Neostigmine decreases bupivacaine use by patient-controlled epidural analgesia during labor: a randomized controlled study

Abstract

Background: Intrathecal neostigmine not only produces analgesia but also severe nausea. In contrast, epidural neostigmine enhances opioid and local anesthetic analgesia without causing nausea. Previous studies examined only single epidural neostigmine bolus administration and did not assess the efficacy of continuous epidural infusion or several aspects of maternal and fetal safety. We therefore tested the hypothesis that epidural neostigmine in combination with bupivacaine by continuous infusion during labor would reduce the amount of bupivacaine required.

Methods: Twelve healthy women scheduled for elective cesarean delivery were assigned to receive epidural neostigmine, 40 microg (first six subjects) or 80 microg (second six subjects) as a single bolus, with fetal heart rate (FHR) and uterine contractions monitored for 20 min. In a subsequent experiment, 40 healthy laboring women were randomized to receive bupivacaine 1.25 mg/mL alone or with neostigmine 4 microg/mL by patient-controlled epidural analgesia. The primary outcome measure was hourly bupivacaine use.

Results: Epidural neostigmine bolus did not alter baseline FHR, induce contractions, or produce nausea. Epidural neostigmine infusion reduced bupivacaine requirement by 19% in all patients and 25% in those with >4 h of treatment (P < 0.05 for both) but might have contributed to the incidence of mild sedation. Mode of delivery, incidence of maternal nausea, and FHR abnormality were similar between groups.

Conclusions: These data show that adding epidural neostigmine 4 microg/mL reduces the hourly bupivacaine requirement by 19%-25% with patient-controlled epidural analgesia during labor. Administered as a bolus and by continuous infusion at the studied doses, epidural neostigmine does not cause nausea and does not induce uterine contractions or FHR abnormalities, but mild sedation can occur.

Figures

Figure 1

A) Mean maternal arterial blood pressure and B) Mean fetal heart rate after epidural analgesia, initiated at time 0, with bupivacaine, 1.25mg/mL, alone (open circles) or with neostigmine, 4 μg/mL (filled circles). No difference between groups by 2-way analysis of variance. The whisker represents the standard deviation of the data.

Figure 2

Incidence of A) sedation (non-zero verbal sedation scores) and B) nausea (non-zero verbal nausea scores) after epidural analgesia, initiated at time 0, with bupivacaine, 1.25mg/mL, alone (open circles) or with neostigmine, 4 μg/mL (filled circles). No difference between groups by 2-way analysis of variance. The sedation score was increased compared to baseline from 5 to 20 min after initiation of analgesia in the bupivacaine + neostigmine group by 1-way repeated measures analysis of variance. (P<0.05)

Figure 3

Mean hourly bupivacaine use (mL/h) in women receiving epidural analgesia with bupivacaine, 1.25mg/mL, alone (open bars) or with neostigmine, 4 μg/mL (filled bars). Data are presented for all patients in the study and for those with study drug duration > 4 hr. *P