Bradley E. Smith

Intrauterine Exposure to Halothane Increases Murine Postnatal Autotolerance to Halothane and Reduces Brain Weight

The effect of halothane on prenatal development was assessed using the appearance of postnatal tolerance to the anesthetic and its effect on brain weight. Eighteen 3-month-old mice were repeatedly tested in a rotating cage for loss of righting reflex during exposure to increasing concentrations of halothane on 15 occasions to determine whether or not tolerance to halothane developed. Of these, nine mice were born to dams exposed for 30 min to 2% halothane on days 14 and 17 of gestation. The other nine mice (controls) were born to dams exposed to 100% oxygen for 30 min at the same stage of pregnancy. There was no significant difference in tolerance to halothane between the groups during the first nine days of repeated exposure to halothane. By the 13th and 15th days, however, mice exposed to halothane in utero became more tolerant to 1% halothane than did controls (P < 0.025). In addition, the mean total brain weight of six 7-week-old mice exposed to 2% halothane in utero for 30 min on days 14 and 17 of gestation was found to be significantly less than the mean total brain weight of six control mice not exposed to halothane in utero (20.83 ± 0.27 g and 23.07 ± 0.51 g, respectively, P < 0.0025). This difference occurred mainly in the brain stem rather than in the forebrain and cerebellum.

Continuous Infusion Epidural Analgesia during Labor: A Randomized, Double-blind Comparison of 0.0625% Bupivacaine/0.0002% Fentanyl Versus 0.125% Bupivacaine

The analgesic efficacy of the continuous epidural infusion of 0.0625% bupivacaine/0.0002% fentanyl was compared with the infusion of 0.125% bupivacaine alone in a randomized, double-blind study of nulliparous women. Each patient received, in sequence: 1)3 ml of 0.5% bupivacaine with 1:200,000 epinephrine; 2) 6 ml of study solution 1 (bupivacaine-fentanyl group: 0.125% bupivacaine/ 0.0008% fentanyl; bupivacaine-only group: 0.25% bupivacaine alone); and 3) a continuous epidural in fusion of study solution 2 at a rate of 12.5 ml/h (bupivacaine-fentanyl group: 0.0625% bupivacaine/0.0002% fentanyl; bupivacaine-only group: 0.125% bupivacaine alone). The epidural infusion was discontinued at full cervical dilatation, but patients who lacked perineal anesthesia received one or two 5-ml boluses of study solution 3 (bupivacaine-fentanyl group: 0.0625% bupivacaine alone; bupivacaine-only group: 0.125% bupivacaine alone). During the first stage of labor, 36 of 41 (88%) women in the bupivacaine-fentanyl group, and 37 of 39 (95%) women in the bupivacaine-only group, had analgesia of excellent or good quality (P = NS). During the second stage, 22 of 37 (59%) women in the bupivacaine-fentanyl group, and 23 of 35 (66%) women in the bupivacaine-only group, rated their analgesia as excellent or good (P = NS). Women in the bupivacaine-only group were more likely to have motor block at full cervical dilatation (P <.001). There was no significant difference between groups in duration of the second stage of labor, duration of pushing, position of the vertex before delivery, method of delivery, Apgar scores, or umbilical cord blood gas and acid-base values. The authors conclude that the continuous epidural infusion of 0.0625% bupivacaine/0.0002% fentanyl produced analgesia similar to that provided by the infusion of 0.125% bupivacaine alone. However, the less intense motor block experienced by women in the bupivacaine-fentanyl group did not significantly shorten the second stage or result in a greater frequency of spontaneous delivery.

Effect of Naloxone on Gastric Emptying During Labour

The rate of gastric emptying was studied in 30 women during labour. All the women had received pethidine 100 mg i.m. for analgesia and, subsequently, extradural analgesia had been established for obstetric indications. The women were allocated randomly to two groups: 15 received naloxone 1.2 mg i.v. and 15 were given saline 3 ml (placebo). All 30 patients were then given paracetamol 1.5 g orally with water 100 ml. The amount of paracetamol absorbed, and hence gastric emptying, was significantly greater in the naloxone group in the first 30 min following the administration of the paracetamol.

