| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
 
|
|
|
||
|
|
Anesth Analg 2005;100:66-70 © 2005 International Anesthesia Research Society doi: 10.1213/01.ANE.0000140246.78944.A5
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
In this clinical trial, we evaluated the clinical effects of ropivacaine for spinal anesthesia in children. An open, prospective study was performed on 93 children, aged 1–17 yr, undergoing elective lower abdominal or lower limb surgery. A plain solution of ropivacaine 5 mg/mL at a dose of 0.5 mg/kg body weight (up to 20 mg) was administered via the L3-4 or L4-5 interspace with the patient in the lateral decubitus position. After injection, the patients were placed supine. The spread and duration of sensory analgesia and the degree of motor block were recorded. Satisfactory surgical anesthesia was achieved in 92 of the 93 children. Three children received general anesthesia; in one child spinal anesthesia failed, and in two cases surgery outlasted the duration of the sensory block. Four children received supplemental analgesia for skin incision. The mean highest level of sensory block was T6 (range, T2 to T12), and the mean time to the regression of sensory block to T10 was 96 min (range, 34–210 min). One child developed transient bradycardia and one hypotension. After discharge four children developed mild transient radiating neurologic symptoms and one epidural blood patch was performed for persistent position-dependent headache. We conclude that the block performance of intrathecal isobaric ropivacaine in children (>1 yr) is similar to that obtained in adults but the safety of the larger dose used in children warrants further studies.
IMPLICATIONS: This study showed that spinal ropivacaine at a dose of 0.5 mg/kg (maximum dose 20 mg) is an appropriate anesthetic for children aged 1–17 yr for surgery below the umbilicus with duration of <90 min.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Ropivacaine is a long-acting, amide type local anesthetic with local anesthetic properties closely similar to those of bupivacaine. Ropivacaine was synthesized simultaneously with bupivacaine by af Ekenstam almost 50 years ago (1), and it was first launched in 1996, being the first pure S-(–)-enantiomeric local anesthetic to be clinically introduced. The reason for introducing ropivacaine was the need for a long acting local anesthetic that is less cardiotoxic than bupivacaine (2,3). Several experimental and clinical studies confirm ropivacaine’s lower and different toxicity profile compared to bupivacaine (2,4).
Ropivacaine has been used for local infiltration, epidural, brachial plexus, and peripheral nerve blocks in children, and clinical data show that ropivacaine is also effective and safe for regional anesthesia in children (5). The lipid solubility of ropivacaine is less than that of bupivacaine, which explains its somewhat lower potency compared with bupivacaine (2). In an equal milligram dose ropivacaine provides a shorter duration of analgesia and a less profound motor block than bupivacaine, especially when small concentrations are used.
Spinal anesthesia with ropivacaine is well documented in adults (6–8), and preservative free isobaric ropivacaine 5 mg/mL was recently approved for intrathecal administration for surgery (9). However, there are no clinical data concerning the use of ropivacaine for spinal anesthesia in children. Therefore we designed this prospective, open, noncomparative clinical trial to evaluate the clinical efficacy of ropivacaine 5 mg/mL in 3 age groups of children aged 1 to 17 yr. The test variables were quality and spread of analgesia and anesthesia, regression of sensory block, and perioperative and postoperative adverse events.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Ninety-three healthy, ASA physical status I–II children aged 1 to 17 yr who were scheduled for surgery below the umbilicus with spinal anesthesia were enrolled. The study population was classified into 3 age categories: preschool-age children (1–4 yr), school-age children (5–11 yr), and adolescents (12–17 yr). All the children were included unless they had any contraindications for spinal puncture or ropivacaine. Children were excluded if they had neurologic, neuromuscular, psychiatric, seizure, or blood clotting disorders or a known allergy to local anesthetics. The study was approved by our ethics committee and conducted in accordance with the Declaration of Helsinki (10), and the National Agency for Medicines was notified of the trial protocol. Written informed consent was obtained from parents and children old enough to understand provided assent.
All children were premedicated with buccal midazolam and ketamine to minimize discomfort of procedures. Topical local anesthetic cream was used at puncture sites, and IV thiopental was given for intraoperative sedation in small incremental doses. All children were closely monitored by an anesthesiologist and an anesthetic nurse.
