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Supplementation of retrobulbar block with clonidine in vitreoretinal surgery: effect on postoperative pain
Journal of Clinical Anesthesia (2011) 23, 393–397
Original contribution
Supplementation of retrobulbar block with clonidine in vitreoretinal surgery: effect on postoperative pain☆,☆☆,★ Vanda G. Yazbeck-Karam MD (Associate Professor)a,b , Sahar M. Siddik-Sayyid MD (Associate Professor)b , Elie L. Abi Nader MD (Assistant Professor)a , Daisy E. Barakat MD (Instructor)a , Hoda S. Karam MD (Lecturer)a , Georges M. Cherfane MD (Lecturer) c , Jalal N. Hajj Hussein MD (Resident)c , Marie T. Aouad MD (Associate Professor)b,⁎ a
Department of Anesthesiology, Rizk Hospital, Beirut, Lebanon Department of Anesthesiology, American University of Beirut Medical Center, Beirut, Lebanon c Department of Ophthalmology, Rizk Hospital, Beirut, Lebanon b
Received 10 September 2009; revised 18 November 2010; accepted 13 December 2010
Keywords: Anesthesia, regional; Clonidine; Eye surgery; Postoperative pain; Retrobulbar block; Vitreoretinal surgery
Abstract Study Objective: To evaluate the effect of clonidine when added to local anesthetics on duration of postoperative analgesia during retrobulbar block. Design: Prospective, randomized controlled trial. Setting: Operating room and Postanesthesia Care Unit of a university-affiliated hospital. Subjects: 80 ASA physical status 1, 2, and 3 patients undergoing vitreoretinal surgery with or without scleral buckling. Interventions: Patients in the control group (n = 40) received a retrobulbar block with 4.5 mL of lidocaine-bupivacaine and 0.5 mL of saline. Clonidine group patients (n = 40) received 4.5 mL of lidocaine-bupivacaine and 0.5 μg/kg of clonidine in a 0.5 mL volume. Measurements: The time to first analgesic request, frequency of postoperative pain, and number of postoperative analgesic requests per patient were assessed. Main Results: 37 patients in the control group (92.5%) versus 24 patients (60%) in the clonidine group reported pain postoperatively (P = 0.001), with a shorter time to first analgesic request noted in the control group (4.9 ± 3 vs 11.9 ± 5.3 hrs; P b 0.001). The median number of postoperative analgesic requests per patient during the first 24 hours was higher in the control group than the clonidine group [2 (0-3) vs. 1 (0-3); P b 0.001]. Conclusions: The addition of clonidine 0.5 μg/kg to the local anesthetics of a retrobulbar block for vitreoretinal surgery decreases the frequency of postoperative pain and prolongs the time of analgesia. © 2011 Elsevier Inc. All rights reserved.
☆
Presented in part at the Annual Meeting of the European Society of Regional Anesthesia, Valencia, Spain, Sept. 12-15, 2007. Supported by the Department of Anesthesiology, Rizk Hospital, Beirut, Lebanon, only. ★ The authors have no conflicts of interest to disclose. ⁎ Corresponding author. Tel.: +961 1 35 0000x6380; fax: +961 1 74 5249. E-mail address: [email protected] (M.T. Aouad). ☆☆
0952-8180/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2010.12.014
394
1. Introduction The use of regional anesthesia for vitreoretinal surgery has become increasingly popular because it is associated with fewer respiratory and hemodynamic untoward events, better postoperative pain relief, and less nausea and vomiting than general anesthesia [1,2]. Regional anesthesia is especially advantageous in vitreoretinal surgery when very early positioning is required following gas bubble injection, as in the case of retinal relocation surgery for macular degeneration [3]. Vitreoretinal surgery is a lengthy procedure that sometimes requires intraoperative supplementation of the block [4], and it may be associated with significant postoperative pain [5]. Most patients with vitreoretinal pathology are elderly and exhibit multiple systemic diseases such as diabetes or cardiovascular diseases that may limit the use of systemic analgesics such as nonsteroidal anti-inflammatory drugs [6]. The use of opioids for postoperative analgesia also is associated with an increased incidence of postoperative nausea and vomiting, which may be detrimental if accompanied by an increase in intraocular pressure (IOP) [7]. Additives have been used to prolong the duration of retrobulbar block. Epinephrine has been used for this purpose. However, its use in orbital regional anesthesia is controversial because in elderly patients it may reduce the blood supply to the vital structures of the globe [8]. Furthermore, epinephrine may potentiate myotoxicity of local anesthetics [9]. Postoperative analgesia extending beyond the duration of a long-acting local anesthetic such as ropivacaine or bupivacaine may be achieved by a continuous local anesthetic technique with the insertion of a catheter into the retrobulbar or peribulbar space [4,10]. However, many ophthalmic surgeons are reluctant to use continuous catheter techniques postoperatively. The addition of clonidine, an alpha(2)-agonist, to local anesthetics prolongs analgesia and akinesia in retrobulbar and peribulbar blocks for cataract surgery [11-14]. Our hypothesis was that the addition of clonidine to the local anesthetic mixture of the retrobulbar block would prolong the time to first analgesic request following vitreoretinal surgery (primary outcome). Secondary outcomes were the need for intraoperative supplementation, frequency of postoperative pain, number of postoperative analgesic requests per patient, and patients' satisfaction.
