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Biomedical subjects

E Ornstein

Publications and source records attributed to E Ornstein.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetics and pharmacodynamics of vecuronium in the obese surgical patient.

The effect of obesity on the disposition and action of vecuronium was studied in 14 surgical patients. After induction of anesthesia with thiopental and maintenance of anesthesia by inhalation of nitrous oxide and halothane, seven obese patients (93.4 +/- 13.9 kg, 166% +/- 30% of ideal body weight, mean +/- SD) and seven control patients (60.9 +/- 12.3 kg, 93% +/- 6% of ideal body weight) received 0.1 mg/kg of vecuronium. Plasma arterial concentrations of muscle relaxant were determined at 1, 3, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, and 360 min by a spectrofluorometric method. Simultaneously, neuromuscular blockade was assessed by stimulation of the ulnar nerve and quantification of thumb adductor response. Times to 50% recovery of twitch were longer in the obese than in the control patients (75 +/- 8 versus 46 +/- 8 min) as were 5%-25% recovery times (14.9 +/- 4.0 versus 10.0 +/- 1.7 min) and 25%-75% recovery times (38.4 +/- 13.8 versus 16.7 +/- 10.3 min). However, vecuronium pharmacokinetics were similar for both groups. When the data were calculated on the basis of ideal body weight (IBW) for obese and control patients, total volume of distribution (791 +/- 303 versus 919 +/- 360 mL/kg IBW), plasma clearance (4.65 +/- 0.89 versus 5.02 +/- 1.13 mL.min-1.kg IBW-1), and elimination half-life (119 +/- 43 versus 133 +/- 57 min) were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Pharmacokinetics and pharmacodynamics of pipecuronium bromide (Arduan) in elderly surgical patients.

The neuromuscular response to pipecuronium bromide (Arduan), 70 micrograms/kg, was studied in 20 elderly (greater than 70 yr) and 10 younger patients (less than 60 yr) during nitrous oxide, fentanyl, and droperidol anesthesia. The adductor pollicis response to single 0.2-ms supramaximal pulses was recorded. Although all younger patients were completely paralyzed, 2 of 20 elderly patients did not attain 90% paralysis. Onset time in the elderly was prolonged (6.9 +/- 2.6 vs 4.3 +/- 1.5 min, P less than 0.02). Spontaneous recovery was similar in both groups, with 75% recovery occurring at 133 +/- 52 min in the elderly and 146 +/- 46 min in the younger patients. The pharmacokinetic variables were similar for the two groups, and pharmacodynamic analysis revealed a similar sensitivity at the neuromuscular junction. The pharmacologic actions of pipecuronium in otherwise healthy patients do not differ between young and elderly adults.

Aged↗
PubMed1992

Effects of hypocarbia on the pharmacodynamics of sufentanil in humans.

Descriptors of power and frequency derived from power spectral analysis of the electroencephalogram (EEG) were used to determine the effects of low-dose sufentanil (0.1 micrograms/kg) on brain activity. The effects of hypocarbia alone and of hypocarbia with sufentanil in patients receiving a N2/O2 (70%:30%) anesthetic were also studied. Hypocarbia alone caused changes in most EEG descriptors from both the anterior (F3-C3) and posterior (P3-O1) EEG montages. All EEG descriptors in both hypocarbic and normocarbic patients significantly changed when sufentanil was administered, reflecting a shift of power into the lower frequency ranges. When the anterior EEG montages from the two groups that received sufentanil were compared, the delta power band, spectral edge 50 (median power frequency), and the relative power in the delta power band divided by the alpha plus beta power bands [D/(A + B)] in the hypocarbic group exhibited a significantly greater shift of power into the lower frequency range. It is concluded that (a) power spectral analysis is a sensitive measure of the effects of hypocarbia and small doses of sufentanil on the brain; (b) the power spectral analysis descriptors--delta power band, spectral edge 50, and [D/(A + B)]--are statistically the most sensitive to EEG changes induced by sufentanil; and (c) hypocarbia intensifies patient EEG response to sufentanil, as judged by changes in EEG descriptors.

