J. Moore

Evaluation of midazolam as an intravenous induction agent

Midazolam, a new water‐soluble benzodiazepine, was investigated as an intravenous anaesthetic agent in 260 adult patients in doses ranging from 0.15 to 0.5 mg/kg using a variety of premedications. Its onset of action was generally slow, taking up to 3 minutes to exert its maximum effect. A wide variability in response was found in that some unpremedicated patients were satisfactorily anaesthetised with 0.15 mg/kg while others were only moderately sedated following doses of 0.5 mg/kg. Less variability was found in the elderly who also required smaller doses. Narcotic premedication potentiated the sedative effect of midazolam. Few respiratory or cardiovascular effects were noted apart from hiccough following the larger doses. The incidence of venous sequelae was much lower than that found following diazepam.

Changes in serum enzyme levels following ketamine infusions

The levels of four serum enzymes, known to be elevated in toxic hepatitis, were measured preoperatively and on the 3–4th and 13–15th postoperative days in patients anaesthetised with ketamine infusions (54) or with a standard technique (64). Significant elevations in enzyme levels were considered to have occurred when the postoperative levels were outside the accepted normal range and had increased by more than 3 × SD from controls. About half the patients in each group had minor gynaecological operations and 2120 in the ketamine series had postoperative elevation of enzyme levels, with no changes in the non‐ketamine group. Following intermediate operations 14134 anaesthetised with ketamine showed abnormal enzyme levels compared with 7/34 who had standard operations. None, of the latter had more than one abnormal test as compared with six in the ketamine series. The causes and significance of these findings are not known.

A comparison between propofol and thiopentone as induction agents in obstetric anaesthesia

Two comparable series of 21 patients who had elective Caesarean section had general anaesthesia induced by thiopentone sodium 4.53 (SD 0.65) mg/kg or propofol 2.15 (SD 0.26) mg/kg. Maintenance was similar for both groups. Blood pressure was lower in the propofol group during the induction‐delivery interval. Umbilicallmaternal vein ratios for thiopentone and propofol were 8.5 and 7.2 respectively. Infant wellbeing as judged by Apgar score and cord blood analysis showed little difference between the two induction agents. Factors associated with uterine relaxation and bleeding were similar in the two groups.

The placental transfer of cimetidine

The placental transfer of cimetidine 200 mg intravenously was investigated in 16 patients in normal labour and 40 patients undergoing elective Caesarean section. Cimetidine crosses the placental barrier, blood levels at delivery in mothers and infants being lower with increasing time from injection. Umbilical cord blood cimetidine levels are markedly lower than those of the mother during the first hour following administration but thereafter levels are similar. The mean fetal–maternal ratio at delivery was highest (0.84) at 1 1/2–2 hours following administration. Postdelivery infant and maternal blood samples showed that cimetidine could not be detected, in most cases, 19 hours following administration. The relevance of these findings is discussed.

Effect of single-dose omeprazole on intragastric acidity and volume during obstetric anaesthesia

Various antacid or antisecretory agents are used to reduce the risk to patients of aspiration of gastric contents during general anaesthesia and a trial of the gastric proton pump inhibitor, omeprazole, is reported here. Twenty women admitted for elective Caesarean section under general anaesthesia received a single 80‐mg oral omeprazole dose at 2000 hours on the evening before surgery. Intragastric pH and volume were measured immediately after induction of anaesthesia and on completion of surgery. Eighty‐five percent of pH measurements at induction and extubation and 80% and 95% of volume measurements at induction and extubation respectively met the defined success criteria (pH ≥ 2.5, volume < 25 ml). Omeprazole treatment was well tolerated by the women and Apgar scores and subsequent progress of the babies were acceptable. These results indicate that gastric acidity and volume were acceptable in the majority of women after omeprazole treatment, but the interval from drug administration to induction of anaesthesia may have been too long in some cases and resulted in unacceptably low pHs.

A double‐blind comparison of intramuscular pethidine and nalbuphine in labour

A double‐blind, between‐patient comparison of intramuscular pethidine 100 mg and nalbuphine 20 mg for the relief of pain during labour in 80 patients is described. Severity of pain was assessed before and after treatment by subjective pain scores and visual analogue scales. Neither of these methods showed a significant difference between the treatments. Nalbuphine was associated with less maternal nausea and vomiting than pethidine, but this possible advantage was somewhat offset by a tendency of the drug to produce more maternal sedation and dizziness. The mean umbilical vein/maternal vein ratio was significantly higher for nalbuphine (0.78. SEM 0.03) than for pethidine (0.61, SEM 0.02). which suggests easier placental transfer of the former. This finding was reflected in significantly lower 2–4 hour neurobehavioural scores for the infants of mothers given nalbuphine, but there was no significant difference between these scores at 24 hours. On the basis of this study, nalbuphine does not offer a substantial improvement over pethidine for pain relief in labour.

