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Biomedical subjects

J G Reves

Publications and source records attributed to J G Reves.

At least 145 records · Page 8Linked to original sources
PubMed1987

Pharmacokinetics of esmolol in anesthetized patients receiving chronic beta blocker therapy.

The pharmacokinetics of esmolol, a new, ultra-short-acting beta adrenergic blocking drug, were studied in 19 patients undergoing coronary artery surgery. Esmolol was administered as a continuous infusion, and blood concentrations were measured at intervals up to 40 min after discontinuation of the infusion. In all patients, a bi-exponential equation best described the esmolol concentration--time curve. Half-lives for the distribution and elimination phases were 1.34 +/- 0.77 min and 9.9 +/- 4.55 min (mean +/- SD), respectively. The mean values for V beta and V epsilon were 1.9 +/- 1.24 l X kg-1 and 0.41 +/- 0.31 l X kg-1, respectively, and the total clearance was 128 +/- 41 ml X kg-1 X min-1.

Adrenergic beta-Antagonists↗
PubMed1987

Effects of preoperative calcium entry blocker therapy on alpha-adrenergic responsiveness in patients undergoing coronary revascularization.

Calcium entry blocking drugs (CaEBs) produce vasodilation and, in high doses, modify alpha adrenergic receptor function. Previous laboratory data suggested that CaEBs might alter the response to alpha-adrenergic stimulation. The authors tested the hypothesis that CaEB therapy altered alpha-adrenergic responsiveness in patients chronically treated with CaEBs. Twenty-six consenting patients with coronary artery disease were given a phenylephrine challenge before anesthesia induction and during cardiopulmonary bypass while the aorta was cross-clamped. A log dose response curve was constructed for each patient, and the ED30 (dose producing 30% increase in systemic vascular resistance) was calculated. Nine patients not treated with CaEB served as controls, and 17 patients were treated with nifedipine (n = 7) or diltiazem (n = 10). Mean ED30 was increased approximately three-fold in the CaEB treated groups compared to the control group. However, there was no statistical difference in the ED30 or phenylephrine dose response slopes between CaEB treated and untreated patients. In awake patients, ED30 correlated with nifedipine levels (R = 0.953, P = 0.01). There was a significant (P less than .02) shift in the ED30 from prior to anesthesia to during aortic cross-clamp and cardiopulmonary bypass; ED30 was approximately 50% less and correlated with CaEB level (R = 0.713, P = 0.03). Hemodynamic variables were not different between groups at any interval. Our data suggest that vascular responsiveness to phenylephrine in patients treated with CaEBs is diminished, but similar to that in untreated patients. Vascular responsiveness decreases in awake patients with increasing nifedipine levels.

Adult↗
PubMed1987

Hemodynamic effects of esmolol in chronically beta-blocked patients undergoing aortocoronary bypass surgery.

The hemodynamic effects of esmolol were studied in 40 patients scheduled for elective coronary artery surgery to determine whether the administration of esmolol in chronically beta-blocked patients would result in additional attenuation of sympathetically mediated hemodynamic stress responses to noxious stimuli. Patients were randomly assigned to receive IV infusions of esmolol or 5% dextrose in water (D5W). All received their regular dose of beta-adrenergic blocker within 6 hr of surgery and were anesthetized with diazepam, pancuronium, and enflurane. Increases (greater than 25% above baseline) in systolic blood pressure were treated with sodium nitroprusside (SNP). Esmolol was started before induction of anesthesia and continued until 5 min after maximal sternal spread. There were no statistically significant differences between the esmolol and control groups in any hemodynamic parameter during induction, intubation, skin incision, and sternotomy. Only at 5 min after maximal sternal spread was there a statistically significant lower systolic blood pressure in the esmolol-treated group. However the incidence and magnitude of SNP use in the control group was significantly (P less than 0.05) greater. Thus, the lower blood pressure, in the absence of changes in systemic vascular resistance, cardiac index, heart rate, and pulmonary capillary wedge pressure points toward a decrease in myocardial contractility, suggesting that the addition of esmolol to chronically used beta-blockers resulted in an additional negative inotropic effect. We conclude that in patients with coronary artery disease in whom chronic beta-blocker therapy is continued until the time of surgery, esmolol does not further attenuate the heart rate response but does attenuate the increase in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1987

Comparison of hemodynamic responses to isoproterenol infusion and surgical stress in patients given cardioselective and noncardioselective beta-adrenergic antagonists.

