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Biomedical subjects

D M Fisher

Publications and source records attributed to D M Fisher.

At least 91 records · Page 5Linked to original sources
PubMed1990

Pharmacokinetics and pharmacodynamics of atracurium in the elderly.

To evaluate the effect of aging on the distribution, clearance, and neuromuscular junction sensitivity to atracurium, the authors determined the pharmacokinetics and pharmacodynamics of atracurium in five healthy elderly subjects (74-76 yr) during halothane-nitrous oxide anesthesia and compared these values to those obtained previously in five healthy young adults (22-44 yr). A brief (6.0-13.0 min) infusion of atracurium was administered until twitch tension was suppressed by approximately 70%, and atracurium plasma concentration and twitch tension data were used to determine pharmacokinetic and pharmacodynamic parameters for each patient. Total clearance (Cltotal) was similar in elderly and young adults. However, clearance via the liver and/or kidney (Clorgan) was lower in elderly patients, whereas clearance due to Hofmann elimination and ester hydrolysis (Clnonorgan) was higher. Volume of distribution at steady state (Vss) was larger in elderly patients. The increase in Vss without an age-related increase in Cltotal resulted in a longer elimination half-life [21.8 (+)/- 3.3 vs. 15.7 (+)/- 2.5 min (mean (+)/- SD)] in elderly patients. The steady state plasma concentration of atracurium required to suppress twitch tension by 50% was similar in elderly and young adults. The authors conclude that the pharmacokinetics, but not the pharmacodynamics, of atracurium differ significantly between elderly and young adults. As a result, repeated doses will be required with similar frequency in young and elderly adults, but recovery from comparable levels of neuromuscular blockade may be slightly prolonged in elderly patients.

Adult↗
PubMed1990

Pharmacokinetics and pharmacodynamics of atracurium in infants and children.

To determine whether maturational changes in body composition and organ function affect distribution and elimination of and sensitivity to atracurium, the authors determined the pharmacokinetics and pharmacodynamics of atracurium in six infants and five children and compared these results with those obtained in five adults. Atracurium, 15.8 +/- 1.7 micrograms.kg-1.min-1, was infused iv for 6-11 min to subjects anesthetized with nitrous oxide (60%) and halothane (0.9 MAC, age-adjusted) and twitch tension of the adductor pollicis muscle was measured. Plasma samples were obtained for 120 min; concentrations of atracurium were determined using a liquid chromatographic assay. A two-compartment pharmacokinetic model, adapted to account for elimination of atracurium from both central and peripheral compartments, was fit to the plasma concentration data; an effect-compartment model was fit to the twitch tension data. Volume of distribution at steady state (210 +/- 118, 129 +/- 44, and 100 +/- 22 ml/kg for infants, children, and adults, respectively) and total clearance (7.9 +/- 2.0, 6.8 +/- 1.6, and 5.3 +/- 0.9 ml.kg-1.min-1 for the three groups) decreased with increasing age. Neither elimination half-life (20.0 +/- 5.1, 17.2 +/- 5.1, and 15.7 +/- 2.5 min for the three groups) nor the steady state plasma concentration that resulted in 50% neuromuscular blockade (363 +/- 118, 444 +/- 121, and 436 +/- 122 ng/ml for the three groups) varied with age. The authors conclude that these results are consistent with and explain the previously reported findings that recovery from the neuromuscular effects of atracurium is minimally affected by age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The management of pain associated with pediatric procedures.

This article provides guidelines for the psychological and pharmacologic management of pain and anxiety for children undergoing medical procedures. The goals of intervention are presented, as well as issues warranting consideration in planning intervention to reduce procedure-related distress.

Analgesics, Opioid↗
PubMed1989

Modification of central nervous system effects of laudanosine by inhalation anaesthetics.

To determine the effect of inhalation anaesthetics on the plasma concentration of laudanosine necessary to produce CNS excitation, we administered laudanosine 0.5 mg kg-1 min-1 i.v. to 40 rabbits under eight study conditions: 1.0 or 0.7% halothane, 1.6% isoflurane, 2.0% enflurane, during normocapnia and hypocapnia; 70% nitrous oxide, alone and with 1.0% halothane, and room air (control). At the onset of purposeless, unco-ordinated movements of the entire body, blood samples were obtained to determine the CNS excitation-threshold plasma concentration (ETPC) of laudanosine. During normocapnia, 1.0% halothane, 1.6% isoflurane and 2.0% enflurane increased ETPC (mean (SD) 11.8 (2.5), 11.3 (2.8) and 9.1 (1.4) micrograms ml-1, respectively) from control (5.0 (0.9) microgram ml-1). ETPC during enflurane anaesthesia did not change significantly with hypocapnia. Nitrous oxide, alone or in combination with halothane, did not change ETPC. The combination of nitrous oxide with 1.0% halothane significantly decreased ETPC to less than that for halothane alone (6.7 (1.2) v. 11.8 (2.5) micrograms ml-1, respectively).

