Anesth Analg 2004;98:56-59
© 2004 International Anesthesia Research Society
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
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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.
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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.
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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 C0.25 received bupivacaine added with clonidine: 25 µg in 20 mL, so that 0.25 µg/kg clonidine was given. C0.5, 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.
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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.
Cardiopulmonary effects during anesthesia are presented in Table 2. Individual alterations of MAP ranged from +6% to -58% and median alterations ranged from -22.5% to -40%. No statistical difference appeared among the groups for these data. The number of patients having experienced MAP <40 mm Hg during spinal anesthesia increased in Group C2 (P = 0.039), compared with C0. HR decreased mildly compared with preoperative values: individual alterations ranged from +2.7% to -47%, and no patient had <100 bpm. Median HR decreased by 11.7% to 26.5%, and no statistical difference was identified among the groups. In the PACU, MAP and HR returned to preoperative values in all patients as soon as the block disappeared. The lowest SpO2 did not differ significantly in any group during spinal anesthesia (P = 0.19). Caffeine requirements did not differ among the groups during the stay in the PACU, as shown in Table 2 (P = 0.23).
Table 3 shows the spread of the spinal block. Sensory block appeared within 3 min in all cases and the upper level ranged from C2 to T10. No statistical difference was found among the groups in the extent of sensory block. Median duration of spinal anesthesia gradually increased from 67 (58–82) min in Group C0 up to 111 (93–125) min in Group C1, and did not progress further in Group C2 (111 [99–130] min), as reported in Figure 1. These differences became highly significant in Groups C1 and C2 compared with C0 (P < 0.003 and 0.006, respectively). Figure 2 shows that the number of blocks <60 min decreased from 4 in Group C0 to 1 in both Groups C1 and C2 (P = 0.56). However, the number of blocks lasting at least 120 min increased from 1 in Group C0 to 6 in Groups C1 and C2 (P = 0.08). Because of a too short block, 6 patients received a supplementary general anesthesia to complete surgery: 2 in Group C0.25 after 56 and 75 min, 2 in Group C0.5 after 25 and 50 min, and 1 in Groups C1 and C2 after 80 and 50 min, respectively. These differences did not reach statistical significance (P = 0.82). Median duration of surgery was similar in all groups (P = 0.27), although the range was very wide (Table 3). However, the patients who received general anesthesia were never those with the longest surgery. Some patients exhibited clinical sedation, scored 3 or 4, when arriving in the PACU as shown in Table 3: Groups C0.5 and C2 were significantly different from C0 (P = 0 0.043) in this respect. Profound sedation—scored 4—was observed in only 1 patient in both Groups C0.5 and C1 and resolved with the block.
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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.
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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.
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Discussion
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We prospectively compared the duration of spinal anesthesia after increasing doses of clonidine added to isobaric bupivacaine in 5 groups of neonates, including 50% of former preterm infants. The potential side effects were also investigated. We found that 1 µg/kg clonidine increased the duration of blocks twofold compared with plain isobaric bupivacaine. This dose of clonidine was not associated with hemodynamic or respiratory clinically significant alterations, whereas 2 µg/kg was associated with more side effects and the same duration of blockade.
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 C0.5 and C2, but not in C0.25 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.
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References
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- Coté CJ, Zaslavsky A, Downes JJ, et al. Postoperative apnea in former preterm infants after inguinal herniorrhaphy: a combined analysis. Anesthesiology 1995; 82: 809–22.[ISI][Medline]
- William JM, Stoddart PA, Williams SA, Wolf AR. Post-operative recovery after inguinal herniotomy in ex-premature infants: comparison between sevoflurane and spinal anaesthesia. Br J Anaesth 2001; 86: 366–71.[Abstract/Free Full Text]
- Krane EJ, Haberkern CM, Jacobson LE. Postoperative apnea, bradycardia and oxygen desaturation in formerly premature infants: prospective comparison of spinal and general anesthesia. Anesth Analg 1995; 80: 7–13.[Abstract]
- Bonnet F, Brun-Buisson V, Saada M, et al. Dose-related prolongation of hyperbaric tetracaine spinal anesthesia by clonidine in humans. Anesth Analg 1989; 68: 619–22.[Abstract/Free Full Text]
- Constant I, Gall O, Gouyet L, et al. Addition of clonidine or fentanyl to local anesthetics prolongs the duration of surgical anesthesia after single shot caudal block in children. Br J Anaesth 1998; 80: 294–8.[Abstract/Free Full Text]
- Mahé V, Ecoffey C. Spinal anesthesia with isobaric bupivacaine in infants. Anesthesiology 1988; 68: 601–3.[ISI][Medline]
- Webster A, McKishnie JD, Kenyon CF, Marshall DG. Spinal anesthesia for inguinal hernia repair in high-risk neonates. Can J Anaesth 1991; 38: 281–6.[Abstract/Free Full Text]
- Chiari A, Lorber C, Eisenach JC, et al. Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first stage of labor: a dose-response study. Anesthesiology 1999; 91: 388–96.[ISI][Medline]
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Accepted for publication August 13, 2003.
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Abstract
Introduction
