Dose requirements of ICI 35,868 (propofol, 'Diprivan') in a new formulation for induction of anaesthesia.

In order to avoid Cremophor-related reactions and reduce the incidence of pain on injection, diisopropylphenol (ICI 35,868; propofol) has been reformulated as an emulsion. One hundred and fifteen patients received an induction dose of propofol in the new formulation. The dose required to induce anaesthesia in 95% of healthy, unpremedicated patients was 2.5 mg/kg. Induction was associated with a degree of cardiovascular and respiratory depression. There were no adverse reactions although there were a number of minor side-effects. The incidence of pain on injection was low (3%) and the overall quality of induction was assessed as good or adequate in 92% of patients.

Dose-response relationship for disoprofol (ICI 35868; Diprivan). Comparison with methohexitone.

The duration of sleep following intravenous administration of three doses of disoprofol (1.2 and 3 mg/kg) was compared with that following methohexione 1 or 2 mg/kg. Disoprofol and methohexitone were shown to be approximately equipotent. Side-effects were dose-related for both drugs, but the incidence was significantly less following disoprofol than methohexitone 2 mg/kg. The most frequent side-effects were pain on injection, myoclonia and hiccup. Studies of blood concentrations of disoprofol show that the profile is dose-independent and conforms to a two-compartment model with a very short distribution phase (about 2 minutes) and short elimination phase (about 70 minutes). Waking blood levels gave no indication of acute tolerance. Disoprofol would appear to be particularly useful for induction of a short period of sleep using a small dose given quickly, or for maintenance of sleep by continuous infusion.

ICI 35868 (Diprivan): a new intravenous anaesthetic. A comparison with Althesin.

ICI 35868 (Diprivan), 1-2 mg/kg was used to induce anaesthesia in 20 patients, and the results compared with induction of anaesthesia by Althesin 0.5 ml/kg given to a similar group of 20 patients. ICI 35868 was effective in inducing anaesthesia, but produced more respiratory depression, and cardiovascular effects which were significantly different from those produced by Althesin. ICI 35868 gave a smoother induction. It is concluded that ICI 35868 is a promising new induction agent which may also find application for the maintenance of anaesthesia.

Alfentanyl (R39209): initial clinical experience with a new narcotic analgesic.

R39209 (Alfentanyl), a new narcotic analgesic with a uniquely short duration of effect, was used to supplement nitrous oxide and oxygen for the maintenance of anaesthesia. Twenty-two patients undergoing minor surgery were studied. Clinical anaesthesia was excellent or good in most (16) of the patients, and recovery was excellent or good in 18 patients, waking time being less than one minute in 15 patients. However the incidence of complications and side-effects, mainly movement, apnoea, difficulty in assisting ventilation, nausea and vomiting was high. Intravenous administration of R39209 during anaesthesia induced significant depression of respiratory rate and minute volume during the second, third and fourth minutes after injection. There was an unexplained significant rise in respiratory rate and minute volume in the first 30 seconds after the first injection. The first administration of R39209 also caused an unexplained, significant reduction in cardiac rate. An insignificant rise in mean systolic blood pressure followed injection of the drug. The transient effect of R39209 was confirmed in clinical practice, and the drug exhibited the features of a typical narcotic analgesic. It is concluded that R39209 will have a useful place in anaesthetic practice, and that better clinical results will be obtained with more experience of the drug, and better selection of indications for its use.

Mass spectrometry in anesthesia. Problems in using mass spectrometer for monitoring anesthetic gases and vapours.

The use of mass spectrometers for total gas monitoring during anesthesia presents a number of problems which stem from the Cracking Pattern of the gases present, inlet design, viscosity variations, water vapour and machine deterioration. Some of these have been adequately solved, by making mechanical modifications to the inlet system, and by using more complex electronic circuitry to process the signals obtained. Remaining problems, however, still limit accuracy and ease of operation. CO2 measurements are particularly prone to error, especially when sampling halothane-containing gas which leads to significant internal production CO2. A study of the principal sources of error remaining in the machine suggests that the only definitive solution is to develop a microprocessor system which could cope with complex Cracking Patterns and non-linearities, and which would allow complete automation of the calibration procedure.