SummaryIn order to avoid Cremophor-related reactions and reduce the incidence of pain on injection, diisopropylphenol (ICI 35,868; propof)
Key wordsAnaesthetics, intravenous; propofol.2,6-di-isopropylphenol (ICI 35,868; propofol; 'Diprivan,' formerly disoprofol) is one of a series of alkylphenols which were found to have anaesthetic properties in animals.' Initial investigations of the pharmacological properties of propofol were conducted using a formulation containing the surfactant Cremophor EL.2 Anaesthetic properties were demonstrated in who received 1-3 mg/kg intravenously although in unpremedicated patients 2 mg/kg was generally successful. s * 7 There was pain on when the drug was given into veins on the dorsum of the hand. To reduce the frequency of this side-effect, and because of circumstantial evidence of a n association of Cremophor-containing agents with anaphylactoid reactions,10-12 an emulsion formulation of propofol has been developed. We have determined the effective dose of propofol* in the new emulsion formulation for induction of anaesthesia in 95% (AD 95) of healthy, unpremedicated patients.
MethodsFive hospitals in the United Kingdom participated in an open study for which individual hospital ethics committee approval had been G
Three doses (1.5, 2.0 and 2.5 mg kg-1) of diisopropyl phenol (ICI 35 868) were compared for induction and maintenance of anaesthesia in healthy females undergoing short gynaecological procedures. Induction of anaesthesia was smooth and rapid. Cardiovascular changes (which were dose-dependent) included a decrease in arterial pressure and an increase in heart rate. These changes were magnitudes comparable to those reported for other induction agents. Recovery from the effects of the drug was rapid and uneventful.
Summary
In a randomised cross‐over trial, midazolam, a new water soluble benzodiazepine was compared with the conventional diazepam preparation (Valium) in 34 patients aged 16—45 years who were undergoing outpatient conservation dentistry. Midazolam hydrochloride (0.17 mg/kg) was virtually free of venous complications and showed advantages over diazepam (0.32 mg/kg) in providing a faster onset of action, higher incidence of amnesia and more rapid recovery. Midazolam produced a higher incidence of respiratory side effects: hiccough (17.6% compared with 2.9%), brief apnoea following induction (11.8% compared with 5.8%), and airway obstruction during maintenance (8.8%, compared with 0%). These may be related to the greater potency of midazolam as suggested by the smaller total dose required. Cardiovascular changes and operating conditions were similar.
a!. Metabolic acid(osis attd fatal msocardial failure after propofol infusion in children: five case rcports. B.lI' 1992;305: 61 3-6. (1 September.) 2 O'Flahertv D. Catania A, Krishnan S (icsecke AH, Lipton J. Differential effects of total anaesthesia sersus inhalational anaestltesia on neurttendocrinc and immunc reactions during standardized surgical stress. EutrJAtaltasih/sh lOt) :S:A41S.
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