Editorial II

Ropivacaine in children

N.S. Morton

Ropivacaine is the s-enantiomer of a new amide local anaesthetic which has been extensively evaluated in adults and older children.1 Recently, it has been used in younger children and several studies have reported its clinical efficacy and safety when administered for caudal epidural analgesia,213 for lumbar epidural block,14 for peripheral nerve blockade,15 16 and as a continuous epidural infusion.1720 Pharmacokinetic parameters have been calculated for several different age groups and the pharmacodynamics in children are becoming clearer as clinical experience grows. A meta-analysis of neonatal outcome after maternal administration of ropivacaine has also been published recently.21

Ropivacaine has several properties which may be useful in paediatric practice, namely the potential to produce differential neural blockade with less motor block and reduced cardiovascular and neurological toxicity.1 These features are particularly attractive for day case surgery in children, which is increasing in frequency.

Studies of ropivacaine in children have reported pharmacodynamics and/or kinetics after single caudal or lumbar epidural injection of doses between 1 and 3 mg kg–1, peripheral nerve blockade with up to 3 mg kg–1, plexus blockade, epidural infusion analgesia with up to 0.4 mg kg–1 h–1 via caudal or lumbar epidural catheters, and the effects of adding clonidine or preservative-free ketamine to caudal ropivacaine.

For single injection caudal epidural block, comparisons between equal masses of ropivacaine and bupivacaine have shown virtually identical profiles in terms of onset time, efficacy, duration of analgesia and incidence of motor blockade.3 4 911 14 22 As has been demonstrated for bupivacaine, ropivacaine caudal blocks can be prolonged by a factor of 2- to 3-fold by the addition of clonidine or ketamine to the caudal injectate.23 24 A number of studies of caudal block have compared ropivacaine with the same volume and/or mass of bupivacaine.3 4 911 14 22 The 2 mg ml–1 concentration of ropivacaine gives results comparable to 2.5 mg ml–1 bupivacaine while 3.75 mg ml–1 solution gives less motor block than bupivacaine when equal volumes are administered. When the same mass of ropivacaine is given but in a larger volume than bupivacaine, analgesia is prolonged.9 When a larger mass of ropivacaine is given in a similar volume, analgesia is prolonged when compared with bupivacaine or with ropivacaine itself.12 The more concentrated solutions of ropivacaine do produce motor block but the frequency, intensity and duration is shorter than an equal mass of bupivacaine.3 4 In a detailed study of a standard volume (1 ml kg–1) of caudal ropivacaine in three concentrations (1, 2 and 3 mg ml–1), the weakest solution produced a block to L4, with a shorter duration of analgesia and no motor block. Both 2 and 3 mg ml–1 produced higher blocks to T12 with a longer and equal duration of analgesia and motor block in 13 and 28% of children, respectively, which lasted up to 4 h. The 2 mg ml–1 solution appears to be optimal in terms of producing adequate analgesia with an acceptable degree of motor blockade.2

The pharmacokinetics of ropivacaine in children beyond 1-yr-old after a single injection caudal block are very variable but are broadly similar to those in adults and no age related effects are seen in the key kinetic parameters.2 5 6 8 12 13 15 After single injection blocks, the plasma concentration profiles show that peak concentrations of total and free ropivacaine are well below the threshold for toxicity of 0.3–0.9 mg l–1. Free fraction seldom reaches 10%. A very small proportion of the administered dose is excreted unchanged in the urine and most of the ropivacaine is excreted in the urine as hydroxylated or dealkylated metabolites. The weight-corrected values for clearance, volume of distribution and elimination half life do not vary with age between 1 and 12 yr.2 5 6 8 12 13 15

In younger infants, below 6 months, clearance decreases and below 3 months, significantly higher free plasma concentrations (0.099 vs 0.038 mg litre–1) and free fractions (10% vs 5%) occur than in infants over 3 months old8 after a single caudal injection of 2 mg kg–1 (1 ml kg–1 of 2mg ml–1 solution).

