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H R Vinik

Publications and source records attributed to H R Vinik.

14 recordsLinked to original sources
PubMed1991

Sedation in the ICU.

The effect of midazolam on the induction dose-response curve for alfentanil was studied in non-premedicated ASA physical status I or II patients. The response to the verbal command was used as an end point of anaesthesia. Dose-response curves for midazolam, alfentanil, and their combination were determined with a probit procedure, and compared with algebraic (fractional) analysis of drug interaction. Interaction between midazolam and alfentanil was found to be synergistic (supra-additive). The results suggest that the use of this combination is advantageous not only because it helps to achieve different anaesthetic goals with specific drugs (a benzodiazepine for unconsciousness and an opioid for blockade of the responses to noxious stimulation), but also because its components are complementary for unconsciousness.

Adolescent↗
PubMed1990

Alfentanil potentiates midazolam-induced unconsciousness in subanalgesic doses.

The effects of alfentanil on the midazolam dose-response curve for hypnosis was studied with response to the verbal command as an end point in 95 patients. The analgesic effect of alfentanil was studied by measuring the threshold for pain caused by pressure on the trapezius muscle with the use of a dolorimeter in 21 patients. The study was randomized, double-blind, and performed on the unpremedicated patients with ASA physical status I or II. Alfentanil was found to reduce the midazolam ED50 value for the induction of anesthesia in a dose-dependent fashion. The smallest dose of alfentanil (3 micrograms/kg) that caused a marked shift of the midazolam dose-response curve to the left along the dose axis (from the ED50 of 270 micrograms/kg to the ED50 of 142 micrograms/kg, P less than 0.0005) represents approximately 2% of the alfentanil ED50 for induction of unconsciousness (130 micrograms/kg). Alfentanil (10 micrograms/kg) caused only a tendency for increase in the pain threshold, whereas a dose of 15 micrograms/kg significantly increased the pain threshold by 37% (P less than 0.05). The results demonstrate that alfentanil potentiates the hypnotic effect of midazolam in very small doses. The high potency of alfentanil in this respect, as compared to its analgesic potency, suggests a very specific mechanism of alfentanil-midazolam hypnotic interaction, one that most likely is based on a functional relationship between the GABA receptor-benzodiazepine receptor system and the opioid receptor system in mediation of hypnosis.

Adult↗
PubMed1989

Midazolam-alfentanil synergism for anesthetic induction in patients.

The effect of midazolam on the induction dose-response curve for alfentanil was studied in nonpremedicated ASA physical status I or II patients. The response to the verbal command was used as an end point of anesthesia. Dose-response curves for midazolam, alfentanil, and their combination were determined with a probit procedure, and compared with algebraic (fractional) analysis of drug interaction. Interaction between midazolam and alfentanil was found to be synergistic (supraadditive). The results suggest that the use of this combination is advantageous not only because it helps to achieve different anesthetic goals with specific drugs (a benzodiazepine for unconsciousness and an opioid for blockade of the responses to noxious stimulation), but also because its components are complementary for unconsciousness.

Adolescent↗
PubMed1987

Barbiturates inhibit stress-induced analgesia.

The effect of pentobarbitone and thiopentone on stress-induced analgesia was studied in 40 male Sprague-Dawley rats. Antinociception was determined by measuring motor reaction threshold to the noxious pressure on the tail with the use of an "Analgesymeter." Stress was induced by placement of a clamp on the hind paw. The stress procedure was found to cause an increase in reaction threshold, which was partially suppressed by naloxone 0.5 mg X kg-1. Pentobarbitone in a subanaesthetic dose of 25 mg X kg-1, SC, almost completely abolished the stress-induced increase in the reaction threshold (an increase in reaction threshold from 329 +/- 33 g to 486 +/- 62 g in control group, and from 250 +/- 26 g to 273 +/- 35 g in pentobarbitone group, p less than 0.02 for the difference in the threshold changes). Thiopentone used in a dose of 25 mg X kg-1, IV, caused a loss of the righting reflex for 37 +/- 10 minutes; stress procedure applied ten minutes after regaining the righting reflex did not cause any increase in the reaction threshold (with an increase in the reaction threshold in control group from 355 +/- 50 g to 540 +/- 26 g, p less than 0.001 for the difference between the groups). The results suggest that the barbiturates in subanaesthetic doses inhibit stress-induced analgesia. Thiopentone used in an anaesthetic dose has the potential for inhibition of stress-induced analgesia in the period of recovery from anaesthesia.

Animals↗
PubMed1985

Midazolam: pharmacology and uses.