2. Materials and methods After obtaining approval from Rizk Hospital Ethics Committee and patients' informed consent, 80 ASA physical status 1, 2, and 3 patients who were scheduled for elective vitreoretinal surgery were enrolled in the study. Exclusion criteria were allergy to local anesthetic solutions, uncontrolled hypertension, chronic cough, chronic clonidine or
V.G. Yazbeck-Karam et al. analgesic therapy, coagulation impairment, orbital abnormalities, glaucoma, and patients who were unable to cooperate in maintaining a relatively motionless supine position or who refused the anesthetic technique. After a routine preoperative evaluation, all patients were premedicated with diazepam 5 mg orally one hour before the surgical procedure. Patients were randomly allocated by a computer-generated table of random numbers to receive the eye block with 5 mL of the following solution: 4.5 mL of a 1:1 mixture of bupivacaine 0.5% and lidocaine 2%, and hyaluronidase 5 units/mL and either 0.5 mL of normal saline (control group: n = 40) or 0.5 mL of clonidine (Catapres; clonidine group: n = 40). Clonidine 150 μg/mL was diluted with normal saline to obtain 0.5 μg/kg in 0.5 mL. The results of the randomization were concealed in opaque envelopes and opened sequentially. The mixtures were prepared by an anesthesia resident who was not involved in data collection. Standard monitoring, including noninvasive arterial blood pressure (BP), electrocardiogram (lead II), and oxygen saturation by pulse oximetry (SpO2), were applied. The eye block was performed by one of two anesthesiologists (VGY, ELAN) who had substantial expertise in administering regional anesthesia for ophthalmic surgery. Both the anesthesiologist performing the block and the patient were blinded to the composition of the anesthetic mixture. Topical anesthesia to the conjunctiva with 0.4% oxybuprocaine drops was given before performing the block. The globe was maintained in a neutral gaze position; then a 25-gauge, 30 mm needle ophthalmic cannula (Streriseal; Unomedical, Ltd, Redditch, UK) was introduced percutaneously in the inferotemporal quadrant as far laterally as possible. The initial direction of the needle was tangential to the globe; the needle was then passed below the globe. Once past the equator, as gauged by the axial length of the globe, the needle was allowed to go upwards and inwards. Five mL of anesthetic solution was slowly injected after aspiration. This was followed by a percutaneous injection of 2.0 mL of lidocaine-bupivacaine mixture at the level of the supraorbital notch to block the orbicularis muscles and obtain lid anesthesia. To promote spread of the local anesthetic solution and decrease IOP, gentle digital massage was done. Motor block was assessed 5, 10, and 15 minutes after injection. Ocular globe motility was evaluated in the four quadrants using a 3-point scoring system, where 0 = no movement, 1 = reduced movement, and 2 = normal movement, with a maximum possible score of 8 for the four muscles. A score ≤ 2 indicated successful block. If inadequate motor blockade was observed 10 minutes after placement of the block, an additional injection of 2.0 to 4 mL of lidocaine-bupivacaine mixture inferolaterally was given before the surgery was allowed to start. Supplemental injections of lidocaine 2% also were given by the surgeon by sub-Tenon infiltration to patients who experienced pain during the surgery. The time of occurrence of intraoperative pain was recorded. No intravenous (IV) sedation or analgesia was administered.
Clonidine for vitreoretinal surgery Table 1
395 the first analgesic request. Total analgesic requirement during the first 24 hours also was recorded. At the end of the study period, patients were asked to grade their satisfaction with the quality of perioperative comfort and pain relief as “very good”, “good”, or “not satisfied”. This study was powered on the basis of preliminary results that showed a mean of 4 hours for the time to first analgesic request in the control group, with a standard deviation of 3. If we consider a 50% prolongation of this time with the addition of clonidine as clinically significant, a sample size of 40 in each group would be required, with α = 0.05 and β = 0.2. Continuous data were reported as means ± standard deviation and were analyzed using independent sample t-test. Categorical data were reported as numbers and percentages and were analyzed using chi-squared test or Fisher's exact test as appropriate. Nonparametric data such as scores were reported as medians and ranges and were analyzed using Mann-Whitney U test. A P-value less than 0.05 was considered statistically significant.
Patient and surgical characteristics Control group Clonidine group (n = 40) (n = 40)
Age (yrs) Weight (kg) Gender (M/F) Duration of surgery (min) Type of surgery Vitrectomy without scleral buckling Vitrectomy with scleral buckling
60.3 ± 9.4 70.5 ± 11.2 33/7 58.7 ± 9.6
64.9 ± 9.9 71.5 ± 12.2 31/9 59.2 ± 12.8
17
15
23
25
Values are means ± SD or numbers. No statistically significant differences were noted between the two groups. The control group received a retrobulbar block with 4.5 mL of lidocaine-bupivacaine and 0.5 mL of saline. The clonidine group received 4.5 mL of lidocaine-bupivacaine and 0.5 μg/kg of clonidine in a 0.5 mL volume.
