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© 2001 International Anesthesia Research Society
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Abstract |
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Clonidine prolongs anesthesia and analgesia of local anesthetics in various neural blocks as well as the duration of retrobulbar block. We assessed the dose-response relationship of clonidine added to lidocaine in peribulbar block. Sixty patients undergoing cataract surgery were given peribulbar block with 7 mL of 2% lidocaine and hyaluronidase with either saline (Control) or clonidine in 0.5-µg/kg (0.5 Clon), 1.0-µg/kg (1.0 Clon), or 1.5-µg/kg (1.5 Clon) doses. The onset and duration of lid and globe akinesia, globe anesthesia and analgesia, postoperative analgesic requirement, and adverse effects (hypotension, bradycardia, hypoxia, sedation, and dizziness) were recorded. The success rate and onset of block were comparable in all groups. The duration of lid and globe akinesia, globe anesthesia and analgesia was significantly (P < 0.01) prolonged in patients receiving 1.0 and 1.5 µg/kg clonidine as compared with the Control group. Perioperative pain scores and analgesic requirement were significantly less in these groups. 0.5 µg/kg clonidine did not increase the duration of anesthesia and analgesia significantly. Hypotension and dizziness were observed more in patients receiving 1.5 µg/kg clonidine as compared with other groups. We conclude that 1.0 µg/kg clonidine with a mixture of lidocaine (2%) significantly prolonged the duration of anesthesia and analgesia after peribulbar block with limited side effects.
IMPLICATIONS: We studied the effect of the addition of 0.5, 1.0 and 1.5 µg/kg clonidine to a lidocaine-hyaluronidase mixture on the onset and duration of peribulbar block and perioperative analgesia. A dose of 1.0 µg/kg produced a significant increase in duration of anesthesia and analgesia with minimal side effects.
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Introduction |
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The ability of clonidine to enhance the central and peripheral neural blockade when added to local anesthetics has been widely demonstrated in various animal and human studies (1–5) during the last two decades. There are very few studies using clonidine in ophthalmic blocks, and these have shown contradictory results. Mjahed et al. (6) used clonidine with local anesthetic for retrobulbar block and found increased duration of analgesia and akinesia with a decrease in intraocular pressure and recommended its use. However, Connelly et al. (7) did not find any significant effect of clonidine added to lidocaine on the onset time and postoperative analgesic requirement after peribulbar block; they, however, did not study the duration of anesthesia and analgesia.
The aim of this study was to evaluate the optimal dose of clonidine required when added to lidocaine to prolong the duration of anesthesia, akinesia and analgesia after peribulbar block with minimal side effects.
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Methods |
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After obtaining approval from our hospital ethics committee and written informed consent, 60 patients of ASA physical status I and II, scheduled for elective cataract surgery were selected for the study. The exclusion criteria were impaired orbital/periorbital sensations, impaired consciousness, uncontrolled hypertension, recent myocardial infarction, glaucoma, chronic clonidine or analgesic therapy. Details of the anesthetic technique and study protocol were explained to the patients at the preoperative visit. Patients were not premedicated. No topical anesthetic or IV sedative/hypnotic medication (Midazolam/Propofol) was used before or during the block. The patients were randomly assigned to 1 of the 4 groups (n = 15) receiving either 2% lidocaine alone (Control) or supplemented with clonidine in 0.5-µg/kg (0.5 Clon), 1.0-µg/kg (1.0 Clon), or 1.5-µg/kg (1.5 Clon) doses, respectively. Hyaluronidase 16 IU/mL was added to all solutions. Each patient received 7 mL of lidocaine hyaluronidase solution with either saline or clonidine made up to 1 mL. The Control group received no clonidine. In the other groups increasing doses of clonidine were added. The patients and anesthesiologist were unaware of group assignment.
Monitoring consisted of continuous electrocardiogram lead II, heart rate, SpO2, and intermittent noninvasive blood pressure by Datex Cardiocap II (Datex, Helsinki, Finland) monitor. An IV cannula was inserted into a peripheral vein. Peribulbar block was performed by using modified Fry and Henderson (8) technique with a 26-gauge 13 mm needle. First 5 mL was injected at the junction of lateral one-third and medial two-thirds of the inferior orbital margin with the bevel directed towards the equator of the eyeball and an additional 3 mL was given 2 mm medial and inferior to the supraorbital notch. Gentle digital massage was done and then super pinky ball (9) was applied for 10 min.