Recent studies have demonstrated the presence of physiologically active beta 2 receptors in the myocardium. We hypothesized that activation of cardiac beta 2 receptors by endogenously released epinephrine and norepinephrine during surgical stress would add to the positive chronotropic response mediated by beta 1 stimulation. Twenty patients scheduled for coronary artery bypass grafting were studied. Ten patients received a beta 1-selective antagonist (atenolol, 6; metoprolol, 4) and ten patients received a nonselective beta 1 and beta 2 antagonist (propranolol) preoperatively. An isoproterenol dose-heart rate response test was performed. After stabilization, general anesthesia was induced followed by tracheal intubation and surgery. Hemodynamic data were recorded before induction, 1 min after induction, 5 min after intubation, 1 min before and after skin incision, 1 min before and after sternotomy. The ten patients on cardioselective beta-blocker drugs had significantly greater increases in heart rate during isoproterenol administration than did the non-cardioselectively blocked group of patients. Heart rate responses to tracheal intubation and surgical stress were not significantly different between the two groups at any point. We conclude that changes in heart rate during perioperative stress are primarily mediated through activation of beta 1 receptors in the myocardium and that patients on either cardioselective or noncardioselective beta-blockers have similar protection to adrenergic-mediated stressful hemodynamic events.

Adrenergic beta-Antagonists↗
PubMed1987

The changing survival benefits of coronary revascularization over time.

Previous comparisons of medical and surgical therapy for coronary artery disease were performed in the 1970s and may need to be updated to reflect current treatment efficacy. The purpose of this investigation was to determine the impact on long-term patient survival of changes over time in medical and surgical therapy. Among 5125 patients referred for catheterization between 1969 and 1984, 2261 underwent surgery, and 2864 received medical therapy. Survival in both medically and surgically treated patients improved over time. The improvement in medical patients was due to less sick patients being treated (a decreasing baseline risk), while that observed in surgical patients was due to refinements in care. The rate of improvement in survival over time was much greater in surgical patients, and the difference as compared with medical therapy was highly significant (treatment interaction with time p less than .0001). Estimates of 5 year survival adjusted for baseline risk factors for a patient in 1977 with one-, two-, or three-vessel disease and an ejection fraction of 0.40 were 0.88, 0.80, and 0.64 in medically treated, and 0.88, 0.87, and 0.80 in surgically treated patients. Corresponding projected estimates for 1984 were unchanged for medical patients but improved for surgical patients (0.93, 0.92, and 0.90). Thus, the projected survival benefits of surgery in 1984 appear more significant for all categories of coronary artery disease because of a differential improvement in surgical therapy. These data are relevant to therapeutic decision making for current patients and emphasize the importance of continued analysis of this topic as treatment efficacies change over time.

Coronary Artery Bypass↗
PubMed1986

Effects of protamine administration after cardiopulmonary bypass on complement, blood elements, and the hemodynamic state.

Nineteen patients were prospectively selected and studied before and after the administration of protamine sulfate following cardiopulmonary bypass (CPB). After protamine administration, C3a, C4a, and C4d were elevated; the peak levels of C3a and C4a were in samples taken 10 minutes after protamine administration while those of C4d were in those obtained at 5 hours. Only C3a was elevated after CPB and before protamine administration. In vitro, only the combination of protamine sulfate and heparin, and neither alone, resulted in increased C3a and C4a. Administration of protamine was associated with small and transient decreases in total white blood cells, granulocytes, and platelets, and with small and transient reductions in systemic and pulmonary arterial and left and right atrial pressures. Systemic vascular resistance fell (p = 0.07), and pulmonary vascular resistance rose but the change could be due to chance (p = 0.29). These data and those reported by others support the inference that complement activation occurs during CPB by the alternative pathway and again during protamine administration by the classic pathway; and that this accompanies a whole-body inflammatory reaction with blood cell and hemodynamic changes which, when extreme, could result in a severe hemodynamic derangement.

Blood Cell Count↗
PubMed1986

Clinical and angiographic assessment of complex mammary artery bypass grafting.