A decrease in mean arterial pressure greater than 25% below preanesthetic baseline was treated by incremental doses of ephedrine 5 mg IV. Decreases in heart rate below 50 beats per minute were treated with incremental doses of atropine 0.25 mg IV. Sedation levels were monitored on a 4-point scale (0 = alert, 1 = drowsy, 2 = asleep but easily aroused, 3 = comatose) every 15 minutes for two hours and then every 30 minutes for 6 hours. Patients were asked to report any pain during the intraoperative and postoperative periods up to 24 hours on a verbal rating scale from 0 (no pain) to 10 (unbearable pain). Postoperatively, patients were given instructions for asking for analgesics (two tablets of paracetamol 500 mg, followed by two tablets of tramadol 50 mg if there was no relief within 30 min) as soon as they complained of discomfort. The time was recorded as time to Table 2
3. Results Both groups were comparable with regard to patient and surgical characteristics (Table 1). Four blocks, two in each group, were considered inadequate 10 minutes after the performance of the block and satisfactory after supplementation with local anesthetics. Ten patients required intraoperative supplementation by sub-Tenon block using lidocaine 2% in the control group versus four patients in the clonidine group (P = 0.08) (Table 2). The mean time to intraoperative supplementation was close to 50 minutes in both groups, with most of the supplementations occurring toward the end of surgery (Table 2). No patient from
Intraoperative and postoperative analgesia and patients' satisfaction
Patients requiring intraop supplementation with sub-Tenon injection of lidocaine Time of occurrence of intraop pain (min) a Patients requesting postop analgesics Time to first analgesic request (hrs) b Median VAS at first analgesic request Patients' satisfaction very good good not satisfied
Control group (n = 40)
Clonidine group (n = 40)
10 (25)
4 (10)
47.8 ± 12 37 (92.5) 4.9 ± 3 7 (4-8)
49.2 ± 13.2 24 (60) 11.9 ± 5.3 6 (4-8)
22 15 3
31 7 2
P-value 0.08 0.84 0.001 b 0.001 0.14 0.1
Values are numbers (%), means ± SD, or medians (ranges). P b 0.05 was considered statistically significant between the two groups. The control group received a retrobulbar block with 4.5 mL of lidocaine-bupivacaine and 0.5 mL of saline. The clonidine group received 4.5 mL of lidocaine-bupivacaine and 0.5 μg/kg of clonidine in a 0.5 mL volume. a Only patients who needed intraoperative (intraop) supplementation were included in this analysis (n = 10 in the control group and n = 4 in the clonidine group). b Only patients who requested postoperative (postop) analgesia were included in the analysis (n = 37 in the control group and n = 24 in the clonidine group).
396
Fig. 1 Distribution of patients by number of postoperative analgesic requests during the first 24 hours.
either group required ephedrine or atropine. All but two patients had a sedation score of 0; the two patients, one from each group, had a sedation score of 1. In the postoperative period, all patients were fully awake and alert, with no difference in sedation levels noted between the two groups. In the control group, 37 patients required postoperative analgesia versus 24 clonidine group patients (P = 0.001), with significantly shorter time to first analgesic request observed in the control group (P b 0.001) (Table 2). The median number of postoperative analgesic requests per patient during the first 24 hours was higher in the control group than the clonidine group [2 (0-3) vs. 1 (0-3); P b 0.001]; most of the clonidine group patients made 0 or one analgesic request, while most control group patients made two or three analgesic requests (Fig. 1). Satisfaction scores were comparable between the two groups (Table 2). When patients from both groups were pooled and analyzed according to surgery type, 41 of 48 patients (85.4%) required postoperative analgesia following vitrectomies that involved scleral buckling versus 20 of 32 patients (62.5%) whose vitrectomies involved the intraocular compartment only (P = 0.018).
4. Discussion The ability of the alpha(2)-adrenergic agonist clonidine to enhance the central and peripheral neural block when added to local anesthetics has been shown in various animal and human studies [15]. In ophthalmic surgery, clonidine was initially used as an oral premedication [16]. At a dose of 100150 μg, clonidine resulted in a reduction in intraoperative stress associated with surgery and a decrease in IOP [17]. There are few studies using clonidine in ophthalmic blocks, most of them combining clonidine with local anesthetics for peribulbar blocks in cataract surgery [12-14]. Cataract