Anesthesia, Inhalation↗
PubMed1989

The influence of renal failure on the pharmacokinetics and duration of action of pipecuronium bromide in patients anesthetized with halothane and nitrous oxide.

The authors determined the pharmacokinetics and duration of action of a bolus dose of pipecuronium bromide (0.07 mg.kg-1) in 40 patients anesthetized with halothane and nitrous oxide. Twenty were patients with normal renal function, undergoing a variety of surgical procedures, and 20 were undergoing cadaver renal transplantation because of end-stage renal disease. Plasma concentrations of pipecuronium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by nonlinear regression and fit to a two-compartment or three-compartment model; in addition, the data were analyzed by a non-compartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the mechanical evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The pharmacokinetic parameters derived by compartmental modelling were (normal vs. renal failure, respectively): volume of distribution at steady state (309 +/- 103 vs. 442 +/- 158 ml.kg-1, mean +/- SD), plasma clearance, (2.4 +/- 0.6 vs. 1.6 +/- 0.6 ml.kg-1.min-1), mean residence time (140 +/- 63 vs. 329 +/- 198 min), and elimination half-life (137 +/- 68 vs. 263 +/- 168 min). The same parameters as derived by the non-compartmental method were (normal vs. renal failure, respectively): volume of distribution at steady state (307 +/- 80 vs. 426 +/- 119 ml.kg-1, mean +/- SD), plasma clearance (2.4 +/- 0.6 vs. 1.6 +/- 0.6 ml.kg-1.min-1), mean residence time (134 +/- 41 vs. 323 +/- 228 min), and elimination half-life (118 +/- 35 vs. 247 +/- 168 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Fentanyl-induced ventilatory depression: effects of age.

To determine whether infants are more sensitive than older patients to the ventilatory-depressant effects of fentanyl, patients were anesthetized with fentanyl and nitrous oxide (N2O) and ventilatory depression was assessed following elimination of N2O and in the immediate postoperative period. Three groups of patients were studied: infants (1-12 mo old, n = 14), children (1-5 yr old, n = 14), and adults (23-38 yr old, n = 13). Skin-surface PCO2 was measured to determine the peak PCO2 occurring at the end of anesthesia when end-tidal N2O concentration was less than 6%. Naloxone was administered if PCO2 exceeded 70 mmHg. During recovery from anesthesia, ventilatory pattern was recorded using impedance pneumography to determine the longest breath-to-breath interval and the number of episodes of central apnea (defined as breath-to-breath intervals greater than or equal to 10 s in infants and children and greater than or equal to 20 s in adults). Elevation of PCO2 correlated with increasing plasma fentanyl concentrations but did not differ between groups. Four patients (two infants, one child, and one adult) required naloxone. The only subject who had a low plasma fentanyl concentration but required naloxone was a 6-wk-old infant; this was the only subject younger than 3 mo. For each range of fentanyl concentrations, the incidence of apnea increased with age, as did the number of episodes of apnea per subject. Fentanyl-induced ventilatory depression, as assessed by elevation of resting PCO2 during emergence from anesthesia and disruption of ventilatory pattern during recovery from anesthesia, is not greater in infants older than 3 mo than in children and adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Washin and washout of isoflurane administered via bubble oxygenators during hypothermic cardiopulmonary bypass.

