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PEDIATRIC ANESTHESIA

Clonidine Prolongs Spinal Anesthesia in Newborns: A Prospective Dose-Ranging Study

Alain Rochette, MD^*, Olivier Raux, MD^*, Rachel Troncin, MD^*, Christophe Dadure, MD^*, Régis Verdier, MD, and Xavier Capdevila, MD, PhD^*

Departments of *Anesthesia and Intensive Care "A" and Medical Statistics, Hôpital Lapeyronie, CHU de Montpellier, France

Address correspondence and reprint requests to Dr. Alain Rochette, DAR A, Hôpital Lapeyronie, CHU de Montpellier, 371, Avenue du doyen G. Giraud, 34295 Montpellier Cedex 5, France. Address e-mail to a-rochette{at}chu-montpellier.fr

	Abstract

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Spinal anesthesia may reduce the incidence of morbidity that follows general anesthesia in neonates and in former preterm infants. However, bupivacaine alone provides a block too short for complete surgery in up to 40% of the patients. Clonidine lengthens spinal anesthesia in adults and caudal block in children without significant side effects. We conducted a controlled, prospective, dose-ranging study of clonidine in spinal anesthesia in 75 neonates, including 50% of former preterm infants, undergoing elective inguinal herniorrhaphy. Patients were given a spinal anesthetic with either 0.5% plain isobaric bupivacaine (1 mg/kg), or bupivacaine plus 0.25, 0.5, 1, or 2 µg/kg clonidine. Mean arterial blood pressure, heart rate, SpO₂, sensory block extension and duration were the main data recorded. Mean arterial blood pressure, heart rate, SpO₂, and block extension were similar in the five groups. Duration of spinal block increased from 67 (58–82) min in the control group up to 111 (93–125) min in the group receiving 1 µg/kg clonidine (P < 0.003). Transient hypotension occurred more often (P < 0.05), and caffeine was given more often, when 2 µg/kg clonidine was given. We conclude that 1 µg/kg clonidine provides a significant improvement in spinal anesthesia duration in newborns without significant side effects.

IMPLICATIONS: Spinal anesthesia is suitable but often too short for complete surgery in newborns. This controlled, randomized, prospective, dose-ranging study was conducted in 75 neonates to test the hypothesis that clonidine could significantly lengthen bupivacaine spinal block. Clonidine 1 µg/kg, added to spinal isobaric bupivacaine, doubles the duration of the block without significant deleterious hemodynamic or respiratory side effects.

	Introduction

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Preterm infants 60 wk postconception age have been identified as a high-risk population for apnea, desaturation, and bradycardia after general anesthesia (1). Spinal anesthesia has been recommended as an alternative anesthetic (2). Krane et al. (3) have examined infants undergoing hernia repair receiving spinal or general anesthesia and found no alteration in the respiratory patterns in the spinal group, whereas general anesthesia was associated with decreased oxygen saturation and heart rate (HR). They concluded that spinal anesthesia was more suitable than general anesthesia.

As an adjunct to spinal anesthesia, clonidine increases, in a dose-dependent manner, the duration of both sensory and motor blockade in adults (4). Caudal clonidine prolongs surgical anesthesia in children (5) and is widely used for this purpose.

We conducted a prospective study in newborns undergoing inguinal hernia repair to investigate the duration of surgical blockade provided by various dosages of clonidine added to bupivacaine spinal anesthesia. The secondary aim of the study was to investigate the short-term hemodynamic, respiratory, and sedative consequences of spinal clonidine.

	Methods

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Patients <60 wk postconception scheduled for elective inguinal hernia repair were studied. Approval of our institutional committee for the protection of human subjects and parental informed consent were obtained. Patients with coagulation disorders, spinal or medullar malformation, skin infection at the puncture site, or preexisting unstable cardiac, neurologic, or metabolic disease were excluded.

The patients were admitted the day before operation and fasted for 4 h before anesthesia. One hour before anesthesia, an EMLA® patch was applied at the lumbar puncture site and rectal atropine, 20 µg/kg, was given as premedication. Once in the operation room, standard IV infusion was started, and routine monitoring was applied. Lumbar puncture was performed in the lateral position at the L45 interspace. After a free flow of cerebrospinal fluid was obtained, 0.2 mL/kg of the anesthetic solution was injected over 30 s for spinal anesthesia. The patients were randomly allocated to 1 of the 5 groups according to the dosage of clonidine added to bupivacaine: Group C₀ received plain 0.5% isobaric bupivacaine, 1 mg/kg. Group C_0.25 received bupivacaine added with clonidine: 25 µg in 20 mL, so that 0.25 µg/kg clonidine was given. C_0.5, C₁, and C₂ groups received bupivacaine added with 50, 100, and 200 µg in 20 mL, so they were given 0.5, 1, and 2 µg/kg clonidine, respectively. The patients were then turned back to the supine position.

