Anesth Analg 2007;105:516-519
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000268709.67572.09
ANALGESIA
Clonidine 1 µg/kg Is a Safe and Effective Adjuvant to Plain Bupivacaine in Spinal Anesthesia in Adolescents
Olfa Kaabachi, MD*,
Amine Zarghouni, MD*,
Rami Ouezini, MD*,
Ahmed Ben Abdelaziz, MD ,
Olfa Chattaoui, MD*, and
Hannu Kokki, MD, PhD 
From the *Department of Anesthesiology and Intensive Care, Kassab Orthopedic Institute, Tunis, Tunisia; Department of Statistics, Farhat Hached Hospital, Sousse, Tunisia; Department of Pharmacology and Toxicology, University of Kuopio; and Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland.
Address correspondence and reprint requests to Hannu Kokki, MD, PhD, Department of Anesthesiology and Intensive Care, Kuopio University Hospital, PO Box 1777, FI-70211 Kuopio, Finland. Address e-mail to hannu.kokki{at}kuh.fi.
Abstract
BACKGROUND: Spinal anesthesia is increasingly used in adolescents. However, the anesthesia provided by bupivacaine alone may be too short for the planned surgery. The addition of clonidine 2 µg/kg to bupivacaine provides a prolonged anesthetic action but may be associated with hypotension. In the present study, we investigated the efficacy and safety of intrathecal clonidine 1 µg/kg in adjunction to bupivacaine in spinal anesthesia in adolescents.
METHODS: Eighty-three adolescents, 51 males, aged 10–15 yr, scheduled for orthopedic surgery were enrolled in this placebo-controlled, randomized study. Patients were given spinal anesthesia either with plain 0.5% isobaric bupivacaine 0.2–0.4 mg/kg or bupivacaine with clonidine 1 µg/kg. The duration of sensory block was the primary outcome measure.
RESULTS: Clonidine prolonged the duration of both the sensory and motor block. The time to regression of sensory block by two dermatomes was 136 (mean) (sd, 56) min in the adolescents with clonidine versus 107 min (sd, 42) in the controls (95% CI for diff: 5–53 min, P = 0.02). The time to full recovery of motor block was 251 min (sd, 79) in the adolescents with clonidine versus 181 min (sd, 59) in the controls (95% CI: 39–103 min, P = 0.001). Time to the first dose of rescue analgesia was longer in the adolescents with clonidine, 461 min (sd, 147) versus 330 min (sd, 138) in the controls (95% CI: 53–207 min, P = 0.01). There was no difference in the frequency of hypotension or bradycardia between the groups.
CONCLUSION: In adolescents, clonidine 1 µg/kg prolonged the duration of sensory block achieved with bupivacaine by 30 min and postoperative analgesia by 120 min without severe adverse events.
Intrathecal clonidine 1–2 µg/kg prolongs the sensory block achieved with plain bupivacaine in newborns and adults. In preterm infants, spinal clonidine increases the incidence of apnea and episodes of hypotension, but in term infants and adults, clonidine has been combined with bupivacaine without any severe adverse events (1,2). On the contrary, in adolescents, 2 µg/kg of clonidine with bupivacaine for spinal anesthesia is associated with a significant incidence of hypotension (1), but to our knowledge, the safety and efficacy of the lower dose of clonidine, 1 µg/kg, has not been tested in adolescents.
We hypothesized that clonidine 1 µg/kg of body weight would prolong the sensory block achieved with intrathecal bupivacaine in adolescents without risk of severe hypotension, bradycardia, or other adverse events. This was tested in the present study where the main outcome measures were the duration of sensory and motor blocks, and the hemodynamic stability during spinal anesthesia with bupivacaine.
METHODS
The study was approved by the local ethics committee. Written informed consent was obtained from the parents and all adolescents provided an assent.
Eighty-three adolescents, aged 10–16 yr, 51 male, scheduled for orthopedic surgery of the lower extremities associated with at least one osteotomy were enrolled. Adolescents with any known contraindication for spinal anesthesia, such as increased intracranial pressure, neurological disorders, hemorrhagic diathesis, or infection at the puncture site, were excluded, as were those having contraindications for intrathecal bupivacaine or clonidine; allergy to bupivacaine or clonidine or cardiorespiratory disease. Data were collected between March 2004 and September 2005.