The Effect of Halothane Anaesthesia on the Asphyxiated foetal Lamb in Utero

In a previous study, we examined the effects of halothane on the normal foetal lamb in utero. The most significant finding was a 33 per cent fall in foetal mean arterial blood pressure (MABP). Cardiac output and placental blood flow were not affected. To determine if the asphyxiated foetus would respond similarly, the following study was performed. Seven pregnant ewes were surgically prepared two days prior to study with maternal and foetal indwelling arterial and venous cannulas. An inflatable occlusion loop was secured around the umbilical cord. On the day of study, a tracheostomy was performed on each ewe. Microspheres were injected into the foetal circulation during the control period. The occlusion loop was inflated to produce foetal asphyxia and microspheres were again injected. The ewe was then anesthetized with halothane; and after 15 minutes, microspheres were injected into the asphyxiated foetus and halothane levels were measured. The asphyxiated foetuses showed a significant rise in MABP, fall in heart rate and fall in cardiac output from control. Blood flow to the brain was significantly increased and flow to the placenta and gut decreased. Exposure of the asphyxiated foetus to halothane resulted in a fall of MABP to control but no significant change in cardiac output or brain blood flow. The mean halothane level in the foetus was 46.0 mg X l-1 or 0.32 vol%. Exposure of the asphyxiated foetus to halothane for 15 minutes does not produce significant further deterioration of the foetal lamb in utero.

Effects of Low Intermittent Concentrations of Nitrous Oxide on the Developing Rat Fetus

Five groups of 12 gravid female rats were exposed, during their entire gestation, intermittently for 6 h a day, 5 days per week, to 0.5% (5000 p.p.m.), 0.1% (1000 p.p.m.), 0.05% (500 p.p.m.) and 0.025% (250 p.p.m.) nitrous oxide-air mixtures (v/v), respectively. After killing the gravid rats on the 19th day of their pregnancies the numbers of corpora lutea of pregnancy were counted. Each uterus was examined for placentation sites and embryonic remnants and a detailed examination of the fetuses was undertaken. A significant reduction in mean litter size occurred only in the group exposed to 0.5% nitrous oxide in air (v/v). The mean litter sizes of the control and other exposed groups were comparable. No signs of fetal resorption or skeletal malformation were found in any group. The threshold of pollution for reduction in litter size has been shown in this study to lie between 0.1% and 0.5% nitrous oxide in air (v/v). A previous study on continuous exposure reported the threshold pollution to lie between 0.05% and 0.1% nitrous oxide in air (v/v). This investigation confirms that intermittent exposure to nitrous oxide-air mixtures increases the threshold for reproductive effects in rats.

ABSTRACTS AND COMMENTS—ANESTHETIC CONSIDERATIONS INHALATION ANESTHESIA: Halothane Requirement During Pregnancy and Lactation in Rats

Near-term pregnancy is associated with a decrease in the minimum alveolar concentration (MAC) for halothane in ewes. Although increased progesterone levels might account for this change, a correlation between MAC and the known variations of progesterone levels which occur throughout gestation and the postpartum period has not been performed. Therefore, MAC for halothane was determined in nonpregnant, 10 days pregnant, term, and postpartum lactating rats. MAC values were significantly decreased by 19 per cent on the tenth day of pregnancy, and by 16 per cent at term, but they returned to control values 5 days postpartum. These changes did not correlate with the known changes in progesterone levels during pregnancy and lactation, and the authors conclude that progesterone is not responsible for the reduction in halothane MAC.

Maternal and Paternal Chronic Exposure to Enflurane and Halothane: Fetal and Histological Changes in the Rat

Adult male and female rats were exposed chronically to halothane 10 p.p.m., enflurane 20 p.p.m. or air for up to 64 days before mating and subsequently throughout the pregnancy of the females. The parents, progeny and, in a few cases, the subsequent generation, were studied. No abortifacient effect was seen with either agent. The groups exposed to anaesthetic had larger litters with lighter fetuses compared with their control groups. Skeletal examination did not reveal any major teratological effects for either agent. No consistent organ injury could be associated with chronic exposure to the agents under the conditions of this study.