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Biomedical subjects

J G Reves

Publications and source records attributed to J G Reves.

At least 109 records · Page 6Linked to original sources
PubMed1990

Pharmacokinetic model-driven infusion of fentanyl: assessment of accuracy.

Computer-assisted continuous infusion (CACI) is a pharmacokinetic model-driven infusion device that enables physicians to administer intravenous (iv) drugs in a quantitative fashion, specifying a theoretical blood or plasma concentration. This study evaluated the accuracy of CACI administration of fentanyl using a newly developed CACI device programmed with a well-known set of pharmacokinetic parameters for fentanyl. Patients received diazepam 1 or 2 h before surgery. Anesthesia was induced by a combination of 70% N2O and fentanyl administered by CACI to a predicted concentration of 15-25 ng.ml-1. After neuromuscular blockade and tracheal intubation, the desired plasma fentanyl concentration (setpoint) entered into CACI was 3-6 ng.ml-1, and then the setpoint fentanyl concentration was titrated according to strict criteria of adequate or inadequate anesthesia. Plasma samples for subsequent assay of fentanyl concentration then were taken: at predefined stimuli, when inadequate anesthesia occurred, or 5 min before an anticipated decrease in the fentanyl setpoint. The predictive accuracy of CACI was assessed by calculating for each patient the tenth, 50th, and 90th percentile of the performance error and absolute performance error from each measured and predicted plasma sample pair. Cumulative probability functions for each of these were then plotted. Precision was defined as the dispersion of the tenth to 90th percentile of the median percent performance error for the population and was found to be -31-26%. The median population performance error was -4%, and the median population absolute performance error was 21%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Safety of rapid administration of flumazenil in patients with ischaemic heart disease.

The purpose of this study was to determine if higher (36 micrograms.kg-1) doses of flumazenil (a new benzodiazepine (BZ) antagonist) produced an effect on haemodynamics. Twelve patients with class III-IV angina were entered into this double-blind randomised placebo-controlled study. BZ were withheld for 2 weeks prior to surgery. Patients were placed on an ambulatory monitor 18 h prior to surgery to record changes in heart rate rhythm and ST segment changes. The patients were given secobarbital 100-200 mg and morphine 0.12 mg.kg-1 90 min prior to surgery. Flumazenil or placebo was given in divided doses every 3 min (1 mg, 1 mg, 1 mg). Complete haemodynamic profiles were obtained at baseline and 2 min following each injection of flumazenil. Flumazenil produced a minimal but statistically significant reduction in systolic blood pressure (147 +/- 13.9 to 137 +/- 18.4 mmHg) and diastolic blood pressure (74 +/- 14.8 to 67 +/- 13 mmHg). There was no consistent effect on heart rate, pulmonary capillary wedge pressure or cardiac index. We conclude that flumazenil is safe when administered in relatively high doses to patients with ischaemic heart disease who have not received benzodiazepines.

Coronary Disease↗
PubMed1990

Isoflurane-induced vasodilation: role of the alpha-adrenergic nervous system.

Isoflurane is a potent systemic vasodilator. Because isoflurane vasodilation is clinically significant, we sought to explore whether decreases in systemic vascular resistance caused by isoflurane involve the alpha-adrenergic nervous system in humans. Specifically, we tested the hypothesis that isoflurane systemic vasodilation is mediated via inhibition of vascular alpha 1-adrenergic responsiveness. Phenylephrine pressor dose-response curves were established before anesthesia and during isoflurane/oxygen anesthesia in patients undergoing coronary artery bypass surgery; all patients included in the study (n = 11) demonstrated significant (P = 0.0001) decreases in systemic vascular resistance when isoflurane was given in concentrations adequate to produce a 20% decrease in mean arterial blood pressure. Polynomial regression of the phenylephrine dose-response curve was used to estimate the phenylephrine dose required to increase mean arterial blood pressure 15 mm Hg, designated PD15 mm Hg. Each patient served as his or her own control. Preanesthetic baseline PD15 mm Hg values (115 +/- 23 micrograms [1.4 +/- 0.3 micrograms/kg], mean +/- SEM) were not significantly different from isoflurane PD15 mm Hg values (124 +/- 20 micrograms [1.5 +/- 0.3 micrograms/kg]). End-tidal isoflurane concentration ranged from 0.6%-1.5%; isoflurane PD15 mm Hg was not correlated with end-tidal isoflurane concentration. Patient characteristics and hemodynamics did not affect PD15 mm Hg. These results suggest that isoflurane-induced systemic vasodilation is not mediated via inhibition of alpha 1-adrenergic responsiveness, disproving our hypothesis. This finding has clinical importance because it demonstrates that alpha 1-adrenergic stimulation with phenylephrine is effective in correcting hypotension in patients receiving isoflurane anesthesia.

