Neostigmine, Atropine, and Glycopyrrolate

(Clark) Professor, Departments of Anesthesiology and Obstetrics/Gynecology, College of Medicine.(Brown) Assistant Professor, Department of Anesthesiology, College of Medicine.(Lattin) Professor, Department of Biopharmaceutical Sciences, College of Pharmacy.Received from the University of Arkansas for Medical Sciences Campus, Little Rock, Arkansas. Submitted for publication May 19, 1995. Accepted for publication October 5, 1995.Address reprint requests to Dr. Clark: Department of Anesthesiology, College of Medicine, Mail Slot 515, University of Arkansas for Medical Sciences Campus, 4301 West Markham, Little Rock, Arkansas 72205-7199.Key words: Anesthesia, obstetric: atropine; glycopyrrolate; neostigmine; placental transfer.DRUGS administered to the mother can cross the placenta and affect the fetus. Following is a description of such an event.The patient was a 22-yr-old pregnant woman (gravida 1, para 0). The gestational age of the fetus was estimated to be 31 weeks. The patient was diagnosed as suffering from paranoid schizophrenia and was receiving haloperidol and lorazepam. She required open reduction of a fractured elbow. General endotracheal anesthesia was used (the patient would not cooperate for regional anesthesia); the primary anesthetics were isoflurane and nitrous oxide. Thiopental was used for induction of anesthesia, succinylcholine to facilitate intubation, and vecuronium to prevent patient movement during the operation. The fetal heart rate and uterine contractions were monitored externally during the procedure. Left uterine displacement was performed. The patient was not in labor. Surgery proceeded satisfactorily, and the muscle relaxant effect was reversed at the termination of the anesthetic with neostigmine (5 mg) and glycopyrrolate (1 mg) intravenously. Preoperatively, the fetal heart rate was 153 beats/min but varied between 115 and 130 beats/min intraoperatively. Fetal heart rate immediately decreased to the range of 90-110 beats/min after administration of neostigmine and glycopyrrolate. Left uterine displacement was increased, and the fetal heart rate gradually returned to 120 beats/min. No atropine was given. The rate eventually reached 130 beats/min after 1 h. Four days postoperatively, however, the surgical repair was deemed unsatisfactory, and the patient underwent surgery. As before, general anesthesia was used along with vecuronium. Fetal heart rate and uterine contractions were monitored, and left uterine displacement was performed. At the end of the anesthetic, the muscle relaxant was antagonized with neostigmine (5 mg) and atropine (0.4 mg) intravenously. There was no change in fetal heart rate. The patient awoke satisfactorily from the anesthetic without complication and delivered a healthy infant at term.It is well known that atropine will cross the placenta and that maternal administration results in an increase in fetal heart rate. [1]The placental transfer of quaternary ammonium anticholinesterases, such as neostigmine, has been incompletely described. Proakis and Harris found that a maximal fetal:maternal serum concentration ratio at equilibrium for atropine of 1.0 occurs after maternal administration. [2]They studied glycopyrrolate, a quaternary ammonium salt, and found a ratio of 0.4 indicating partial transfer. They did not study neostigmine.Most of the studies involving quaternary ammonium anticholinesterases in pregnancy involve patients suffering from myasthenia gravis. [3]McNall and Jafarnia presented five case reports and discussed management of labor and the postpartum period in patients with myasthenia. [4]One of the patients received edrophonium, and another received neostigmine. Chambers et al. presented two case reports and reviewed the etiology, diagnosis, course, and treatment of pregnant patients with myasthenia gravis and who were receiving either neostigmine or pyridostigmine. [5]Plauche presented three case reports and described current developments; two of these patients received pyridostigmine. [6]Eden and Gall presented eight case reports. [7]All eight patients underwent thymectomy, with improvement in their clinical condition. Fetal anticholinesterase levels were not determined in any of these reports. None of the reports mentioned fetal or neonatal heart rates. Neonatal myasthenia developed in several of the infants. With regard to neonatal myasthenia, Plauche related,