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PEDIATRIC ANESTHESIA: Research Report

A Comparison of Three Different Concentrations of Levobupivacaine for Caudal Block in Children

Ivani, Giorgio MD*; De Negri, Pasquale MD; Lonnqvist, Per-Arne PhD; Eksborg, Staffan PhD§; Mossetti, Valeria MD*; Grossetti, Roberto MD*; Italiano, Simona MD*; Rosso, Franca MD*; Tonetti, Federica MD*; Codipietro, Luigi MD*

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doi: 10.1213/01.ANE.0000068881.01031.09
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The racemic long-acting local anesthetic bupivacaine is currently in the process of being substituted by two new single-isomer local anesthetic formulations: ropivacaine and levobupivacaine. The rationale for substituting bupivacaine for one of the newer single-isomer local anesthetics is to reduce the risk for unwanted motor blockade (1,2) and also to provide a wider margin of safety for both central nervous system and cardiac toxicity in comparison with racemic bupivacaine (1–3).

Ropivacaine has been well documented both in adults and children (1,4–8). However, fundamental information concerning the use of levobupivacaine in children is still lacking despite an adequate bibliography with regard to adult practice (2). Thus, the aim of the current study was to investigate the dose-response relationship of levobupivacaine for caudal blockade in children.

Methods

After Ethical Committee approval and written parental consent, 60 children aged 1–7 yr, undergoing elective subumbilical surgery, were included in the study. The patients were randomized in a prospective fashion to receive a caudal block with one of three different concentrations (0.125%, 0.20%, and 0.25%) of levobupivacaine (Chirocaine, Abbott, Latina, Italy). All patients received oral premedication with 0.3 mg/kg of midazolam approximately 45 min before the induction of anesthesia. Anesthesia was induced either with IV propofol (2–3 mg/kg) or with inhaled induction of sevoflurane 8% in oxygen-air depending on the presence or absence of a peripheral venous cannula. Airway management was performed by either a face mask or a laryngeal mask airway (Laryngeal Mask Co, Henley-on-Thames, UK), and anesthesia was subsequently maintained with sevoflurane 1%–3% in oxygen-air using spontaneous ventilation. Heart rate (HR), noninvasive blood pressure (NIBP), respiratory rate, ETco2, and Spo2 were monitored throughout the anesthetic.

After the induction of anesthesia, patients were placed in the lateral decubitus position, and a caudal blockade (total volume of local anesthetic 1 mL/kg) was performed. The patients were randomized to receive one of three different concentrations of levobupivacaine by means of a computer-generated random list.

An intraoperative successful blockade was defined as a hemodynamic (HR or NIBP) reaction <20% compared with baseline in response to surgical incision. After emergence from anesthesia, the degree of motor blockade was registered using a simple 3-point scale (0 = no movements, 1 = possible to move the legs, and 2 = able to stand) (9).

Postoperative analgesia was evaluated by the Children and Infants Postoperative Pain Scale (CHIPPS) (10). CHIPPS is a well-validated five-item behavioral scale where each variable (crying, facial expression, posture of the trunk, posture of the legs, and motor restlessness) is given a score of 0–2 with a total score of ≥4 identifying the need for supplemental analgesia (10). The CHIPPS score was assessed every 30 min for the first 4 h, hourly for the next 16 h, and thereafter every 2 h when awake until the end of the observation time (24 h). The duration of analgesia, as defined as the time to the first rescue drug administration, was also noted. All postoperative observations were registered by nurses who were blinded to the study. A paracetamol-codeine suppository, based on a paracetamol dose of 40 mg/kg (resulting in approximately 1–2 mg/kg of codeine because of the fixed drug composition of the suppository), was administered as rescue analgesia if the CHIPPS score was ≥4.

Data are reported as median (range). The influence of the drug concentration on motor blockade was analyzed by Fisher’s exact test. Time to first supplemental analgesic request was compared using the Mann-Whitney U-test. A P value <0.05 was considered statistically significant.

Results

All blockades were judged to be clinically successful based on the lack of significant intraoperative hemodynamic response to surgical incision. No significant differences with regard to demographic data, duration of surgery, or HR, NIBP, ETco2, and Spo2 could be observed among study groups (Table 1).

T1-12
Table 1:
Patient-Related Data, Number of Patients, or Median (range)

No signs of motor blockade could be observed after the first postoperative hour in any of the patients. However, during the first postoperative hour, four children in Group 2 and eight children in Group 3 had a motor blockade score of 1, whereas all patients in Group 1 were without any signs of motor blockade during the first postoperative hour. This difference in motor blockade during the first postoperative hour was statistically significant between Group 1 and Group 3 (P = 0.003; Group 1 versus Group 2, P = 0.106; Group 2 versus Group 3, P = 0.301).

Rescue analgesia (caused by a CHIPPS score of ≥4) was administered to seven patients (35%) in Group 1, eight patients (35%) in Group 2, and six patients in Group 3 (30%) (P = ns). The highest CHIPPS score registered for each individual patient during the first 4 postoperative h is displayed in Table 2. The median times from the end of the surgical procedure to the first administration of supplemental analgesics in these children were 60 min (range, 45–75 min), 118 min (range, 60–210 min), and 158 min (range, 60–660 min) in Group 1, 2, and 3, respectively (Group 1 versus Group 2, P < 0.037; Group 1 versus Group 3, P < 0.053; Group 2 versus Group 3, P < 0.52). The fraction of patients without a need for supplemental analgesia as a function of time is shown in Figure 1. No nausea or vomiting were noted in any of the patients during the observation period.

