Dexamethasone Compared to Dexmedetomidine as an Adjuvant to Local Anesthetic Mixture in Peribulbar Block for Vitreoretinal Surgery. A Prospective Randomized Study.

BACKGROUND: Dexamethasone or dexmedetomidine may improve the quality of peribulbar block. AIM: The aim of this study is to compare the effects of adding either dexamethasone or dexmedetomidine to peribulbar block on the efficacy, intraocular pressure (IOP), time to first analgesic request, total analgesic requirement, and side effects in patients undergoing vitreoretinal surgery.
DESIGN: This was a clinical prospective randomized study. PATIENTS AND METHODS: One hundred and fifty adult patients scheduled for vitreoretinal surgery with peribulbar block were randomized into three groups (50 patients each). Group I received 3.5 ml of 0.5% bupivacaine and 3.5 ml of 2% lidocaine + 1 ml normal Saline. 4 mg dexamethasone and 25 μg dexmedetomidine in 1 ml were added to the local anesthetic mixture in Groups II and III respectively. Onset and duration of sensory and motor blocks, adequate time to start surgery, IOP, time to first request of rescue analgesia, total analgesic consumption, and side effects were recorded. The statistical software SPSS 16 was utilized for statistical analysis.
RESULTS: Dexamethasone and dexmedetomidine groups showed significantly prolonged duration of corneal anesthesia (234.07 ± 1.37 and 233.54.1.97 min respectively), prolonged lid and globe akinesia (194.27 ± 1.63 and 194.73 ± 2.35 min respectively) with prolonged time to first request of analgesia and less consumption of rescue analgesia as compared to control group (P < 0.05) with non significant differences between both groups (P > 0.05). The onset of corneal anesthesia as well as lid and globe akinesia were enhanced in dexmedetomidine group compared to the other two groups (P < 0.05). In addition, the measurement of IOP was significantly less in the dexmedetomidine group after 10 min. All the patients were hemodynamically stable with no side effects observed.
CONCLUSION: The addition of dexamethasone and dexmedetomidine to local anesthetic mixture in peribulbar block for vitreoretinal surgeries provided safe and effective block with prolonged duration and decreased requirements of postoperative analgesia with better quality for dexmedetomidine group regarding the fast onset of the block and reduced IOP.

INTRODUCTION

Regional anesthesia has gained wider popularity over general anesthesia, especially in different ophthalmic surgeries.[1] The majority of patients undergoing ophthalmic surgeries are elderly, with multiple chronic diseases, with increased risk of morbidity and mortality under general anesthesia.[2] Different eye blocks have been practiced with great success. Peribulbar anesthesia is widely practiced now as a safe local block for ophthalmic surgeries. However, the limited duration of these blocks was shown to be the main problem encountered during vitreoretinal surgery.[3] Several drugs were added as adjuvants to local anesthetics, such as adrenaline, sodium bicarbonate, and hyaluronidase, and their effects have been studied.[456] The aim of these additives is to improve the quality and duration of anesthesia and the postoperative analgesia.

Dexamethasone is a potent long-acting steroid which has shown efficacy as an adjuvant to local anesthetics in various studies.[789]

Dexmedetomidine is a highly selective alpha 2-adrenoreceptor agonist that has an alpha 2-to-alpha 1 selectivity ratio of 1600:1; therefore, it is eight times potent than clonidine.[10] Dexmedetomidine enhances central and peripheral neural blockades when added to local anesthetics as an adjuvant, thus providing better quality of anesthesia as well as postoperative analgesia.[111213]

The purpose of this study was to compare the efficacy of dexamethasone or dexmedetomidine when added to a mixture of local anesthetic in the peribulbar block for microscopic vitreoretinal surgery.

PATIENTS AND METHODS

This prospective double-blind randomized controlled study was conducted for 1 year from April 2015 to April 2016. After approval of local ethical committee and informed consent was obtained, 150 adult patients of both sexes, aged between 18 and 70 years old, with the American Society of Anesthesiologists physical status (ASA) I–III and scheduled for microscopic vitreoretinal surgery using peribulbar anesthesia were enrolled in the study.

Exclusion criteria included allergy to any of the study drugs, single-eyed patients, ocular infection, glaucoma, patients with bleeding or coagulation disorders, patients with difficult communication, patients unable to maintain prolonged supine position, patients with excessive tremors or agitation, and those who refused to sign informed consent.

