Skeletal Muscle Relaxant
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Human pregnancy experience with rocuronium is limited to the 2nd and 3rd trimesters. Although the absence of exposures during organogenesis prevents a more thorough assessment, neuromuscular blocking agents generally do not appear to represent a significant risk for an embryo or fetus. The animal data for rocuronium suggest low embryo–fetal risk. Moreover, the agent contains a quaternary ammonium site in its structure that will limit its placental transfer. One review predicted that the maternal drug concentrations would always exceed fetal levels (1). Neuromuscular blockade in a newborn is probably a rare but potential toxicity (2). If indicated, rocuronium should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Rocuronium (rocuronium bromide) is a competitive (nondepolarizing) neuromuscular blocking agent. Structurally, it is a quaternary ammonium compound that is an analog of vecuronium. Rocuronium is indicated as an IV adjunct to general anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. In normal adult patients, the elimination half-life is about 2.4 hours. Approximately 30% is bound to plasma proteins (3).
Reproduction studies have been conducted in rats and rabbits. In these species, the maximum tolerated IV dose administered 3 times daily during organogenesis was not teratogenic. The doses were 15%–30% and 25%, respectively, of the human intubation dose of 0.6–1.2 mg/kg based on BSA. In rats, the incidence of fetal death was increased, an effect that was thought to be due to oxygen deficiency that resulted from acute symptoms of respiratory dysfunction in the dams (3).
Consistent with the molecular weight (about 610 for rocuronium bromide) and the limitation placed on placental passage by ionization at physiologic pH, small amounts of rocuronium cross the placenta. In 32 patients from the study below, the mean maternal venous (MV) and umbilical venous (UV) blood was about 2412 and 390 ng/mL, respectively. The UV:MV ratio was 0.16. In 12 patients, the mean drug concentration in umbilical arterial (UA) plasma was about 271 ng/mL, resulting in a UA:UV ratio of 0.62 (4).
In a 1994 prospective, nonrandomized, multicenter study, 40 women undergoing cesarean section at term received anesthesia induction with rocuronium and thiopental, followed by isoflurane and nitrous oxide maintenance (4). No adverse effects on the newborns attributable to rocuronium were observed as evaluated by Apgar scores, time to sustained respiration, total and muscular neuroadaptive capacity scores, acid–base status, and blood–gas tensions in umbilical arterial and venous blood (4). This study generated a number of letters referring either to the doses used or to what was considered the drug of choice (succinylcholine) (5–9).
A 1996 report described the use of rocuronium in a 31-year-old patient at 28 weeks’ gestation who presented with a penetrating injury of her left eye secondary to a motor vehicle accident (10). Prior to induction of anesthesia, she was started on IV magnesium sulfate to treat newly onset uterine contractions. Anesthesia was induced with rocuronium (0.9 mg/kg), fentanyl (200 mcg), and sodium thiopental (400 mg). The fetal heart rate (140–150 beats/minute) was monitored throughout the 6-hour surgical procedure. Except for a decrease in short-term variability attributable to anesthesia of the fetus, no other effects on the fetal heart rate were observed. Although the authors were aware of the interaction with magnesium, they choose a higher dose (usual dose is 0.6 mg/kg) to allow for more rapid intubation. As expected, the duration of paralysis was prolonged secondary to the high dose and interaction with magnesium, but the authors thought that this was acceptable given the patient’s condition. The woman was discharged from the hospital 6 days after surgery with an apparently normal ongoing pregnancy (10). Information on the pregnancy outcome was not provided. Later correspondence regarding this case report discussed the benefits and risks of the therapy and dose (11,12).
Rocuronium was used in a 35-year-old patient undergoing a combined cesarean section delivery and posterior fossa craniotomy at 37 weeks’ gestation (13). The patient had von Hippel-Lindau disease and surgery was required for an enlarged hemangioblastoma. General anesthesia was induced with rocuronium (50 mg), fentanyl (200 mcg), and sodium thiopental (300 mg). A male infant (weight not specified) was delivered with Apgar scores of 5, 7, and 9 at 1, 5, and 10 minutes, respectively. Naloxone was required because of weak respiratory efforts 2 minutes after delivery (13).
A 1997 study compared thiopental–rocuronium with ketamine–rocuronium (20 in each group) for rapid sequence intubation in women undergoing cesarean section (14). The authors concluded that either drug combination was suitable. Based on 1- and 5-minute Apgar scores, no significant differences in neonatal condition were found between the two groups.
BREASTFEEDING SUMMARY
No reports describing the use of rocuronium in a lactating woman have been located. Because of the indications for this agent, it is doubtful if such reports will be forthcoming. The molecular weight (about 610 for rocuronium bromide) is low enough for excretion into breast milk, but the amount excreted will be limited because the drug is ionized at physiologic pH. The effects of this exposure on a nursing infant are unknown, but are probably not clinically significant.
References
1.Guay J, Grenier Y, Varin F. Clinical pharmacokinetics of neuromuscular relaxants in pregnancy. Clin Pharmacokinet 1998;34:483–96.
2.Atherton DP, Hunter JM. Clinical pharmacokinetics of the newer neuromuscular blocking drugs. Clin Pharmacokinet 1999;36:169–89.
3.Product information. Zemuron. Organon USA, 2004.
4.Abouleish E, Abboud T, Lechevalier T, Zhu J, Chalian A, Alford K. Rocuronium (Org 9426) for caesarean section. Br J Anaesth 1994;73:336–41.
5.Kwan WF, Chen BJ, Liao KT. Rocuronium for caesarean section. Br J Anaesth 1995;74:347.
6.Abouleish E, Abboud T. Rocuronium for caesarean section. Br J Anaesth 1995;74:347–8.
7.McSiney M, Edwards C, Wilkins A. Rocuronium for caesarean section. Br J Anaesth 1995;74:348.
8.Swales HA, Gaylord DG. Rocuronium for caesarean section. Br J Anaesth 1995;74:348.
9.Abouleish E, Abboud T. Rocuronium for caesarean section. Br J Anaesth 1995;74:348.
10.Gaiser RR, Seem EH. Use of rocuronium in a pregnant patient with an open eye injury, receiving magnesium medication, for preterm labour. Br J Anaesth 1996;77:669–71.
11.James MFM. Use of rocuronium in a pregnant patient receiving magnesium medication. Br J Anaesth 1997;78:772.
12.Gaiser K. Use of rocuronium in a pregnant patient receiving magnesium medication (Reply). Br J Anaesth 1997;78:772.
13.Boker A, Ong BY. Anesthesia for cesarean section and posterior fossa craniotomy in a patient with von Hippel-Lindau disease. Can J Anesth 2001;48:387–90.
14.Baraka AS, Sayyid SS, Assaf BA. Thiopental-rocuronium versus ketamine-rocuronium for rapid-sequence intubation in parturients undergoing cesarean section. Anesth Analg 1997;84:1104–7.