Randomized, double-blind, phase III, controlled trial comparing levobupivacaine 0.25%, ropivacaine 0.25% and bupivacaine 0.25% by the caudal route in children{dagger}

B. Locatelli1, P. Ingelmo2,*, V. Sonzogni1, A. Zanella2, V. Gatti3, A. Spotti2, S. Di Marco1 and R. Fumagalli2

1 Anaesthesia and Intensive Care Department, Ospedali Riuniti di Bergamo, Largo Barozzi 1 (24100) Bergamo, Italy. 2 Anaesthesia and Intensive Care Department, Ospedali Riuniti di Bergamo, School of Anaesthesia and Intensive Care, Milan Bicocca University, Italy. 3 Department of Pharmacy, Ospedali Riuniti di Bergamo, Italy

* Corresponding author: Via Pignolo 69 (24121) Bergamo, Italy. E-mail: pabloingelmo{at}libero.it

Accepted for publication October 21, 2004.


    Abstract
 Top
 Footnotes
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Background. The rationale for replacing racemic bupivacaine with the s-enantiomers levobupivacaine and ropivacaine is to provide a wider margin of safety with the same analgesic efficacy and less postoperative motor block. In a randomized, double-blind, phase III, controlled trial we compared the caudal administration of levobupivacaine 0.25% and ropivacaine 0.25% with bupivacaine 0.25% in children.

Methods. Ninety-nine ASA I–II children less than 10 yr old scheduled for elective sub-umbilical surgery were randomized to receive caudal block with bupivacaine 0.25%, ropivacaine 0.25% or levobupivacaine 0.25%. The primary outcome of the study was the clinical efficacy of the caudal block during the operation. Secondary outcome measures were analgesic onset time, pain relief after the operation and residual motor blockade.

Results. The proportion of children with effective analgesia during the operation was similar among groups. There were no significant differences in the analgesic onset time of the caudal block. Bupivacaine produced a significant incidence of residual motor block compared with levobupivacaine or ropivacaine at wake-up (P<0.01). There were no significant differences in the number of patients receiving rescue analgesia after surgery. However, analgesic block lasted significantly longer in patients receiving bupivacaine (P=0.03).

Conclusion. During sub-umbilical surgery, caudal levobupivacaine, ropivacaine and bupivacaine provided comparable analgesic efficacy. Bupivacaine produced a higher incidence of residual motor blockade and a longer analgesic block than ropivacaine and levobupivacaine.

Keywords: anaesthesia, paediatric ; analgesic techniques, regional, caudal ; anaesthetics local, bupivacaine ; anaesthetics local, levobupivacaine ; anaesthetics local, ropivacaine


    Introduction
 Top
 Footnotes
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Caudal anaesthesia is a useful adjunct during general anaesthesia and for providing postoperative analgesia after genital, lower abdominal and lower limb operations. In children, caudal anaesthesia is performed with the patient sedated or anaesthetized and detection of early symptoms of systemic toxicity due to intravascular local anaesthetics injection is extremely difficult.1 Racemic bupivacaine 0.25% is the most widely used local anaesthetic by the caudal route in paediatric patients. However, preliminary evidence suggests that levobupivacaine and ropivacaine may be associated with less systemic toxicity.2 3

The rationale for replacing racemic bupivacaine with the s-enantiomers levobupivacaine and ropivacaine is to provide a wider margin of safety with the same analgesic efficacy and less postoperative motor block. Ropivacaine and levobupivacaine have been shown to be effective and well tolerated by the caudal route in children.46 However, only two studies have compared the efficacy of levobupivacaine 0.25% with bupivacaine 0.25% or with ropivacaine 0.25% by the caudal route in children.7 8

The aim of this randomized, double-blind, phase III, controlled trial was to compare the clinical efficacy of a single-dose administration of caudal levobupivacaine 0.25%, ropivacaine 0.25% and bupivacaine 0.25% in children undergoing day-case surgery.