Patients were randomly assigned at a ratio 1:1:1 into three equal groups (50 patients each). Randomization was done using a computer-generated random numbers concealed in sealed opaque envelopes indicating the group of assignment. A nurse who did not participate in the study reads the number contained in the envelope and made group assignment. The anesthesiologist who performed the block was blinded to the group assignment. Peribulbar block was performed in all patients using a total volume of 8 ml, 7 ml of the local anesthetic mixture composed of 3.5 ml of 0.5% bupivacaine and 3.5 ml of 2% lidocaine plus 1 ml of the test drug. Group I (control group) received local anesthetic mixture + 0.9% sodium chloride (1 ml), Group II (dexamethasone group) received local anesthetic mixture + 4 mg of dexamethasone disodium phosphate in 1 ml, and Group III (dexmedetomidine group) received local anesthetic mixture + 25 μg dexmedetomidine in 1 ml of 0.9% sodium chloride.

Preoperative assessment was performed for routine history taking, full clinical examination, and evaluation of routine laboratory investigations. Detailed anesthetic technique was explained to the patients as well as how to use the visual analog scale at preoperative visit. The patients were allowed to fast according to ASA guidelines and no premedication was given.

On arrival at the operation theater, venous access was secured with 20-gauge cannula, routine monitoring in the form of automated noninvasive blood pressure, pulse oximetry, and electrocardiogram were connected, and oxygen (2 L/min) was administered through nasal cannula. Topical anesthesia using benoxinate hydrochloride eye drops was given to all patients.

All operations were performed by the same experienced surgeon, the medications were prepared by an anesthesiologist not involved in the study, and the block was done by an another anesthetist who was unaware of the nature of the solution injected. Patients were asked to fix their eyes looking straight forward toward the ceiling. After sterilizing the site of surgery by Betadine solution 10% concentration, the local anesthetic solution was injected using a 25-G short bevel sharp tip needle (13 mm in length) into the medial canthal peribulbar area (inferonasal approach), and the needle is then advanced percutaneously in an anteroposterior direction. Patients were asked to move their eyes in the four cardinal directions before injection of anesthetic solution. After aspiration, 8 ml of the local anesthetic solution was injected. Injection of the intended volume of the study drug was stopped when there was fullness of the orbit and/or drooping of the upper eyelid during injection.

The following parameters were assessed:

Onset of sensory block was evaluated by assessing corneal anesthesia using a small piece of cotton wool every 30 s after injection till loss of corneal sensation.

Motor block evaluation included:

Evaluation of lid akinesia at 1, 3, 5, 7, and 10 min after injection (the patients were asked to open their eyelids and then squeeze them together) using a three-point scale (0–2) in which:

0 referred to complete akinesia

1 referred to partial movement in either or both eyelid margins

2 referred to normal movement in either or both eyelid margins.

Evaluation of globe akinesia at 1, 3, 5, 7, and 10 min after injection, using a three-point scale (0–2) for each of the four cardinal directions (upward, downward, nasal, and temporal). Ocular movement in each direction was scored as 2 if it was normal, 1 if it was limited, and 0 if there was no directional movement (total score of 8).

Time of adequate condition to begin surgery defined as the presence of corneal anesthesia together with an ocular movement score ≤1 in each direction and an eyelid akinesia score of 0. If the total ocular movement score was >4 or there was full movement in any direction, reflecting incomplete block after 10 min from injection, supplementary anesthesia was provided with a further injection of 3 ml of 2% lidocaine in the same manner as given before, and the patient was excluded from the study

Duration of sensory block defined as the time from injection till onset of pain

Duration of akinesia (motor block) measured from the time of injection of the anesthetic mixture till recurrence of full range muscle movements (score 8)

Intraocular pressure (IOP) was measured 30 min before injection of the local anesthetics as a baseline reading (P0). The other reading was 10 min after injection of local anesthetics (P1) using Schiotz tonometer

Hemodynamic parameters: The heart rate (HR) and the mean arterial pressure (MAP) were assessed before the peribulbar block (baseline reading), 15 min after injection and every 15 min till the end of surgery

Sedation level was evaluated by Ramsay sedation scale every 15 min during surgery, at the end of surgery, and at (30, 60, and 120 min) postoperatively where 1 – the patient is anxious or agitated or both, 2 – the patient is cooperative, oriented, and tranquil, 3 – the patient responds to commands only, 4 – a brisk response to a light glabellar tap, 5 – a sluggish response to a light glabellar tap, and 6 – no response

Pain scores: Pain assessment using 10-point visual analog scale (VAS) score. (0 no pain and 10 the worst pain imaginable) at the following points: at 0 h (end of surgery) then 1, 2, 4, and 6 h postoperative. Patients with VAS 3 and 4 were treated by paracetamol 500 mg tablets. If the score was >4, meperidine 15 mg was administered by intravenous route, repeated every 30 min if no response with maximum dose of 100 mg.