The internal mammary artery has become the coronary bypass graft of choice in recent years because of enhanced long-term patency. Along with this trend, sequential, bilateral, and free mammary grafts have been employed more frequently in an effort to maximize the number of distal internal mammary anastomoses. This approach of maximally using the internal mammary artery (complex mammary grafting) seems logical, but at present little information about patency of the newer types of internal mammary artery grafts is available to justify the more complicated procedures. Over a 15 month period, 207 patients underwent bypass graft angiography from 1 to 32 weeks after operation. This is an 85% restudy rate for a consecutive series of coronary bypass procedures. Patency was defined as complete filling of the graft and distal vessel bypassed. A total of 841 distal vessels were grafted, or 4.1 per patient. The overall patency rate was 91% for 503 distal vein graft anastomoses and 99% for 338 internal mammary artery grafts. Individual patency rates of distal anastomoses, expressed as number patent/total (percent patent), were as follows: simple vein grafts, 262/285 (92%); sequential vein grafts, 196/218 (90%); left internal mammary artery to left anterior descending coronary artery, 109/110 (99%); left internal mammary to circumflex marginal artery, 14/14 (100%); right internal mammary to right coronary artery, 19/20 (95%); right internal mammary to left anterior descending coronary artery, 10/10 (100%); right internal mammary to circumflex marginal artery via transverse sinus, 18/20 (90%); sequential left internal mammary artery to left anterior descending system, 133/134 (99%); sequential left internal mammary to circumflex marginal system, 15/15 (100%); free internal mammary artery, 9/9 (100%); free sequential internal mammary artery, 6/6 (100%). Of the 18 patent transverse sinus right internal mammary grafts to the circumflex marginal artery, three exhibited very slow flow and probably were not functional. The hospital mortality associated with internal mammary revascularizations was 0.4% for nonemergency cases and 3.1% for emergency procedures. On the basis of clinical and postoperative graft patency data, expanded use of more complicated types of mammary grafts seems justified. Function of the right internal mammary graft to the circumflex marginal artery was suboptimal, and this method has been discontinued. All other complex mammary techniques had excellent patency rates as compared to vein grafts, and these differences may become even more significant in the late postoperative period.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1986

Comparison of sufentanil and enflurane-nitrous oxide anesthesia for myocardial revascularization.

This study compared the stress response in patients with coronary artery disease undergoing myocardial revascularization anesthetized with either sufentanil and oxygen or enflurane-nitrous oxide and oxygen. Throughout induction and maintenance of anesthesia, and while the patients were in the intensive care unit, hemodynamics plus plasma catecholamine, sufentanil, and enflurane concentrations were recorded and compared. Three groups were studied: sufentanil, 15 micrograms/kg at induction; sufentanil, 15 micrograms/kg at induction plus 10 micrograms/kg on initiation of cardiopulmonary bypass (CPB); and enflurane anesthesia. Hemodynamics were remarkably stable in all groups but required considerable fine tuning when enflurane was administered. The "stress" of CPB was blunted by the additional dose of sufentanil, as well as by enflurane. This was reflected in those patients receiving the extra sufentanil or enflurane by less severe increases in their epinephrine or norepinephrine concentrations and by less frequent use of sodium nitroprusside to control mean arterial pressure compared to the group of patients given the lower-dose sufentanil. This study suggests that higher blood levels of sufentanil can attenuate, but not eliminate, the stress response to CPB, as can enflurane, and that both the narcotic and inhalation anesthetic techniques for patients with coronary artery disease were quite satisfactory.

Anesthesia↗
PubMed1986

Isoflurane decreases the cortisol response to cardiopulmonary bypass.

Eighteen patients with normal left ventricular function scheduled for elective myocardial revascularization were anesthetized with fentanyl (52-58 micrograms/kg). At the beginning of hypothermic cardiopulmonary bypass (CPB) they were assigned to a control (C) group (n = 6) that did not receive further anesthesia, or to a group given either 1% isoflurane (n = 6) or 2% isoflurane (n = 6). Blood samples for measurement of total plasma cortisol concentrations were obtained before, during, and after CPB. Hemodynamic measurements before and after CPB were not different among groups. Patients in group C required higher infusion rates of sodium nitroprusside (P less than or equal to 0.05) and patients given 2% isoflurane received more phenylephrine (P less than or equal to 0.05) to keep mean arterial pressure at 50 +/- 10 mm Hg during CPB. Isoflurane caused a dose-related decrease in total plasma cortisol concentrations during and after CPB. We conclude that increased depth of anesthesia attenuates the cortisol (stress) response to cardiopulmonary bypass.