Adrenergic alpha-Agonists↗
PubMed1990

Esmolol for treatment of intraoperative tachycardia and/or hypertension in patients having cardiac operations. Bolus loading technique.

Esmolol, administered as a bolus followed by continuous infusion, was used to treat the occurrence of transient tachycardia and hypertension or tachycardia alone before cardiopulmonary bypass in 45 patients. The study was conducted in two phases. Phase I (15 patients) was a dose-finding study and phase II (30 patients) was a randomized, double-blind, placebo-controlled efficacy study. All patients received the last dose of their usual beta-adrenergic blocker the night before the operation and were anesthetized with midazolam, vecuronium, and enflurane in oxygen. Treatment criteria were either a systolic blood pressure greater than 140 mm Hg and a heart rate greater than 70 or a heart rate greater than 80 beats/min. In phase I, graduated doses of esmolol were given to successive patients. A dose of 80 mg followed by a 12 mg/min infusion was declared effective. Phase II patients were randomized to receive esmolol (n = 16) or placebo (n = 14). Hemodynamic data were collected at baseline and 1, 3, 5, and 10 minutes after the administration of esmolol. Plasma norepinephrine was measured at baseline, 1, and 10 minutes. Esmolol significantly (p less than 0.05) reduced heart rate at 1, 3, 5, and 10 minutes but did not change blood pressure, pulmonary artery diastolic pressure, right atrial pressure, cardiac output, or systemic vascular resistance. Our results show that a bolus loading dose of esmolol is safe and effective in the treatment of tachycardia in patients with ischemic heart disease and that esmolol rapidly blocks the beta-adrenergic effects of norepinephrine associated with surgical stress.

Adrenergic beta-Antagonists↗
PubMed1990

Clinical evaluation of single versus multiple mammary artery bypass.

The superior patency and clinical advantages of internal mammary artery (IMA) grafting are well established. However, the relative benefits of routine multiple IMA grafting remain uncertain. To determine whether routine multiple compared with single IMA utilization improved survival of patients undergoing coronary bypass procedures, 1,063 patients were prospectively allocated, beginning in 1984, to divergent management strategies of single (group 1, n = 420) versus multiple IMA grafting (group 2, n = 643). Subsequent analysis of anatomical extent of disease and preoperative baseline risk factors showed no differences (p = NS) between the two groups. All variables reflecting operative technique were similar (p = NS) for the two groups, except 74% of group 1 patients with multivessel disease received a single IMA graft, whereas 71% of group 2 patients with multivessel disease received multiple IMAs (p less than 0.05). By multivariate analysis, impairment of left ventricular ejection fraction, acute evolving myocardial infarction, advanced age, and unstable angina were incremental risk factors for mortality (all p less than 0.03), but group assignment (p = 0.4) and ultimate therapy were not (p = 0.6). Survival probabilities (expressed as 30-day group 1/group 2; 4-year group 1/group 2) were overall (0.97/0.98; 0.93/0.90), elective (0.98/0.99; 0.97/0.92), acute (0.95/0.97; 0.89/0.88), age of less than 65 years (0.98/0.99; 0.97/0.93), age of 65 years or older (0.93/0.97; 0.84/0.89), ejection fraction of 0.40 or more (0.97/0.99; 0.95/0.94), ejection fraction of less than 0.40 (0.95/0.96; 0.87/0.82), nondiabetic (0.98/0.98; 0.94/0.91), and diabetic (0.92/0.97; 0.88/0.87). No differences in survival were significant (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1990

Diabetic patients have abnormal cerebral autoregulation during cardiopulmonary bypass.

