Pentobarbitone premedication for anaesthesia. The influence of the preparation and route of administration on its clinical action.

Studies were carried out in the pre-operative period on patients premedicated with 100 mg pentobarbitone given by mouth or by intramuscular injection into the buttock. The injections were given by doctors using a 4 cm needle or by nurses using the needle of their choosing and two preparations were used. One was a freshly prepared aqueous solution and the other the commercially available organic solution (Nembutal) with propylene glycol, alcohol and water as solvents. An unacceptably high incidence of persistent injection site pain occurred after the use of the organic preparation but not with the aqueous solution. Otherwise no difference was detected between the effects of the two preparations. Drugs injected by doctors were, on the whole, more effective as premedicants than those injected by nurses. Oral pentobarbitone was not as effective a premedicant as the intramuscular preparation and its anxiolytic action did not differ from that of the placebo. Relief of apprehension was disappointing with all preparations of 100 mg pentobarbitone and was not as good as with diazepam. This may be attributed to the use of too small doses but larger injection volumes would have caused their own problems.

Studies of drugs given before anaesthesia XXV: Medazepam, a new benzodiazepine.

Medazepam, a new benzodiazepine, was studied as an oral preanaesthetic medication in adult women in a dose of 10 mg, and the findings compared with those obtained with diazepam 10 mg or a dummy capsule using a double-blind technique. In the doses used medazepam produced less drowsiness than diazepam and was no more anxiolytic than the placebo.

The influence of the route of administration on the clinical action of diazepam.

The relative efficacy of diazepam 10 mg as a premedicant was assessed following its oral and intramuscular administration, using a "double-blind, double-dummy" technique, as well as its effect when given by both routes. Drugs were given to a standard patient population who were undergoing the same type of operation and receiving a standard anaesthetic. The most rapid onset of soporific action occurred when diazepam was given by mouth and this produced the best effect throughout the period of the study although its efficacy began to pass off after 60 minutes. It was superior in effect to the same dose injected into the thigh. The combined effect of oral and intramuscular diazepam was not notably greater than tht of the single oral dose. The injection of diazepam was followed by an unacceptably high incidence of pain, particularly when this was given into the thigh. There were no significant differences in either the course of anaesthesia or the incidence of post-operative nausea and vomiting. When the undesired effects are taken into consideration, the oral administration of diazepam should be the route of choice.

Plasma diazepam levels after single dose oral and intramuscular administration.

Plasma diazepam levels were estimated by gas-liquid chromatography following a single 10 mg dose administered to a health adult female population by the oral and intramuscular routes. The highest levels were achieved following oral administration, reaching a peak at 60 minutes, although injection into the thigh resulted in a more rapid rise initially. Injection into this site produced higher levels than when the buttock was used. Injection by nurses into the latter site produced particularly low plasma levels over the 90-minute period of study. The plasma levels found at 90 minutes following the oral and thigh routes were found to be closely correlated with the weight of the patient.

Immediate changes in plasma potassium, sodium and chloride concentrations induced by suxamethonium.

Four groups of healthy female patients were anaesthetized with wither thiopentone, Althesin or nitrous oxide-oxygen with and without halothane. The concentrations of the plasma electrolytes were measured before and at varying times up to 10 min after the administration of suxamethonium 1 mg/kg. Asmall, but significant, biphasic increase in plasma potassium concentration was found when suxamethonium was administered to patients in whom anaesthesia was induced with thiopentone, Althesin and nitrous oxide-oxygen. The initial increase in plasma potassium concentration was greater in the Althesin group thanin the other two groups. A more delayed, but sustained, increase in plasma potassium concentration was found following induction with nitrous oxide-oxygen-halothane. There were no significant changes in the plasma concentrations of sodium or chloride exceptin the halothane-nitrous oxide-oxygen series.

Estimation of plasma diazepam. Critique of a method using gas-liquid chromatography and benzene extraction.

Plasma diazepam can be reliably estimated using a simple benzene extraction and gas-liquid chromatography with griseofulvin as internal standard. This gives reproducible results within the clinical range of plasma levels. Storage at minus 20 degrees C is recommended but is not essential for the 1st week.

Studies of drugs given before anaesthesia. XXIV: Metocloramide with morphine and pethidine.

When given with pethidine 100 mg or morphine 10 mg as preanaesthetic medication, 10 and 20 mg of metoclopramide cause a reduction in postoperative nausea and vomiting in women undergoing a standard operation with a standard anaesthetic technique. The preoperative emetic effects of pethidine are almost completely abolished by metoclopramide. An additional 10-20 mg of metoclopramide, given i.m. at the end of the operation markedly reduces the emetic effects of pethidine premedication but has less effect when morphine has been given. The evidence suggests that the ineffectiveness of metoclopramide, relative to other antiemetics, is because of its brevity of action.