T2-12
Table 2:
Highest CHIPPS Score Registered in Each Individual Patient During the First 4 Postoperative Hours. Assessment Were Performed Every 30 Minutes During This Time Period
F1-12
Figure 1:
Fraction of patients without a need for supplemental analgesia in relation to various concentrations of levobupivacaine.

Discussion

The present study found a clear dose-response relationship for levobupivacaine within the concentration range of 0.125%–0.25% with regard to both early postoperative motor blockade and the time to first administration of supplemental postoperative analgesia after caudal anesthesia in children.

No differences were observed between the intraoperative efficacies of the various concentrations of levobupivacaine used in the study. However, during the early postoperative phase, an obvious dose-response effect was seen with regard to motor blockade. Only patients receiving 0.125% levobupivacaine were free of postoperative motor blockade, whereas the number of patients with residual motor blockade increased with increasing concentrations of levobupivacaine. In the group treated with 0.25% levobupivacaine, as many as 40% of the patients experienced residual motor blockade during the first postoperative hour. This finding is similar to what has been reported for use of ropivacaine in children. Thus, using ropivacaine concentrations in excess of 0.2% for caudal blockade in children is also associated with an increased incidence of early motor blockade (11,12). The use of ropivacaine 0.2% for caudal blockade rarely causes any effects on early motor function (4–8), a finding that somewhat contrasts with the 20% incidence of residual motor blockade found in the 0.2% levobupivacaine group. However, the equipotency between ropivacaine and levobupivacaine has been disputed, and the minimum effective local anesthetic concentration studies have found the potency of ropivacaine to be only 60% of racemic bupivacaine (13). Thus, the difference with regard to early postoperative motor function between 0.2% ropivacaine and 0.2% levobupivacaine could only be a reflection of a potency difference between the two drugs.

In patients developing a CHIPPS score of ≥4 during the postoperative period, a clear relationship between the concentration of levobupivacaine and duration of analgesia was seen. This somewhat contrasts the previous findings by Wolf et al. (14) who were unable to find such a correlation between bupivacaine concentration used and the duration of analgesia. The exclusion of epinephrine as an additive to the local anesthetic in the present study might explain this difference in outcome of the two studies. The use of 0.2% or 0.25% levobupivacaine was associated with a two-fold and 2.6-fold increase in the duration of the block, respectively, compared with the 0.125% solution. However, these results must be interpreted with a certain degree of caution because a similar number of patients in each group had appropriate analgesia (CHIPPS score <4) throughout the 24-hour observation period and thus did not require the administration of supplemental analgesics. In line with the studies by Wolf et al. (14) and Gunter et al. (15), a considerable number of patients in the present study underwent surgical corrections of inguinal hernia or hydrocele. Although this group of patients represents a significant part of the pediatric surgical population, these patients might be suboptimal for the study of postoperative analgesia because a large proportion does not experience pain to the extent that supplemental analgesia is required. Thus, despite the problem with patient recruitment, further studies in this field should perhaps be performed on a patient population with more pronounced problems with postoperative pain relief, e.g., orchidopexy. Furthermore, Verghese et al. (16) have recently shown that efficacy of a caudal block for orchidopexy patients is not only related to the concentrations of the local anesthetic but also to the volume injected. Because the injected volume of local anesthetic was fixed (1 mL/kg), no conclusions in this regard can be drawn for the present study.

Although a moderate degree of residual motor blockade during the first postoperative hour might not be considered a major problem, such an effect can be quite distressing for the child during emergence from anesthesia and could potentially contribute to postoperative agitation and confusion. Therefore, the use of 0.125% levobupivacaine may have a clinical advantage. On the other hand, the use of the 0.125% solution was associated with a quite limited duration of postoperative analgesia in certain patients, and thus, maybe 0.2% levobupivacaine would represent a better clinical compromise between postoperative analgesia and degree of residual motor blockade.

Only limited information has been available regarding the pediatric use of levobupivacaine (9,17–20), and no information has been published with regard to the use of different concentrations of levobupivacaine for caudal blockade in children.

The rationale for choosing the concentrations of levobupivacaine used in the present study was based on the following: First, because racemic bupivacaine and levobupivacaine are considered to be equipotent (2), we decided to use the concentrations 0.125% and 0.25%, which previously have been investigated with regard to the optimum concentration of racemic bupivacaine for caudal blockade in children (14,15). Second, there is a relatively large body of data with regard to the use of 0.2% ropivacaine in the setting of pediatric caudal blockade (4–8). Because of the current discussion relating to the potency of ropivacaine versus levobupivacaine (see below), we decided to include 0.2% levobupivacaine to allow a comparison with previously reported data for ropivacaine.

In conclusion, a dose-response relationship for levobupivacaine was observed both with regard to duration of postoperative analgesia and early postoperative motor blockade. The 0.125% concentration was associated with less early motor blockade but resulted in a shorter duration of postoperative analgesia. Based on the current results, the use of 0.20% levobupivacaine might represent the best clinical option if a plain levobupivacaine solution is to be used for caudal blockade in children.

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