Studies of the pharmacology and pathology of intrathecally administered 4-anilinopiperidine analogues and morphine in the rat and cat.

In rats, intrathecal alfentanil, lofentanil, sufentanil, fentanyl, and morphine produced dose-dependent elevations in the hot-plate and tail-flick latencies and a powerful suppression of the writhing response. The slopes of the monotonic dose-response curves for the five opioids did not differ significantly. In terms of the hot-plate ED50 after intrathecal injection, the order of potency was as follows: lofentanil (210), sufentanil (29), fentanyl (3), morphine (1), and alfentanil (1). Comparable results were observed in the tail flick. The duration of action was proportional to dose. However, at doses that produced an equal magnitude of inhibition, the duration of action was lofentanil greater than morphine greater than sufentanil greater than alfentanil greater than or equal to fentanyl. Systemically administered naloxone (0.03-1 mg/kg, sc) resulted in dose-dependent antagonism of the antinociceptive effect of intrathecal morphine, fentanyl, alfentanil, and sufentanil. In contrast, intrathecal lofentanil was extremely resistant to antagonism by naloxone. In cats, similar dose-dependent blockade of the thermally evoked skin-twitch response was observed after intrathecal morphine, sufentanil, alfentanil, and fentanyl. As in the rat, the slope of the monotonic dose-response curves did not differ. The relative potency and duration of action after equipotent intrathecal doses were similar to those observed in the rodent. These results suggest that sufentanil, alfentanil, and fentanyl exert their analgesic effects in vivo at a spinal cord site that has properties comparable to those of the site acted upon by morphine. Except for catalepsy in rats, no major behavioral dysfunctions were noted at the ED50 dose of any of the drugs administered. No abnormal morphologic effects of acutely or chronically administered alfentanil and sufentanil were seen, aside from an inflammatory reaction secondary to catheter placement.

Pseudocholinesterase activity and atracurium v. suxamethonium block.

Serum pseudocholinesterase activity in pregnant women was assayed spectrophotometrically using either propionylthiocholine or suxamethonium as substrate. All patients had a normal phenotype as indicated by normal dibucaine and fluoride numbers. However, the mean cholinesterase activity was lower than in the general population. There was a negative correlation between cholinesterase activity and the duration of neuromuscular blockade following suxamethonium, but no correlation was observed between the cholinesterase activity and the duration of block following atracurium.

Continuous infusion epidural analgesia in parturients receiving bupivacaine, chloroprocaine, or lidocaine--maternal, fetal, and neonatal effects.

The effects of epidural analgesia for labor and delivery using a continuous infusion technique on fetal heart rate, uterine activity, maternal blood pressure, Apgar scores, neonatal acid-base status, and the Neurologic and Adaptive Capacity Scoring System were studied in 61 parturients. Group I (n = 23) received initial test and therapeutic doses of 2 and 6 ml of 0.5% bupivacaine followed by an infusion of 0.125% at a rate of 14 ml/hr. Group II (n = 19) received 2 and 6 ml of 2% chloroprocaine followed by an infusion of 0.75% at a rate of 27 ml/hr. Group III (n = 19) received 2 and 6 ml of 1.5% lidocaine followed by an infusion of 0.75% at a rate of 14 ml/hr. None of the three local anesthetics used had any significant effect on baseline fetal heart rate or uterine activity. In cases in which monitoring of fetal heart rate was both technically satisfactory and continuous, late and variable decelerations in fetal heart rate were seen in 10 of 17, 3 of 18, and 2 of 19 of the fetuses in groups I, II, and III, respectively. The incidence was significantly higher in group I than in groups II or III (P less than 0.05). Apgar scores and neonatal acid-base status were equally good in all three groups. Neurologic and adaptive capacity scores did not differ among the three groups of neonates, nor did any of the neonates in the three groups score lower than a control group of 19 neonates whose mothers did not receive any analgesia or medications for labor and delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidural bupivacaine, chloroprocaine, or lidocaine for cesarean section--maternal and neonatal effects.

The effects of epidural anesthesia on maternal blood pressure, newborn Apgar scores, neonatal acid-base status, and the early neonatal neurobehavioral scale (ENNS) were studied in 54 pregnant women undergoing cesarean section. Maternal and neonatal blood levels of the local anesthetics were also determined. Group 1 (n = 16) received 0.75% bupivacaine, group 2 (n = 18) received 3% chloroprocaine, group 3 (n = 11) received 2% lidocaine, and group 4 (n = 9) received 2% lidocaine with 1:200,000 epinephrine. The incidence of maternal hypotension did not differ significantly among the four groups. Fetal outcome as determined by Apgar scores, acid-base status, and neurobehavioral testing was equally good in all four groups. At delivery, the fetal/maternal concentration ratio of bupivacaine was 0.27, that of lidocaine without epinephrine 0.48, and that of lidocaine with epinephrine 0.58. Chloroprocaine was detected in 12 maternal samples, in seven umbilical venous samples, and in six umbilical arterial samples. It is concluded that epidural anesthesia as administered in this study had no adverse effect on the newborn Apgar scores, cord acid-base status, or the ENNS.