Adult↗
PubMed1991

Metabolism of desflurane and isoflurane to fluoride ion in surgical patients.

The metabolism of isoflurane and the investigational volatile anaesthetic desflurane to fluoride ion was examined in 25 surgical patients. The patients were randomly assigned to four groups, to receive isoflurane or desflurane at either 0.65 MAC or 1.25 MAC. Anaesthesia was induced in all patients with thiopentone and midazolam and included nitrous oxide 60% in addition to the volatile agent. Blood was drawn before induction and at the end of the operation for determination of serum fluoride ion concentration. Plasma fluoride ion concentrations increased (+ 1.36 +/- 0.93 microM, P less than 0.01) in patients receiving isoflurane but were unchanged (-0.13 +/- 0.50 microM) in patients receiving desflurane. Metabolic release of fluoride ion is less with desflurane than with isoflurane during administration of the anaesthetics to surgical patients, and is unlikely to be of clinical significance.

Adult↗
PubMed1991

Cerebral blood flow reactivity to changes in carbon dioxide calculated using end-tidal versus arterial tensions.

We retrospectively examined arerial and end-tidal estimations of CO2 tension used to calculate cerebrovascular reactivity in 68 anesthetized patients. CBF was measured using the intravenous 133Xe technique at mean +/- SD PaCO2 values of 28.2 +/- 5.2 and 38.8 +/- 4.8 mm Hg. The correlation between all PaCO2 and end-tidal PCO2 (PetCO2) values was y = 0.85x - 0.49 (r = 0.93, p = 0.0001). There was a moderate correlation between age and the difference between PaCO2 and PetCO2 (y = 0.11x + 0.79; r = 0.73, p = 0.0001). Cerebrovascular reactivity to changes in CO2 (ml 100 g-1 min-1 mm Hg-1) was similar (p = 0.358) when calculated by using either PaCO2 (1.9 +/- 0.8) or PetCO2 (1.8 +/- 0.8) and highly correlated (y = 0.86x + 0.23; r = 0.91, p = 0.0001). The CBF response to changes in CO2 tension can be reliably estimated from noninvasive measurement of PetCO2.

Adult↗
PubMed1991

Desflurane and isoflurane in surgical patients: comparison of emergence time.

In order to examine the clinical potential of desflurane (difluoromethyl-1-fluoro-2,2,2-trifluoroethyl ether) in humans, a randomized, controlled study was designed to compare time of emergence from anesthesia in patients undergoing elective surgery under desflurane anesthesia to that of patients under isoflurane anesthesia. Twenty-eight patients were randomly divided into four groups. Group 1 received isoflurane 0.65 MAC; group 2, desflurane 0.65 MAC; group 3, isoflurane 1.25 MAC; and group 4, desflurane 1.25 MAC. Anesthesia was induced with sodium thiopental, and N2O 60% was added to the volatile agent. Mean anesthetic exposure times (min [mean +/- SD]) were 108 +/- 49 in group 1, 132 +/- 46 in group 2, 147 +/- 74 in group 3, and 166 +/- 71 in group 4, with no significant differences between groups. The times from discontinuation of anesthetic gases until patients opened their eyes and squeezed the investigator's hand in response to a command were averaged and recorded as "emergence time." Emergence time was significantly less with desflurane than with isoflurane given at the same MAC. Patients receiving isoflurane 0.65 MAC responded to commands 15.6 +/- 4.3 min after discontinuation of the anesthetic; patients in the desflurane 0.65 MAC group responded in 8.8 +/- 2.7 min (P less than 0.01). Emergence time for isoflurane 1.25 MAC was 30.0 +/- 11.0 min; for desflurane 1.25 MAC it was 16.1 +/- 6.0 min (P less than 0.05). Our results confirm that emergence from desflurane anesthesia is more rapid than from isoflurane.

Adult↗
PubMed1991

Deliberate hypotension in patients with intracranial arteriovenous malformations: esmolol compared with isoflurane and sodium nitroprusside.