Patients were assessed for the ocular sensations (globe anesthesia) and the movements of eyelid (lid akinesia) and ocular muscles (globe akinesia) at 30-s intervals until the block was considered adequate for surgery and then every 15 min until recovery. We used a scoring system as used by Dopfmer et al. (10), and subsequently by Nicoll et al. (11) on a 3-point scale from 0 to 2 (0 = no movement, 1 = reduced movement, and 2 = normal movement). Scoring was done by an independent trained observer who was blinded to the anesthetic mixture used. The ocular movements were scored in each direction of gaze (superior, inferior, medial, and lateral) with a maximum score of 2 points for each direction with a possible maximum total of 8 points. In the absence of complete akinesia in any direction after 10 min, supplementary anesthesia was provided with a further injection of 2–4 mL of the test solution in the same manner as given before. The duration of anesthesia and akinesia was assessed by the occurrence of pain and the recovery of ocular and eyelid movements, respectively.
Sedation levels were monitored on a 4-point scale (0 = alert, 1 = drowsy, 2 = asleep but easily aroused, 3 = comatose) every 15 min for 2 h and then every 30 min for 6 h. Patients were asked to report the presence of pain during the intraoperative period and postoperative period up to 24 h. This was reported on a verbal rating scale from 0 (no pain) to 10 (unbearable pain). The pain was assessed at the time of subconjunctival injection (given at the end of surgery), every 60 min up to 2 h and then at 6 h and 24 h. A tablet of paracetamol 500 mg was given if a verbal rating scale score was 
5. The time of first request for analgesic and total analgesic requirement in 24 h was recorded. Patients were also asked to report any adverse effect such as dry mouth, nausea, vomiting, dizziness, diplopia and blindness for 24 h. The incidence of hypotension, bradycardia (defined as 20% decrease of mean arterial pressure and heart rate from preblock value) and hypoxia (SpO2 <90% on room air) were also recorded. On the day after surgery, the overall satisfaction with the anesthetic during intraoperative as well as the postoperative period was scored on a 3-point scale (1 = very uncomfortable, 2 = mild discomfort, 3 = comfortable).
Results are reported as mean ± SD of the mean. Intergroup comparison of demographic data, onset and duration of anesthesia and analgesia, pain scores, total anesthetic and analgesic requirement and hemodynamic variables was made by Bartlett’s 
2 test followed by Kruskal-Wallis one-way analysis of variance (ANOVA). For within-group comparison of data paired Student’s t-test was used. A value of P < 0.05 was considered statistically significant. The poststudy power was computed for duration of anesthesia, lid and globe akinesia, and analgesia with 95% confidence interval.
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Results |
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The demographic data, duration of surgery and the number of patients requiring supplementary injection to achieve perfect akinesia were comparable among the four groups (Table 1).
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The incidence of successful block was also comparable in all the groups. There was no significant difference between the groups regarding the onset times of lid akinesia, globe anesthesia and globe akinesia. However, the duration of lid akinesia as well as globe anesthesia and akinesia was significantly (P < 0.05) prolonged in patients receiving 1.0 µg/kg and 1.5 µg/kg clonidine as compared with the Control group (Table 2).
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The time interval from injection of local anesthetic to first analgesic intake was significantly longer in the 1.0 and 1.5 Clon groups (340 ± 32 and 352 ± 22 min respectively) as compared with the Control group (188 ± 24 min). These patients also required smaller doses of rescue pain medication during 24 h. Clonidine 0.5 µg/kg did not increase the duration of anesthesia and analgesia significantly. The differences between the 1.0 Clon group and the 1.5 Clon group were also not significant statistically. The verbal rating scale scores were significantly lower in all the patients receiving clonidine as compared with the Control group. However the difference was highly significant (P < 0.001) between the Control and 1.0 Clon and 1.5 Clon groups, especially during the intraoperative period, at the time of subconjunctival injection, and the early postoperative period (Table 3). The poststudy power considering 95% confidence interval for comparison of duration of globe anesthesia, lid and globe akinesia, and analgesia was more than 95% among all the groups except between the 1.0 Clon and 1.5 Clon groups. This was 16%, 69%, 66%, and 22% respectively for the four variables.