We tested the hypothesis that insulin-dependent diabetic patients with coronary artery bypass graft surgery experience altered coupling of cerebral blood flow and oxygen consumption. In a study of 23 patients (11 diabetics and 12 age-matched controls), cerebral blood flow was measured using 133Xe clearance during nonpulsatile, alpha-stat blood gas managed cardiopulmonary bypass at the conditions of hypothermia and normothermia. In diabetic patients, the cerebral blood flow at 26.6 +/- 2.42 degrees C was 25.3 +/- 14.34 ml/100 g/min and at 36.9 +/- 0.58 degrees C it was 27.3 +/- 7.40 ml/100 g/min (p = NS). The control patients increased cerebral blood flow from 20.7 +/- 6.78 ml/100 g/min at 28.4 +/- 2.81 degrees C to 37.6 +/- 8.81 ml/100 g/min at 36.5 +/- 0.45 degrees C (p less than or equal to 0.005). The oxygen consumption was calculated from jugular bulb effluent and increased from hypothermic values of 0.52 +/- 0.20 ml/100 g/min in diabetics to 1.26 +/- 0.28 ml/100 g/min (p = 0.001) at normothermia and rose from 0.60 +/- 0.27 to 1.49 +/- 0.35 ml/100 g/min (p = 0.0005) in the controls. Thus, despite temperature-mediated changes in oxygen consumption, diabetic patients did not increase cerebral blood flow as metabolism increased. Arteriovenous oxygen saturation gradients and oxygen extraction across the brain were calculated from arterial and jugular bulb blood samples. The increase in arteriovenous oxygen difference between temperature conditions in diabetic patients and controls was significantly different (p = 0.01). These data reveal that diabetic patients lose cerebral autoregulation during cardiopulmonary bypass and compensate for an imbalance in adequate oxygen delivery by increasing oxygen extraction.

Brain↗
PubMed1989

Continuous infusion of alfentanil for maintenance of anesthesia: comparison with halothane anesthesia.

This study compares anesthetic maintenance, hemodynamic stability, and speed of recovery obtained with inhalational halothane versus intravenous alfentanil anesthesia administered continuously. In two groups of patients, anesthesia was induced with sodium thiopental, maintained with 70% nitrous oxide in 30% oxygen, and either halothane (n = 10) or a continuous infusion of alfentanil (n = 10). The administration of the allocated anesthetic was adjusted according to strict predefined criteria of inadequate anesthesia. After endotracheal intubation, hemodynamics (heart rate, systolic and diastolic pressure) changed less in the alfentanil group (P less than .01). Overall hemodynamic stability was the same in both groups. In neither group was there recall of intraoperative events. Recovery was assessed by the time from cessation of nitrous oxide administration to return of spontaneous ventilation, response to simple command, extubation, orientation, and discharge from the recovery area. The time taken to respond to simple command was significantly shorter in the alfentanil group (P less than .05), but other indices of recovery were similar.

Adult↗
PubMed1989

Current management of mitral valve incompetence associated with coronary artery disease.

At a time when hospital mortality for adult cardiac operations is continuing to fall, the combined mitral valve coronary bypass subset remains at relatively high risk. Efforts to improve results should be directed toward a more general application of mitral reconstruction in this population, tailoring the type of repair to the pathological anatomy of valve dysfunction. Other promising therapeutic measures include the liberal use of reperfusion therapy in the acute papillary muscle dysfunction group, better selection patients for operation, and perhaps operative recommendation to a greater proportion of the more stable patients that previously were treated medically. Finally increasing the general awareness of this problem should hasten the development of improved management strategies.

Coronary Artery Bypass↗
PubMed1989

Evaluation of pentamorphone in humans: a new potent opiate.

We evaluated the analgesic properties of 14-beta-n-pentylaminomorphinone (pentamorphone), a new morphinan derivative, in 23 male volunteers divided into 6 groups who were given either placebo (1 per group) or 0.015, 0.03, 0.06, 0.12, 0.24, 0.48 microgram.kg-1 pentamorphone intravenously. Analgesia was evaluated by the maximal tolerance to a spring-loaded rod on the tibia and manubrium. Analgesic assessments and arterial blood samples were taken prior to and at set time intervals following drug administration. Pentamorphone produced a linear increase in pain tolerance with increasing dose as well as a dose-dependent depression of ventilation. Pentamorphone had no effect on blood pressure or heart rate in the doses used. Plasma histamine levels at 5 minutes were not elevated with any of the dosages. Pentamorphone appears to be an analgesic with clinically tolerable side effects in the range 0.12 to 0.24 microgram.kg-1 that merits further evaluation under clinical conditions.

Analgesics↗
PubMed1989

The effect of nitroglycerin on response to tracheal intubation. Assessment by radionuclide angiography.

