitrous oxide and 0.9 MAC halothane. Vecuronium was infused intravenously at a rate of 2.5 micrograms/kg/min while twitch tension of the adductor pollicis muscle was recorded and venous blood samples were drawn for determination of vecuronium concentrations by mass spectrometry. The elimination t1/2 was determined by linear regression of the log postdistribution concentration-time data; these values and noncompartmental techniques were used to calculate total plasma clearance (Cl), volume of distribution at steady state (Vdss), and mean residence time. The steady-state plasma concentration resulting in 50% depression of twitch tension (Cpss50) was determined by an effect compartment and a sigmoid concentration vs. paralysis model. Vdss was larger in infants (357 +/- 70 ml/kg; mean +/- SD) than in children (204 +/- 116 ml/kg), and Cl was of the same order for infants and children (5.6 +/- 1.0 and 5.9 +/- 2.4 ml/kg/min). Mean residence time was longer in infants (66.3 +/- 22.9 minutes) than in children (34.3 +/- 8.0 minutes). Cpss50 was lower in infants (57 +/- 18 ng/ml) than in children (110 +/- 28 ng/ml). The quantity of vecuronium in the body at steady state at 50% depression of twitch tension (Vdss X Cpss50) was similar in infants and children (21.2 +/- 9.9 and 19.0 +/- 3.3 micrograms/kg). During comparable nitrous oxide-halothane anesthesia, age-related changes in Vdss, Cl, and Cpss50 were much like those found for d-tubocurarine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

Effect of renal failure on laudanosine excretion in man.

Patients with renal failure and undergoing a cadaver renal transplant were found to have plasma concentrations of laudanosine, following the administration of a single bolus dose of atracurium 0.5 mg kg-1, higher than those found in patients without renal failure. Since laudanosine is a known central nervous system stimulant in a variety of animal species, its actions should be investigated further in man, and particularly in patients with renal failure.

Atracurium↗
PubMed1985

Laudanosine (a metabolite of atracurium) increases the minimum alveolar concentration of halothane in rabbits.

The authors hypothesized that laudanosine, a metabolite of atracurium and a central nervous system stimulant, might increase the minimum alveolar concentration (MAC) of halothane. An initial study in five rabbits anesthetized with halothane used a two-compartment model to produce estimates of pharmacokinetic variables for laudanosine. These estimates were used to determine the rates of infusion that would produce steady state plasma concentrations of laudanosine of approximately 200, 400, and 800 ng . ml-1. Subsequent infusion of laudanosine in eight rabbits produced mean (+/- SD) steady state plasma concentrations of laudanosine of 234 +/- 56, 457 +/- 66, and 873 +/- 105 ng . ml-1. The control value for MAC of halothane was 1.08 +/- 0.28%. At the lowest steady state plasma laudanosine concentration, MAC did not significantly differ from control (MAC = 1.15 +/- 0.23%, P less than 0.1). However, at 457 and 873 ng . ml-1, laudanosine significantly increased the MAC of halothane by 23% and 30%, respectively. Infusion with saline in two additional rabbits did not affect MAC. Therefore, at the plasma concentrations of laudanosine found in humans after administration of atracurium, laudanosine increased the MAC of halothane in rabbits.

Animals↗
PubMed1985

Comparison of enflurane, halothane, and isoflurane for diagnostic and therapeutic procedures in children with malignancies.

The authors performed a randomized, prospective trial comparing enflurane, halothane, and isoflurane (each administered with nitrous oxide) to establish which inhaled anesthetic produced the fewest complications and the most rapid induction of anesthesia for children undergoing general anesthesia for diagnostic procedures as oncology outpatients. Sixty-six children, ranging from 8 months to 18 years, underwent a total of 124 anesthetics. Induction of anesthesia (time from placement of facemask to beginning of skin preparation) was faster with halothane (2.7 +/- 1.0 min, mean +/- SD, n = 46) than with enflurane (3.2 +/- 0.8 min, n = 43) or isoflurane (3.3 +/- 1.2 min, n = 35). Emergence from anesthesia (time from completion of the procedure to spontaneous eye opening) was more rapid with enflurane (4.7 +/- 4.4 min) than with halothane (6.2 +/- 4.5 min) or isoflurane (6.2 +/- 3.9 min). Total time from the start of procedure until discharge was longer with isoflurane (25.1 +/- 6.8 min) than with enflurane (21.5 +/- 8.6 min) or halothane (22.3 +/- 7.6 min). During induction, the incidence of laryngospasm was greatest with isoflurane (23%) and the incidence of excitement least with halothane (13%). During the maintenance of, emergence from, and recovery from anesthesia, coughing occurred most frequently with isoflurane. During the recovery period, headache occurred most frequently with halothane (9%); there were no significant differences in the incidence of nausea, vomiting, hunger, or depressed effect. The authors conclude that the rapid induction and minimal airway-related complications associated with halothane anesthesia make it an excellent anesthetic agent for pediatric patients undergoing short diagnostic procedures.