A double-blind, randomized, placebo-controlled study design with two parallel groups was used. The patients were randomly allocated (a computer-generated allocation sequence) to receive bupivacaine either alone, the placebo group, or with clonidine 1 µg/kg (Catapressan 150 µg/mL, Boehringer Ingelheim International GmbH, Ingelheim, Germany), the clonidine group. Both the patients and the person measuring the block spread were unaware of the injection used for spinal anesthesia. The randomization was concealed using the sealed, opaque envelope method until the patient entered the study. Syringes were prepared immediately before the spinal injection.
All children were premedicated with IV midazolam up to 2 mg. During surgery, supplemental doses of midazolam 0.5 mg were given to 20 adolescents because of anxiety or uncomfortable position. Normal saline 6 mL · kg–1 · h–1 was infused and supplemental oxygen 3 L/min was administered by a facemask. Lumbar puncture was performed with the patient in the sitting position at the L4–5 interspace, with a 90-mm 26-gauge pencil-point needle (Pencan, B. Braun, Melsungen AG, Germany) with an introducer needle after subcutaneous lidocaine infiltration. During the injection, the needle aperture was directed caudally. Isobaric bupivacaine 5 mg/mL (Bupivacaine 0.5%, UNIMED, Nabeul, Tunisia) at a dose of 0.2–0.4 mg/kg of body weight up to 15 mg (2) was administered intrathecally after a free aspiration of cerebrospinal fluid was obtained. Because of the addition of clonidine the volume of the injection was 0.1–0.5 mL larger in the clonidine-group.
Noninvasive arterial blood pressure, heart rate, and oxygen saturation were assessed at baseline and every 2 min for the first 10 min after spinal injection, and thereafter, every 5 min during the surgery. Hypotension, defined as a decrease of systolic blood pressure of more than 20% from baseline, was treated with an infusion of normal saline 20 mL/kg and with IV ephedrine 3 mg, while bradycardia, defined as a heart rate decrease of more than 20% from baseline, was treated with atropine.
Assessment of the spread and duration of sensory and motor blocks, and adverse events was done by one independent anesthesiologist or one nurse anesthetist who were blinded to the intrathecal injection used. Sensory and motor blocks were assessed at 15 and 30 min after intrathecal injection and every 5 min in the postanesthesia care unit. The spread of sensory block was tested with a pinprick method at midline and the motor block was tested with the Bromage scale (0 = able to flex ankle, knee and hip, 3 = complete block of the lower limb). The extent of sensory and motor block, the time to regression of the sensory block by two dermatomes, the time to full recovery of motor block, and the time to the first rescue analgesic were recorded.
An incremental dose of fentanyl 1 µg/kg or general anesthesia was given for inadequate anesthesia such as a reaction to skin incision, increase in heart rate, systolic arterial blood pressure, or respiratory frequency more than 20% from baseline. These cases were designated as failed spinal anesthesia.
All adverse effects were recorded. Nausea and vomiting, urinary retention, sedation on a 3-point scale (0 = awake, 1 = asleep, arousable if stimulated moderately, 2 = not arousable), and shivering were also recorded.
After a full regression of motor block, the adolescents were discharged to the ward and all study adolescents stayed in the hospital for at least 48 h. All adolescents were assessed at 48 h after surgery for any complaints after spinal anesthesia. Postoperative headache was categorized as position-dependent headache if it occurred or worsened within 15 min of assuming the upright position and disappeared or improved after resuming the recumbent position (3).
Postoperative pain was assessed using an 100-mm visual analog scale every hour during the first 6 h and at every 3–4 h thereafter. Tramadol 1–2 mg/kg IV was used for rescue analgesia if the pain score was 30 mm or higher.
The sample size calculation was based on the assumption of a minimum difference of 25% in the duration of sensory block between the two groups (1). Power analysis suggested that 37 patients would be needed in each group in order to have a 90% chance at the two-sided 0.05 level of significance to detect a difference between groups.
Data were entered and analyzed with the Statistical Package for Social Sciences (SPSS software version 13.0 for Windows, SPSS Inc., Chicago). Statistical tests used for categorical data were the  2 test and the Fisher’s exact test. For continuous data, analysis of variance (ANOVA) and the Student’s t-test were applied. Results are presented as mean (sd) and number (%) of cases as appropriate. The level of significance was set at P < 0.05, and 95% confidence intervals were calculated for the main outcome measures.