Thirty patients undergoing resection of arteriovenous malformations with deliberate hypotension were randomized to receive 1 of 3 hypotensive agents. Anesthesia was maintained with isoflurane and nitrous oxide in all patients. Mean arterial pressure was reduced 20% to 60-65 mm Hg with use of either isoflurane (less than or equal to 4%), sodium nitroprusside (less than or equal to 8 micrograms.kg-1.min-1), or esmolol (less than or equal to 24 mg/min). Esmolol was associated with a decrease in cardiac output from 6.2 +/- 1.3 to 3.8 +/- 0.8 L/min, which, because of a 22% increase in systemic vascular resistance, far exceeded the reduction in mean arterial pressure. Systemic vascular resistance increased despite a 32% decrease in plasma renin activity. In contrast, with sodium nitroprusside or isoflurane, the decrease in mean arterial pressure was associated with decreases in systemic vascular resistance of similar magnitude, with no change in cardiac output. Plasma renin activity levels increased 48% with sodium nitroprusside and 126% with isoflurane. Heart rate increased 13% with sodium nitroprusside, remained unchanged with isoflurane, and decreased 23% with esmolol. Although esmolol may be used as a primary hypotensive agent, the potential for marked myocardial depression must be recognized. The differences in pharmacologic properties for the different hypotensive agents suggest that combinations of these agents may provide a pharmacologic profile superior to either agent alone.

Adrenergic beta-Antagonists↗
PubMed1991

Distribution, elimination, and action of vecuronium in the elderly.

The effects of age on the pharmacokinetics and pharmacodynamics of vecuronium in eight elderly patients aged 72-86 yr and eight younger adults aged 26-48 yr undergoing elective surgical procedures under nitrous oxide-fentanyl anesthesia were studied. Vecuronium (0.1 mg/kg) was given as an intravenous bolus, and the ulnar nerve was stimulated with a square-wave impulse of 0.2-ms duration. The response to stimulation at a frequency of 0.1 Hz was measured and recorded with a force displacement transducer applied to the thumb. Spontaneous recovery was significantly longer in elderly patients than in younger patients (50% recovery time, 97.1 +/- 29 vs 39.8 +/- 14 min, mean +/- SD; recovery index [25%-75%], 49.4 +/- 11 vs 15.0 +/- 8 min). In addition, in elderly patients elimination half-life of vecuronium was significantly prolonged (125 +/- 55 vs 78 +/- 21 min, P = 0.04) and plasma clearance reduced (2.6 +/- 0.6 vs 5.6 +/- 3.2 mL.kg-1.min-1, P = 0.049). The prolonged duration of action of vecuronium in the elderly surgical patients thus appears to be secondary to altered pharmacokinetics consistent with an age-related decrease in renal and hepatic functions.

Adult↗
PubMed1991

Pharmacokinetics of sufentanil in obese patients.

The pharmacokinetics of sufentanil were determined in eight obese (94.1 +/- 14 kg, mean +/- SD) and eight control patients (70.1 +/- 13 kg) anesthetized for neurosurgery. After induction of anesthesia, 4 micrograms/kg of sufentanil was administered in a single intravenous bolus. Multiple arterial samples were obtained at timed intervals over 6 h, and plasma concentrations of sufentanil were measured by radioimmunoassay. Calculation of pharmacokinetic variables from the derived compartmental models demonstrated an increased volume of distribution of sufentanil in the obese (9098 +/- 2793 mL/kg ideal body weight, mean +/- SD) when compared with a control group (5073 +/- 1673 mL/kg ideal body weight) (P less than 0.01) and a prolonged elimination half-life (208 +/- 82 min vs 135 +/- 42 min, P less than 0.05). The total volume of distribution correlated linearly with the degree of obesity, as expressed in percent ideal body weight (r = 0.67). In contrast, plasma clearance was similar in both obese and control groups (32.9 +/- 12.5 vs 26.4 +/- 5.7 mL/kg ideal body weight). The high lipid solubility of sufentanil probably explains the altered pharmacokinetics of this opioid in obese patients.

Adult↗
PubMed1991

A comparison of cerebral blood flow reactivity to CO2 during halothane versus isoflurane anesthesia for carotid endarterectomy.