For peripheral nerve blockade, a more concentrated solution of ropivacaine, 5 mg ml–1, in a volume of 0.6 ml kg–1 (3 mg kg–1) has been found to be effective and safe in children from 1–12 yr when administered as an ilio-inguinal block.15 This dose and route of administration resulted in low peak plasma concentrations of total ropivacaine. Maximum free plasma ropivacaine concentrations at 0.02–0.14 mg litre–1 were well below the toxic threshold.15

For single injection lumbar epidural administration in infants between 1 and 12 months,14 a volume of ropivacaine, 0.7 ml kg–1 (2 mg ml–1) solution produced a similar onset, duration and efficacy to the same volume of bupivacaine, 2.5 mg ml–1.

In this issue, Hansen and colleagues7 have added to the body of information on the pharmacokinetics and pharmacodynamics of ropivacaine during continuous epidural infusion in children from 3 months.7 1720 A loading dose of 1–2 mg kg–1 has been described,7 17 18 20 followed by a constant rate continuous infusion of 0.4 mg kg–1 h–1 (0.2 ml kg–1 h–1 of 2 mg ml–1 solution). This has been used successfully in children, infants and neonates although pharmacokinetic data are limited to those over 3 months old.7

Neonatal outcome after maternal administration of ropivacaine by intermittent boluses or continuous infusions compared favourably with similar doses of bupivacaine in terms of neurological and adaptive capacity scores (NACS) at 24 h, spontaneous vaginal delivery rates, instrumental delivery rates and intensity of motor block.21

Popliteal fossa block has been described in children with ropivacaine for analgesia after foot and ankle surgery in infants and children from 6 months.16 The duration of effective pain relief ranged from 8 to 12 h.

In summary, for single injection caudal block, a volume of 1 ml kg–1 of ropivacaine 2 mg ml–1 solution (2 mg kg–1) will reliably produce analgesia for inguinal surgery with an acceptable incidence and duration of motor block. A longer duration of analgesia can be achieved at the expense of more frequent and long lasting motor blockade by the use of a larger volume of the same concentration of ropivacaine or by using the same volume of a more concentrated solution, to a maximum dose of 3 mg kg–1. Where a longer duration is needed with no motor block, clonidine, 2 µg kg–1 or preservative-free ketamine, 0.5 mg kg–1 will prolong analgesia some 2- to 3-fold. For ilioinguinal block a single injection of 3 mg kg–1 (0.6 ml kg–1 of 5 mg ml–1 solution) is safe and effective. For continuous epidural infusion analgesia, ropivacaine at a rate of 0.4 mg kg–1 h–1 (0.2 ml kg–1 h–1 of 2 mg ml–1 solution) is safe and effective. Further research is required to define the safe dosing limits in neonates, young infants and less healthy children. Clearance decreases below 6 months and protein-binding capacity in the neonate is reduced.8 As suggested in this issue,7 reducing the dose and limiting the duration of continuous infusions to 36–48 h are recommended in neonates and young infants until further data are available.

N. S. Morton

Royal Hospital for Sick Children

Glasgow

References

1 McClure J. Ropivacaine. Br J Anaesth 1996; 76: 300–7[Free Full Text]

2 Bosenberg A, Thomas J, Lopez T. Caudal block in children with ropivacaine in different concentrations (1, 2 and 3 mg ml–1). In: Proceedings of the ESRA European Meeting 1999 IMRA 1999; 11: 29

3 Da Conceicao MJ, Coelho L. Caudal anaesthesia with 0.375% ropivacaine or 0.375% bupivacaine in paediatric patients. Br J Anaesth 1998; 80: 507–8[ISI][Medline]

4 Da Conceicao MJ, Coehlo L, Khalil M. Ropivacaine 0.25% compared with bupivacaine 0.25% by the caudal route. Paediatr Anaesth 1999; 9: 229–33[ISI][Medline]

5 Habre W, Bergesio R, Johnson C, Hackett P, Joyce D, Sims C. Plasma ropivacaine concentrations following caudal analgesia in children. Anesthesiology 1998; 89: A1245

6 Habre W, Bergesio R, Johnson C, Hackett P, Joyce D, Sims C. Pharmacokinetics of ropivacaine following caudal analgesia in children. Paediatr Anaesth 2000; 10: 143–7[ISI][Medline]

7 Hansen TG, Ilett KF, Lim SI, Reid C, Hackett LP, Bergesio R. Pharmacokinetics and clinical efficacy of long-term postoperative epidural ropivacaine infusion in children. Br J Anaesth 2000; 85: 347–53[Abstract/Free Full Text]