Ranitidine as an antacid before elective Caesarean section

In a preliminary study, 20 women in labour received ranitidine 50 mg intravenously. No significant changes were seen in the height, frequency or amplitude of uterine contractions or in fetal heart rate or pattern. No neonatal problems attributable to ranitidine were found. Ranitidine crossed the placenta, the mean fetal‐maternal ratio being 0.9. Levels in the infants 12 hours following delivery were all very low. Ranitidine 150 mg orally was given to 80 healthy women undergoing elective Caesarean section at varying times from 75 to 510 minutes pre‐operatively. From 2 to 6 hours following ingestion, the pH of gastric contents was greater than 2.5 in all but one patient. The mean volume aspirated (8 ml) was significantly lower than in a control group receiving magnesium trisilicate (mean volume 30 ml). Neonatal assessment included Apgar scoring, neurobehavioural examination, feeding progress, measurement of acidity and culture of gastric aspirates. No significant differences between groups were found. Blood levels indicated that the oral drug is readily absorbed by the parturient and that a smaller proportion is transferred to the fetus, mean fetal‐maternal ratio at delivery being 0.38.

Thiopente one and methohexital

The search for an intravenous anasthetic, with a more rapid recovery than thiopentone, is still continuing and interest in this field has been re-awakened by recent reports on the use of methohexital (Lilly 25398)’-4. The structural formula of this drug and thiopentone are shown in F I G . 1. Methohexital has been undergoing an extensive clinical trial by the authors and their colleagues during the past four years. This preliminary report deals with a comparison of the actions of methohexital and thiopentone in strictly comparable series in which they were used as the main anasthetic agents. This trial was undertaken to obtain basic data on the complications associated with the use of the new drug and is not intended to include all facets of its action nor to estimate its ultimate place in anzsthesia.

Effects of omeprazole, with and without metoclopramide, in elective obstetric anaesthesia.

We report the results of a study comparing two dose regimens of the gastric antisecretory agent, omeprazole, used as prophylaxis against pulmonary aspiration of gastric contents during general anaesthesia for elective Caesarean section. Since antisecretory agents do not clear stomach contents already present at the start of treatment, two groups of patients who had received both omeprazole and a prokinetic drug, metoclopramide, were also studied. Thirty patients received oral omeprazole 40 mg on the evening before and on the morning of the operation (group 1), 33 received oral omeprazole 80 mg on the morning of the operation (group 2), and 15 (group 3) and 16 (group 4) patients respectively received the oral omeprazole doses stated above and in addition metoclopramide 10 mg given intramuscularly at least 20 min before induction of anaesthesia. Gastric aspirate pH and volume were measured at induction of anaesthesia and on completion of surgery. At induction of anaesthesia, treatment was judged successful (pH ≥2.5 and volume < 25 ml) in 87%, 73%, 100% and 81% of patients in groups 1–4 respectively. The corresponding results on completion of surgery were 100%, 88%, 100% and 100%. While omeprazole is useful as prophylaxis against pulmonary aspiration during general anaesthesia for elective Caesarean section, the addition of a prokinetic agent seems to be necessary la maximise its effects.

Ketamine infusions. Observations on technique, dosage and cardiovascular effects.

A continuous infusion of ketamine, following an initial dose of 1 mg/kg, has been used as sole anaesthetic in over 200 adult patients. The pre-operative use of 4 mg lorazepam has made this acceptable with respect to emergence sequelae and dreams. The technique can be used with neuromuscular blocking drugs and controlled ventilation with air, but here pancuronium is best avoided because of excessive tachycardia and hypertension. Hypertonus was the main problem encountered in the non-relaxant cases. The amount of ketamine required for anaesthesia has been analysed in detail and recommendations on dosage are given. The cardiovascular effects have also been analysed in detail. There is a need for a similar investigation to be carried out in circumstances where inhalation agents are not available and where there is a shortage of anaesthetists.