Elimination of pethidine and bupivacaine in the newborn.

Abstract

SUMMARY Pethidine or an epidural injection of bupivacaine are common forms of obstetric analgesia in Britain. Bupivacaine has been thought to have little effect on the fetus, but neurobehavioural studies have cast doubt on this. We therefore investigated the elimination of these drugs by babies in similar population groups. Bupivacaine was largely eliminated in just over one day, while pethidine required between 2 and 6 days. This could account for the persisting depression in babies whose mothers had received pethidine.At present in Britain the most commonly used analgesics in labour are pethidine or epidural bupivacaine. Pethidine is known to depress the respiration of the newborn baby (Schnider and Moya, 1964). This effect was least if the analgesic was given in a single dose within one hour of delivery. Bupivacaine, though known to cross the placenta (Belfrage et al., 1975a), was thought to have little effect on the baby. Neurobehavioural scoring has given new information on the assessment of these drugs. Pethidine decreased the newborn response to behavioural tests as did lignocaine and mepivacaine (Brackbill et al., 1974;Scanlon et al., 1974). We have studied the elimination of pethidine and bupivacaine in the first few days of life. Method There were 19 mothers in each group. All were aged between 20 and 35 years. The mean weight of the mothers given bupivacaine was 73-4 kg (± 12 1 SD) and duration of labour averaged 6 hours 40 minutes. The mean weight of the group of mothers given pethidine was 72-9kg (±8 5SD) and average duration of labour was 6 hours 58 minutes. None had cardiovascular or respiratory disease. The purpose of the study was explained in detail to each woman and her consent obtained. The babies were all normal and of more than 36 weeks' gestation, mean birthweight being 3 *4 kg (±0 33 SD). Analgesics were given as required. 16 mothers received a single dose of pethidine 150 mg intramuscularly and in 3 this was repeated once. Bupivacaine was administered epidurally in 0 *25 % concentration, Received 24 December 1976 *We regretfully report the death of Miss Cooper on April 15. Editors. usually in 10 ml doses, and the total amount necessary for patient comfort ranged from 25-185 mg with an average of 84 mg. After a pilot study it seemed inappropriate to take blood samples for each drug at the same time intervals. Therefore, in the pethidine group samples were taken at delivery from the mother and from cord blood, then at 2, 4, 8, 12, 24 hours and at 2, 3, 4, and 5 days from the baby. With the mothers receiving bupivacaine samples were taken at delivery, then at 2, 4, 8, 12, and 24 hours. Delivery samples were taken from the maternal antecubital vein and the umbilical vein. Samples were obtained from the babies by heel prick.Pethidine was extracted by a method described by Beckett and Taylor (1967), and bupivacaine as described by Reynolds and Beckett (1968). After extraction from plasma the drugs were estimated by gas chromatography using a nitrogen detector.

Clinical Pharmacokinetics Pethidine

“…In addition, Caldwell et al (f 978) found a positive correlation between CIM ratio and time from pethidine administration to delivery. Cooper et al (1977) have pointed out that although neonates whose mothers received pethidine within I hour of delivery had the highest blood COlt-· centrations, they also had minimum depression. All of these data are consistent with the hypothesis that significant amounts of pethidine cross from mother to fetus over a period of several hours.…”

“…On the basis of their urinary excretion data, Hogg et al (I 977) estimated approximately 60 hours would be required to eliminate 95 % of pethidine from these neonates. Cooper et al (1977) and Caldwell et al (1978) studied concentrations of pethidine in I 9 and I 0 neonates respectively whose mothers had received pethidine during labour. Cooper et al (J 977) estimated that neonates took from 3 to 6 days to completely eliminate the drug, while Caldwell et al (I 978) estimated the 'elimination' half-life to be 22.7 (SD ± 10) hours.…”

Effects of pethidine and its antagonists on the newborn.

“…Despite this frequent but careful use of pethidine, our results confirm that significant depression of respiratory function was produced in these babies and, although slight, the differences were still apparent 12-24 hours after delivery. The fact that the effects of pethidine can be detected for even longer has been confirmed by Cooper et al (1977) who found that it may take the newborn 3 to 6 days finally to eliminate the drug. Although not presented in detail, the respiratory function results were divided according to the pethidine-to-delivery time interval, and more obvious respiratory depression was found when the pethidine had been administered more than one hour before delivery.…”

Preliminary studies on the disposition of meptazinol in the neonate.

“…depression. Furthermore pethidine readily crosses the placenta and yet the neonate is less well able to dispose of the drug than is the mother (Cooper, Stephen & Aggett, 1977). The average neonatal elimination half-life has been estimated to be 22 h which is approximately 7 times longer than that of healthy adults (Caldwell et al, 1978).…”