    Materials and methods
 Top
 Footnotes
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
After approval by the research ethics committee of the Ospedali Riuniti di Bergamo, informed written consent was obtained from the parents of 99 healthy children (ASA I or II). Patients were between 6 months and 10 yr old, 5–35 kg and scheduled for elective sub-umbilical surgery with an anticipated duration of <90 min.

Children were excluded in case of emergency surgery; known hypersensitivity to amide local anaesthetics, fentanyl or propofol; a known history of active and severe renal, hepatic, respiratory or cardiac disease (including dysrhythmias or atrioventricular block); a history of seizures; neurological or neuromuscular disorders; a history of chronic pain or analgesic drugs use; the presence of a blood-clotting disorder, platelet count <100 000 mm3; blood dyscrasia; refusal of or inability to receive a caudal epidural block; cutaneous infections or anatomical malformation at the puncture site; and any other reason considered appropriate by the investigator.

All children were fasted and received premedication with rectal atropine 0.01 mg kg–1 and midazolam 0.5 mg kg–1 (maximum 15 mg) 30 min before surgery, and EMLA® cream (Astra Zeneca, Milan, Italy) was applied on both hands and arms. Peripheral i.v. access was secured and i.v. induction with propofol 2 mg kg–1 and fentanyl 0.002 mg kg–1 was administered. Anaesthesia was maintained with a propofol infusion of 0.125–0.130 mg kg–1 min–1 and the airway was controlled with a facial mask or laryngeal mask. Thereafter a caudal block was performed in the left lateral decubitus position using an i.v. cannula.

Patients were randomized to receive bupivacaine 0.25% (Marcaina®; Astra-Zeneca), ropivacaine 0.25% (Naropina®; Astra-Zeneca) or levobupivacaine 0.25% (Chirocaina®; Abbott, Latina, Italy). A total dose of 1 ml kg–1 was used for orchidopexy or inguinal hernia repair, and of 0.5 ml kg–1 for phimosis or incision level lower than L3.

The randomization sequence was computer-generated and prepared in a double-blind manner. Each local anaesthesia solution was prepared in a coded transparent 20-ml syringe and labelled with the child's study number by the hospital central pharmacy. If the child was enrolled but did not undergo surgery, the child and the randomization assignment were replaced. In the case of emergency related or possibly related to the study or study drugs, the pharmacist was authorized to disclose the contents of the syringe to the staff anaesthetist. The study blinding was broken after the statistical analysis.

Heart rate, systolic and diastolic arterial blood pressure, respiratory rate, oxygen saturation, and end-tidal CO2 were monitored continuously. In case of inadequate analgesia during operation, a supplementary bolus of fentanyl 2 µg kg–1 was administered.

The propofol infusion was stopped at the beginning of skin suture. After surgery, patients were transferred to the recovery room. Pain intensity and Aldrete score9 were recorded every 10 min until an Aldrete score of 8 was achieved. Thereafter patients were transferred to the paediatric surgery general ward.

The primary outcome of the study was the clinical efficacy of the caudal block during operation. Caudal block efficacy was defined as the absence of gross movements or significant (>20%) change in pulse rate and/or respiratory rate on application of forceps to the foreskin in patients undergoing circumcision, or with the inguinal incision in those undergoing inguinal hernia repair or orchidopexy. In case of changes in two of these three clinical parameters, the block was considered clinically ineffective. Secondary outcome measures were analgesic onset time, pain relief with the caudal block and residual motor blockade.

