Bioassay, potency, and intravenous anesthetics.
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Anesthetics↗
Biomedical subjects
I Kissin
Publications and source records attributed to I Kissin.
Midazolam potentiates thiopental sodium anesthetic induction in patients.
STUDY OBJECTIVE: To test the hypothesis that midazolam potentiates thiopental sodium-induced unconsciousness. DESIGN: Randomized, double-blind study. SETTING: A university medical center. PATIENTS: Fifty nonpremedicated ASA physical status I and II adult patients scheduled for eye surgery. INTERVENTIONS: Intravenous (IV) injections of thiopental sodium in doses ranging from 1.0 mg/kg to 4 mg/kg with or without the addition of midazolam 0.02 mg/kg. MEASUREMENTS AND MAIN RESULTS: Inability to open eyes on command was used as an end point of anesthesia and the dose-response curves were determined using a probit procedure. A dose of 0.02 mg/kg, which constitutes less than one-tenth of the hypnotic ED50 value for midazolam, potentiated thiopental sodium anesthesia. The thiopental sodium ED50 value was decreased from 2.4 mg/kg to 1.6 mg/kg (p less than 0.001). Midazolam also reduced individual variability in the response to thiopental sodium. As a result, the thiopental sodium dose that reliably induced any nonpremedicated patient decreased from 6 mg/kg (ED99 of 5.57 mg/kg) to 2.5 mg/kg (ED99 of 2.37 mg/kg). CONCLUSIONS: A subhypnotic dose of midazolam potentiates thiopental sodium-induced unconsciousness. This effect suggests the possibility that midazolam enhances barbiturate binding.
Adult↗
Effect of alfentanil on hypnotic and antinociceptive components of thiopental sodium anesthesia.
STUDY OBJECTIVE: To determine the effects of alfentanil on the hypnotic and antinociceptive components of thiopental sodium anesthesia. DESIGN: Randomized double-blind study. SETTING: Inpatients at a university-affiliated county hospital. PATIENTS: Eighty unpremedicated ASA physical status I or II female patients aged 18 to 60 years, with a weight range of 50 to 90 kg. INTERVENTIONS: Intravenous injection of thiopental sodium in doses ranging from 1.0 mg/kg to 6.0 mg/kg with or without the addition of alfentanil, 0.01 mg/kg. MEASUREMENTS AND MAIN RESULTS: Dose-response curves were determined for the following three endpoints of anesthesia: eye opening in the response to voice command; eye opening in the response to noxious stimulation induced by pressure on the trapezius muscle; and purposeful movement in the response to the same type of noxious stimulation. The addition of alfentanil, 0.01 mg/kg, markedly decreased thiopental ED50 values for all three endpoints: from 2.6 mg/kg to 1.9 mg/kg (p less than 0.02) for eye opening to voice command, from 3.2 mg/kg to 1.9 mg/kg (p less than 0.0005) for eye opening to noxious pressure, and from 4.2 mg/kg to 2.4 mg/kg (p less than 0.0001) for purposeful movement to noxious pressure. The alfentanil-induced increase in thiopental potency for the antinociceptive effect was greater than that for the hypnotic effect (75% vs 36%, p = 0.02). CONCLUSIONS: Alfentanil strengthened both the hypnotic and antinociceptive components of thiopental anesthesia, although to a different degree: the antinociceptive component more so than the hypnotic, possibly because each component of anesthesia has different underlying mechanisms.
Adult↗
Subarachnoid bupivacaine blockade decreases midazolam and thiopental hypnotic requirements.
STUDY OBJECTIVE: To test the hypothesis that subarachnoid bupivacaine blockade decreases hypnotic requirements for thiopental sodium and midazolam. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Teaching hospital. PATIENTS: 53 nonpremedicated ASA physical status I and II adult male patients scheduled for elective lower abdominal, pelvic, or lower limb surgery. INTERVENTIONS: Intravenous injections of midazolam or thiopental were administered with or without subarachnoid bupivacaine blockade (12.5 mg) at the L3-L4 level. Thiopental or midazolam hypnotic requirements were determined using loss of ability to open eyes in response to verbal command as an endpoint. The thiopental requirements were determined by titration; the midazolam requirements were determined from dose-response curves obtained with bolus injections of predetermined doses of the drug. MEASUREMENTS AND MAIN RESULTS: Subarachnoid bupivacaine blockade decreased the hypnotic dose of thiopental from 3.40 +/- 0.68 mg/kg (mean +/- SD) with a dose range of 2.3 to 4.5 mg/kg (intramuscular saline) to 2.17 +/- 0.48 mg/kg with a dose range of 1.3 to 2.8 mg/kg (p < 0.005 for the difference). The ED50 value of midazolam decreased with the bupivacaine blockade, from 0.23 mg/kg (95% confidence limits: 0.08 to 0.38 mg/kg) to 0.06 mg/kg (0.01 to 0.14 mg/kg), with p < 0.0001 for the difference. CONCLUSION: Subarachoid bupivacaine blockade decreases hypnotic requirements for both thiopental and midazolam. The results suggest that the reduction in hypnotic requirements is due to the decrease in afferent input induced by spinal anesthesia.