The effects of isoflurane or halothane on cerebral blood flow (CBF) reactivity to changes in arterial carbon dioxide tension (PaCO2) during carotid endarterectomy were compared using the intravenous method of 133Xe-CBF determination. Patients, aged 65 +/- 3 yr (mean +/- SE), received O2 and N2O (1:1) and either 0.75% isoflurane (n = 7) or 0.5% halothane (n = 7). Patient demographic and clinical data were similar for both groups and followed the expected strata of patients with ischemic cerebrovascular disease. Measurements were made during the period of temporary bypass shunting. In the isoflurane group, increasing PaCO2 from 33.3 +/- 1.4 to 43.4 +/- 1.3 mm Hg resulted in a significant (P less than 0.05) increase in CBF from 21 +/- 1 to 35 +/- 4 mL.100 g-1.min-1. In the halothane group, increasing PaCO2 from 31.1 +/- 1 to 39.4 +/- 1.6 mm Hg resulted in a significant increase in CBF from 26 +/- 3 to 37 +/- 3 mL.100 g-1.min-1. Mean CBF reactivity to changes in PaCO2 (mL.100 g-1.min-1.mm Hg-1) was 1.74 +/- 0.39 for isoflurane and 1.78 +/- 0.4 for halothane (not significant), corresponding to a relative change of 4.8% +/- 0.8% and 5.2% +/- 1.3% per mm Hg, respectively. There is no significant difference between halothane and isoflurane in their effects on CO2 reactivity in the mildly hypocapnic to normocapnic range.

Aged↗
PubMed1990

Pharmacokinetics of sufentanil in the elderly surgical patient.

The effect of age on the distribution and elimination of sufentanil was studied in seven elderly (77 +/- 5 yr, mean +/- SD) and seven younger (41 +/- 15 yr) neurosurgical patients. Following a single IV bolus of sufentanil 2 micrograms.kg-1 multiple arterial samples were obtained at timed intervals and plasma concentrations of sufentanil were measured by radioimmunoassay. Pharmacokinetic variables were calculated from the derived compartmental models. The initial volume of distribution was significantly smaller in the elderly patients (310 +/- 109 ml.kg-1 vs 491 +/- 112 ml.kg-1 mean +/- SD). Elimination half-lives, plasma clearances, and total volumes of distribution were similar for elderly and younger subjects. Six of seven elderly patients required administration of naloxone at the termination of surgery to achieve an adequate rate of ventilation (greater than eight breaths.min-1) while only one younger patient required antagonism of ventilatory depression. The authors believe that age-related differences in the action of sufentanil cannot be accounted for by the observed differences in the initial volume of distribution. It is concluded that alterations in pharmacodynamics appear to be of greater importance in the prolonged opioid effect seen in the elderly.

Adult↗
PubMed1990

The effect of arteriovenous malformation resection on cerebrovascular reactivity to carbon dioxide.

To investigate the cerebral hemodynamic changes associated with obliteration of arteriovenous malformations (AVMs), we studied 26 patients undergoing total microsurgical AVM resection during isoflurane and N2/O2 anesthesia. Detectors were placed 5 to 6 cm from the margin of the lesion and in a homologous contralateral position. Cerebral blood flow (CBF) was measured using the intravenous xenon-133 technique before and after AVM resection, during both hypocapnia and normocapnia at each stage. Intraoperative changes in CBF were related to a risk score system based on the patient's history and preoperative angiograms. Seven otherwise healthy patients undergoing spinal surgery were studied to control for anesthetic effects. Patient demographic and clinical data for the AVM group conformed to the expected strata of a large AVM population. The CBF increased after excision (22 +/- 1 ml/100 g/min before excision to 30 +/- 2 ml/100 g/min after excision; mean +/- SE, n = 25, P less than 0.002) without a hemispheric difference. CO2 reactivity increased slightly after excision (4.2 +/- 0.3% change/mm Hg before excision to 4.7 +/- 0.3% change/mm Hg after excision; n = 14, P less than 0.02). The baseline CBF and CO2 reactivity were not different from the control group. There was a weak correlation between the risk score and the percentage of change in the ipsilateral CBF, with a trend for the patients with the lowest risk to have the lowest CBF changes after resection. There was no relationship between CO2 reactivity and risk grade. None of the patients awoke from anesthesia with unexpected neurological deficits. The highest CBF increases were associated with postoperative brain swelling in one patient and fatal intracerebral hemorrhage in another. Both patients had normal CO2 reactivity before excision. One patient suffered postoperative intracerebral hemorrhage, attributable to technical problems, and had no increase in CBF. We conclude that, with an acute increase in the arteriovenous pressure gradient (and cerebral perfusion pressure) that results from shunt obliteration, there is an immediate global effect of AVM resection to increase CBF. Cerebrovascular reactivity to CO2 remains intact both before and after excision.