8 Hansen TG, Ilett KF, Reid C, Lim SI, Hackett LP, Begesio R. Caudal ropivacaine in infants: population pharmacokinetics and plasma concentrations. In: Proceedings of the Association of Paediatric Anaesthetists Annual Scientific Meeting 2000; Birmingham, UK. Paediatr Anaesth 2000 (in press)

9 Ivani G, Mereto N, Lampugnani E, DeNegri P, Torre M, Mattioli G, Jasonni V, Lonnqvist PA. Ropivacaine in paediatric surgery: preliminary results. Paediatr Anaesth 1998; 8: 127–9[ISI][Medline]

10 Ivani G, Lampugnani E, Torre M, Calevo Maria G, DeNegri P, Borrometi F, Messeri A, Calamandrei M, Lonnqvist PA, Morton NS. Comparison of ropivacaine with bupivacaine for paediatric caudal block. Br J Anaesth 1998; 81: 247–8[Abstract/Free Full Text]

11 Ivani G, Mattioli G, Lampugnani E, De Negri P, Torre M, Lonnqvist PA. Ropivacaine for central blocks in children. Anaesthesia 1998; 53 (Suppl 2): 74–6

12 Koinig H, Krenn CG, Glaser C, Marhofer P, Wildling E, Brunner M, Wallner T, Grabner C, Klimscha W, Semsroth M. The dose-response of caudal ropivacaine in children. Anesthesiology 1999; 90: 1339–44[ISI][Medline]

13 Lonnqvist PA, Westrin P, Larsson BA, Olsson GL, Lybeck A, Huledal G. Ropivacaine pharmacokinetics following paediatric caudal block. In: Proceedings of the ESRA European Meeting 1999 IMRA 1999; 11: 32

14 Ivani G, Lampugnani E, De Negri P, Lonnqvist PA, Broadman L. Ropivacaine vs bupivacaine in major surgery in infants. Can J Anaesth 1999; 46: 467–9[Abstract]

15 Joly A, Giaufre E, Ecoffey C, Gustafsson U, Huledal G, Dalens B. Ilioinguinal nerve block in children with ropivacaine. A multicentre clinical and pharmacokinetic study. In: Proceedings of the ESRA European Meeting 1999 IMRA 1999; 11: 57

16 Tobias JD, Mencio GA. Popliteal fossa block for postoperative analgesia after foot surgery in infants and children. J Ped Orthoped 1999; 19: 511–4

17 Moriarty A. Use of ropivacaine in postoperative infusions. Paediatr Anaesth 1997; 7: 478.

18 Moriarty A. Infusions of local anaesthetic via caudal catheters in neonates and small infants for analgesia after major surgery. In: Proceedings of the Association of Paediatric Anaesthetists; 2000; Birmingham, UK; Paediatr Anaesth 2000 (in press)

19 Gustorff B, Lierz P, Felleiter P, Knocke TH, Hoerauf K, Kress HG. Ropivacaine and bupivacaine for long-term epidural infusion in a small child. Br J Anaesth 1999; 83: 673–4[Abstract/Free Full Text]

20 Moriarty A. Postoperative extradural infusions in children: preliminary data from a comparison of bupivacaine/diamorphine with plain ropivacaine. Paediatr Anaesth 1999; 9: 423–7[ISI][Medline]

21 Writer WD, 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[Abstract/Free Full Text]

22 Khalil S, Campos C, Farag AM, Vije H, Ritchey M, Chuang A. Caudal block in children: ropivacaine compared with bupivacaine. Anesthesiology 1999; 91: 1279–84[ISI][Medline]

23 De Negri P, Visconti C, Ivani G, Borrelli F, De Vivo P. Caudal additives to ropivacaine in children: preservative free S-ketamine vs. clonidine. In: Proceedings of the Association of Paediatric Anaesthetists; 2000; Birmingham, UK; Paediatr Anaesth 2000 (in press)

24 Ivani G, De Negri P, Conio A, Amati M, Reero S, Giannone S, Lonnqvist PA. Ropivacaine-clonidine combination for caudal blockade in children. Acta Anaesth Scand 2000; 44: 446–9[ISI][Medline]