Washin and washout of a volatile anesthetic given through the oxygenator during hypothermic (23.4 +/- 2.1 degrees C) cardiopulmonary bypass were studied in nine patients. The authors administered isoflurane and measured its partial pressure in arterial (Pa) and venous (Pv) blood and the gas exhausted from the oxygenator (PE) at 1, 2, 4, 8, 16, 32, and 48 min during washin. These measurements were repeated during washout, which coincided with rewarming. During washin, PE, Pa, and Pv progressively rose toward inlet gas partial pressure (PI). Equilibration of Pa with PI was 41% after 16 min, 51% after 32 min, and 57% after 48 min of washin. During washout, Pa declined to 24% of its peak after 16 min and to 13% after 32 min. Washin and washout were considerably slower in mixed venous blood. Washin of isoflurane appeared to occur more slowly during cardiopulmonary bypass than during administration via the lungs in normothermic patients, presumably because hypothermia increases tissue capacity, compensating for the effect of hemodilution that otherwise would decrease the blood/gas partition coefficient. During rewarming, washout appeared to occur as rapidly as from the lungs of normothermic patients. This may have resulted from the declining blood/gas partition coefficient (due to rewarming) and relatively limited tissue stores of isoflurane. The relationship between exhaust and arterial partial pressures was reasonably consistent; for clinical purposes, measurement of PE can be used to estimate Pa.

Cardiopulmonary Bypass↗
PubMed1988

Surface-induced hypothermia: effects on coronary blood flow autoregulation and vascular reserve.

Surface-induced hypothermia has been shown to exert a protective effect in canine models of myocardial infarction. However, its effects on coronary blood flow (CBF) autoregulation and coronary vascular reserve (CVR) have not been investigated. The effects of mild (32 degrees C) and moderate (27 degrees C) hypothermia on CBF autoregulation and CVR (at 60 mm Hg diastolic pressure) were studied using a chronically instrumented canine preparation. Coronary artery pressure-flow relations were obtained over a wide range of coronary diastolic pressures (10 to 106 mm Hg) with autoregulation intact and during adenosine-induced maximal coronary conductance (MCC) at 37, 32, 27 degrees C (n = 7 dogs), and after rewarming (n = 5 dogs). Halothane (1 MAC end-tidal concentration, temperature adjusted) was the anesthetic. Autoregulation remained intact during hypothermia. CBF remained relatively constant between diastolic pressures of 43.1 +/- 9.0 and 84.0 +/- 14.4 mm Hg (mean +/- SD). No significant differences were observed between temperatures in the autoregulated pressure range. CBF correlated well with myocardial oxygen consumption (MVO2) (r2 = 0.81, P less than 0.0001). There were no significant changes in MVO2, CBF, MCC, or CVR at 32 degrees C. At 27 degrees C, MVO2 (3.65 +/- 1.3 at 37 degrees C vs 2.35 +/- 1.4 ml O2.min-1 at 27 degrees C), autoregulated CBF (34.9 +/- 15.1 vs 19.5 +/- 10.8 ml.min-1), the slope of the line of MCC (4.31 +/- 0.7 vs 2.7 +/- 0.4 ml.mm-1.min-1), and CVR (147.1 +/- 24.6 vs 90.1 +/- 27.3 ml.min-1) were all less than control (P less than 0.05). After rewarming to 37 degrees C, no significant changes from control were noted. The authors conclude that coronary autoregulation remains intact at both 32 and 27 degrees C, although MCC and CVR are significantly decreased at 27 degrees C.

Animals↗
PubMed1988

Pharmacokinetics of fentanyl in the elderly.

The pharmacokinetics of fentanyl were determined in seven elderly (71-82 yr) and seven younger adults (18-41 yr) anaesthetized with thiopentone, nitrous oxide in oxygen and morphine. Fentanyl was administered as a 2-min i.v. infusion at doses of 15 micrograms kg-1 for elderly patients and 20 micrograms kg-1 for the younger patients. Plasma samples were obtained for 4 h and fentanyl concentrations determined by radioimmunoassay. Fentanyl concentration, per microgram kg-1 administered, was higher in elderly than in young patients at 2 min (7.73 +/- 3.14 v. 4.54 +/- 1.83 ng ml-1 (mean +/- SD), respectively) and at 4 min after the start of infusion (3.26 +/- 1.44 v. 1.78 +/- 0.72 ng ml-1, respectively). Concentrations were similar at all other sampling times. Pharmacokinetic variables were determined by non-compartmental techniques. Total plasma clearance was similar for the two age groups. Volume of distribution at steady-state (VDss) was smaller in elderly patients (1.36 +/- 0.44 v. 2.27 +/- 0.82 litre kg-1). Despite age-related changes in VDss, plasma fentanyl concentrations for the two groups were similar throughout the 4-h sampling period except immediately following administration. These results suggest that, if there are age-related differences in response to fentanyl, the likely pharmacokinetic explanation is the higher concentration of fentanyl in the elderly immediately following its administration.