Midazolam is an imidazobenzodiazepine with unique properties when compared with other benzodiazepines. It is water soluble in its acid formulation but is highly lipid soluble in vivo. Midazolam also has a relatively rapid onset of action and high metabolic clearance when compared with other benzodiazepines. The drug produces reliable hypnosis, amnesia, and antianxiety effects when administered orally, intramuscularly, or intravenously. There are many uses for midazolam in the perioperative period including premedication, anesthesia induction and maintenance, and sedation for diagnostic and therapeutic procedures. Midazolam is preferable to diazepam in many clinical situations because of its rapid, nonpainful induction and lack of venous irritation. Compared with thiopental, midazolam is not as rapid acting nor predictable in hypnotic effect. It will not replace thiopental as an induction agent. Advantages of midazolam over thiopental are those of the more versatile pharmacologic properties of a benzodiazepine compared with a barbiturate such as amnestic and anxiolytic properties. Midazolam should be a useful addition to the formulary.

Adult↗
PubMed1985

Morphine--caffeine analgesic interaction in rats.

The ability of caffeine to modify the effect of morphine on motor response to noxious stimulation was studied in 195 rat experiments. Motor reaction responses to noxious stimuli were studied in three series of experiments with three different techniques of mechanical tail stimulation. In each series of experiments, dose-response curves for morphine (probit analysis) were determined with and without the addition of caffeine (30 mg X kg-1). It was found that caffeine decreased morphine ED50 values in all three series of experiments, from 1.1 to 0.6 mg X kg-1 (P less than 0.002), from 3.2 to 2.5 mg X kg-1 (P less than 0.01), and from 13.2 to 6.2 mg X kg-1 (P less than 0.002). When caffeine was used alone in a dose of 30 mg X kg-1, there were no significant changes in motor reaction responses with any of the three methods applied for the assessment of morphine-caffeine combinations. These data indicate that caffeine potentiates the inhibitory effect of morphine on motor response to noxious stimulation in rats. It has been suggested that the effect of morphine on the motor response to somatic noxious stimulation results primarily from activation of inhibitory control systems concerned with this response. Caffeine may modulate the antinociceptive effect of morphine by stimulating one of these systems.

Analgesics↗
PubMed1983

The pharmacokinetics of midazolam in chronic renal failure patients.

Fifteen patients with chronic renal failure (CRF) were given midazolam 0.2 mg/kg iv over 15 s. All but one lost consciousness in a time ranging from 22-100 s (mean +/- SD was 55 +/- 26 s) after drug administration. Patients regained consciousness from 6-105 min (mean 53 +/- 32) after drug administration. The calculated mean plasma level of midazolam at arousal was 81 +/- 47 ng/ml. Pharmacokinetics parameters were determined from midazolam plasma levels measured in 16 consecutive venous blood samples. The pharmacokinetic parameters in CRF patients were compared with those of healthy volunteers matched for age, sex, and body size with the CRF patients. Protein binding was determined by equilibrium dialysis. CRF patients had a significantly higher (P less than 0.005) plasma-free drug fraction (6.5% +/- 0.7) compared with the control patients (3.9% +/- 0.1). Total (bound plus unbound) kinetics differed in the two groups: volume of distribution 3.8 +/- .3 1/kg in CRF patients versus 2.2 +/- .2 1/kg in controls (P less than 0.001), and clearance 11.4 +/- 1.6 ml X min-1 X kg-1 in CRF patients versus 6.7 +/- 0.9 ml X min-1 X kg-1 in controls (P less than 0.02). When kinetic parameters were corrected for protein binding, CRF patients unbound volume of distribution (63.5 +/- 6.8 1/kg) and free drug clearance (189 +/- 29 ml X min-1 X kg-1) were not different from the control group's volume of distribution (55.6 +/- 5.7 1/kg) and free drug clearance (176 +/- 24 ml X min-1 X kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Midazolam.

Explore the source record for details and available documents.

Anesthetics↗
PubMed1982

Premedication with intramuscular midazolam: a prospective randomized double-blind controlled study.

One hundred A.S.A. physical status I and II surgical patients were randomized to receive midazolam, 0.07 mg/kg (group M, 31 patients), hydroxyzine, 1.0 mg/kg (group H, 34 patients), or midazolam diluent as a placebo (group P, 35 patients). Drugs were administered in the vastus lateralis muscle 60 to 90 minutes before anesthesia induction. Anesthesia was induced with thiopental, 3.0 mg/kg, followed by 1.0-mg/kg increments if required. An entry criterion was that patients score greater than or equal to 50% on a subjective Anxiety Visual Analog Test (AVAT). Anxiety was also objectively rated on a six-point scale by a trained observer. Patients and observer were unaware of type of premedication used. Midazolam and hydroxyzine produced significantly (p less than 0.05) greater reduction of anxiety than placebo on both the AVAT and objective anxiety evaluations. Peak onset appeared between 30 and 60 minutes after drug administration. Hemodynamic changes were similar in all groups, and no untoward reactions were encountered before anesthesia. The injection site 24 and 48 hours after administration showed evidence of mild tissue irritation in 68% of patients in group H, 26% of patients in group M, and none of the patients in group P. Midazolam is an efficacious, safe premedicant in relatively healthy patients. It has a prompt onset of action with only minimal tissue irritation.

Anxiety↗
PubMedDate not supplied

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↗