Anesth Analg 2006;102:395-399
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000194590.82645.4c
PEDIATRIC ANESTHESIA
Caudal Regional Anesthesia, Ropivacaine Concentration, Postoperative Analgesia, and Infants
Samia Khalil, MD,
Hemanth Lingadevaru, MD,
Mariana Bolos, MD,
Mary Rabb, MD,
Maria Matuszczak, MD,
Douglas Maposa, MD, and
Alice Chuang, PhD
Department of Anesthesiology, Department of Ophthalmology, The University of Texas Medical School at Houston, Houston, Texas
Address correspondence to Samia Khalil, MD, The University of Texas Medical School at Houston, Department of Anesthesiology, 6431 Fannin, MSB 5.020, Houston, TX 77030-1503. Address e-mail to samia.n.khalil{at}uth.tmc.edu.
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Abstract
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In this randomized, double-blind trial we evaluated the quality and duration of analgesia and motor effects after caudal block using 1 mL/kg of ropivacaine 0.1% (Group 1), 0.15% (Group 2), 0.175% (Group 3) compared to 0.2% (Group 4) in infants 1–12 mo old. Postoperatively, the number of infants who received pain medication differed among the groups (P < 0.0005). There were more infants in Groups 1 and 2 compared with Group 4 and there was no difference between Groups 3 and 4. In the postanesthesia care unit, infants in Groups 1 and 2 received more pain medication than did those in Group 4 (P = 0.0098). In the day surgery unit, there was a significant difference among the groups (P = 0.0326); infants in Groups 3 and 4 required no pain medication. The analgesia duration differed among the groups (P = 0.034). Infants in Groups 1 and 2 had a shorter duration, and there was no difference between Groups 3 and 4. Infants in Group 4 took longer to regain their motor power compared with those in Group 3 (P = 0.0347). We conclude that in infants, ropivacaine 0.175% provided postoperative analgesia and duration similar to that of ropivacaine 0.2%, whereas ropivacaine 0.1% and 0.15% did not, and it was associated with fewer motor effects.
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Introduction
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Caudal blocks are commonly placed in newborns, infants, and children (1,2). They are administered for both intraoperative and postoperative pain relief after urologic or lower abdominal procedures. This allows anesthesiologists to avoid or decrease narcotic administration and thus avoid their potential side effects.
The use of a long-lasting local anesthetic is advantageous for a single injection caudal block. However, the amide local anesthetics have a rather narrow margin of safety (3), and they show diminished clearance in neonates as they mature over the first 3–8 mo of age (4,5).
Infants are more sensitive to local anesthetic toxicity than older children. One explanation is that those plasma proteins that bind with the local anesthetics are quantitatively reduced (primarily 
1-acid glycoprotein), and therefore there is more free local anesthetic for a given drug dose. This free fraction is the active portion of the drug and is therefore the portion that contributes to toxicity (6,7). Recent studies have demonstrated that after placing a caudal block (0.2%, 2 mg/kg) in infants, the total and free plasma ropivacaine concentrations are within the range of concentrations previously reported in adults and older children. However, age and the percentage of free ropivacaine are significant covariates for drug clearance (8–10), and administering the smallest effective concentration of a local anesthetic may be safer in newborns and infants
The primary outcomes of this randomized, double-blind study were to compare the quality of analgesia in the postoperative period (by comparing the number of infants who required pain medication in each group), duration of analgesia (defined as period from caudal placement until time of administration of first pain medication), and motor effects after a single, presurgical caudal block with ropivacaine 0.10%, 0.15%, or 0.175%, compared with 0.2%, in anesthetized infants 1–12 mo old.
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Methods
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After institutional approval and parental written informed consent were obtained, healthy boys, age 1–12 mo, ASA physical status I–II, scheduled for elective, outpatient urologic or lower abdominal procedures were randomized using a computer generated randomization table to receive caudal anesthesia with either ropivacaine 0.10% (Group 1), 0.15% (Group 2), 0.175% (Group 3), or 0.20% (Group 4) after induction of a general anesthetic. Premature infants, infants with neuromuscular disease, back problems, skin infection of the caudal area, or those with delayed development were excluded.
Infants were fasted and received no premedication. After applying standard monitors, general anesthesia was induced with halothane and nitrous oxide 60% in oxygen via mask. An IV catheter was placed and glycopyrrolate, 5 µg/kg, was given. Lactated Ringer’s solution was used to correct fluid deficit and for maintenance. The airway was maintained with a mask, laryngeal mask, or endotracheal tube. IV rocuronium, 0.5 mg/kg, was administered to facilitate orotracheal intubation.