The analgesic onset time was studied using a mechanical stimulus applied with a modified Allis clamp (m 30-132-15; Martin, Germany).10 To assure a non-harmful repeated stimulus, the clamp was machined to a flat surface of 50 mm2 and covered with a silk tape. The mechanical stimulus applied with the Allis clamp activates both A and C fibres, produces no tissue damage and is capable of measuring pain detection threshold within a range that is physiologically relevant. It produces a rapid increase in intensity over time, is reproducible and applies a nociceptive stimulus to a larger area than pinprick stimulation (50 vs 1–2 mm2).11 By attaching the clamp to a ratchet, there is no possibility of inter-observer variability, which is one of the limits of pin-prick evaluation.12 In a previous study this method showed 87% sensibility and 98% specificity in the detection of infective caudal block with different concentrations of ropivacaine.13

Three minutes after the local anaesthetic injection, the skin at the surgical site was clamped and the third ratchet of the clamp engaged for a maximum of 15 s. Any related movement or significant change in the heart/respiratory rate resulted in discontinuation of the stimulus. Patients were stimulated every 3 min after caudal block up to block effectiveness or up to five stimuli. Analgesic onset time was defined as the time in minutes between local anaesthetic injection and the absence of gross movements or significant (±20%) change in pulse rate and/or respiratory rate on application of the mechanical stimulus. In case of movements or physiological response with the fifth stimulus, the caudal block was considered ineffective and the patient data were not included in the onset time analysis.

The proportion of patients receiving analgesic medication after operation and the time between the caudal block and the administration of analgesics were used to measure pain relief. Postoperative pain was evaluated using the Children and Infants Postoperative Pain Scale (CHIPPS) in patients younger than 6 yr and with a numerical scale from 0 to 10 points (N-S) in patients older than 6 years old (Table 1).14 15 If the CHIPPS score or the N-S scale score was 4 points, a suppository of codeine 0.5–1 mg kg–1 plus paracetamol 10–15 mg kg–1 (Lonarid®, Boehringer, Firenze, Italy) was administered.


View this table:
[in this window]
[in a new window]
 
Table 1 Children and Infants Postoperative Pain Scale (CHIPPS)10

 
Residual motor block was evaluated using a modified Bromage scale (Table 2). Significant residual motor block was defined as a motor block score of ≥1 point at wake-up and 180 min after caudal block. In case of asymmetrical block, the highest numerical value was recorded.


View this table:
[in this window]
[in a new window]
 
Table 2 Motor block scale

 
Times between local anaesthetic injection and skin incision, surgery duration and wake-up time (minutes from the end of propofol infusion and Aldrete scale 8 points) were recorded. All adverse events from premedication until patient discharge were recorded. An anaesthetist not involved with the caudal block or anaesthesia performed data collection and analgesic onset time evaluation.

The population size for this trial was 99 patients. Based on a review of 60 consecutive patients undergoing caudal block with bupivacaine 0.25% at the Ospedali Riuniti di Bergamo, we found an incidence of effective block during operation of 98%. We considered a 20% reduction in caudal block effectiveness to be clinically significant (22% ineffective block). Based on the formula for normal theory and assuming a two-sided type I error of 0.05 and a power of 0.80, 33 patients in each of the three groups were required to reveal a significant difference in block effectiveness during operation.

Quantitative data are presented as means and standard deviation and qualitative data as frequency and 95% confidence interval (CI). The Avona or Kruskal–Wallis test was used for the analysis of differences in age, weight, analgesic onset time, time between local anaesthetic injection and incision, surgical time, wake-up time and analgesic time. The type of surgery, ASA physical status, sex, the number of patients with analgesic onset within 15 min, block effectiveness during operation, residual motor blockade, and the number of patients requiring analgesics after operation were analysed with the {chi}2 test or Fisher's exact test. Significance was defined as P<0.05. All statistical comparisons were accomplished with Epi Info®, version 2002.


    Results
 Top
 Footnotes
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Ninety-nine children were enrolled, 33 in each group, and all were analysed on the basis of intention to treat. There were no significant differences in age, weight, ASA physical status, gender, surgery, dose of fentanyl and propofol during induction, propofol infusion, time between block and incision, duration of surgery and time from end of propofol infusion and Aldrete score 8 (wake-up time) (Table 3).