V.G. Yazbeck-Karam et al. surgery is recognized as a procedure associated with minimal pain; phacoemulsification is even performed with topical anesthesia [18]. In contrast, vitreoretinal surgery is considered a painful procedure, especially if it is associated with scleral buckling [6]; hence, the efficacy of clonidine is better assessed in this condition. Supplementation of eye blocks with clonidine in vitreoretinal surgery has not been investigated in randomized controlled trials. Our study shows that, in this setting, clonidine prolongs the time for the first analgesic request and reduces the frequency of pain and number of analgesic requests during the first 24 hours without causing any hemodynamic side effects or sedation. Clonidine prolongs anesthesia via a mechanism involving direct action on nerve fibers [19]. A very low dose of clonidine increased the C-fiber blockade from lidocaine in an isolated nerve model [20]. Furthermore, the effect could be a result of direct alpha(2) receptor stimulation, both locally and in the central nervous system through the optic nerve sheath [21]. Barioni et al showed that prolonged anesthesia and analgesia were evident only in patients receiving peribulbar injections of clonidine whereas oral clonidine did not show the same effect, thus favoring a local action [14]. Studies that used clonidine in ophthalmic blocks have reported contradictory results [11-14,22]. In a dose-response study of 2% lidocaine peribulbar block for cataract surgery, Madan et al found a dose-dependent prolongation of anesthesia and analgesia [12]. The authors concluded that 1.0 μg/kg was the optimal dose required to prolong the duration of anesthesia and analgesia without important side effects; the 0.5 μg/kg dose was ineffective while the 1.5 μg/kg dose was associated with hypotension and dizziness [12]. However, Barioni et al found that 30 μg of peribulbar clonidine decreased the onset time to anesthesia and prolonged the time to the first rescue analgesic [14]. We used a dose of 0.5 μg/kg as the closest dose to the 30 μg used in the Barioni et al study. In contrast, Connelly et al did not find any significant effect of 100 μg clonidine when added to lidocaine-peribulbar block on onset of akinesia, sedation, perioperative analgesic requirement, and satisfaction score [22]. However, they did not study the duration of block. This result may be explained by the fact that only a 1% concentration of lidocaine was used. For retrobulbar block, only one study evaluated clonidine at a dose of 2.0 μg/kg added to 2% lidocaine in cataract surgery [11]. It resulted in a significant increase in duration of analgesia and akinesia, and a decrease in IOP. However, a reduction in systolic and diastolic blood pressures at 20 minutes, and increased sedation, were observed in these patients [11]. Although there is a reduced risk of complications with peribulbar (extraconal) versus retrobulbar (intraconal) injections [18], retrobulbar injection is still a common procedure at many institutions, especially when fast and reliable sensory and motor blocks are needed for complex and lengthy procedures such as vitreoretinal surgery. As compared with peribulbar block, a retrobulbar block requires
Clonidine for vitreoretinal surgery a smaller volume of local anesthetics and probably a lower dose of clonidine, since the drug is deposited in the vicinity of the optic nerve. This difference may explain the efficacy of the relatively low dose of clonidine added to the retrobulbar block in our study versus higher doses used with peribulbar blocks in previous studies [12,22]. Our study also showed that postoperative pain occurs more often when scleral buckling is part of the procedure. Surgery for pathology involving the retina may require an approach from outside the globe applying instruments such as a cryoprobe or bands, or from inside the globe through the vitreous cavity of the eye, or both [3]. The degree of surgical stimulus and postoperative pain varies significantly depending on the specific procedure; pain produced by the intraocular component of vitrectomy is mild with the exception of laser application, whereas pain associated with scleral buckling and cryotherapy may be moderate to severe [5]. During scleral buckling, tissue dissection on the exterior of the globe is required to permit an encircling band to be applied over the detachment site to indent or buckle the sclera towards the detached retina. The cryoprobe is applied to encourage an inflammatory response, welding the retinal layers to the buckled wall of the globe. There is significant manipulation of the globe and tissues, resulting in considerable painful stimulus both intraoperatively and postoperatively. In conclusion, the addition of clonidine 0.5 μg/kg to the local anesthetic mixture when performing a retrobulbar block for vitreoretinal surgery prolongs the time to first analgesic request and reduces the frequency of postoperative pain and number of analgesic requests without hemodynamic side effects or sedation. Clonidine may be particularly beneficial in vitreoretinal surgery, especially when scleral buckling is anticipated. This type of surgery is associated with increased postoperative pain and discomfort compared with vitrectomies that involve the intraocular component only.
References [1] Friedman D, Bass E, Lubomski L, et al. Synthesis of the literature on the effectiveness of regional anesthesia for cataract surgery. Ophthalmology 2001;108:519-29. [2] Cannon CS, Gross JG, Abramson I, Mazzei WJ, Freeman WR. Evaluation of outpatient experience with vitreoretinal surgery. Br J Ophthalmol 1992;76:68-71. [3] Johnson RW. Anaesthesia for vitreoretinal surgery. In: Kumar C, Dodds C, Fanning G, editors. Ophthalmic anaesthesia. Lisse, The Netherlands: Swets and Zeitlinger Publishers; 2002. p. 157-65.