The upper extent of the block was tested by pinching at 2, 5, and 10 min, and the operation was allowed to begin when both legs became flaccid. The routine data were recorded every 5 min during surgery, then every 15 min in the postanesthesia care unit (PACU). The widest alteration in mean arterial blood pressure (MAP), HR, and SpO₂, expressed in percent of preoperative MAP, HR, and SpO₂ was recorded for each patient and considered for further analysis. Postoperatively, the upper limit of the block was assessed every 15 min until hip flexion recovered. The duration of spinal anesthesia was measured from the completion of injection to hip flexion recovery. If general anesthesia appeared necessary to complete surgery, the duration was counted from injection to the decision of conversion to general. Sedation was recorded upon entering the recovery room. In addition to SpO₂, respiratory rate and clinical evidence of respiratory distress were carefully evaluated. If apnea (>10 s) and desaturation (<95%) occurred, caffeine citrate 20 mg/kg was given IV. The patients were discharged from the PACU when the block disappeared and a stable hemodynamic and respiratory condition was ascertained.

The number of patients to be included was calculated from the mean duration and standard deviation of neonatal spinal anesthesia as reported in the literature (6,7), to ensure an increase by 50% in the duration of the block, accepting = 0.05 and ß = 0.1. Thirteen patients were required in each group. The results were presented as median and 25–75 confidence intervals. To compare continuous data, the Kruskal-Wallis test was first applied to the entire population to ensure global comparison. Whether significant differences appeared, each group was separately compared with C₀ by means of the Wilcoxon’s test with Bonferroni correction if appropriate. Fisher’s exact test was applied for analysis of nonparametric data. P < 0.05 was considered significant.

	Results

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Seventy-five patients completed the study. Demographic data are presented in Table 1. No statistical difference among groups was found with respect to age (P = 0.34), weight (P = 0.27), or birth term (P = 0.67) and weight (P = 0.58). The ratio of ex-preterm infants—i.e., born younger than 36 wk—was similar in all groups (P = 0.92) and ranged between 50% and 60% as shown in Table 1.

View larger version (14K): [in this window] [in a new window]   Figure 1. Duration of the spinal block: median and (25–75 confidence interval). *P < 0.003 and **P < 0.006 versus C0 in Groups C1 and C2, respectively. C = clonidine.

View larger version (13K): [in this window] [in a new window]   Figure 2. Number of short (<60 min), intermediate (60–120 min), and long (>120 min) blocks in each group. There is a trend toward statistical significance in the number of long-lasting blocks in Groups C1 and C2 versus C0 (P = 0.08). C = clonidine.

	Discussion

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The extent of the sensory block, as tested by pinching, did not differ when various amounts of clonidine were added to bupivacaine. This is consistent with findings in adults (4). The upper limit of the sensory block was sometimes very high, but motor block was less extensive, as the remaining spontaneous arm movements showed, and ventilation or circulation were not impaired. The duration of the block in our study improved with increasing dosages of clonidine and reached statistical significance when 1 µg/kg was given. A dose-response correlation was established in adult studies in which 1–4 µg/kg clonidine was given (4,8), but no ceiling effect was established in duration of analgesia, as it seems to appear from our results. We demonstrated that MAP or HR were not significantly altered when clonidine was added to spinal anesthesia. However, hypotensive episodes were significantly more common in Group C₂ than in Group C₁. Another limiting factor to the use of clonidine is the possibility of prolonged effects. After general anesthesia, delayed and early apneas are closely related (1,3). We did not find an increase in early apneas in the clonidine groups that received up to 1 µg/kg, but a specifically designed, 24-hour investigation on a large number of patients should be conducted to address this important question. High sedation scores were significantly more often observed in Groups C_0.5 and C₂, but not in C_0.25 or C₁. The sedative effect of clonidine is well known (9), but this finding appears erratic in our series and may be attributable to the small number of patients. We did not find any correlation between sedation and respiratory impairment in the recovery room: indeed, sedation resolved together with the block.

Our study demonstrates that clonidine 1 µg/kg doubles neonatal spinal anesthesia duration without providing undesirable hemodynamic effects in the immediate postoperative period. Investigations on a larger number of patients for a longer period should be conducted to address long-term effects of spinal clonidine in newborns.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Rochette, A. Articles by Capdevila, X. Search for Related Content PubMed PubMed Citation Articles by Rochette, A. Articles by Capdevila, X.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999