Adult↗
PubMed1990

Pharmacokinetics and pharmacodynamics of edrophonium in elderly surgical patients.

The effect of age (over 70 yr) on the pharmacokinetics and pharmacodynamics of edrophonium was evaluated in seven patients aged 76-87 yr and in seven patients aged 27-57 yr. When elderly patients were compared with younger controls, the elderly exhibited a statistically significant decreased plasma clearance (5.9 +/- 2 versus 12.1 +/- 4 mL.kg-1.min-1) and a prolonged elimination half-life (84.2 +/- 17 versus 56.6 +/- 16 min). Pharmacodynamically, a higher concentration of edrophonium is required in elderly patients to produce the same effect as in the younger controls. This observation may be explained in part by changes in neuromuscular transmission that are a function of the aging process. In addition, even though plasma concentrations were significantly greater at every sampling point in the elderly than the younger group, there was no difference between either the maximum duration or the total duration of action of edrophonium in the two groups. The maximum duration of action of edrophonium in both groups was very brief (1.3-2.2 min). These results contrast with a previous study of the anticholinesterases neostigmine and pyridostigmine, in which the action of these drugs was significantly prolonged in elderly patients. Explanations for the observed differences between edrophonium and other anticholinesterases may relate to differences in chemical structure and the possibility that edrophonium produces antagonism of neuromuscular blockade by a different mechanism than neostigmine or pyridostigmine.

Adult↗
PubMed1989

Pharmacokinetics of sufentanil in neurosurgical patients undergoing hyperventilation.

The pharmacokinetics of sufentanil were determined in 11 hypocapnic (arterial PCO2 2.9-3.7 kPa) and seven normocapnic (arterial PCO2 5.3-6.0 kPa) neurosurgical patients. Following a single i.v. bolus of sufentanil 4 micrograms kg-1, multiple arterial samples were obtained at timed intervals and plasma concentration of sufentanil was measured by radioimmunoassay. Calculation of the pharmacokinetic parameters from the derived compartmental models demonstrated an increased total volume of distribution of sufentanil in hypocapnic patients (mean 5427 (SD 1866) ml kg-1 v. 3518 (1097) ml kg-1; P less than 0.05) in the control patients and a more prolonged elimination half-life (232 (60) min v. 143 (51) min; P less than 0.01). The increased distribution of sufentanil with hyperventilation was probably caused by an increased proportion of opioid in the nonionized state.

Adult↗
PubMed1989

A comparison of the cerebral hemodynamic effects of sufentanil and isoflurane in humans undergoing carotid endarterectomy.