RESULTS
There were no significant differences in the patient demographics (Table 1).
There was a similar cephalic spread of the sensory block in the two groups, but the time to regression of the sensory block by two segments was significantly longer in the clonidine group (Table 2).
There was no difference between the two groups in motor blockade, but the time to recovery of motor block was significantly longer in the clonidine group compared with that in the placebo group.
There was no difference in the need for rescue analgesics between the two groups. However, the time to the first dose of rescue analgesic was longer in the clonidine group than in the placebo group (Table 3).
There was no difference between the two groups regarding the incidence of perioperative adverse events (Table 4).
DISCUSSION
The results of the present study indicate that clonidine is an effective adjuvant to bupivacaine in spinal anesthesia in adolescents. At a dose of 1 µg/kg of body weight, clonidine prolonged the duration of sensory block achieved with bupivacaine 0.2–0.3 mg/kg by 30 min, motor block by 60 min, and postoperative analgesia by 120 min. This could be considered a significant effect, because it makes spinal anesthesia with bupivacaine a feasible option in cases where the procedure is expected to last longer than what can be covered by a single injection of plain bupivacaine. These results confirm our previous experience in younger children, where clonidine 2 µg/kg was used as an adjuvant to bupivacaine 5 mg/mL for spinal anesthesia (1). However, in adolescents, clonidine 1 µg/kg of body weight seems to be a more appropriate dosage. In fact, a dose of 2 µg/kg clonidine added to bupivacaine seems to cause more frequent and severe bradycardia and hypotension than that observed in the present study. In neonates, one study with clonidine as an adjuvant in spinal anesthesia reported a significant prolongation in the duration of both the sensory block and postoperative analgesia, and the effect was dose-proportional (2). Also, in neonates, clonidine 1 µg/kg seems to be the most appropriate dosage, because 2 µg/kg of clonidine intrathecally was associated with a frequent incidence of cardiovascular instability, just as in adolescents.
In the present study, the cephalic spread of sensory blockade was lower than that reported in previous studies with similar doses of bupivacaine (4,5). Kokki and Hendolin (4) and Imbelloni et al. (5) reported a mean of mid-thoracic block with bupivacaine 0.2–0.3 mg/kg, while in the present study, only one-fifth of patients given plain bupivacaine and one-third given bupivacaine–clonidine developed a sensory block above T10. These differences could be attributed to two factors. In the present study, lumbar puncture was performed with the patient in the sitting position at the L4–5 interspace, whereas in most of the previous studies, it was performed in lateral decubitus position at the L3–4 interspace. We believe that patient position during puncture, lower puncture site, and caudal direction of the aperture during injection should have affected the spread of local anesthetic. In addition, the method used to test the spread of anesthesia and analgesia was different. We used the pinprick technique, whereas other studies used transcutaneous electrical stimulation (2,6,7), which is a reproducible stimulus and may be better than pinprick, touch sensation or cold stimulus with ice for accurate testing of block levels in sedated patients (4).
In the present study, hypotension was more frequent, 29% in the clonidine group and 17% in the control group, than the incidence of 1%–10% in adolescents with spinal anesthesia reported by others (4,5,8,9). We hypothesized that lumbar puncture performed in the sitting position may have induced the frequent incidence of hypotension, which was also observed in the placebo group. Moreover, the incidence of hypotension in the clonidine group was less than that reported with clonidine 2 µg/kg in school-age children 54% (1) and in neonates 71% (2). The incidence of bradycardia was also less, 21% in the present study, than that found in our previous trial with clonidine 2 µg/kg, 30% (6). However, it should be noted that the present study was not powered to detect any differences of the incidence of adverse effects with spinal clonidine as an adjuvant to bupivacaine. Because the incidence of all adverse events was higher in the clonidine group, further studies are needed to evaluate the safety of the present technique.
In conclusion, the present study indicates that adding clonidine 1 µg/kg to bupivacaine prolongs spinal anesthesia in adolescents without causing severe adverse effects.
Footnotes
Accepted for publication April 19, 2007.
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