Succinylcholine-vecuronium (Org NC 45) sequence for cesarean section.

Vecuronium (Org NC 45) was used in 27 parturients undergoing elective cesarean section under general anesthesia. One of the parturients had a twin pregnancy. Neuromuscular transmission was assessed clinically by stimulating the ulnar nerve and observing the contraction of the fingers. An initial bolus of 0.05 mg . kg-1 of vecuronium was injected after recovery from succinylcholine block. Complete neuromuscular block resulted in all cases and lasted for a mean duration of 19.3 +/- 6.02 min. Muscular relaxation was maintained by incremental doses of 0.01 mg . kg-1 of vecuronium. Administration of vecuronium did not cause significant changes in blood pressure, pulse rate, or plasma cholinesterase activity. Also, there was no correlation between the plasma cholinesterase activity and the duration of neuromuscular block of vecuronium. The residual neuromuscular block could be antagonized at the end of the procedure by a mixture of 0.005 mg . kg-1 of glycopyrrolate and 0.025 mg . kg-1 of neostigmine. In all parturients, antagonism was adequate as evidenced by maintained tetanic response (50 Hz for 5 sec) and sustained head lift. Nine infants were delivered before the injection of vecuronium; 19 infants were delivered after its injection. There was no significant difference between the Apgar scores in the two groups, suggesting that vecuronium does not cross the placenta in concentrations that affect the newborn. Vecuronium may be advantageous in parturients undergoing cesarean section under general anesthesia because it maintains cardiovascular stability, is noncumulative, is readily antagonized by neostigmine, has no effect on the plasma cholinesterase activity, and has no deleterious effect on the newborn.

Effects of induction of general and regional anesthesia for cesarean section on maternal plasma beta-endorphin levels.

Plasma beta-endorphin was measured in 40 healthy pregnant women undergoing cesarean section. Group 1 patients (N = 14) received general anesthesia by rapid-sequence induction and endotracheal intubation with curare, thiopental, and succinylcholine. Anesthesia was maintained with nitrous oxide, oxygen, and muscle relaxant until delivery. Group 2 patients (N = 26) received regional anesthesia (spinal, 14, and epidural, 12). Maternal blood samples were drawn from indwelling venous catheters prior to and after induction of either general or regional anesthesia. Plasma beta-endorphin was determined by radioimmunoassay following silicic acid extraction and gel chromatography. In the 14 patients who underwent general anesthesia, the mean (+/- SEM) plasma beta-endorphin increased significantly (p less than 0.025) from 46 +/- 7.4 to 111.6 +/- 8.9 fmol/ml. There was no significant change in plasma beta-endorphin level of the 26 patients who underwent regional anesthesia; beta-endorphin levels averaged 44.5 +/- 5.1 and 47.6 +/- 4.8 fmol/ml prior to and after induction of anesthesia, respectively. These data demonstrate that plasma beta-endorphin concentrations are elevated following induction of general anesthesia but not with induction of regional anesthesia, which suggests that less stress is associated with regional than with general anesthesia induction in patients undergoing cesarean section.

Effects of epidural anesthesia during labor on maternal plasma beta-endorphin levels.

Plasma beta-endorphin (beta-EP) was measured in 48 women. Twenty-three were in labor. In 13 of the 23 patients in labor, beta-EP was determined prior to and after complete onset of epidural anesthesia, and in 10 women, who served as controls, prior to and after injection of saline into the epidural space as part of the loss of resistance technique, but before injection of the local anesthetic. Venous blood also was obtained for plasma beta-EP determinations from 10 healthy non-pregnant women and from 15 patients scheduled for elective repeat cesarean section and who were not in labor. Human beta-EP was determined by radioimmunoassay following silicic acid extraction of plasma samples and separation of the beta-EP fraction by gel chromatography. In the 10 non-pregnant volunteers, plasma beta-EP averaged 11.3 +/- 1.5 fmol/ml (mean +/- SE) as compared with 43.7 +/- 6.5 fmol/ml observed in the 15 women with term pregnancies who were not in labor (P less than 0.005). In the 13 patients in labor who underwent epidural anesthesia, plasma beta-EP concentrations decreased (P less than 0.005) from 54.5 +/- 9.0 to 28.2 +/- 3.5 fmol/ml, whereas there was no significant change in plasma beta-EP levels in the 10 controls who averaged 64 +/- 20.5 and 55.8 +/- 13.6 fmol/ml prior to and following saline injection. These data confirm that plasma beta-EP levels are significantly higher in women with term pregnancies in labor than in non-pregnant women and also demonstrate that epidural anesthesia during labor is accompanied by a significant decrease in maternal plasma beta-EP concentrations.