Local Anesthetic
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
The human and animal data suggest that the risk to a human fetus from the use of ropivacaine in pregnancy is very low or nonexistent. However, there is no human pregnancy experience in the 1st trimester. The amounts measured in the maternal circulation are very low and do not appear to represent a significant embryo–fetal risk.
FETAL RISK SUMMARY
Ropivacaine is a member of the amino amide class of local anesthetics. It is indicated for local or regional anesthesia for surgery and for acute pain management. Ropivacaine is a pure S-enantiomer that is structurally similar to bupivacaine. It has been used for local and regional anesthesia before cesarean section and during labor. Plasma protein binding (94%) is primarily to α1-glycoprotein. The mean terminal half-life is 4.2 hours after epidural administration (1).
Reproduction studies have been conducted in rats and rabbits. In rats, daily SC doses up to about 0.33 times the maximum recommended human dose (epidural, 770 mg/24 hours) based on BSA (MRHD) during organogenesis revealed no teratogenic effects. When rats were given daily SC doses from gestational day 15 through postpartum day 20, there were no treatment-related effects on late fetal development, parturition, lactation, neonatal viability, or growth of the offspring. In another study, female rats were given daily SC doses that were about 0.3 times the MRHD for 2 weeks before mating, then during mating, pregnancy, and lactation, up to day 42 post-coitus. There was an increased loss of pups during the first 3 days postpartum, an effect thought to have occurred because of reduced maternal care due to maternal toxicity. In rabbits, SC doses up to about 0.33 times the MRHD during organogenesis revealed no teratogenicity (1).
Pregnant sheep were given a 60-minute IV infusion of a local anesthetic (ropivacaine, bupivacaine, or levobupivacaine) at a rate that obtained a maternal serum concentration equivalent to that obtained during routine epidural anesthesia for cesarean delivery (2). No significant changes (heart rate, mean arterial blood pressure, arterial blood pH, and arterial oxygenation) in the fetuses were observed. Maternal hemodynamic parameters also were not affected. All three anesthetics crossed the placenta to the fetus with varying concentrations measured in all fetal tissues tested (heart, brain, liver, lung, kidney, and adrenals). The ropivacaine fetal:maternal serum ratio was approximately 0.3 (2).
A 1999 study used a dual perfused, single cotyledon human placental model to compare the placental transfer of ropivacaine and bupivacaine (3). Simulation of the actual in vivo plasma protein concentration (using a 4% albumin solution) resulted in a 50% decrease in the amounts transferred compared with a 2% albumin solution. In addition, decreasing the pH on the fetal side resulted in a significant increase in placental transfer. The investigators concluded that the placental transfer of both anesthetics was highly influenced by the amount of maternal and fetal protein binding and fetal pH (3).
In another study, epidural ropivacaine was given to women for cesarean section (4). The umbilical:maternal (U:M) veins ratio of unbound drug at delivery was 0.72 (4). A 1997 report measured mean U:M vein ratios for total and unbound ropivacaine after epidural of 0.31 and 0.74, respectively (5). In a third study, total ropivacaine concentrations in the umbilical vein and artery were 0.13–0.52 and 0.12–0.41 mg/L, respectively, whereas the concentrations of unbound drug were 0.027–0.063 and 0.027–0.058 mg/L, respectively (6).
A number of studies have reported normal Apgar scores, umbilical acid–base values, and neurobehavioral assessments when ropivacaine epidurals were used in women in labor (4–11). In one study conducted at six different centers, fewer infants delivered vaginally from mothers receiving ropivacaine had abnormal neurological and adaptive capacity scores at 24 hours compared with those delivered vaginally from mothers receiving bupivacaine (11).
BREASTFEEDING SUMMARY
No reports describing the use of ropivacaine during human lactation have been located. As noted above, the primary use in pregnancy of this local anesthetic occurs during labor. Only very small amounts appear in the maternal circulation after epidural use and these concentrations would be cleared within 24 hours. Therefore, there appears to be no risk for a nursing infant.
References
1.Product information. Naropin. AstraZeneca, 2001.
2.Santos AC, Karpel B, Noble G. The placental transfer and fetal effects of levobupivacaine, racemic bupivacaine, and ropivacaine. Anesthesiology 1999;90:1698–703.
3.Johnson RF, Cahana A, Olenick M, Herman N, Paschall RL, Minzter B, Ramasubramanian R, Gonzalez H, Downing JW. A comparison of the placental transfer of ropivacaine versus bupivacaine. Anesth Analg 1999;89:703–8.
4.Datta S, Camann W, Bader A, VanderBurgh L. Clinical effects and maternal and fetal plasma concentrations of epidural ropivacaine versus bupivacaine for cesarean section. Anesthesiology 1995;82:1346–52.
5.Morton CPJ, Bloomfield S, Magnusson A, Jozwiak H, McClure JH. Ropivacaine 0.75% for extradural anaesthesia in elective caesarean section: an open clinical and pharmacokinetic study in mother and neonate. Br J Anaesth 1997;79:3–8.
6.Irestedt L, Ekblom A, Olofsson C, Dahlstrom AC, Emanuelsson BM. Pharmacokinetics and clinical effect during continuous epidural infusion with ropivacaine 2.5 mg/ml or bupivacaine 2.5 mg/ml for labour pain relief. Acta Anaesthesiol Scand 1998;42:890–6.
7.Gaiser RR, Venkateswaren P, Cheek TG, Persiley E, Buxbaum J, Hedge J, Joyce TH, Gutsche BB. Comparison of 0.25% ropivacaine and bupivacaine for epidural analgesia for labor and vaginal delivery. J Clin Anesthesia 1997;9:564–8.
8.McCrae AF, Jozwiak H, McClure JH. Comparison of ropivacaine and bupivacaine in extradural analgesia for the relief of pain in labour. Br J Anaesth 1995;74:261–5.
9.Eddleston JM, Holland JJ, Griffin RP, Corbett A, Horsman EL, Reynolds F. A double-blind comparison of 0.25% ropivacaine and 0.25% bupivacaine for extradural analgesia in labour. Br J Anaesth 1996;76:66–71.
10.Irestedt L, Emanuelsson BM, Ekblom A, Olofsson C, Reventlid H. Ropivacaine 7.5 mg/ml for elective caesarean section. A clinical and pharmacokinetic comparison of 150 mg and 187.5 mg. Acta Anaesthesiol Scand 1997;41:1149–56.
11.Writer WDR, Stienstra R, Eddleston JM, Gatt SP, Griffin R, Gutsche BB, Joyce TH, Hedlund C, Heeroma K, Selander D. Neonatal outcome and mode of delivery after epidural analgesia for labour with ropivacaine and bupivacaine: a prospective meta-analysis. Br J Anaesth 1998;81:713–7.