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Although there was more decrease in mean arterial pressure and heart rate 30–45 min after performing the block in patients receiving 1.0 µg/kg and 1.5 µg/kg clonidine as compared with the Control group, this was not clinically significant in the 1.0 Clon group. However one patient in the 1.5 Clon group had marked hypotension. No episode of bradycardia was reported in any group. Clonidine produced a dose-related sedation 15–90 min after the block (3/15 patients in 1.5 Clon group had grade 2 sedation as compared with 1/15 in the 1.0 Clon group and none in the Control group), but the highest sedation score noted during the observation period was 2. No episode of hypoxia and respiratory depression was reported. Two patients of the 1.5 Clon group complained of marked dizziness. No other significant adverse effect or complication was recorded except dry mouth in patients receiving clonidine. Significantly more patients rated their intraoperative and postoperative period as comfortable in the 1.0 and 1.5 Clon groups as compared with the Control group (Table 4).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The result of the present study shows that clonidine with 2% lidocaine and hyaluronidase mixture produces a dose-dependent prolongation of anesthesia and analgesia after peribulbar block, although there was no difference in the success rate of block and onset times.
Various previous studies (1–3,6,12,13) on axillary plexus, intrathecal, epidural and retrobulbar block have shown that analgesia was prolonged by clonidine (40%–100%). Opinions differ on the onset times, quality of block, and incidence of side effects (3, 6, 12). In a dose-response study Buttner et al. (3) found that 120 and 240 µg clonidine with local anesthetic produces a dose-dependent prolongation of anesthesia and analgesia after brachial plexus block, but had no effect on the onset time and quality of block. They also noticed sedation in most patients receiving clonidine. In another study Bernard and Macaire (12) also found a dose-dependent prolongation of analgesia when 30, 90, and 300 µg clonidine was added to 1% lidocaine for brachial plexus block. In this study clonidine produced a decrease in blood pressure and increased incidence of sedation and hypoxia in a 300-µg dose. Mjahed et al. (6) reported a significant increase in duration of analgesia and akinesia after administration of 2 µg/kg clonidine with 2% lidocaine for retrobulbar block. They also observed marked reduction in systolic and diastolic blood pressure at 20 min and increased sedation in patients receiving clonidine. In a dose-response study for brachial plexus block Singelyn et al. (13) reported that the minimum dose of clonidine to significantly prolong the duration of anesthesia and analgesia is 0.5 µg/kg and that at this dose clonidine may be used without important side effects even in outpatients. Therefore we used 0.5 µg/kg as the minimum dose in our study.
However, in a study for peribulbar block Connelly et al. (7) did not find any significant effect of 100 µg clonidine added to lidocaine on the onset of akinesia, sedation, perioperative analgesic requirement, and satisfaction score. They did not study the duration of block. The differences between this study and our observations may be attributable to concomitant use of midazolam and propofol in their study masking the occurrence of mild sedation that was produced by clonidine in our study 30–90 min after the block. The analgesic effect of clonidine was also more marked during the intraoperative and early postoperative period in our study. In the previous study the time to first analgesic and total analgesic requirement was reported by telephoning the patients (as the patients were discharged on the same day) and many patients had taken the analgesic medication irrespective of discomfort. In our study the patients were discharged a day after surgery and they received the supplementary analgesic only when the pain score was 5 or more. In the present study, the Control group did not have any sedation and had higher pain scores. Patients in the 1.0 and 1.5 Clon groups were significantly more comfortable as shown by lower pain scores and mild sedation contributing to overall satisfaction with the operative experience.
Similar to other dose-response studies on the interaction of clonidine with local anesthetics (1,3,12), our results support a dose-dependent prolongation of anesthesia and analgesia after neural blockade. The possible mechanisms for this interaction may be because of clonidine’s blocking conduction of C and A 
fibers and increasing potassium conductance in isolated neurons. Second, clonidine may enhance lidocaine-induced inhibition of C-fiber compound action potential. Clonidine also causes 
2-adrenoceptor blockade at primary afferent terminals (both spinal as well as peripheral nerve endings) (4,5,14).