Lumbar puncture was performed via the L3-4 or L4-5 interspace with the patient in the lateral decubitus position in the midline with a 50-mm long, 25-gauge (n = 13) or a 90-mm long, 27-gauge (n = 80) cutting-point needle. Correct placement was verified by free aspiration of cerebrospinal fluid (CSF). Plain, isobaric ropivacaine (Naropin® 5 mg/mL; AstraZeneca, Kirkkonummi, Finland) was administered intrathecally at a dose of 0.5 mg/kg up to a maximum dose of 20 mg. After injection of the local anesthetic over 10 s, free aspiration of CSF was again verified.
An electric stimulator (Microstim Plus®, Neuro Technology, Houston, TX) was used to evaluate the upper border of the analgesic area at 10, 20, and 30 min (11). Motor block was assessed using a Bromage scale (12). If there were any signs of inadequate spread or duration of anesthesia, fentanyl 1 µg/kg IV was given for supplementary analgesia, and if no signs of analgesia were noted within the first 10 min after intrathecal injection, general anesthesia with inhaled sevoflurane was administered.
After surgery all children received ketoprofen 1 mg/kg IV and paracetamol 40 mg/kg rectally to prevent postoperative pain, and they were transferred to the postanesthesia care unit (PACU) for continuous monitoring of vital signs and regression of block. The time for regression of sensory block by 2 segments and to T10 (umbilicus) was tested every 5 min from 30 min after injection. If the child was in pain fentanyl 1 µg/kg IV or oxycodone 0.05 mg/kg IV was given and the time was recorded.
Children were discharged when they were awake, had full recovery of motor block, had stable vital signs for at least 1 h, had no or mild pain, had no nausea/retching or vomiting, and were able to tolerate clear fluids.
The follow-up of the children at home was recorded by means of diaries, which were to be returned a week after surgery with a prepaid envelope. Nonresponders were contacted by telephone.
We reasoned that 30 children for each age group would be an adequate number to obtain a good estimate for block performance, and no formal sample size calculations were performed. The 
2 test or the Fisher’s exact test was used to analyze the frequency data (e.g., gender, ASA classification, need for rescue analgesia, and number of children with adverse events). The differences among the three groups concerning continuous variables, such as the height and time to regression of sensory block, were analyzed by the Kruskal-Wallis test, and the Mann-Whitney U-test with Bonferroni correction was used for post hoc analysis. Two-tailed significance was obtained, and a P value of <0.05 was considered statistically significant. The results are presented as the number of cases or mean with SD and range as appropriate. All the data were analyzed using a statistical program (SPSS for Windows 11.5, SPSS Inc., Chicago, IL).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
All 95 children asked participated in the study. Two children were withdrawn from the study; one was 7-mo-old, and levobupivacaine instead of ropivacaine was used for one. The demographic and surgical data are shown in Table 1. Herniotomy (nine of 26 procedures) and orchidopexy (9) were the most common procedures in the preschool-age children, whereas knee arthroscopy (11 of 32) and other lower limb orthopedic surgery (16) were the most common procedures in the adolescents.
|
The spinal anesthesia was successful in 92 of 93 children. One 13-yr-old boy undergoing ankle surgery was given general anesthesia because no sensory or motor block developed in 10 min, although CSF aspiration before and after the lumbar puncture had been easy. In a 14-yr-old boy and a 6-yr-old boy, the duration of surgery outlasted the duration of sensory blockade (140 min and 50 min, respectively), necessitating the use of general anesthesia to complete the surgery. Two preschool-age children and 2 adolescents required supplemental analgesia during skin incision at 10 min after ropivacaine injection, but thereafter the blocks performed sufficiently. In the other 86 children, adequate sensory block was accompanied by complete motor block.
There were no differences among the groups in the height and regression of the sensory block. The time to discharge was longest in adolescents (P = 0.027 compared with school-age children). The characteristics of sensory block are presented in Table 2.
|
In 6 of 35 school-age children and in 28 of 32 adolescents the body weight was more than 40 kg, and these children were therefore given 20 mg of ropivacaine (0.2–0.49 mg/kg). The mean height of the sensory block was lower in these 34 children (T6.5 [2.7]) than in 58 children with ropivacaine 0.5 mg/kg (T5.0 [2.8], P = 0.013), but the duration of the sensory block was similar (regression to T10 104 (34) versus 91 (30) minutes, P = 0.09) (Fig. 1).
|
One adolescent developed transient bradycardia and two developed nausea during surgery. One preschool child, nine school-age children, and eight adolescents developed nonserious adverse events in the PACU (Table 3). Twenty-seven children required opioids for rescue analgesia in the PACU, and there was a significant difference among the different types of procedures in the need for rescue analgesia (P = 0.036,
2-test). Half of the children undergoing orchidopexy (58%) and orthopedic surgery (42%) were provided opioid analgesics in the PACU.