397 [4] Falcó-Molmeneu E, Sorlí-Clemente E, Ramos-Martí F, Cabrera-Peset A, Andrés-Calvo G, Peris-Molés M. Anesthesia for vitreoretinal surgery using a retrobulbar catheter technique. Arch Soc Esp Oftalmol 2007;82:147-52. [5] Fekrat S, Elsing SH, Raja SC, Campochiaro PA, de Juan E Jr, Haller JA. Eye pain after vitreoretinal surgery: a prospective study of 185 patients. Retina 2001;21:627-32. [6] Coppens M, Versichelen L, Mortier E. Treatment of postoperative pain after ophthalmic surgery. Bull Soc Belge Ophtalmol 2002;(285):27-32. [7] Mandelcorn M, Taback N, Mandelcorn E, Ananthanarayan C. Risk factors for pain and nausea following retinal and vitreous surgery under conscious sedation. Can J Ophthalmol 1999;34:281-5. [8] Hessemer V, Heinrich A, Jacobi KW. Ocular circulatory changes caused by retrobulbar anesthesia with and without added adrenaline. Klin Monbl Augenheilkd 1990;197:470-9. [9] Kumar CM, Dodds C. Ophthalmic regional block. Ann Acad Med Singapore 2006;35:158-67. [10] Jonas JB, Hemmerling TM, Budde WM, Dinkel M. Postoperative analgesia by reinjections of local anesthetic through an indwelling retrobulbar catheter. Am J Ophthalmol 2000;129:54-8. [11] Mjahed K, el Harrar N, Hamdani M, Amraoui M, Benaguida M. Lidocaine-clonidine retrobulbar block for cataract surgery in the elderly. Reg Anesth 1996;21:569-75. [12] Madan R, Bharti N, Shende D, Khokhar SK, Kaul HL. A dose response study of clonidine with local anesthetic mixture for peribulbar block: a comparison of three doses. Anesth Analg 2001;93:1593-7. [13] Bharti N, Madan R, Kaul HL, Khokhar SK, Mishra S. Effect of addition of clonidine to local anaesthetic mixture for peribulbar block. Anaesth Intensive Care 2002;30:438-41. [14] Barioni MF, Lauretti GR, Lauretti-Fo A, Pereira NL. Clonidine as coadjuvant in eye surgery: comparison of peribulbar versus oral administration. J Clin Anesth 2002;14:140-5. [15] McCartney CJ, Duggan E, Apatu E. Should we add clonidine to local anesthetic for peripheral nerve blockade? A qualitative systemic review of the literature. Reg Anesth Pain Med 2007;32:330-8. [16] Kumar A, Bose S, Bhattacharya A, Tandon OP, Kundra P. Oral clonidine premedication for elderly patients undergoing intraocular surgery. Acta Anaesthesiol Scand 1992;36:159-64. [17] Weindler J, Kiefer RT, Rippa A, Wiech K, Ruprecht KW. Low-dose oral clonidine as premedication before intraocular surgery in retrobulbar anesthesia. Eur J Ophthalmol 2000;10:248-56. [18] Fernández SA, Dios E, Diz JC. Comparative study of topical anaesthesia with lidocaine 2% vs levobupivacaine 0.75% in cataract surgery. Br J Anaesth 2009;102:216-20. [19] Eisenach JC, De Kock M, Klimscha W. alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology 1996;85:655-74. [20] Gaumann DM, Brunet PC, Jirounek P. Clonidine enhances the effects of lidocaine on C-fiber action potential. Anesth Analg 1992;74: 719-25. [21] Jarrott B, Conway EL, Maccarrone C, Lewis SJ. Clonidine: understanding its disposition, sites and mechanism of action. Clin Exp Pharmacol Physiol 1987;14:471-9. [22] Connelly NR, Camerlenghi G, Bilodeau M Hall S, Reuben SS, Papale J. Use of clonidine as a component of the peribulbar block in patients undergoing cataract surgery. Reg Anesth Pain Med 1999;24:426-9.
Original contribution
Supplementation of retrobulbar block with clonidine in vitreoretinal surgery: effect on postoperative pain☆,☆☆,★ Vanda G. Yazbeck-Karam MD (Associate Professor)a,b , Sahar M. Siddik-Sayyid MD (Associate Professor)b , Elie L. Abi Nader MD (Assistant Professor)a , Daisy E. Barakat MD (Instructor)a , Hoda S. Karam MD (Lecturer)a , Georges M. Cherfane MD (Lecturer) c , Jalal N. Hajj Hussein MD (Resident)c , Marie T. Aouad MD (Associate Professor)b,⁎ a
Department of Anesthesiology, Rizk Hospital, Beirut, Lebanon Department of Anesthesiology, American University of Beirut Medical Center, Beirut, Lebanon c Department of Ophthalmology, Rizk Hospital, Beirut, Lebanon b
Received 10 September 2009; revised 18 November 2010; accepted 13 December 2010
Keywords: Anesthesia, regional; Clonidine; Eye surgery; Postoperative pain; Retrobulbar block; Vitreoretinal surgery
Abstract Study Objective: To evaluate the effect of clonidine when added to local anesthetics on duration of postoperative analgesia during retrobulbar block. Design: Prospective, randomized controlled trial. Setting: Operating room and Postanesthesia Care Unit of a university-affiliated hospital. Subjects: 80 ASA physical status 1, 2, and 3 patients undergoing vitreoretinal surgery with or without scleral buckling. Interventions: Patients in the control group (n = 40) received a retrobulbar block with 4.5 mL of lidocaine-bupivacaine and 0.5 mL of saline. Clonidine group patients (n = 40) received 4.5 mL of lidocaine-bupivacaine and 0.5 μg/kg of clonidine in a 0.5 mL volume. Measurements: The time to first analgesic request, frequency of postoperative pain, and number of postoperative analgesic requests per patient were assessed. Main Results: 37 patients in the control group (92.5%) versus 24 patients (60%) in the clonidine group reported pain postoperatively (P = 0.001), with a shorter time to first analgesic request noted in the control group (4.9 ± 3 vs 11.9 ± 5.3 hrs; P b 0.001). The median number of postoperative analgesic requests per patient during the first 24 hours was higher in the control group than the clonidine group [2 (0-3) vs. 1 (0-3); P b 0.001]. Conclusions: The addition of clonidine 0.5 μg/kg to the local anesthetics of a retrobulbar block for vitreoretinal surgery decreases the frequency of postoperative pain and prolongs the time of analgesia. © 2011 Elsevier Inc. All rights reserved.