Cardiopulmonary Bypass↗
PubMed1985

Perioperative use of esmolol.

Stressful surgical stimuli, such as endotracheal intubation, surgical incision, organ manipulation and emergence from anesthesia, elicit adrenergic responses that precipitate transient but intense increases in heart rate and blood pressure. Although this response is well tolerated in healthy patients, patients with ischemic heart disease are at significant risk of myocardial ischemia and infarction owing to the sudden increase in myocardial oxygen demand. Parenteral beta blockers are effective in blunting this adrenergic response, but the duration of action of these agents is long-lasting and the degree of beta blockade is often difficult to predict. Further, long-acting parenteral beta blockers may cause adverse effects, the reversal of which presents a difficult clinical problem in patients with ischemic heart disease. The availability of esmolol, an ultrashort-acting parenteral beta-adrenergic antagonist with a half-life of 9 minutes, brings obvious advantages to the perioperative management of hypertension and tachycardia. With esmolol treatment, the difficulties of therapy with long-lasting beta blockers are avoided. Also, to blunt the adrenergic response, the anesthesiologist will have an alternative to increasing the depth of anesthesia, which can accentuate cardiovascular depression and prolong awakening and postoperative respiratory depression. Clinical studies performed during the perioperative period reveal that esmolol is safe and effective in this setting. Esmolol has been shown to be safe and efficacious in patients in ASA classifications I through IV and patients undergoing carotid endarterectomy and coronary artery bypass surgery. The pharmacokinetic profile, rapid onset and elimination half-life make this agent particularly well suited to treat the very intense but transient adrenergic responses to surgical stress in patients undergoing cardiac and noncardiac surgery.

Adrenergic beta-Antagonists↗
PubMed1985

Computer-assisted continuous infusions of fentanyl during cardiac anesthesia: comparison with a manual method.

The design and implementation of a computer-assisted continuous infusion (CACI) system to rapidly attain and maintain a constant plasma fentanyl concentration (PFC), as well as a CACI system that allowed the anesthesiologist to change the plasma level of fentanyl during cardiac anesthesia, were developed. In 30 patients (three groups of 10 patients each) these two automated methods of fentanyl infusion were compared with a manual fentanyl administration method. There was excellent agreement in the measured/predicted PFC ratios with the CACI stable fentanyl level system (ratio = 0.99, n = 91) and in the CACI variable fentanyl level system (ratio = 1.08, n = 79). The stable fentanyl level group of patients received significantly more (P less than 0.05) fentanyl than did the other groups. The CACI variable fentanyl level group of patients had greater hemodynamic stability, required significantly (P less than 0.05) fewer adjuvant drug interventions and experienced significantly (P less than 0.05) fewer hypotensive and hypertensive episodes than the manual, bolus fentanyl (control) group. These data show that a computer-assisted automated infusion of fentanyl is safe and as good as manual methods. CACI has greater potential as a new method of intravenous anesthesia administration.

Adult↗
PubMed1985

Midazolam pharmacodynamics and pharmacokinetics during acute hypovolemia.

This study was designed to test the hypothesis that acute hypovolemia would compromise the compensatory hemodynamic mechanisms to midazolam and decrease its metabolic clearance. Experiments were performed on seven chronically instrumented female beagle dogs. Animals received a single intravenous dose of midazolam, 10 mg/kg, 4 days apart during normovolemic (N) and hypovolemic (H) states in a random sequence. Hypovolemia was achieved by the withdrawal of 26 ml/kg of blood, equivalent to one-third of the calculated blood volume. Midazolam plasma concentrations were determined at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 h after midazolam injection. Elimination half-life (t 1/2 beta) was significantly longer and total clearance was significantly lower during H than during N. Initial distribution half-life, central compartment volume, total volume of distribution, and plasma protein binding were similar in both N and H states. Midazolam caused a significant decrease in systolic blood pressure (SBP) and an increase in heart rate (HR) during N, and produced significant decreases in SBP, diastolic blood pressure (DBP), and mean arterial pressure (MAP) during H. Midazolam led to similar per cent decreases in blood pressure and cardiac output in states N and H; however, the absolute values of blood pressure and cardiac output were significantly (P less than 0.001) lower in the hypovolemic state than in the normovolemic state. These data suggest that the hypotensive effects of midazolam, like those of other intravenous induction agents, could be potentiated by volume depletion.

Anesthetics↗