W. McCaughey

The respiratory depression of epidural morphine. Time course and effect of posture.

In order to investigate the time course of the late respiratory depression which has been reported following epidural opiates, the response to CO2 was measured in 11 patients. Epidural morphine 2 mg was given 1 hour after operation under bupivacaine epidural anaesthesia, and the patients nursed supine. The results show a consistent pattern of respiratory depression commencing at approximately 4–8 hours, and continuing until 18–24 hours after administration of morphine. A similar group of 10 patients nursed in a sitting position did not show the same degree of depression, and a modifying effect of posture on the development of central effects is suggested.

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.

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.

Cimetidine as an oral antacid before elective Caesarean section

The H2‐receptor antagonist cimetidine was used as a pre‐operative antacid in 64 women scheduled for elective Caesarean section. All were given cimetidine 400 mg 90–215 minutes before induction, with 20 of them having an extra 400 mg dose the previous night. The intragastric pH at induction of anaesthesia was reliably above 2.5 if the treatment was given 90 150 minutes beforehand. The volume of gastric contents was reduced when compared with a control series of women receiving either no pre‐operative antacid or 30 ml magnesium trisilicate mixture BPC. No adverse effects on mothers or infants were detected.

Oral ranitidine in labour

Ranitidine 150 mg orally was given every 6 hours to 909 women in labour, while a control group of 378 women received conventional alkali therapy. No differences in incidences of operative intervention, placental retention or post‐partum haemorrhage were observed between groups. Gastric sampling during emergency anaesthesia revealed a pH less than 2.5 in four of 51 women who received ranitidine and in two of 31 women who received magnesium trisilicate. Gastric volumes were slightly lower (mean 83 ml) in the study group than in the control group (mean 122 ml). Absorption of ranitidine was greatly slowed following narcotic administration and gastric volume was significantly higher in those patients given narcotics in labour. Apgar scores were similar in both groups of infants, and babies whose mothers were given ranitidine showed no delay in achieving high gastric acidity and no increase in bacterial colonization of the gastro‐intestinal tract. Low levels only of ranitidine were found in the blood of babies at 2—3 hours and approximately 12 hours after birth.

A field trial of cimetidine as the sole oral antacid in obstetric anaesthesia

Cimetidine was used as the routine antacid treatment for 1323 parturients. The findings from 70 of those who needed an emergency general anaesthetic are reported. Once sufficient time had elapsed for absorption of the drug, and provided that the dosage regime was adhered to, 96% of the women studied had an intragastric pH above 2.5. Neonatal monitoring revealed no abnormalities related to the cimetidine treatment.

Oral Ranitidine in Labour

Ranitidine 150 mg orally was given every 6 hours to 909 women in labour, while a control group of 378 women received conventional alkali therapy. No differences in incidences of operative intervention, placental retention or post-partum haemorrhage were observed between groups. Gastric sampling during emergency anaesthesia revealed a pH less than 2.5 in four of 51 women who received ranitidine and in two of 31 women who received magnesium trisilicate. Gastric volumes were slightly lower (mean 83 ml) in the study group than in the control group (mean 122 ml). Absorption of ranitidine was greatly slowed following narcotic administration and gastric volume was significantly higher in those patients given narcotics in labour. Apgar scores were similar in both groups of infants, and babies whose mothers were given ranitidine showed no delay in achieving high gastric acidity and no increase in bacterial colonization of the gastro-intestinal tract. Low levels only of ranitidine were found in the blood of babies at 2-3 hours and approximately 12 hours after birth.