☆
Presented in part at the Annual Meeting of the European Society of Regional Anesthesia, Valencia, Spain, Sept. 12-15, 2007. Supported by the Department of Anesthesiology, Rizk Hospital, Beirut, Lebanon, only. ★ The authors have no conflicts of interest to disclose. ⁎ Corresponding author. Tel.: +961 1 35 0000x6380; fax: +961 1 74 5249. E-mail address: [email protected] (M.T. Aouad). ☆☆
0952-8180/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2010.12.014
394
1. Introduction The use of regional anesthesia for vitreoretinal surgery has become increasingly popular because it is associated with fewer respiratory and hemodynamic untoward events, better postoperative pain relief, and less nausea and vomiting than general anesthesia [1,2]. Regional anesthesia is especially advantageous in vitreoretinal surgery when very early positioning is required following gas bubble injection, as in the case of retinal relocation surgery for macular degeneration [3]. Vitreoretinal surgery is a lengthy procedure that sometimes requires intraoperative supplementation of the block [4], and it may be associated with significant postoperative pain [5]. Most patients with vitreoretinal pathology are elderly and exhibit multiple systemic diseases such as diabetes or cardiovascular diseases that may limit the use of systemic analgesics such as nonsteroidal anti-inflammatory drugs [6]. The use of opioids for postoperative analgesia also is associated with an increased incidence of postoperative nausea and vomiting, which may be detrimental if accompanied by an increase in intraocular pressure (IOP) [7]. Additives have been used to prolong the duration of retrobulbar block. Epinephrine has been used for this purpose. However, its use in orbital regional anesthesia is controversial because in elderly patients it may reduce the blood supply to the vital structures of the globe [8]. Furthermore, epinephrine may potentiate myotoxicity of local anesthetics [9]. Postoperative analgesia extending beyond the duration of a long-acting local anesthetic such as ropivacaine or bupivacaine may be achieved by a continuous local anesthetic technique with the insertion of a catheter into the retrobulbar or peribulbar space [4,10]. However, many ophthalmic surgeons are reluctant to use continuous catheter techniques postoperatively. The addition of clonidine, an alpha(2)-agonist, to local anesthetics prolongs analgesia and akinesia in retrobulbar and peribulbar blocks for cataract surgery [11-14]. Our hypothesis was that the addition of clonidine to the local anesthetic mixture of the retrobulbar block would prolong the time to first analgesic request following vitreoretinal surgery (primary outcome). Secondary outcomes were the need for intraoperative supplementation, frequency of postoperative pain, number of postoperative analgesic requests per patient, and patients' satisfaction.
2. Materials and methods After obtaining approval from Rizk Hospital Ethics Committee and patients' informed consent, 80 ASA physical status 1, 2, and 3 patients who were scheduled for elective vitreoretinal surgery were enrolled in the study. Exclusion criteria were allergy to local anesthetic solutions, uncontrolled hypertension, chronic cough, chronic clonidine or
V.G. Yazbeck-Karam et al. analgesic therapy, coagulation impairment, orbital abnormalities, glaucoma, and patients who were unable to cooperate in maintaining a relatively motionless supine position or who refused the anesthetic technique. After a routine preoperative evaluation, all patients were premedicated with diazepam 5 mg orally one hour before the surgical procedure. Patients were randomly allocated by a computer-generated table of random numbers to receive the eye block with 5 mL of the following solution: 4.5 mL of a 1:1 mixture of bupivacaine 0.5% and lidocaine 2%, and hyaluronidase 5 units/mL and either 0.5 mL of normal saline (control group: n = 40) or 0.5 mL of clonidine (Catapres; clonidine group: n = 40). Clonidine 150 μg/mL was diluted with normal saline to obtain 0.5 μg/kg in 0.5 mL. The results of the randomization were concealed in opaque envelopes and opened sequentially. The mixtures were prepared by an anesthesia resident who was not involved in data collection. Standard monitoring, including noninvasive arterial blood pressure (BP), electrocardiogram (lead II), and oxygen saturation by pulse oximetry (SpO2), were applied. The eye block was performed by one of two anesthesiologists (VGY, ELAN) who had substantial expertise in administering regional anesthesia for ophthalmic surgery. Both the anesthesiologist performing the block and the patient were blinded to the composition of the anesthetic mixture. Topical anesthesia to the conjunctiva with 0.4% oxybuprocaine drops was given before performing the block. The globe was maintained in a neutral gaze position; then a 25-gauge, 30 mm needle ophthalmic cannula (Streriseal; Unomedical, Ltd, Redditch, UK) was introduced percutaneously in the inferotemporal quadrant as far laterally as possible. The initial direction of the needle was tangential to the globe; the needle was then passed below the globe. Once past the equator, as gauged by the axial length of the globe, the needle was allowed to go upwards and inwards. Five mL of anesthetic solution was slowly injected after aspiration. This was followed by a percutaneous injection of 2.0 mL of lidocaine-bupivacaine mixture at the level of the supraorbital notch to block the orbicularis muscles and obtain lid anesthesia. To promote spread of the local anesthetic solution and decrease IOP, gentle digital massage was done. Motor block was assessed 5, 10, and 15 minutes after injection. Ocular globe motility was evaluated in the four quadrants using a 3-point scoring system, where 0 = no movement, 1 = reduced movement, and 2 = normal movement, with a maximum possible score of 8 for the four muscles. A score ≤ 2 indicated successful block. If inadequate motor blockade was observed 10 minutes after placement of the block, an additional injection of 2.0 to 4 mL of lidocaine-bupivacaine mixture inferolaterally was given before the surgery was allowed to start. Supplemental injections of lidocaine 2% also were given by the surgeon by sub-Tenon infiltration to patients who experienced pain during the surgery. The time of occurrence of intraoperative pain was recorded. No intravenous (IV) sedation or analgesia was administered.