|
Parents of 77 children returned the follow-up diary, and 16 parents gave the information by phone. One of the seven children with position-dependent headache required an epidural blood patch to relieve the symptoms. Four children developed transient radiating neurologic symptoms (TNS) after discharge. In all cases the child and/or parents described the symptoms as mild or moderate, and in all cases the symptoms disappeared within a few days. No serious adverse events were recorded (Table 3).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The present study demonstrates that ropivacaine is an effective local anesthetic for spinal applications in children because the success rate of the block, 92%, was the same as has been reported with racemic bupivacaine (11) and levobupivacaine (13). In addition, there was only one failed spinal block with ropivacaine, similar to that with bupivacaine (11,13). However, whether ropivacaine should replace bupivacaine in intrathecal use is open for discussion. Bupivacaine is the most commonly used local anesthetic for spinal anesthesia in children, and for that indication it has a good record of safety (11,14). The reason for developing ropivacaine was the need for a long acting local anesthetic that is less cardiotoxic than bupivacaine. After intrathecal administration, however, systemic toxicity is not expected to occur because of the small dose administered.
With intrathecal drugs, the concern is the direct toxicity to the spinal cord. In large doses all local anesthetics are neurotoxic. Animal studies suggest that the margin of safety of ropivacaine in subarachnoidal application is favorable; it is similar to that of bupivacaine but more than that of lidocaine and tetracaine (15,16). TNS are interpreted as a sign of possible neurotoxicity of local anesthetics, although the mechanism of TNS is not fully understood (15,16). In the present trial four children developed mild TNS after spinal application of ropivacaine. The incidence is similar to that reported with racemic bupivacaine in children (11). In adults, similar signs have not been reported with intrathecal ropivacaine (7,8). Whether the larger dose of ropivacaine used in children than in adults may explain this discrepancy, or whether the developing body is more susceptible to neurotoxic effects, warrants further studies (14). However, it should be noted that in all four children the symptoms were mild or moderate, and in all cases transient. No permanent neurological deficits developed.
There are no dosage recommendations for spinal administration of ropivacaine in children, but clinical studies in adults suggest less potency of intrathecal ropivacaine compared with bupivacaine (7,17). We therefore chose a ropivacaine dose of 0.5 mg/kg up to a maximum dose of 20 mg. The doses of ropivacaine we used were higher than the commonly used doses for bupivacaine. With bupivacaine at a mean dose of 0.4 mg/kg (11) and with levobupivacaine at a mean dose of 0.3 mg/kg (13), sensory block characteristics seem to be similar to those obtained in the present study with ropivacaine. With racemic bupivacaine and levobupivacaine the peak height of sensory block ranged between T2 and L1 (mean T5), which is similar to the range between T2 and T12 (T6) in the present trial with ropivacaine. With bupivacaine the regression of sensory block by 2 segments occurs after 78 minutes compared to 77 minutes, which we obtained here with ropivacaine, to T7 after 87 minutes compared to 85 minutes with ropivacaine, and to T10 after 100 minutes compared to 96 minutes with ropivacaine.
The motor block of ropivacaine is less profound than that of bupivacaine, allowing for a better separation between sensory and motor block when the local anesthetic is given epidurally (5). In a recent study in adults Whiteside et al. (17) also demonstrated that in a spinal application there is a greater degree of sensory-motor separation when using ropivacaine compared with bupivacaine. The present study indicates that this may also be the case in children because the time to the first dose of rescue analgesia was 163 minutes compared to 120 minutes with bupivacaine in our previous trials (11,13). However, further direct comparisons between these compounds are needed before any conclusions may be drawn.
Ropivacaine has been investigated in spinal anesthesia in adults. Malinovsky et al. (7) compared ropivacaine with bupivacaine in patients undergoing endoscopic urological surgery. Isobaric ropivacaine appeared to be less potent than bupivacaine; inadequate intrathecal anesthesia was observed in 16% of patients with 0.2 mg/kg of ropivacaine, whereas intensity and duration of motor blockade was not different in comparison to 0.14 mg/kg of isobaric bupivacaine. Consistent with findings in adults, in the present study 15 children (16%) reported some sensation at incision and 6 of them were provided supplemental analgesia for comfort. It is not known whether hyperbaric local anesthetics perform better in children (11), but in adults hyperbaric solutions may provide more reliable spinal anesthesia than isobaric solutions. Whiteside et al. (17) compared hyperbaric ropivacaine 0.18 mg/kg with hyperbaric bupivacaine 0.19 mg/kg. In contrast to an isobaric solution hyperbaric ropivacaine provided an adequate block for the proposed surgery in all patients. However, hyperbaric ropivacaine also appeared to be less potent than bupivacaine because the onset of sensory and motor block was slower, and maximum extent and duration of sensory and motor block was less with ropivacaine than with bupivacaine.
