J. G. Reves

Factors and Their Influence on Regional Cerebral Blood Flow during Nonpulsatile Cardiopulmonary Bypass

Abstract In this study we examined the relationship of regional cerebral blood flow (CBF) to mean arterial pressure, systemic blood flow, partial pressure of arterial carbon dioxide (PaCO 2 ), nasopharyngeal temperature, and hemoglobin during hypothermic nonpulsatile cardiopulmonary bypass (CPB). Regional CBF was determined by clearance of xenon 133 in 67 patients undergoing coronary bypass grafting procedures. There was a significant decrease in regional CBF (55% decrease) during CPB, with nasopharyngeal temperature and PaCO 2 being the only two significant factors ( p 2 did not significantly affect regional CBF. We conclude that cerebral autoregulation is retained during hypothermic CPB. Under the usual conditions of CPB, variations in flow and pressure are not associated with important physiological or detrimental clinical affects.

Hemodynamic responses to anesthetic induction with midazolam or diazepam in patients with ischemic heart disease.

Hemodynamic responses to induction of anesthesia with midazolam maleate and diazepam were compared in patients with ischemic heart disease. While breathing 100% oxygen, 10 patients (group M) received midazolam maleate, 0.2 mg/kg, and 10 patients (group D) received diazepam, 0.5 mg/kg. In addition, 10 patients (group MN) breathing 50% nitrous oxide in oxygen received midazolam, 0.2 mg/kg. Patients in group M had a small but statistically significant (p < 0.05) decrease (vs awake control values) in systemic and pulmonary arterial blood pressure, pulmonary arterial occluded pressure, stroke index, and left and right ventricular stroke work indices. Patients in group D experienced statistically significant decreases in systemic blood pressure. The only statistically significant differences between groups M and D occurred 5 minutes following drug administration: heart rates were higher and systemic pressures and left ventricular stroke work indices were lower following midazolam. Hemodynamic changes following midazolam and nitrous oxide were similar to those observed in patients given midazolam and 100% oxygen. Patients in all three groups responded to endotracheal intubation with transient increases in blood pressure, heart rate, and systemic vascular resistance, but the hemodynamic values spontaneously returned toward control levels within 2 to 5 minutes. Although differing somewhat, midazolam, like diazepam, provided rapid, hemodynamically stable induction of anesthesia in patients with ischemic heart disease.

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 < 0.05) fentanyl than did the other groups. The CACI variable fentanyl level group of patients had greater hemodynamic stability, required significantly (P < 0.05) fewer adjuvant drug interventions and experienced significantly (P < 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.

Calcium entry blockers: uses and implications for anesthesiologists.

Calcium Entry Blockers: Uses and Implications for Anesthesiologists J G Reves;Igor Kissin;William Lell;Steve Tosone; Anesthesiology

Comparison of two benzodiazepines for anaesthesia induction: midazolam and diazepam.

SummaryRo 21-3981 is a newly synthesized water soluble benzodiazepine derivative. Its pharmacological properties are similar to diazepam. This investigation was designed to establish the effective induction dosage of Ro 21-3981 and to compare it with diazepam for induction of anaesthesia. The ED50 for Ro 21-3981 induction is 0.15 mg/kg and ED100 is 0.2 mg/kg. Ro 21-3981 is one and one-half times as potent as diazepam (0.3 rng/kg) and more rapid in action. There is significantly less pain on injection with Ro 21-3981 as compared to diazepam. Cardiovascular stability and apnoea were observed with both drugs. Ro 21-3981 is a promising anaesthetic induction drug that merits further human study.RésuméLe RO-21-3981 est une nouvelle benzodiazépine de synthèse soluble dans ľeau. Ses propriétés pharmacologiques sont semblables àa celles du diazepam.Cette étude avait pour but de déterminer la dose efficace ďinduction de cet agent et de comparer le RO-21-3981 au diazepam comme agent ďinduction.Ľinduction (perte du réflexe ciliaire et absence de réponse aux commandements) se produisait chez 50 pour cent des sujets àa une dose de 0.15 mg/kilo et chez 100 pour cent des sujets avec 0.2 mg/kilo. Le RO-21-3981 est une fois et demie plus puissant que le diazepam (dose efficace : 0.3 mg/kilo) et plus rapide ďaction que ce dernier.Il est moins irritant que lui et cause moins de douleur en injection. On a observé avec les deux médicaments une grande stabilité cardiovasculaire. Avec ľun comme avec ľautre, on peut rencontrer de ľhypoventilation et une apnée nécessitant une assistance respiratoire.Le RO-21-3981 nous semble un agent ďinduction prometteur et mérite une étude plus poussée chez ľhumain.

Cardiovascular effects of esmolol in anesthetized humans.