Prompted by reports of potentially deleterious cerebral vasodilation by the synthetic opioid sufentanil, the authors compared the effects of either isoflurane/N2O and sufentanil/N2O on cerebral blood flow (CBF), arteriovenous difference in oxygen content (AVDO2), and CBF reactivity to changes in PaCO2 during carotid endarterectomy. Cerebral blood flow was measured using the iv method of 133-Xe CBF determination and AVDO2 was measured using systemic arterial-jugular venous oxygen content differences. Patients, age 68 +/- 1 yr (mean +/- SE), received either isoflurane (n = 10), 0.75% in O2 and N2O, 1:1; or sufentanil (n = 10), 1.5-2 micrograms/kg bolus and then 0.2-0.3 micrograms.kg-1.h-1 infusion in addition to O2 and N2O, 2:3. Measurements were made immediately before carotid occlusion, and then at two levels of PaCO2 (approximately 32 and 42 mmHg) after insertion of a temporary in-dwelling bypass shunt. Prior to carotid occlusion, there was no significant difference in CBF (ml.100 g-1.min-1) between patients receiving isoflurane (22 +/- 3) or sufentanil (20 +/- 2). Similarly, there was no difference in AVDO2 (vol-%) between isoflurane (4.5 +/- 0.7) and sufentanil (5.4 +/- 0.8) groups. Using a two-way ANOVA design with anesthetic as the between-group factor and elevation of PaCO2 as the within-group repeated measure, there was a significant effect of hypercarbia to increase CBF (P less than 0.0001) and decrease AVDO2 (P less than 0.001). The product of AVDO2 and CBF, which reflects cerebral metabolic oxygen consumption, remained constant (P = 0.364).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Cerebral blood flow and metabolism in patients undergoing anesthesia for carotid endarterectomy. A comparison of isoflurane, halothane, and fentanyl.

The effects of isoflurane, halothane, and fentanyl on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) during anesthesia prior to carotid endarterectomy were compared using the intravenous method of 133-Xenon CBF determination. Patients, mean (+/- SE) age 68 +/- 2, received either isoflurane (N = 16), 0.75% in O2 and N2O, 50:50; halothane (N = 11), 0.5% in O2 and N2O, 50:50; or fentanyl (N = 10), 5-6 micrograms/kg bolus and then 1-2 micrograms.kg-1.h-1 infusion in addition to O2 and N2O, 40:60. Measurements were made immediately before carotid occlusion. Mean (+/- SE) CBF (ml.100 g-1.min-1) was 23.9 +/- 2.1 for isoflurane, 33.8 +/- 4.8 for halothane, and 19.3 +/- 2.4 for fentanyl. CMRO2 (ml.100 g-1.min-1) was available from 22 patients and was 1.51 +/- 0.28 for isoflurane (N = 7), 1.45 +/- 0.24 for halothane (N = 6), and 1.49 +/- 0.21 for fentanyl (N = 9). Although CBF was greater during halothane than during isoflurane or fentanyl anesthesia (p less than 0.05), there were no demonstrable differences in CMRO2 among the 3 agents. We conclude that choice of anesthetic agent for cerebrovascular surgery with comparable anesthetic regimens should not be made on the basis of "metabolic suppression." During relatively light levels of anesthesia, vasoactive properties of anesthetics are more important than cerebral metabolic depression with respect to effects on the cerebral circulation.

Aged↗
PubMed1988

Electroencephalographic monitoring for ischemia during carotid endarterectomy: visual versus computer analysis.

In a retrospective study, we compared the use of computer-generated spectral electroencephalographic descriptors with a neurologist's interpretation of raw EEG data. Data were collected from patients undergoing carotid endarterectomy and anesthetized with isoflurane in nitrous oxide and oxygen. The EEG was recorded on magnetic tape during the period immediately before and after occlusion. These tapes were then analyzed off-line using a computer to generate averaged changes in 18 spectral descriptors. A strip-chart of raw EEG before and after the carotid occlusion was interpreted by a neurologist, who assigned changes in the EEG following occlusion to one of four visual inspection groups, depending on the severity of change. A descriptive examination of the distribution of changes in spectral descriptors revealed that no single descriptor adequately reflected the neurologist's interpretation of the raw EEG. Using data from 20 patients, the percent change from preocclusion to postocclusion values for total power, spectral edge frequency, spectral variance, and log spectral variance was examined. Only for the visual inspection group judged by the electroencephalographer to have the most severe ischemic change was there a significant difference in total power and log spectral variance. Although computer-processed EEG devices are of value as trending devices for detecting visual patterns associated with inadequate cerebral perfusion, single descriptors in this study did not consistently reflect a neurologist's diagnosis of ischemia. Single descriptors of spectral EEG analysis may not be sufficient to use as alarm variables in the recognition of cerebral ischemia.

Brain Ischemia↗