Study solutions were provided by the hospital pharmacy and were administered in a double-blind manner. While the infant was lying in the left lateral position, a caudal injection of ropivacaine solution, 1 mL/kg, was administered, using a short B-bevel, 22-gauge needle. All blocks were performed by a senior resident under the supervision of an anesthesiologist or by an attending anesthesiologist. The resident or anesthesiologist repeatedly aspirated the needle and injected the local anesthetic in increments while watching vital signs and the electrocardiographic monitor. End-tidal halothane was adjusted to 1.2% before surgical incision.
An independent, blinded observer recorded arterial blood pressure and heart rate just before and after surgical incision and every 5 min thereafter until anesthesia was discontinued. If there were no changes in vital signs in response to the initial incision, the end-tidal halothane concentration was decreased gradually to 0.6%. If a child responded to the incision with an increase in arterial blood pressure or heart rate, the halothane concentration was not decreased. At the end of surgery, muscle paralysis was reversed with neostigmine and glycopyrrolate. The infant was tracheally extubated when he had regained muscle power, was breathing regularly, and was awake.
Postoperatively, in the postanesthesia care unit (PACU) an independent observer recorded 1) a modified pain score as described by Hannallah et al. (11) (Table 1), 2) duration of pain relief (defined as the time from caudal placement until the first dose of postoperative analgesia), and 3) motor power and reflexes (Tables 2, 3). Pain relief, motor power recovery, and reflexes were evaluated every 15 min until hospital discharge. In the hospital, IV morphine, 0.05–0.1 mg/kg, was given when an infant scored 4 or higher on the pain scale. After hospital discharge, infants were given acetaminophen-codeine elixir (10 mg/kg with codeine, l mg/kg) as determined by the parents. The number of doses of pain medication required was also recorded.
Secondary outcomes were anesthesia duration, surgery duration, and awakening time (period from end of anesthesia to opening of eyes). Infants were not discharged until they were awake and their pain was controlled. They were not required to drink, pass urine, or regain complete muscle power before hospital discharge.
The independent observer contacted parents the next day to inquire about the infant and noted incidence of pain and pain medication administered after hospital discharge for the 24-h study period.
Assuming that 7.5% of infants who receive 0.2% ropivacaine for caudal block and 60% of infants who receive 0.1% require postoperative analgesia, a sample size of 15 per group required evaluation to detect a difference among the groups with 5% significance level and 80% power.
To compare the caudal duration and motor effects, a sample size of 15 per group allowed us to detect the relative risk of 2.5 using Kaplan-Meier’s analysis and 1.25 standard deviation differences in mean among the groups at a significance level and 80% power. A P value 
0.05 was considered statistically significant.
Descriptive statistics, mean and standard deviation, were calculated for continuous variables, and frequency and percentage were calculated for qualitative measurements. A one-way analysis of variance was used to test whether the means of continuous variables were different among the groups. If statistically significant results were found, Dunnett multiple comparisons were conducted to compare each group with Group 4 (0.2%). Similarly, the Fisher’s exact test was applied to evaluate the equality of proportions. If statistically significant results were detected, logistic regression analysis was used to identify which groups were different from Group 4. However, there were some variables with zero frequency in Group 4, such as taking pain medication in the PACU; therefore, the Fisher’s exact test with Bonferroni correction was used to compare each group with Group 4. Because the numbers of pain medications administered were not normally distributed, a generalized linear regression model with Poisson distribution was used to compare the groups.
Kaplan-Meier’s survival analysis was used to compare caudal duration and motor effect, defined as time from caudal placement until an infant reached a motor power scale of 8 or censored at the time of hospital discharge. If the results reached statistical significance, Cox regression analysis was used to compare the hazard ratio of each group to that of Group 4.
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Results
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Seventy-seven infants were randomly allocated to medication groups, and the anesthesiologist was unable to place the caudal block in 3 infants. Therefore, 74 infants, age 1–12 mo, comprised the study population, and all were included in the analysis. They had urologic or lower abdominal procedures. The type of surgery did not differ among the four groups (Table 4).
In Group 1, 14 infants received ropivacaine 0.1% (1 mg/kg); in Group 2, 21 infants received ropivacaine 0.15% (1.5 mg/kg); in Group 3, 20 infants received ropivacaine 0.175% (1.75 mg/kg); and in Group 4, 19 infants received ropivacaine 0.2% (2 mg/kg).
There was no difference among the four groups in age, weight, race, ASA physical status, baseline arterial blood pressure or heart rate, duration of anesthesia, surgery, awakening time, PACU time, or day surgery unit (DSU) time (Table 5). After surgical incision, the four groups did not differ in intraoperative vital signs.
None of the infants received intraoperative narcotics. None of the infants developed a hemodynamic problem, respiratory difficulty, or any other adverse side effect.
During the hospital stay, there was a significant difference in the number of infants who required pain medication among the four groups (P < 0.0005) (Table 6). The number of infants who required pain medication was significantly more in Group 1 compared with Group 4 (P = 0.0006) and in Group 2 compared with Group 4 (P = 0.0042). There was no difference between Group 3 and Group 4.
