Risk Factor: CM
Class: Autonomics/ Skeletal muscle relaxants

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary

Fetal Risk Summary

Pancuronium (pancuronium bromide) is a competitive (nondepolarizing) neuromuscular blocking agent. Structurally, it is a bisquaternary ammonium compound (i.e., contains two quaternary ammonium groups) and is commercially available as the dibromide. Pancuronium is used to induce skeletal muscle relaxation during anesthesia and other procedures, and has been used to produce fetal muscle paralysis during intrauterine procedures.

Unpublished reproduction studies in rats and rabbits with pancuronium did not reveal any effect on the number of resorptions, litter size, birth weight and vitality, or the frequency of malformations (gross, skeletal, and internal organs) (1). Pregnant rats (average gestational length 2122 days [2]) received intraperitoneal doses of 0.16 mg/kg/day either from the 7th to the 14th day or from the 1st to the 20th day of gestation, whereas pregnant rabbits (average gestational length 3134 days [2]) were given IV doses of 0.02 mg/kg/day from day 8 to day 16 of gestation.

Theoretically, the combination of relatively high molecular weight (about 733 for the dibromide) and the presence of two quaternary ammonium groups that are ionized at physiologic pH should limit the placental transfer of pancuronium. An animal study, published in 1973, appeared to confirm the lack of significant transfer when cumulative IV doses up to 16.3 mg/kg administered to pregnant ferrets (neuromuscular block in the mother complete at 0.015 mg/kg) did not cause neuromuscular blockade in the fetus during a 1-hour observation period (3). The fetus was responsive to pancuronium-induced blockade by direct administration. Further, the lack of adverse effects in newborns after mean doses of 0.0875 mg/kg at cesarean section led some authors to conclude that the drug did not cross the placenta (4). However, several human studies have demonstrated placental transfer, at least near term, when pancuronium was used during cesarean section (5,6,7,8,9,10 and 11).

Maternal IV bolus doses between 0.04 mg/kg and 0.12 mg/kg (approximately 2.88.6 times the maternal ED50, the dose producing a 50% depression of evoked twitch tension [12]), resulted in mean umbilical vein:maternal vein ratios ranging from 0.19 to 0.26. These ratios were higher than those measured with atracurium, fazadinium, pipecuronium, rocuronium, d-tubocurarine, and vecuronium (13). No clinical evidence of neuromuscular blockade was observed in five studies in which the neonatal condition was noted (5,6,7,8 and 9), but in one of the studies (9) the Neurologic and Adaptive Capacity Scores (NACS) system indicated that neonatal depression was present. The NACS evaluates adaptive capacity, passive and active muscular tone, primary reflexes, and general assessment (13). The maximum score possible is 40, with a score of 3540 denoting a normal, vigorous baby.

The NACS was measured at 15 minutes, 2 hours, and 24 hours in seven newborns whose mothers had been given IV doses of d-tubocurarine (3 mg), thiopental (4 mg/kg), succinylcholine (1.5 mg/kg), and pancuronium (0.04 mg/kg) immediately prior to cesarean section (9). Five newborns (71%) had a NACS value
The direct administration of pancuronium has been reported in animals and humans (14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29, 30,31,32,33,34,35,36,37 and 38) . A 1989 report compared the effects of pancuronium (0.5 mg/kg IV over 5 minutes) and d-tubocurarine (3.0 mg/kg IV over 5 minutes) on the heart rate and mean arterial pressure of fetal lambs (14). Whereas pancuronium significantly increased both rate and pressure, both measures were significantly decreased by d-tubocurarine. Only pancuronium effected fetal pH and Pco2, increasing the former and decreasing the latter. The human studies, discussed below, all involve pancuronium administration during the second half of gestation.