View this table:
[in this window]
[in a new window]
 
Table 3 Patients' characteristics. Data are mean (range) for age, mean (SD) for weight, time between block and incision, dose of fentanyl, dose of propofol, duration of surgery and wake-up time; and number of children for type of surgery, ASA physical status and sex

 
More patients receiving levobupivacaine underwent surgery for phimosis, but there was no significant difference in the type of surgery between the groups.

The proportion of children with an effective caudal block during operation, the primary end-point of the study, was similar. Thirty-one patients in the bupivacaine group (95% CI 80–99) and 30 patients in the levobupivacaine group and in the ropivacaine group (95% CI 76–98) experienced adequate analgesia during operation (P=0.87). Two patients in the bupivacaine group (95% CI 1–20) and three patients in the levobupivacaine group and in the ropivacaine group (95% CI 2–24) responded with movement or changes in heart rate or respiratory rate during operation and received an extra dose of fentanyl.

There were no significant differences among groups in the analgesic onset time of the caudal block. The mean onset time was 8 (4) min in the bupivacaine group, 8 (3) min in the levobupivacaine group and 7 (3) min in the ropivacaine group (P=0.37). Two patients receiving bupivacaine 0.25%, two patients receiving ropivacaine 0.25% (95% CI 1–20) and three patients receiving levobupivacaine 0.25% (95% CI 2–24) responded with movement to all five mechanical stimulus during the onset time evaluation (P=0.85). These patients were considered as having an ineffective caudal block during the onset evaluation and were not included in the analgesic onset time analysis.

Bupivacaine produced a significant incidence of residual motor block at wake-up compared with levobupivacaine 0.25% or ropivacaine 0.25% (Table 4). Three hours after caudal injection of local anaesthetic, patients receiving levobupivacaine 0.25% had significantly less residual motor blockade than patients receiving bupivacaine 0.25% (Table 5). In a post hoc analysis excluding patients receiving 0.5 ml kg–1 of local anaesthetics, bupivacaine still produced a significant incidence of residual motor block at wake-up (P<0.01). However, there were no significant differences between groups on the residual motor blockade 3 h after the caudal block (P=0.08).


View this table:
[in this window]
[in a new window]
 
Table 4 Residual motor block at wake-up. Data are number of children and 95% confidence interval (%).

 

View this table:
[in this window]
[in a new window]
 
Table 5 Residual motor block 180 min after caudal block. Data are number of children and 95% confidence interval (%).

 
There were no significant differences in the number of patients receiving rescue analgesia, as guided by a CHIPPS score or a N-S score of 4 points. Rescue analgesia was administered to seven patients in the bupivacaine group (95% CI 9–39), five patients in the levobupivacaine group (95% CI 5–32%) and to five patients in the ropivacaine group (95% CI 5–32%) (P=0.75). The mean time from caudal injection to the first administration of analgesic medication was 2.45 (0.6) h in the bupivacaine group, 1.7 (0.4) h in the levobupivacaine group and 1.6 (0.6) h in the ropivacaine group (P=0.03).

Five adverse events were noted during the observation period. All these events were mild or moderate in severity and no serious adverse events were reported. Two patients in the bupivacaine group (95% CI 0.7–20%) exhibited sinus bradycardia not related to visceral traction or surgical stimulation. The first child was a 2-yr-old boy undergoing orchidopexy who received bupivacaine 2.5 mg kg–1 and the second case was a 8-yr-old child with a postinfective phimosis who received caudal bupivacaine 1.25 mg kg–1. In both cases, normal heart rate was restored with a single dose of atropine. These events were considered to be possibly related to the study medications.

One patient in the levobupivacaine group (95% CI 0.1–16%) was extremely agitated before the anaesthetic induction. The situation was considered to be related to the drugs used in the premedication and was controlled during induction of anaesthesia. One patient in the levobupivacaine group (95% CI 0.1–16%) and one patient in the ropivacaine group (95% CI 0.1–16%) complained of nausea or vomited after surgery.