The effect of intravenous (IV) nitroglycerin (NTG) on perioperative myocardial ischemia as detected by single pass radionuclide angiocardiography was studied in 20 patients scheduled for elective coronary artery bypass grafting (CABG). Ten patients, selected at random, received IV NTG 1 microgram.kg-1.min-1 (NTG group) and 10 others, IV saline (control group). Anesthetic induction consisted of midazolam 0.2 mg.kg-1, vecuronium 0.1 mg.kg-1, and 50% N2O in O2. ECG leads I, II, and V5 were monitored for ST segment changes. Single pass radionuclide angiocardiography (RNA) was performed at 5 times: prior to induction, prior to tracheal intubation, and at 1, 3.5, and 6 min following intubation. The presence of new regional wall motion abnormalities (RWMA) was determined from each RNA study as compared with the preinduction measurement. Apart from one patient in the control group who developed a new "v" wave after intubation, there was no evidence of ischemia by pulmonary capillary wedge pressure. No ECG evidence of ischemia was detected in any patient. Despite this, new regional wall motion abnormalities were observed in 3 patients in the control group and 1 patient in the NTG group. Blood pressure and heart rate responses of patients with new RWMA were not significantly different from other patients. The low incidence of ischemia in this population precludes a definitive statement regarding the efficacy of IV NTG, but the lower incidence of RWMA in the NTG group suggests a protective effect.

Coronary Circulation↗
PubMed1989

Alfentanil and midazolam: new anesthetic drugs for continuous infusion and an automated method of administration.

New drugs like alfentanil and midazolam have the primary advantage of metabolizing faster than existing compounds in their class. Because of shorter plasma half-lives, the drugs are well suited for continuous infusion. In our hands, CACI is a valuable clinical instrument and research tool. Although some anesthetic drugs can be given safely and effectively by bolus injection, whenever a titrated continuous infusion is appropriate (and physiologically closed-loop delivery is not possible), use of a CACI-type instrument should be the preferred method of administration. With the availability for continuous infusion of alfentanil and midazolam, with their highly desirable pharmacodynamic properties and relatively effervescent pharmacokinetics, we believe that computerized pharmacokinetic model-driven infusion devices will play a significant role in future anesthetic practice.

Alfentanil↗
PubMed1989

Time course and hemodynamic effects of alpha-1-adrenergic bolus administration in anesthetized patients with myocardial disease.

Phenylephrine (Phe) is frequently administered as an intravenous (IV) bolus to increase blood pressure, yet the acute time course and hemodynamic effects of bolus Phe in patients with myocardial disease have not been reported. Therefore 50 randomized IV bolus doses of Phe (50, 100, 150, or 200 micrograms) were given to 18 patients during anesthesia for elective coronary artery surgery. Esophageal Doppler techniques were used to continuously monitor cardiac output (CO); mean arterial pressure (MAP), CO, and calculated systemic vascular resistance (SVR) were recorded every 5 seconds for a total of 2 minutes. The hemodynamic changes (mean +/- SEM) for each of the four doses of Phe (50, 100, 150, 200 micrograms) were maximal at about 42 seconds after the drug was given. They consisted of an increase in MAP (11.6 +/- 2.1, 15.6 +/- 2.4, 14.7 +/- 2.4, 18.0 +/- 1.5 mm Hg); increase in SVR (766 +/- 190, 930 +/- 310, 950 +/- 344, 1732 +/- 824 dynes.sec.cm-5); and a decrease in CO (-.58 +/- .11, -.68 +/- .13, -.73 +/- .20, -.77 +/- .18 L.min-1). Hypertension, increased age, low preoperative ejection fraction, high baseline CO, and low baseline SVR significantly (P less than 0.05) decreased hemodynamic responses to Phe (see text). In conclusion, bolus IV Phe in patients with myocardial disease increases MAP and SVR and simultaneously decreases CO; these peak hemodynamic events occur approximately 42 seconds after Phe administration.

Aged↗
PubMed1989

Ischemic mitral regurgitation.

At a time when hospital mortality for adult cardiac operations is continuing to fall, the ischemic mitral regurgitation subset remains at relatively high risk. Based on analysis of available data, efforts to improve results might be directed toward a more general application of mitral valve reconstruction in this population. Other promising therapeutic measures include the liberal use of reperfusion therapy in the acute papillary muscle dysfunction group, better selection of patients for operation, and, perhaps, operative recommendation to a greater proportion of the more stable patients who previously were treated medically. Incorporating these therapeutic concepts into routine clinical practice may improve the overall prognosis of this difficult subgroup.

Actuarial Analysis↗