In a study published in 1988, the baseline fetal heart rate (FHR), number of accelerations, and beat-to-beat variability were assessed before and after an IV bolus dose of pancuronium (0.050.10 mg/kg) was given to 17 fetuses before transfusion (15). Twenty minutes after transfusion, no changes were noted in the baseline FHR, although some heart rate patterns appeared sinusoidal-like, but significant decreases in accelerations (p=0.003) and variability (p=0.0003) were observed (15). The transient FHR changes were not indicative of fetal compromise and returned to normal when the fetus awakened (15). A 1991 abstract reported significantly less bradycardia with the use of pancuronium (0.3 mg/kg) compared with no muscle relaxant after cordocentesis (3.6% [8/224] vs. 8.2% [27/329], p=0.04) and a near significant difference after intravascular transfusion (7.9% [9/114] vs. 40% [2/5], p=0.06) (16).

Pancuronium (0.1 mg/kg IV) was administered to 20 fetuses immediately before blood transfusion at 28 to 34 weeks’ gestation (17). A control group of 20 fetuses matched for gestational age and hematocrit who did not receive pancuronium was used for comparison. After transfusion, compared with controls, fetuses that received pancuronium had significantly fewer FHR accelerations (mean 0 vs. 3.0, p
Fetal death at 25.5 weeks’ gestation, that was apparently the result of a cord hematoma, occurred 2 hours after an intravascular intrauterine transfusion (19). The authors thought that the accident was related to the injection of pancuronium before confirmation of needle placement by aspiration of fetal blood. The results of an autopsy confirmed that the cause of death was compression of the umbilical vein by the hematoma with subsequent umbilical venous thrombosis.

Fetal administration of pancuronium immediately preceding magnetic resonance imaging (MRI) has been described in a number of publications (20,21,22,23,24,25,26,27 and 28). Most used doses varying from 0.08 to 0.3 mg/kg (IV into the umbilical vein or IM) (20,21,22,23,24 and 25), two used 0.5 mg IM (26,27), and one reported 100 mg (sic) into the intrahepatic vein of each twin (28).

Direct fetal administration of pancuronium for intrauterine procedures, such as cordocentesis and intravascular transfusion, has been reported (29,30,31,32,33,34,35,36,37 and 38). The fetal dose ranged from 0.1 to 0.3 mg/kg IV or IM, but in one report a single 0.5-mg IM dose was administered (29). In another study, pancuronium (0.15 mg/kg of the estimated total fetal body weights of twins) was administered in two cases to the smaller of a set of twins (38). The procedure was undertaken in an attempt to diagnose twin-twin transfusion syndrome. In the first case, the FHR patterns of both twins showed lack of accelerations and decreased variability and, in addition, the larger twin had a sinusoidal-like pattern. In the second case, absent accelerations and decreased variability occurred only in the smaller twin (38).

A continuous infusion of morphine, midazolam, and pancuronium was administered for 10 hours to allow mechanical ventilation in a seriously ill, pregnant (about 35 weeks’) woman with pneumonia due to Legionella pneumophila (39). No evidence of fetal harm was observed during the infusion, but the fetus was noted to have a consistent pattern of sleeping. Approximately 3 to 4 weeks later, at 40 weeks’ gestation, the mother gave birth to a healthy female infant.

In summary, pancuronium has been administered directly to the fetus during the last half of pregnancy and to the mother at cesarean section without causing fetal harm. Although no teratogenicity was observed in two animal species, the use of pancuronium in early human pregnancy has not been reported. The drug is known to cross the human placenta to the fetus, at least near term. Placental transfer early in pregnancy has not been reported. Large or repetitive doses and/or prolonged dose-to-delivery intervals may potentially result in newborn depression, but the clinical significance of this appears to be low. Moreover, other anesthetic agents may contribute to the condition. In addition, transient FHR changes, such as decreased accelerations and beat-to-beat variability, and an occasional sinusoidal-like pattern, have been observed after direct fetal administration, but apparently this does not indicate fetal compromise.

Breast Feeding Summary

No reports describing the use of pancuronium in a lactating woman have been located. Because of the nature of the drug and its indications, such reports are unlikely to occur. Moreover, because pancuronium is a bisquaternary ammonium compound, it is ionized at physiologic pH. Only the nonionized form would be available for excretion into milk, and this would probably be only trace amounts (40). In addition, compounds of this type are poorly absorbed from the gastrointestinal tract (40).