Adult↗
PubMed1988

Pipecuronium and pancuronium: comparison of pharmacokinetics and duration of action.

The pharmacokinetics of pipecuronium 0.07 mg kg-1 and pancuronium 0.1 mg kg-1 were compared in 39 ASA class I or II patients. Plasma concentrations of these agents were measured for 6 h following administration, using a sensitive and specific capillary gas chromatographic assay. Concentration v. time data were analysed by non-linear regression and fitted to a two- or three-compartment model as appropriate. Neuromuscular blockade was assessed by measuring the mechanical evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. Pipecuronium had a larger steady-state volume of distribution (Vss) (309 (SD 103) ml kg-1) and greater plasma clearance (Cl) (2.4 (0.6) ml kg-1 min-1) than pancuronium (199 (54) ml kg-1 and 1.5 (0.4) ml kg-1 min-1, respectively). The volumes of the central compartment, distribution and elimination half-lives and mean residence times were similar for both agents and within the range expected for drugs of this type. The durations of action (injection to 25% recovery of twitch tension) of pipecuronium and pancuronium were similar: 98.0 (36.1) min and 117.2 (35.8) min, respectively. We conclude that the time courses of neuromuscular blockade following pipecuronium and pancuronium are similar, despite the differences in Vss and Cl.

Adult↗
PubMed1988

Pre-induction of anesthesia in pediatric patients with nasally administered sufentanil.

To evaluate nasally administered sufentanil, 1.5-4.5 micrograms/kg, for pre-induction (i.e., pre-medication/induction) of anesthesia in pediatric patients, the authors studied ASA PS 1 or 2 patients scheduled for elective surgery. Eighty children, ages 6 months to 7 yr, were randomized to receive sufentanil (1.5, 3.0, or 4.5 micrograms/kg) or placebo (normal saline, 0.03 ml/kg) nasally over 15-20 s. Induction of anesthesia was completed with 5% halothane and O2 via facemask. After tracheal intubation, anesthesia was maintained with N2O (60-70%) and halothane, as clinically indicated. A blinded observer remained with the child from prior to drug administration until discharge from the recovery room. Patients given sufentanil were more likely to separate willingly from their parents and be judged as calm at or before 10 min compared to those given saline. Ventilatory compliance during induction of anesthesia decreased markedly in 25% of subjects given sufentanil, 4.5 micrograms/kg. Subjects given sufentanil moved or coughed less during tracheal intubation and required less halothane compared to those given placebo. During recovery, patients given sufentanil cried less and fewer needed analgesics; recovery times were similar for all groups. However, patients given sufentanil, 4.5 micrograms/kg, had a higher incidence of vomiting in the recovery room and during the first postoperative day. The authors conclude that nasally administered sufentanil, 1.5 or 3.0 micrograms/kg, facilitates separation of children from parents, has minimal side effects, may improve intubating conditions, and can provide postoperative analgesia.

Administration, Intranasal↗
PubMed1988

Pharmacokinetics of fentanyl in neonatal humans and lambs: effects of age.

To determine whether the clearance of fentanyl in neonates varies with age, the authors determined the pharmacokinetics of fentanyl in 14 humans ages 1-71 days and 15 lambs ages 3-37 days. In humans, fentanyl, 54.1 +/- 2.3 (mean +/- SD) micrograms/kg, was administered as a 2-min iv infusion; in lambs, fentanyl, 50 micrograms/kg, was administered as an iv bolus. Ventilation was controlled to maintain end-tidal or arterial PCO2 normal, and potent inhaled anesthetics were not administered; in humans, additional anesthesia was provided with iv morphine. Arterial or venous samples were obtained for 12 h, and plasma concentrations of fentanyl were determined by radioimmunoassay. Plasma concentration versus time data were fitted to two- and three-compartment pharmacokinetic models, and clearance, volume of distribution at steady-state (Vdss), and elimination half-life were determined. Clearance increased with age in both humans and lambs. Two humans who had intraabdominal surgery had no clearance of fentanyl: plasma concentrations of fentanyl remained constant for approximately 10 h after an initial distribution phase. In lambs, but not in humans, Vdss increased with age; elimination half-life did not change with age in either lambs or humans. The authors conclude that at least two factors--postnatal age and the type of surgery--affect fentanyl clearance during the neonatal period. The effect of other factors, such as inhaled anesthetics, remains to be determined.