Adolescent↗
PubMed1984

Pharmacokinetics, placental transfer, and neonatal effects of vecuronium and pancuronium administered during cesarean section.

Vecuronium and pancuronium were compared for placental transfer, pharmacokinetic variables, and neonatal effects during cesarean section under general anesthesia. Eighteen women underwent rapid-sequence intravenous induction using d-tubocurarine, succinylcholine, thiopental, and oxygen. Immediately after tracheal intubation, an intravenous injection of vecuronium (n = 11) or pancuronium (n = 7), 0.04 mg/kg, was given. Maternal venous blood samples were obtained before induction and at frequent intervals for 4 h after administration of vecuronium or pancuronium. Also, maternal venous and umbilical-cord arterial and venous blood samples were obtained at delivery. To describe placental transfer and maternal pharmacokinetics of the drugs, serum drug concentrations were determined using single-ion-monitoring mass spectrometry. The Apgar score and Neurologic and Adaptive Capacity Score (NACS) were used to evaluate neonatal condition. Both drugs crossed the placenta, as demonstrated by low concentrations of vecuronium (8.5-26.4 ng/ml) or pancuronium (12.2-34.2 ng/ml) found in umbilical venous blood. At delivery, the ratio of the drug concentration in umbilical venous blood to that in maternal venous blood was 0.11 +/- 0.02 for vecuronium and 0.19 +/- 0.03 for pancuronium. Vecuronium had a more rapid clearance (6.4 +/- 0.4 ml X kg-1 X min-1, mean +/- SE) and a shorter elimination half-life (36 +/- 1.8 min) than pancuronium (3.0 +/- 0.1 ml X kg-1 X min-1 and 72 +/- 6 min, respectively). No other pharmacokinetic differences were found between the drugs. Neonatal outcome was not affected adversely by either muscle relaxant, as assessed by Apgar scores and NACSs . The short duration of action, the minimal placental transfer, and the apparent lack of clinical neuromuscular effects on the newborn suggest that vecuronium should be a useful muscle relaxant for cesarean section.

Adult↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

The effect of paralysis on oxygen consumption in normoxic children after cardiac surgery.

To determine whether paralysis reduces oxygen consumption (V02) after cardiac surgery in infants, the authors measured V02 before and after paralysis in 17 sedated infants who were ventilated mechanically after cardiac surgery. Oxygen consumption was determined as being the difference between oxygen content of inspired and expired gases. The absence or presence of "movement" (breathing or repeated movement of the extremities) before paralysis was noted. For eight infants who did not "move" before paralysis, VO2 was similar before (9.1 +/- 1.2 ml . kg-1 . min-1, mean +/- SD) and after (9.0 +/- 1.5 ml . kg-1 . min-1) paralysis (P = 0.81). However, for nine infants who did "move" before paralysis, VO2 decreased from 9.2 +/- 1.4 ml . kg-1 . min-1 before paralysis to 8.0 +/- 1.4 ml . kg-1 . min-1 after paralysis (P less than 0.05). One infant in each group had an increase in VO2 greater than 10% of the baseline value (i.e., 12% and 14%). In conclusion, if breathing or repeated movement is present before paralysis, paralysis decreases VO2 by 13% in sedated infants after cardiac surgery. If repeated or regular movement is not present before paralysis, paralysis does not decrease VO2. These data suggest that in normoxic patients, muscle paralysis does not significantly alter V02 and therefore should not be used for this purpose.

Anesthesia↗
PubMed1984

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↗