We studied the cardiovascular effects of esmolol, a newly synthesized β-adrenocepter antagonist, in anesthetized humans. Forty patients (four groups of 10 each) with ischemic heart disease and normal ventricular function were anesthetized with diazepam, pancuronium, and N2O in O2. Esmolol was given by continuous infusion in cumulative doses of 1100 fig/kg (group 1), 2000 μg/kg (group 2), and 2700 μg/kg (group 3); a control group received no esmolol. Infusion of esmolol was begun 3 min prior to and ended 4 min after tracheal intubation. All three doses of esmolol significantly (P < 0.001) attenuated the heart rate responses to intubation. Rate-pressure products were significantly (P < 0.001) lower in esmolol-treated patients than in controls after intubation, but ST-segment changes compatible with ischemia occurred in one patient in each group. Increases in heart rate were associated with significant increases in plasma norepinephrine levels (r = 0.45, P = 0.02) in the control group, but not in esmolol-treated patients, a demonstration that esmolol antagonizes the β-adrenergic effects of norepinephrine. The effect of esmolol on heart rate was absent 5 min after cessation of infusion, and plasma levels of esmolol were undetectable in 26 of 30 treated patients 15 min after the termination of esmolol infusion. Esmolol has a rapid onset and short duration of effect. It can be used safely during anesthesia in patients with normal ventricular function to attenuate cardiac response to sympathetic stimulation.

Midazolam compared with thiopentone as a hypnotic component in balanced anaesthesia: a randomized, double-blind study.

SummaryMidazolam is a short-acting water soluble benzodiazepine derivative. It is a hypnotic used for intravenous anaesthesia induction. The present investigation was designed in a prospective double-blind fashion to compare midazolam with thiopentone as hypnotic components in balanced anaesthesia. The study included 50 healthy patients undergoing relatively short surgical procedures. The results revealed that thiopentone is faster in onset than midazolam for induction of anaesthesia, with less variation of dose response. However, maintenance of anaesthesia was superior with midazolam, requiring fewer supplemental anaesthetic drugs, having better patient acceptance and providing more amnesia. Postoperative complications were very low with both techniques. Midazolam was surprisingly similar to thiopentone in most parameters including emergence time from anaesthesia. Midazolam is a new drug with potential both for induction of anaesthesia and maintenance of balanced anaesthesia.RésuméLe midazolam est un dirivé hydrosoluble de la benzodiazépine à action courte qui peut être employé par la voie veineuse pour l’induction de l’anesthésie. On compare dans la présente étude les effets hypnotiques du midazolam avec ceux du thiopental lors de l’anesthésie générale balancée en utilisant une méthode prospective à double insu. L’étude englobe cinquante patients en bon état subissant des interventions d’une durée relativement courte. Les résultats montrent qu’à l’induction, l’action du thiopental débute plus rapidement que celle du midazolam et que la relation dose-effet est moins variable.Cependant, pour le maintien de l’anesthésie, le midazolam a été considéré supérieur. Moins d’agents anesthésiques supplémentaires ont été requis, l’acceptance par le patient a été plus grande et l’amnésie supérieure. Avec les deux techniques, les complications ont été très minimes. La comparaison de la plupart des paramètres incluant la durée de la période de réveil démontre la suprenante similarité des deux agents. En conclusion, le midazolam est un nouvel agent qui pourrait s’avérer très utile pour l’induction et ce maintien de l’anesthésie générale balancée.

Inotropic and Anesthetic Potencies of Etomidate and Thiopental in Dogs

The effects of etomidate and thiopental on myocardial contractility were compared in 10 experiments on isolated papillary muscle preparation perfused by a conscious donor dog. Equianesthetic doses of etomidate (1.4 mg/kg) and thiopental (15.5 mg/kg) were determined separately in conscious dogs. Tension developed by the papillary muscle decreased significantly less after etomidate (17 ± 2%) than after thiopental (33 ± 3%) (P < 0.002) when injected intravenously in equianesthetic doses in donor dogs. When added to arterial blood perfusing the papillary muscle, etomidate had 4–5 times more negative inotropic effect than thiopental. At the same time, the anesthetic potency of etomidate was approximately 11 times greater than that of thiopental. We conclude that both etomidate and thiopental produce a dose-dependent direct negative inotropic effect but that in equianesthetic doses, etomidate causes less pronounced depression of myocardial contractility than thiopental.

Additive negative inotropic effect of a combination of diazepam and fentanyl.

Hearts were excised from 30 male Sprague-Dawley rats and perfused in a modified Langendorff system to examine the interactions of fantasy and diazepam on myocardial contractility as measured by left ventricular dP/dtmax. Various concentrations of fantasy and diazepam were added to the nonrecirculating 37°C perfusate to determine ED25 and ED50 for depression of dP/dtmax. Combinations of fantasy and diazepam at a fixed negative inotropic potency ratio of 1:1 were used to determine the ED25 and ED50 of this com bination. Is bolographic analyses performed at ED25 and ED50 revealed that the negative inotropic interaction of fantasy and diazepam is purely additive. It is unlikely that a supraadditive negative inotropic effect can explain the supraadditive homodynamic depression reported in humans when diazepam and fantasy are combined; perhaps systemic vascular effects of this drug combination account for the clinical drug interactions.

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 μg/kg at induction; sufentanil, 15 μg/kg at induction plus 10 μg/kg on initiation of cardiopulmonary bypass (CPB); and enflurune 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.