In the PACU, the number of infants who required pain medication differed among the four groups (P = 0.0098). The number in Groups 1 and 2 was significantly larger than those in Group 4 (P = 0.0253) and (P = 0109). There was no difference between Groups 3 and 4.
In the DSU, there was a significant difference among the 4 groups in the number of infants who received pain medication (P < 0.0326). None of the infants in Groups 3 or 4 required pain medication. Three of 14 infants in Group 1 and 1 of 21 infants in Group 2 required pain medication.
At home, there was no difference among groups in the number of children who received pain medication.
The duration of caudal analgesia, defined as the median time from caudal placement to the first pain medication, differed among the four groups (P < 0.034) (Figure 1). The median caudal duration time in Group 1 was 160 min, in Group 2 was 385 min, in Group 3 was 454 min, and in Group 4 was >974 min. Infants in Groups 1 and 2 had significantly shorter caudal duration compared with those in Group 4 (P < 0.0057) and (P < 0.0363). There was no difference in caudal duration among infants in Groups 3 and 4 (P = 0.1148).
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Figure 1. Caudal duration (min). The x-axis represents caudal duration (min), from time of caudal placement until time for first pain medication. The y-axis represents a step function of the probability of not taking pain medication.
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There was a significant difference among the 4 groups in the time infants took to regain their motor power and reach a motor power scale of 8 (P = 0.0307) (Figure 2). Infants in Group 4 took a significantly longer time compared with infants in Group 1 (P = 0.0053) and with those in Group 3 (P = 0.0347) (Fig. 2). There was no difference in motor power recovery between Groups 1and 2 or between Groups 1 and 3. The median time for infants in Group 1 to reach a motor power scale of 8 was 101 min, in Group 2 was 118 min, in Group 3 was 137 min and in Group 4 was 169 min.
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Figure 2. Time (min) to reach a motor power of 8. The x-axis represents time (min) from time of caudal placement until infant reaches motor power of 8. The y-axis represents a step function of the probability of regaining motor power of 8. Censored =  : Represents infants discharged from the hospital before regaining motor power of 8.
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The duration from caudal placement time until hospital discharge time did not differ among the four groups (164.8 ± 42.3 min). At hospital discharge time, all infants in Group 1, 4 of 21 in Group 2, 4 of 20 in Group 3, and 8 of 19 in Group 4 reached a motor power scale of 8.
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Discussion
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In volunteers and in animal studies, ropivacaine has proven to be less cardiotoxic (12–14) and to have a greater separation of sensory and motor effects than bupivacaine (15). Therefore, ropivacaine is increasingly used for caudal blocks in infants and children. Ropivacaine 0.2% is currently used in all ages, from infancy to old age. However, there are age-related differences in pharmacodynamic responses, nerve myelination, spacing of nodes of Ranvier, tissue barriers, and other factors that may contribute to these differences (16–19).
The most important variables determining the effectiveness of caudal analgesia for a specific local anesthetic are the volume and concentration of local anesthetic solution used (20). In our study we evaluated the minimal concentration of ropivacaine that can provide adequate postoperative pain control. Similar studies were conducted in children older than 1 year of age (21). The results of this study demonstrated that there is no difference between ropivacaine 0.175% and ropivacaine 0.2% in the number of infants who required postoperative pain medication and duration of postoperative pain relief; however, ropivacaine 0.175% was associated with fewer motor effects. Both ropivacaine 0.15% and 0.1% did not provide adequate postoperative pain relief and had a shorter duration.
A previous study in children 4–12 years demonstrated that ropivacaine 0.2% provided satisfactory postoperative pain relief and ropivacaine 0.1% showed less efficacy, whereas 0.3% was associated with a more frequent incidence of motor block with minimal improvement in postoperative pain relief (21).
Similar to our study, Luz et al. (22) also demonstrated that in children older than 1 year, ropivacaine 0.1% and 0.15% were less effective in postoperative pain control with a shorter duration than ropivacaine 0.2%.
This study demonstrated there was a significantly more frequent incidence of muscle weakness in infants receiving ropivacaine 0.2%, compared to those receiving 0.175%.
In conclusion, our study demonstrated that, in infants and newborns, ropivacaine 0.175% provided adequate postoperative pain relief similar to ropivacaine 0.2% with a similar duration and fewer motor effects. Ropivacaine 0.1% and 0.15%, 1 mL/kg did not provide similar postoperative pain relief and had shorter duration. Administering ropivacaine 0.175% instead of 0.2% is associated with the theoretical advantage of administering less drug.
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Footnotes
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Supported by the Department of Anesthesiology, The University of Texas Medical School at Houston, Houston, Texas.
Accepted for publication September 19, 2005.
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References
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Abstract
Introduction