  1. Speight TM, Avery GS. Pancuronium bromide: A review of its pharmacological properties and clinical application. Drugs 1972;4:163226.
  2. Shepard TH. Catalog of Teratogenic Agents. 9th ed. Baltimore, MD: Johns Hopkins University Press, 1998.
  3. Evans CA, Waud DR. Do maternally administered neuromuscular blocking agents interfere with fetal neuromuscular transmission? Anesth Analg 1973;52:54852.
  4. Neeld JB Jr, Seabrook PD Jr, Chastain GM, Frederickson EL. A clinical comparison of pancuronium and tubocurarine for cesarean section anesthesia. Anest Analg 1974;53:711.
  5. Speirs I, Sim AW. The placental transfer of pancuronium bromide. Br J Anaesth 1972;44:3703.
  6. Booth PN, Watson MJ, McLeod K. Pancuronium and the placental barrier. Anaesthesia 1977;32:3203.
  7. Duvaldestin P, Demetriou M, Henzel D, Desmonts JM. The placental transfer of pancuronium and its pharmacokinetics during caesarian section. Acta Anaesthiol Scand 1978;22:32733.
  8. Abouleish E, Wingard LB Jr, De La Vega S, Uy N. Pancuronium in caesarean section and its placental transfer. Br J Anaesth 1980;52:5316.
  9. Dailey PA, Fisher DM, Shnider SM, Baysinger CL, Shinohara Y, Miller RD, Abboud TK, Kim KC. Pharmacokinetics, placental transfer, and neonatal effects of vecuronium and pancuronium administered during cesarean section. Anesthesiology 1984;60:56974.
  10. Heaney GAH. Pancuronium in maternal and foetal serum. Br J Anaesth 1974;46:2827.
  11. Wingard LB Jr, Abouleish E, West DC, Goehl TJ. Modified fluorometric quantitation of pancuronium bromide and metabolites in human maternal and umbilical serums. J Pharm Sci 1979;68:9145.
  12. Agoston S, Crul JF, Kersten UW, Scaf AHJ. Relationship of the serum concentration of pancuronium to its neuromuscular activity in man. Anesthesiology 1977;47:50912.
  13. Guay J, Grenier Y, Varin F. Clinical pharmacokinetics of neuromuscular relaxants in pregnancy. Clin Pharmacokinet 1998;34:48396.
  14. Chestnut DH, Weiner CP, Thompson CS, McLaughlin GL. Intravenous administration of d-tubocurarine and pancuronium in fetal lambs. Am J Obstet Gynecol 1989;160:5103.
  15. Pielet BW, Socol ML, MacGregor SN, Dooley SL, Minogue J. Fetal heart rate changes after fetal intravascular treatment with pancuronium bromide. Am J Obstet Gynecol 1988;159:6403.
  16. Weiner C. Pancuronium protects against fetal bradycardia following umbilical cord puncture (abstract). Am J Obstet Gynecol 1991;164:335.
  17. Spencer JAD, Ronderos-Dumit D, Rodeck CH. The effect of neuromuscular blockade on human fetal heart rate and its variation. Br J Obstet Gynaecol 1994;101:1214.
  18. Watson WJ, Atchison SR, Harlass FE. Comparison of pancuronium and vecuronium for fetal neuromuscular blockade during invasive procedures. J Matern Fetal Med 1996;5:1514.
  19. Seeds JW, Chescheir NC, Bowes WA Jr, Owl-Smith FA. Fetal death as a complication of intrauterine intravascular transfusion. Obstet Gynecol 1989;74:4613.
  20. Williamson RA, Weiner CP, Yuh WTC, Abu-Yousef MM. Magnetic resonance imaging of anomalous fetuses. Obstet Gynecol 1989;73:9526.
  21. Lituania M, Passamonti U, Cordone MS, Magnano GM, Toma P. Schizencephaly: prenatal diagnosis by computed sonography and magnetic resonance imaging. Prenat Diagn 1989;9:64955.
  22. Toma P, Lucigrai G, Dodero P, Lituania M. Prenatal detection of an abdominal mass by MR imaging performed while the fetus is immobilized with pancuronium bromide. AJR 1990;154:104950.