Clonidine for vitreoretinal surgery Table 1
395 the first analgesic request. Total analgesic requirement during the first 24 hours also was recorded. At the end of the study period, patients were asked to grade their satisfaction with the quality of perioperative comfort and pain relief as “very good”, “good”, or “not satisfied”. This study was powered on the basis of preliminary results that showed a mean of 4 hours for the time to first analgesic request in the control group, with a standard deviation of 3. If we consider a 50% prolongation of this time with the addition of clonidine as clinically significant, a sample size of 40 in each group would be required, with α = 0.05 and β = 0.2. Continuous data were reported as means ± standard deviation and were analyzed using independent sample t-test. Categorical data were reported as numbers and percentages and were analyzed using chi-squared test or Fisher's exact test as appropriate. Nonparametric data such as scores were reported as medians and ranges and were analyzed using Mann-Whitney U test. A P-value less than 0.05 was considered statistically significant.
Patient and surgical characteristics Control group Clonidine group (n = 40) (n = 40)
Age (yrs) Weight (kg) Gender (M/F) Duration of surgery (min) Type of surgery Vitrectomy without scleral buckling Vitrectomy with scleral buckling
60.3 ± 9.4 70.5 ± 11.2 33/7 58.7 ± 9.6
64.9 ± 9.9 71.5 ± 12.2 31/9 59.2 ± 12.8
17
15
23
25
Values are means ± SD or numbers. No statistically significant differences were noted between the two groups. The control group received a retrobulbar block with 4.5 mL of lidocaine-bupivacaine and 0.5 mL of saline. The clonidine group received 4.5 mL of lidocaine-bupivacaine and 0.5 μg/kg of clonidine in a 0.5 mL volume.
A decrease in mean arterial pressure greater than 25% below preanesthetic baseline was treated by incremental doses of ephedrine 5 mg IV. Decreases in heart rate below 50 beats per minute were treated with incremental doses of atropine 0.25 mg IV. Sedation levels were monitored on a 4-point scale (0 = alert, 1 = drowsy, 2 = asleep but easily aroused, 3 = comatose) every 15 minutes for two hours and then every 30 minutes for 6 hours. Patients were asked to report any pain during the intraoperative and postoperative periods up to 24 hours on a verbal rating scale from 0 (no pain) to 10 (unbearable pain). Postoperatively, patients were given instructions for asking for analgesics (two tablets of paracetamol 500 mg, followed by two tablets of tramadol 50 mg if there was no relief within 30 min) as soon as they complained of discomfort. The time was recorded as time to Table 2
3. Results Both groups were comparable with regard to patient and surgical characteristics (Table 1). Four blocks, two in each group, were considered inadequate 10 minutes after the performance of the block and satisfactory after supplementation with local anesthetics. Ten patients required intraoperative supplementation by sub-Tenon block using lidocaine 2% in the control group versus four patients in the clonidine group (P = 0.08) (Table 2). The mean time to intraoperative supplementation was close to 50 minutes in both groups, with most of the supplementations occurring toward the end of surgery (Table 2). No patient from
Intraoperative and postoperative analgesia and patients' satisfaction
Patients requiring intraop supplementation with sub-Tenon injection of lidocaine Time of occurrence of intraop pain (min) a Patients requesting postop analgesics Time to first analgesic request (hrs) b Median VAS at first analgesic request Patients' satisfaction very good good not satisfied
Control group (n = 40)
Clonidine group (n = 40)
10 (25)
4 (10)
47.8 ± 12 37 (92.5) 4.9 ± 3 7 (4-8)
49.2 ± 13.2 24 (60) 11.9 ± 5.3 6 (4-8)
22 15 3
31 7 2
P-value 0.08 0.84 0.001 b 0.001 0.14 0.1
Values are numbers (%), means ± SD, or medians (ranges). P b 0.05 was considered statistically significant between the two groups. The control group received a retrobulbar block with 4.5 mL of lidocaine-bupivacaine and 0.5 mL of saline. The clonidine group received 4.5 mL of lidocaine-bupivacaine and 0.5 μg/kg of clonidine in a 0.5 mL volume. a Only patients who needed intraoperative (intraop) supplementation were included in this analysis (n = 10 in the control group and n = 4 in the clonidine group). b Only patients who requested postoperative (postop) analgesia were included in the analysis (n = 37 in the control group and n = 24 in the clonidine group).
396
Fig. 1 Distribution of patients by number of postoperative analgesic requests during the first 24 hours.
either group required ephedrine or atropine. All but two patients had a sedation score of 0; the two patients, one from each group, had a sedation score of 1. In the postoperative period, all patients were fully awake and alert, with no difference in sedation levels noted between the two groups. In the control group, 37 patients required postoperative analgesia versus 24 clonidine group patients (P = 0.001), with significantly shorter time to first analgesic request observed in the control group (P b 0.001) (Table 2). The median number of postoperative analgesic requests per patient during the first 24 hours was higher in the control group than the clonidine group [2 (0-3) vs. 1 (0-3); P b 0.001]; most of the clonidine group patients made 0 or one analgesic request, while most control group patients made two or three analgesic requests (Fig. 1). Satisfaction scores were comparable between the two groups (Table 2). When patients from both groups were pooled and analyzed according to surgery type, 41 of 48 patients (85.4%) required postoperative analgesia following vitrectomies that involved scleral buckling versus 20 of 32 patients (62.5%) whose vitrectomies involved the intraocular compartment only (P = 0.018).