    Discussion
 Top
 Footnotes
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
This study indicates that in children undergoing sub-umbilical surgery, levobupivacaine 0.25% is comparable to ropivacaine 0.25% and bupivacaine 0.25%. Caudal levobupivacaine 0.25% produced similar residual motor blockade to ropivacaine 0.25%, but less residual motor blockade than bupivacaine 0.25%. Bupivacaine produced a longer analgesic block compared with ropivacaine and levobupivacaine.

We did not find significant differences between groups in analgesic efficacy during surgery. Studies with small samples may reach the erroneous conclusion that the intervention groups do not differ if too few patients have been studied to make such a claim. In our study, 94% of patients in the bupivacaine group had an effective block compared with 91% of patients in the levobupivacaine or ropivacaine groups. To establish a statistically significant difference, if such exists with a 3% difference, we should include more than 1200 patients per group.

The analgesic onset time was studied using a mechanical stimulus applied with a modified Allis clamp. This method showed 89% sensitivity and 100% specificity on detection of ineffective caudal block before incision. The test can correctly identify patients with an ineffective caudal block within 15 min of injection of the local anaesthetic (no false-positive patients). The method did identify a patient as having an effective block despite responding with movements during surgery. This false-negative patient could be explained by a different duration and spatial distribution between the Allis clamp and the surgical stimulus.11

This study can be criticized because we used different volumes of local anaesthetic for circumcision (0.5 ml kg–1) and for orchidopexy or inguinal hernia repair (1 ml kg–1). Because this was a phase III study, we had to test the efficacy of levobupivacaine under ordinary clinical circumstances. In clinical practice an injection of 0.5 ml kg–1 of local anaesthetic gives a lumbosacral block and an injection of 1 ml kg–1 gives a thoracolumbar (T10 block). Using a double dose of local anaesthetic for a circumcision, we could expose our patients to a double dose of a potentially toxic drug. Furthermore, with an unnecessary higher block, we would overestimate the incidence of residual motor block.

The decision to include a ropivacaine group in this study can be criticized because of the potency difference between ropivacaine, bupivacaine and levobupivacaine. During active labour, the relative potencies of levobupivacaine, ropivacaine and bupivacaine were assessed with the minimum local analgesic concentration (MLAC) method. Using very low concentrations, ropivacaine appears to be 40% less potent than bupivacaine and equipotent with levobupivacaine. However, using higher concentrations there was no significant difference in the quality of analgesia or sensory block.16 17

To the best of our knowledge, the MLAC of local anaesthetics have not been assessed in paediatric patients receiving caudal block. In order to achieve the same analgesic effect in children, a similar or even lower concentration of ropivacaine is required in comparison with the same amount of bupivacaine or levobupivacaine. This may imply that, in children under light general anaesthesia, the local anaesthetic concentrations used in clinical practice (0.2–0.25%), may reach the upper, flatter portion of the dose–response curve, where potency differences are obscured.4 5 7 8 1719

Only two studies have compared the efficacy of levobupivacaine 0.25% with bupivacaine 0.25% or with ropivacaine 0.25% by the caudal route in children. In a randomized double-blind controlled study a caudal injection of levobupivacaine 0.25%, 1 ml kg–1 was compared with ropivacaine 0.2% and bupivacaine 0.25%. Levobupivacaine, ropivacaine and bupivacaine presented comparable onset time and analgesia during and after surgery.8 When compared with caudal ropivacaine 0.25%, caudal levobupivacaine 0.25% provided similar anaesthetic and analgesic block.7

The evidence regarding residual motor block is less clear. Astuto and colleagues did not observe motor blockade after surgery using ropivacaine 0.25% or levobupivacaine 0.25%.7 However, in our study, more than half of our patients receiving levobupivacaine 0.25% and ropivacaine 0.25% presented with some degree of motor block at wake-up. Ivani and colleagues found a significant difference in residual motor block 1 h after operation between 0.2% ropivacaine and bupivacaine 0.25%. No significant differences were noted between levobupivacaine 0.25% and bupivacaine 0.25% or between levobupivacaine 0.25% and 0.20% ropivacaine. One obvious explanation for this result is that the dose of ropivacaine administered was 20% less than the dose of levobupivacaine. Our results showed that, when using the same doses, ropivacaine and levobupivacaine produced almost the same residual motor blockade.8