Adult↗
Effects of nifedipine on myocardial energy balance in experimental coronary vasoconstriction and occlusion.
The effect of nifedipine on the myocardial energy demand--supply imbalance caused by vasopressin-induced vasoconstriction, coronary occlusion, and their combined action was studied in isolated perfused rabbit hearts using the method of NADH fluorometry. Nifedipine (0.015 microgram/ml) completely prevented the development of NAD/NADH imbalance caused by coronary vasospasm. The role of vasoconstriction as an addition to coronary occlusion was very small in the development of regional energy imbalance and the vasopressin-induced detrimental effect was prevented by nifedipine. Energy imbalance caused by the occlusion alone was only partially improved by the drug. There was a delay in the development of energy imbalance and reduction in the final degree of NADH fluorescence response to the occlusion (97 +/- 8% vs. 66 +/- 9%, p less than 0.05).
Animals↗
Effect of halothane on contractile function of ischemic myocardium.
Effects of halothane on the force of myocardial contraction and energy demand-supply balance (NADH fluorescence) were studied in two rabbit heart preparations--the interventricular septum perfused through the septal artery at various flow levels, and a Langendorff whole-heart preparation with ischemia caused by graded reduction of perfusion pressure. The septum experiments showed that halothane [1.2% = 1.5 minimum alveolar concentration of anesthetic preventing movement response to a noxious stimulus (MAC)] increased NADH fluorescence (+9%, p less than 0.02) at a normal level of perfusion (3 ml/g/min) and, at the same time, decreased it (-6%, p less than 0.02) when myocardial energy balance deteriorated from severe hypoperfusion (0.2 ml/g/min). The inhibitory effect of halothane on developed systolic tension was less pronounced at the low (ischemic) level of myocardial perfusion as compared with the high level--leads to 24% (0.2 ml/g/min) vs. leads to 38% (3 ml/g/min), p less than 0.025. However, if control and halothane values of developed tension were compared at equi-NADH levels (the same state of energy balance), the depressive effect of halothane on the force of myocardial contraction was not less pronounced in severe energy imbalance. Similar results were obtained in the Langendorff preparation experiments. The results suggest that halothane partially restores energy balance in hypoperfused myocardium; however, at the normal level of perfusion, its effect is in an opposite direction. Halothane depresses contractility in the hypoperfused myocardium to a lesser degree than at the normal level of myocardial perfusion. This effect is probably determined by the interaction of two influences: direct depressive effect of the agent on contractile mechanisms, and indirect positive inotropic effect due to improvement in energy balance.
Animals↗
Interaction between negative inotropic effects of halothane and nifedipine in the isolated rat heart.
Isobolographic analysis was used to assess quantitatively the combined direct negative inotropic effect of halothane and nifedipine as well as to define the type of interaction between these two agents. Experiments were performed on an isolated rat heart preparation. Developed left ventricular pressure and dP/dtmax were used as indices of inotropic action. It was found that the combination of halothane and nifedipine gives mostly additive direct negative inotropic effect. However, with a small level of myocardial depression (ED25), there was some deviation from the additive interaction toward an infra-additive effect (p less than 0.01), and with a high level of depression (ED75), some deviation toward a supra-additive effect (p less than 0.05).
Animals↗
Effect of propranolol on energy demand -- supply balance in myocardial ischemia.
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Animals↗
Effect of epidural bupivacaine block on midazolam hypnotic requirements.
BACKGROUND AND OBJECTIVES: The aim of the study was to determine the effect of epidural bupivacaine block on midazolam hypnotic requirements. METHODS: Sixty unpremedicated, ASA physical status I or II male patients, aged 45-65 years and scheduled for elective lower abdominal, pelvic, or lower limb surgery participated in this randomized, double-blind, placebo-controlled study. The study population was composed of three groups: Before administration of midazolam, patients in the first group received an intramuscular injection of 15 mL saline (M), those in the second group an intramuscular injection of 15 mL 0.5% bupivacaine (MIB), and those in the third group an epidural injection of 15 mL 0.5% bupivacaine at the L3-L4 level (MEB). Loss of the ability to respond to verbal command was used as an endpoint for the effect of midazolam injected intravenously in predetermined doses (five patients per dose) 30 minutes after a bupivacaine (or saline) injection. Midazolam dose-response curves were obtained by probit analysis. RESULTS: The midazolam median effective dose values for the hypnotic effect were 0.20 mg/kg (95% confidence limit, 0.10-0.27 mg/kg) in the M group; 0.10 mg/kg (0.06-0.22 mg/kg) in the MIB group; and 0.04 mg/kg (0.03-0.07 mg/kg) in the MEB group. The differences between the midazolam median effective dose values had high levels of significance: P < .00001 for MEB versus M, P < .002 for MEB versus MIB, and P < .01 for MIB versus M. CONCLUSIONS: Epidural bupivacaine block profoundly decreases midazolam hypnotic requirements. The most likely explanation for this effect is the reduction in afferent input induced by the block.
Aged↗