Total analgesic consumption was calculated and the time of first analgesic request (defined as time from 0 h at end of surgery till the first order of the patient to analgesia) was also recorded.

Adverse events including chemosis, itching, conjunctival hemorrhage, raised pressure, diplopia, ptosis, local trauma (globe perforation, retrobulbar hemorrhage, and muscle damage), or bradycardia defined as HR <50 beats/min – treated by atropine 0.01 mg/kg IV and hypotension defined as MAP >20% of baseline readings – treated by fluids and vasopressors were recorded and managed appropriately. All resuscitation drugs for local anesthetic toxicity were ready and available.

Statistical analysis

Our primary outcome variable was the time to first analgesic request. Based on the results of a previous study,[13] a sample size was calculated to be 44 patients in each group needed to produce an effect size of 1.8 a standard deviation (SD) of 2.3 at α-error of 0.05 and power of study of 95%. We enrolled 50 cases per group to overcome possible dropouts. Secondary outcomes included onset and duration of sensory and motor blockade, time to adequate condition to start surgery, IOP measurements, hemodynamic parameters, and total analgesic consumption.

The statistical software SPSS 16 (SPSS Inc., Chicago, IL, USA) was utilized for statistical analysis. Normality of data was checked with the Kolmogorov–Smirnov test. Numerical variables were expressed as mean ± SD or as median and interquartile range and were analyzed utilizing one-way ANOVA with post hoc Turkey's honest significant difference test if normally distributed. Nonnormally distributed numerical variables were analyzed among the studied groups utilizing the Kruskal–Wallis test. Categorical data were presented as patients' number or frequencies (%) and were analyzed using Chi-square test. P < 0.05 was considered significant.

RESULTS

Consort flow diagram showed the patient enrollment, allocation, follow-up, and analysis. [Figure 1]. The demographic data of the studied groups showed no statistically significant difference as regards age, sex, ASA physical status, and the duration of surgery [Table 1].

Figure 1

Consort flow diagram

Table 1

Demographic data and duration of surgery of the studied groups

The combination of dexmedetomidine with local anesthetic mixture enhanced the onset of corneal anesthesia as well as the time to adequate condition to start surgery with higher number of patients having rapid onset of lid and globe akinesia at 1 min and s min compared to both control and dexamethasone groups while no statistically significant differences were detected between dexamethasone group and control group as regards either variables. The mean duration of sensory and motor blocks was significantly prolonged in both dexamethasone and dexmedetomidine group as compared to control group (P < 0.0001); however, the difference between the two groups was statistically insignificant (P > 0.05) [Table 2].

Table 2

Characteristic of the block

Baseline measurement of IOP showed no statistically significant difference between the three groups (P = 0.253), whereas at 10 min following local anesthetic injection, a statistically significant decrease of IOP values was observed in dexmedetomidine group compared to control group and dexamethasone group (P < 0.001) [Table 2].

Sedation level among the three groups was comparable (P > 0.05). In addition, the studied groups had also a comparable stable hemodynamic profile at all times of measurements [Figures 2 and 3].

Figure 2

Mean arterial blood pressure changes in the studied groups

Figure 3

Heart rate changes in the studied groups

VAS scores were similar among the three groups at the end of surgery, at 1 h, and at 6 h postoperative (P = 0.877, 0.901, 0.189, respectively). At 2 h and 4 h postoperative, VAS scores were significantly lower in dexamethasone and dexmedetomidine groups as compared to control groups (P < 0.001, P < 0.001, respectively). However, the comparison between the dexamethasone group and the dexmedetomidine group was comparable (P > 0.05) [Table 3].

Table 3

Visual analog scale score among the studied groups

Patients in the dexamethasone group and dexmedetomidine group had a significantly prolonged time to first analgesic request (P < 0.001) with significantly less consumption of rescue analgesia than the control group (P < 0.001) with no significant differences between both groups (P > 0.05) [Table 4].

Table 4

Comparison between groups for first analgesic request and total analgesic consumption

No complications related to either the technique or to the studied drugs were observed in our study.

DISCUSSION

The results of this study showed proven efficacy of both dexamethasone and dexmedetomidine when used as adjuvants to local anesthetics in peribulbar anesthesia as demonstrated by prolonged duration of sensory and motor blocks, delayed onset of first request to rescue analgesia, and reduced consumption of postoperative analgesics as compared to control group with better quality of dexmedetomidine group as regards onset of corneal anesthesia and lid and globe akinesia compared to control and dexamethasone groups.