  23. Toma P, Costa A, Magnano GM, Cariati M, Lituania M. Holoprosencephaly: prenatal diagnosis by sonography and magnetic resonance imaging. Prenat Diagn 1990;10:42936.
  24. Wenstrom KD, Williamson RA, Weiner CP, Sipes SL, Yuh WTC. Magnetic resonance imaging of fetuses with intracranial defects. Obstet Gynecol 1991;77:52932.
  25. Okamura K, Murotsuki J, Sakai T, Matsumoto K, Shirane R, Yajima A. Prenatal diagnosis of lissencephaly by magnetic resonance image. Fetal Diagn Ther 1993;8:569.
  26. Lenke RR, Persutte WH, Nemes JM. Use of pancuronium bromide to inhibit fetal movement during magnetic resonance imaging. A case report. J Reprod Med 1989;34:3157.
  27. Horvath L, Seeds JW. Temporary arrest of fetal movement with pancuronium bromide to enable antenatal magnetic resonance imaging of holoprosencephaly. Am J Perinatol 1989;6:41820.
  28. Zoppini C, Vanzulli A, Kustermann A, Rizzuti T, Selicorni A, Nicolini U. Prenatal diagnosis of anatomical connections in conjoined twins by use of contrast magnetic resonance imaging. Prenat Diag 1993;13:9959.
  29. Seeds JW, Corke BC, Spielman FJ. Prevention of fetal movement during invasive procedures with pancuronium bromide. Am J Obstet Gynecol 1986;155:8189.
  30. Moise KJ Jr, Carpenter RJ Jr, Deter RL, Kirshon B, Diaz SF. The use of neuromuscular blockade during intrauterine procedures. Am J Obstet Gynecol 1987;157:8749.
  31. Copel JA, Grannum PA, Harrison D, Hobbins JC. The use of intravenous pancuronium bromide to produce fetal paralysis during intravascular transfusion. Am J Obstet Gynecol 1988;158:1701.
  32. Moise KJ Jr, Deter RL, Kirshon B, Adam K, Patton DE, Carpenter RJ Jr. intravenous pancuronium bromide for fetal neuromuscular blockade during intrauterine transfusion for red-cell alloimmunization. Obstet Gynecol 1989;74:9058.
  33. Fan SZ, Huang, FY, Lin SY, Wang YP, Hsieh FJ. Intrauterine neuromuscular blockade in fetus. Anaesth Sinica 1990;28:314.
  34. Weiner CP, Wenstrom KD, Sipes SL, Williamson RA. Risk factors for cordocentesis and fetal intravascular transfusion. Am J Obstet Gynecol 1991;165:10205.
  35. Fan SZ, Susetio L, Tsai MC. Neuromuscular blockade of the fetus with pancuronium or pipecuronium for intra-uterine procedures. Anaesthesia 1994;49:2846.
  36. Mouw RJC, Hermans J, Brandenburg HCR, Kanhai HHH. Effects of pancuronium or atracurium on the anemic fetus during and directly after intrauterine transfusion (IUT): a double blind randomized study (abstract). Am J Obstet Gynecol 1997;176:S18.
  37. Mouw RJC, Klumper F, Hermans J, Brandenburg HCR, Kanhai HHH. Effect of atracurium or pancuronium on the anemic fetus during and directly after intravascular intrauterine transfusion. A double blind randomized study. Acta Obstet Gynecol Scand 1999;78:7637.
  38. Tanaka M, Natori M, Ishimoto H, Kohno H, Kobayashi T, Nozawa S. Intravascular pancuronium bromide infusion for prenatal diagnosis of twin-twin transfusion syndrome. Fetal Diagn Ther 1992;7:3640.
  39. Eisenberg VH, Eidelman LA, Arbel R, Ezra Y. Legionnaire’s disease during pregnancy: a case presentation and review of the literature. Eur J Obstet Gynecol Reprod Biol 1997;72:158.
  40. Spigset O. Anaesthetic agents and excretion in breast milk. Acta Anaesthesiol Scand 1994;38:94103.

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