In conclusion, isobaric ropivacaine seems to provide effective spinal anesthesia for children undergoing surgery in the lower part of the body. In children the clinical characteristics of isobaric ropivacaine seem to be fairly similar to those obtained in adults. However, it is unclear whether ropivacaine has any advantages over bupivacaine in spinal anesthesia in children.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
- Af Ekenstam B, Egner B, Petersson G. Local anaesthetics: 1. N-alkyl pyrrolidine and N-alkyl piperidine carboxylic amides. Acta Chem Scand 1957; 11: 1183–90.
- McClure JH. Ropivacaine. Br J Anaesth 1996; 76: 300–7.
[Free Full Text] - Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979; 51: 285–7.[Web of Science][Medline]
- Reiz S, Häggmark S, Johansson G, Nath S. Cardiotoxicity of ropivacaine: a new amide local anaesthetic agent. Acta Anaesthesiol Scand 1989; 33: 93–8.[Web of Science][Medline]
- Ivani G. Ropivacaine: is it time for children? Paediatr Anaesth 2002; 12: 383–7.[Web of Science][Medline]
- van Kleef JW, Veering BT, Burm AG. Spinal anesthesia with ropivacaine: a double-blind study on the efficacy and safety of 0.5% and 0.75% solutions in patients undergoing minor lower limb surgery. Anesth Analg 1994; 78: 1125–30.
[Abstract/Free Full Text] - Malinovsky JM, Charles F, Kick O, et al. Intrathecal anesthesia: ropivacaine versus bupivacaine. Anesth Analg 2000; 91: 1457–60.
[Abstract/Free Full Text] - Buckenmaier CC 3rd, Nielsen KC, Pietrobon R, et al. Small-dose intrathecal lidocaine versus ropivacaine for anorectal surgery in an ambulatory setting. Anesth Analg 2002; 95: 1253–7.
[Abstract/Free Full Text] - Summary of product characteristics for Naropin® 5 mg/ml. Available at: http://spc.nam.fi/humspc/n/46366.xml?Template=/ html/spctemplate.html. Accessed February 29, 2004.
- World Medical Association Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. Available at: http://www.wma.net/e/policy/b3.htm. Accessed February 29, 2004.
- Kokki H. Spinal anaesthesia in infants and children. Best Pract Res Clin Anaesthesiol 2000; 14: 687–707.
- Bromage PR. A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine in epidural analgesia. Acta Anaesthesiol Scand 1965; 16: 55–69.
- Kokki H, Ylönen P, Heikkinen M, Reinikainen M. Levobupivacaine for pediatric spinal anesthesia. Anesth Analg 2004; 98: 64–7.
[Abstract/Free Full Text] - Gunter JB. Benefit and risks of local anesthetics in infants and children. Paediatr Drugs 2002; 4: 649–72.[Medline]
- Kristensen JD, Karlsten R, Gordh T. Spinal cord blood flow after intrathecal injection of ropivacaine and bupivacaine with or without epinephrine in rats. Acta Anaesthesiol Scand 1998; 42: 685–90.[Web of Science][Medline]
- Yamashita A, Matsumoto M, Matsumoto S, et al. A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits. Anesth Analg 2003; 97: 512–9.
[Abstract/Free Full Text] - Whiteside JB, Burke D, Wildsmith JA. Comparison of ropivacaine 0.5% (in glucose 5%) with bupivacaine 0.5% (in glucose 8%) for spinal anaesthesia for elective surgery. Br J Anaesth. 2003; 90: 304–8.
[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
 |
|
  G. Frawley, K. R. Smith, and P. Ingelmo Relative potencies of bupivacaine, levobupivacaine, and ropivacaine for neonatal spinal anaesthesia Br. J. Anaesth., November 1, 2009; 103(5): 731 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Kaabachi, A. Zarghouni, R. Ouezini, A. B. Abdelaziz, O. Chattaoui, and H. Kokki Clonidine 1 {micro}g/kg Is a Safe and Effective Adjuvant to Plain Bupivacaine in Spinal Anesthesia in Adolescents Anesth. Analg., August 1, 2007; 105(2): 516 - 519. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