The results of this study were consistent with Mahmoud et al.[14] who studied the effect of adding dexamethasone 4 mg to bupivacaine 0.5% versus bupivacaine 0.5% without additives for peribulbar block in vitreoretinal surgeries; they demonstrated longer duration of lid and globe akinesia, delayed onset of first rescue analgesia, fewer number of patients requiring rescue medications, as well as decreased inflammatory response to surgery in dexamethasone group compared to bupivacaine group. In addition, no statistically significant difference was detected between the two groups as regards the onset of lid and globe akinesia, and they attributed this finding to the delayed onset of action of dexamethasone which starts after 1–2 h of its administration. Our results were in line with the results of Hafez et al.[15] in their study on the effect of adding dexmedetomidine to local anesthetic mixture for peribulbar block in vitreoretinal surgeries; they showed that addition of 25 mic of dexmedetomidine to a mixture of lidocaine 2% and bupivacaine 0.5% had shortened the onset of sensory and motor block and increased duration of akinesia and anesthesia. Another study was done by El-Ozairy and Tharwat.[16] who studied the effect of adding two different doses of dexmedetomidine (25 μgm and 50 μgm) to levobupivacaine/hyaluronidase mixture and assessed their effects on the onset and duration of globe anesthesia and akinesia; they found that the onset of corneal anesthesia and globe akinesia in group D50 was shorter than D25 which was shorter than in the control group, and these results are in line with our results.

In the current study, IOP was significantly lower in the dexmedetomidine group 10 min after injection compared to baseline reading, and this effect was not detected in the two other groups which showed no significant difference. Dexmedetomidine may decrease IOP by vasoconstriction of the afferent blood vessels in the ciliary body; this leads to decrease in production of aqueous humor. It may also facilitate drainage of aqueous humor by reducing the sympathetic mediated vasomotor tone of the drainage system of the eye.[1718] Our results were similar to those obtained by Channabasappa et al.[19] who reported that a combination of bupivacaine and lidocaine with dexmedetomidine in peribulbar anesthesia helped to decrease the IOP significantly.

No complications were reported apart from ecchymosis, itching, and pain on injection which may be attributed to peribulbar block with no occurrence of hemodynamic or respiratory compromise.

Regional anesthesia has turned out to be the most popular technique for the majority of ophthalmic surgeries as it is associated with more stable hemodynamic profile, fewer respiratory side effects, enhanced postoperative analgesia, and decreased incidence of nausea and vomiting than general anesthesia.[2021] Peribulbar block is a considerably easier, faster, and safe procedure, particularly in geriatric patients with concurrent comorbidities that may restrain the utilization of systemic analgesics.[22]

This study was designed to compare the effect of adding dexamethasone or dexmedetomidine to local anesthetic mixture on the quality of anesthesia and analgesia of peribulbar block in patients undergoing microscopic retinal surgery.

Dexamethasone is thought to produce its pain-relieving impacts by diminishing the discharge of pain impulses along nociceptive C-fibers.[23] Another mechanism suggests that corticosteroids has a vasoconstricting effect which decreases the systemic uptake local anesthetics.[24] In addition, its systemic anti-inflammatory effect may have a contribution.[25]

The analgesic effect of perineural dexamethasone has been extensively evaluated in various regional anesthetic techniques including epidural,[26] brachial plexus,[27] sciatic,[9] and facial blocks.[28] A meta-analysis performed by Albrecht et al. empathized the safety and efficacy of dexamethasone as an adjunct to local anesthetic medications in different nerve block techniques.[29]

Dexmedetomidine is a highly specific centrally acting α2-agonist; it is widely used nowadays with local anesthetic mixture in peripheral nerve blocks, subarachnoid anesthesia,[30] and ophthalmic anesthesia.[17] Alpha 2-agonists acts peripherally by reducing the discharge of norepinephrine and by inhibition of nerve fiber action potential while their central analgesic effect is produced at the level of the dorsal root neuron in pain pathway as well as at the locus coeruleus by preventing the release of substance P and by activation of α2-receptors, respectively.[18]

To our knowledge, only two studies have evaluated the combination of dexamethasone with local anesthetics in eye procedures with no previous published researches comparing between dexamethasone and dexmedetomidine in that framework.[1431]

This study had several limitations. The first was the limited sample size, and a larger population needed to ensure safety and efficacy of the studied drugs. Second: We recorded pain scores and analgesic consumption for only 6 h postoperative which might have influenced our results. Finally, we did not assess patient or surgeon's satisfaction which are important determinants of the efficacy and quality of block.

CONCLUSION

From this study, it can be concluded that the addition of dexamethasone and dexmedetomidine to local anesthetic mixture in peribulbar block for vitreoretinal surgeries provided safe and effective block with prolonged duration and decreased postoperative analgesic requirement with better quality for dexmedetomidine group regarding the fast onset of the block and reduced IOP.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.