Clonidine did not alter the onset time in our study, as reported previously. The decreased onset time in retrobulbar block might be a result of the direct effect of a large concentration of clonidine on neural transmission both locally and centrally through the optic sheath (14). Increased adverse effects, such as a decrease in blood pressure and sedation with an increasing dose of clonidine, may be because of the central action of the drug after systemic absorption (15).
We used lidocaine in our study because the use of potent local anesthetics (bupivacaine, mepivacaine) that provide reliable, dense anesthesia would make the detection of any clonidine effect more difficult. We did not use epinephrine because the use of epinephrine in orbital regional anesthesia is controversial because it may reduce the blood supply to the vital structures of the globe in elderly patients. Furthermore, it has been shown in experimental models that adrenaline may potentiate myotoxicity of local anesthetics (16).
Our results have shown that clonidine enhances the duration of anesthesia and analgesia after peribulbar block in 1.0 µg/kg dose without significant side effects. However, because the power of the study was low between the 1.0 Clon and 1.5 Clon groups, further clinical trials with a larger number of patients are required to make final conclusions.
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Footnotes |
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Presented at the 12th World Congress of Anaesthesiologists, Montreal, Canada, June 4-9, 2000.
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References |
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Bonnet F, Brun-Buissen 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] - Huntoon M, Eisenach J, Boese P. Epidural clonidine after cesarean section: appropriate dose and effect of prior local anesthetic. Anesthesiology 1992; 76: 187–93.[Web of Science][Medline]
- Buttner J, Ott B, Klose R. The effect of adding clonidine to mepivacaine. Axillary brachial plexus blockade. Anaesthetist 1992; 41: 548–54.[Web of Science][Medline]
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Butterworth JF, Strichartz GR. The 2-adrenergic agonists clonidine and guanfacine produce tonic and phasic block of conduction in rat sciatic nerve fibers. Anesth Analg 1993; 76: 295–301.[Web of Science][Medline]
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Gaumann DM, Brunnet PC, Jirounek P. Clonidine enhances the effects of lidocaine on C-fiber action potential. Anesth Analg 1992; 74: 719–25.
[Abstract/Free Full Text] - Mjahed K, Harrar N, Hamdani M, et al. Lidocaine clonidine retrobulbar block for cataract surgery in elderly. Reg Anesth 1996; 21: 569–75.[Medline]
- Connelly NR, Camerlenghi G, Bilodeau M, et al. Use of clonidine as a component of the peribulbar block in patients undergoing cataract surgery. Reg Anesth Pain Med 1999; 24: 426–9.[Medline]
- Fry RA, Henderson J. Local anaesthesia for eye surgery: the periocular technique. Anesthesia 1989; 45: 14–7.
- Jaffe NS, Jaffe MS, Jaffe GF. Intraoperative complications. In: Cataract surgery and its complications. 6th ed. New York: Mosby 1997: 232–64.
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Dopfmer UR, Maloney DG, Gaynor PA, et al. Prilocaine 3% is superior to a mixture of bupivacaine and lidocaine for peribulbar anaesthesia. Br J Anaesth 1996; 76: 77–80.
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[Abstract/Free Full Text] - Bernard JM, Macaire P. Dose-range effects of clonidine added to lidocaine for brachial plexus block. Anaesthesiology 1997; 87: 277–84.[Web of Science][Medline]
- Singelyn FJ, Gouverneur JM, Robert A. A minimum dose of clonidine added to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block. Anesth Analg 1996; 83: 1046–50.[Abstract]
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Eisenach JC, Kock MD, Klimscha W. 2-adrenergic agonists for regional anesthesia: a clinical review of clonidine. Anesthesiology 1996; 85: 655–74.[Web of Science][Medline]
- Jarrott B, Conway EL. Maccarrone C, Lewis SJ. Clonidine: understanding its disposition, sites and mechanism of action. Clin Exp Pharm Physiol 1987; 14: 471–9.[Web of Science][Medline]
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