Patients receiving levobupivacaine or ropivacaine had a significant early resolution of their residual motor block compared with patients receiving bupivacaine. As previously shown by Khalil and colleagues, there were no significant differences between ropivacaine 0.25% and bupivacaine 0.25% in residual motor block 180 min after caudal block.18 Excluding patients receiving 0.5 ml kg–1 of local anaesthetics, there were no significant differences between the groups in residual motor block 3 h after caudal block. This result could be explained by the small number of patients with motor block on the last evaluation of the study.

We did not find any differences between groups in the number of patients requiring analgesia after operation and before hospital discharge. However, patients receiving caudal bupivacaine required analgesic medication ~1 h later after surgery compared with patients receiving levobupivacaine or ropivacaine. The duration of analgesia previously reported varies from 5 to 11 h, compared with a maximum analgesia time of 2.5 h in our study.6 8 18 19

Although local anaesthetics are generally quite safe and effective, they may produce systemic toxic reactions affecting the heart and brain. Toxic reactions can occur from excessive doses of drug injected into an appropriate tissue compartment, by intravascular absorption or by inadvertent intravascular or intraosseous injection.20 The two episodes of sinus bradycardia in our study may be related to the intravascular absorption of bupivacaine.

There is increasing evidence from recent clinical studies that levobupivacaine may be less cardiotoxic than bupivacaine. In a double-blind crossover study in healthy male volunteers, levobupivacaine administration resulted in a significantly smaller reduction in stroke index and ejection fraction compared with racemic bupivacaine.21 Levobupivacaine and ropivacaine produce similar central nervous system and cardiovascular effects when infused i.v. at equal concentrations, doses and infusion rates.22 This implies that, when using a large amount of local anaesthetic, as in caudal blocks, patients receiving levobupivacaine and ropivacaine may tolerate larger doses before manifestation of toxicity compared with those receiving bupivacaine.

In conclusion, caudal levobupivacaine 0.25% provided reliable analgesic efficacy during sub-umbilical surgery in children, which was comparable with ropivacaine 0.25% and bupivacaine 0.25%. Using similar amounts of local anaesthetic, bupivacaine produced a higher incidence of residual motor block and longer analgesic block than ropivacaine and levobupivacaine.


    Acknowledgments
 
The authors wish to thank the nursing and surgical staff of the Pediatric Surgery Service of the Ospedali Riuniti di Bergamo, Dr Nicola Patroniti for methodological support, Dr Marco Barone and Dr Alberto Cadisco for data collection, Dr Cecilia Drago for protocol monitoring, Mrs Daniela Lodetti for protocol supervision and Mr Andrea Paravisi for logistical support.


    Footnotes
 Top
 Footnotes
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
{dagger} Declaration of interest, This study was funded by a restricted grant from Abbott Laboratories, Italy. Back


    References
 Top
 Footnotes
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 Gunter JB. Benefit and risks of local anaesthetics in infants and children. Paediatr Drugs 2002; 4: 649–72[Medline]

2 Mazoit JX, Decaux A, Bouaziz H, Edouard A. Comparative ventricular electrophysiologic effect of racemic bupivacaine, levobupivacaine, and ropivacaine on the isolated rabbit heart. Anesthesiology 2000; 93: 784–92[CrossRef][ISI][Medline]

3 Morrison SG, Dominguez JJ, Frascarolo P, Reiz S. A comparison of the electrocardiographic cardiotoxic effects of racemic bupivacaine, levobupivacaine, and ropivacaine in anesthetized swine. Anesth Analg 2000; 90: 1308–14[Abstract/Free Full Text]