4. Discussion The ability of the alpha(2)-adrenergic agonist clonidine to enhance the central and peripheral neural block when added to local anesthetics has been shown in various animal and human studies [15]. In ophthalmic surgery, clonidine was initially used as an oral premedication [16]. At a dose of 100150 μg, clonidine resulted in a reduction in intraoperative stress associated with surgery and a decrease in IOP [17]. There are few studies using clonidine in ophthalmic blocks, most of them combining clonidine with local anesthetics for peribulbar blocks in cataract surgery [12-14]. Cataract
V.G. Yazbeck-Karam et al. surgery is recognized as a procedure associated with minimal pain; phacoemulsification is even performed with topical anesthesia [18]. In contrast, vitreoretinal surgery is considered a painful procedure, especially if it is associated with scleral buckling [6]; hence, the efficacy of clonidine is better assessed in this condition. Supplementation of eye blocks with clonidine in vitreoretinal surgery has not been investigated in randomized controlled trials. Our study shows that, in this setting, clonidine prolongs the time for the first analgesic request and reduces the frequency of pain and number of analgesic requests during the first 24 hours without causing any hemodynamic side effects or sedation. Clonidine prolongs anesthesia via a mechanism involving direct action on nerve fibers [19]. A very low dose of clonidine increased the C-fiber blockade from lidocaine in an isolated nerve model [20]. Furthermore, the effect could be a result of direct alpha(2) receptor stimulation, both locally and in the central nervous system through the optic nerve sheath [21]. Barioni et al showed that prolonged anesthesia and analgesia were evident only in patients receiving peribulbar injections of clonidine whereas oral clonidine did not show the same effect, thus favoring a local action [14]. Studies that used clonidine in ophthalmic blocks have reported contradictory results [11-14,22]. In a dose-response study of 2% lidocaine peribulbar block for cataract surgery, Madan et al found a dose-dependent prolongation of anesthesia and analgesia [12]. The authors concluded that 1.0 μg/kg was the optimal dose required to prolong the duration of anesthesia and analgesia without important side effects; the 0.5 μg/kg dose was ineffective while the 1.5 μg/kg dose was associated with hypotension and dizziness [12]. However, Barioni et al found that 30 μg of peribulbar clonidine decreased the onset time to anesthesia and prolonged the time to the first rescue analgesic [14]. We used a dose of 0.5 μg/kg as the closest dose to the 30 μg used in the Barioni et al study. In contrast, Connelly et al did not find any significant effect of 100 μg clonidine when added to lidocaine-peribulbar block on onset of akinesia, sedation, perioperative analgesic requirement, and satisfaction score [22]. However, they did not study the duration of block. This result may be explained by the fact that only a 1% concentration of lidocaine was used. For retrobulbar block, only one study evaluated clonidine at a dose of 2.0 μg/kg added to 2% lidocaine in cataract surgery [11]. It resulted in a significant increase in duration of analgesia and akinesia, and a decrease in IOP. However, a reduction in systolic and diastolic blood pressures at 20 minutes, and increased sedation, were observed in these patients [11]. Although there is a reduced risk of complications with peribulbar (extraconal) versus retrobulbar (intraconal) injections [18], retrobulbar injection is still a common procedure at many institutions, especially when fast and reliable sensory and motor blocks are needed for complex and lengthy procedures such as vitreoretinal surgery. As compared with peribulbar block, a retrobulbar block requires
Clonidine for vitreoretinal surgery a smaller volume of local anesthetics and probably a lower dose of clonidine, since the drug is deposited in the vicinity of the optic nerve. This difference may explain the efficacy of the relatively low dose of clonidine added to the retrobulbar block in our study versus higher doses used with peribulbar blocks in previous studies [12,22]. Our study also showed that postoperative pain occurs more often when scleral buckling is part of the procedure. Surgery for pathology involving the retina may require an approach from outside the globe applying instruments such as a cryoprobe or bands, or from inside the globe through the vitreous cavity of the eye, or both [3]. The degree of surgical stimulus and postoperative pain varies significantly depending on the specific procedure; pain produced by the intraocular component of vitrectomy is mild with the exception of laser application, whereas pain associated with scleral buckling and cryotherapy may be moderate to severe [5]. During scleral buckling, tissue dissection on the exterior of the globe is required to permit an encircling band to be applied over the detachment site to indent or buckle the sclera towards the detached retina. The cryoprobe is applied to encourage an inflammatory response, welding the retinal layers to the buckled wall of the globe. There is significant manipulation of the globe and tissues, resulting in considerable painful stimulus both intraoperatively and postoperatively. In conclusion, the addition of clonidine 0.5 μg/kg to the local anesthetic mixture when performing a retrobulbar block for vitreoretinal surgery prolongs the time to first analgesic request and reduces the frequency of postoperative pain and number of analgesic requests without hemodynamic side effects or sedation. Clonidine may be particularly beneficial in vitreoretinal surgery, especially when scleral buckling is anticipated. This type of surgery is associated with increased postoperative pain and discomfort compared with vitrectomies that involve the intraocular component only.
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