Aging↗
PubMed1988

In vitro anesthetic washin and washout via bubble oxygenators: influence of anesthetic solubility and rates of carrier gas inflow and pump blood flow.

The uptake and elimination of volatile anesthetic agents administered to patients under conditions of hemodilution and hypothermia during cardiopulmonary bypass have not been determined. To define the limitations imposed by oxygenators, we defined washin and washout curves for volatile anesthetic agents administered to bubble oxygenators primed with diluted blood (without connection to a patient). There was rapid equilibration of anesthetic partial pressure between delivered gas and blood (85-90% within 16 minutes). Increasing the gas inflow to the oxygenator from 3 to 12 L/min hastened washin and washout slightly, while increasing the pump blood flow from 3 to 5 L/min had no effect. Rates of washin and washout of anesthetics differed as a function of their blood/gas solubilities: enflurane greater than isoflurane greater than halothane during washin; isoflurane greater than enflurane greater than halothane during washout. However, these differences were small. Oxygenator exhaust partial pressures of anesthetic correlated with simultaneously obtained blood partial pressures, suggesting that monitoring exhaust gas may be useful clinically.

Anesthetics↗
PubMed1987

Plasma concentrations of fentanyl in infants, children and adults.

To evaluate whether there are age-related differences in the plasma concentration-vs-time course of fentanyl, the authors administered fentanyl to seven infants (3-10 months), seven children (1-9 years) and seven adults (18-41 years). Anaesthesia was induced with thiopentone, nitrous oxide, and pancuronium; following tracheal intubation, fentanyl (approximately 30 micrograms X kg-1 for infants and children, 20 micrograms X kg-1 for adults) was administered as a 2-min IV infusion. Anaesthesia was maintained with nitrous oxide, pancuronium, and morphine sulphate as clinically indicated. Plasma samples were obtained for 4 h and fentanyl concentrations determined by radioimmunoassay. Plasma concentrations per microgram X kg-1 fentanyl administered were lowest in infants 4-10 and 60-240 min after the start of the 2-min infusion; values for children were lower than those for adults 4, 180 and 210 min after the start of the 2-min infusion. These findings are consistent with the authors' clinical observation that infants tolerate larger doses of fentanyl than do adults.

Adolescent↗
PubMed1987

Pancuronium and vecuronium pharmacokinetics and pharmacodynamics in younger and elderly adults.

To evaluate the effect of aging on the distribution, metabolism, and neuromuscular junction sensitivity to pancuronium and vecuronium, the authors determined the pharmacokinetics and pharmacodynamics of these drugs in 12 healthy elderly subjects (70-84 yr) and 12 young adults (30-57 yr) during halothane-nitrous oxide anesthesia. Plasma concentrations of the muscle relaxants were determined using a selective ion-monitoring mass spectrometric technique specific for the parent compound. For vecuronium, plasma clearance (3.7 +/- 1.0 and 5.2 +/- 0.8 ml X kg-1 X min-1, respectively), and volume of distribution at steady-state (179 +/- 31 and 244 +/- 38 ml X kg-1, respectively) were lower in the elderly than in young adults; values for distribution half-lives, elimination half-life, and sensitivity of the neuromuscular junction were similar for the two groups. For pancuronium, there were no statistically significant differences between groups for these pharmacokinetic or pharmacodynamic parameters. However, there was a trend toward reduced clearance (20%) and prolonged elimination half-life (16%) in the elderly as compared to the younger patients. The authors conclude that healthy elective surgical patients between the ages of 70 and 84 yr of age do not differ markedly from younger adults in their pharmacokinetic/pharmacodynamic response to vecuronium and pancuronium.

Adult↗
PubMed1987

The incidence and degree of scleral show in the normal population.

The degree and incidence of scleral show in a normal population was studied in 100 Caucasian patients. Subjects were fitted with a headband goniometer. The goniometer was related to a standard anatomic landmark (the Frankfort plane), and the subject's head was inclined through angles of 0 to -35 degrees. With the subject fixing on a constant point, the degree of white showing between the lower eyelid and the limbus was measured. The results demonstrated that scleral show was a normal finding, the degree of which increases with increasing inclination of the head from the Frankfort plane. No sex variation or increase with age was noted.

Adult↗