4 Mazoit JX, Dalens BJ. Ropivacaine in infants and children. Curr Opin Anaesthesiol 2003; 16: 305–7[CrossRef]

5 Ivani G. Ropivacaine: is it time for children? Paediatr Anaesth 2002; 12: 383–7[CrossRef][ISI][Medline]

6 Taylor R, Eyres R, Chalkiadis GA, Austin S. Efficacy and safety of caudal injection of levobupivacaine, 0.25%, in children under 2 years of age undergoing inguinal hernia repair, circumcision or orchidopexy. Paediatr Anaesth 2003; 13: 114–21[CrossRef][ISI][Medline]

7 Astuto M, Disma N, Arena C. Levobupivacaine 0.25% compared with ropivacaine 0.25% by caudal route in children. Eur J Anaesth 2003; 20: 826–30[ISI][Medline]

8 Ivani G, De Negri P, Conio A, et al. Comparison of racemic bupivacaine, ropivacaine and levo-bupivacaine for pediatric caudal anesthesia: effects on postoperative analgesia and motor block. Reg Anesth and Pain Med 2002; 27: 157–61[CrossRef][ISI]

9 Aldrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg 1970; 49: 924–34[Medline]

10 Antognoni JF, Carstens E. A simple, quantifiable and accurate method for applying a noxious mechanical stimulus. Anesth Analg 1998; 87: 1446–9[CrossRef][ISI][Medline]

11 Petersen-Felix S, Arendt-Nielsen L. Pain measurement. In: Zbinden AM, Thomson D, eds. Conducting Research in Anaesthesia and Intensive Care Medicine. Oxford: Butterworth, 2001; 372–87

12 Curatolo M, Petersen-Felix S, Arendt-Nielsen L. Sensory assessment of regional analgesia in humans. Anesthesiology 2000; 93: 1517–30[ISI][Medline]

13 Ingelmo PM, Locatelli BG, Di Marco S, et al. Does general anesthesia affect regional anesthesia quality? Double blind randomized controlled trial evaluating the effect of intravenous and balanced anesthesia on caudal ropivacaine pediatric block. Eur J Anaesth 2003; 20 (Suppl 29): 101

14 Buttner W, Finke W. Analysis of behavioral and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young children: a comprehensive report on seven consecutive studies. Paediatr Anaesth 2000; 10: 303–18[CrossRef][ISI][Medline]

15 Finley G, McGrath PJ. Measurement of Pain in Infants and Children. Progress in Pain Research and Management, Vol. 10. Seattle, WA: IASP Press, 1998.

16 Polley LS, Columb MO, Naughton NN, Wagner DS, Van de Ven CJ. Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor: implications for therapeutic indexes. Anesthesiology 1999; 90: 944–50[ISI][Medline]

17 Polley LS, Columb MO, Naughton NN, Wagner DS, Van de Ven CJ, Goralsky KH. Relative analgesic potencies of levobupivacaine and ropivacaine for epidural analgesia in labor. Anesthesiology 2003; 99: 1354–8[CrossRef][ISI][Medline]

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

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

20 Berde CB. Toxicity of local anesthetics in infants and children. J Pediatr 1993; 122: S14–S20.[ISI][Medline]

21 Bardsley H, Gristwood R, Baker H, Watson N, Nimmo W. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998; 46: 245–9[CrossRef][ISI][Medline]

22 Stewart J, Kellett N, Castro D. The central nervous system and cardiovascular effects of levobupivacaine and ropivacaine in healthy volunteers. Anesth Analg 2003; 97: 412–26[Abstract/Free Full Text]





This Article
Abstract
Full Text (PDF)
All Versions of this Article:
94/3/366    most recent
aei059v1
E-Letters: Submit a response to the article
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (1)
Disclaimer
Request Permissions
Google Scholar
Articles by Locatelli, B.
Articles by Fumagalli, R.
PubMed
PubMed Citation
Articles by Locatelli, B.
Articles by Fumagalli, R.