Abstract
Background and Aims:
This prospective randomized study designed to evaluate the efficacy of dexmedetomidine either added to LA mixture or administered IV during subtenon block for cataract surgery.
Material and Methods:
75 patients, undergoing cataract surgery with subtenon anesthesia, were assigned randomly into three equal groups, Group I received subtenon bupivacaine 0.5% (1 ml) + lidocaine 2% (1 ml) + saline 0.9% (0.5 ml) and IV infusion of normal saline. Group II received subtenon bupivacaine 0.5% (1 ml) + lidocaine 2% (1 ml) + 0.5 μg/kg dexmedetomidine (0.5 ml) and IV infusion of normal saline. Group III received subtenon bupivacaine 0.5% (1 ml) + lidocaine 2% (1 ml) + saline 0.9% (0.5 μl) and IV infusion of 0.5 mg/kg dexmedetomidine over 10 min. before subtenon block. We recorded onset and duration of sensory and motor block, pain during subtenon injection, intraoperative hemodynamics, intraocular pressure, sedation and postoperative pain score.
Results:
There was a significant decrease in the onset of action and an increase in the duration of sensory block in Group II. Pain during subtenon injection was significantly less in group III. Sedation Score was higher in Group III, while heart rate showed a significant reduction in the same group. The VAS was significantly decreased in group II. After the end of surgery, the intraocular pressure was significantly decreased in Groups II and III.
Conclusion:
Subtenon dexmedetomidine shortens onset time, prolongs sensory block durations and significantly decreases the postoperative pain score with hemodynamic stability, while, IV dexmedetomidine substantially reduces pain during subtenon block and produces intra-operative sedation.
Keywords: Cataract surgery, dexmedetomidine, subtenon
Introduction
Most ocular surgeries are performed under regional anesthesia rather than general anesthesia because the former is more economical and easier to perform, and the involved risk is lesser.[1] Notably, the subtenon block has become the most widely used regional technique in cataract surgery.[2]
Dexmedetomidine is a selective α-2 receptor agonist that produces sedation and analgesia without causing respiratory depression.[3] It has been used as a sedative and as an adjuvant to local anesthetics.[4,5]
The present study was designed to compare the impact and the safety of adding dexmedetomidine to local anesthetics and its intravenous (IV) administration during subtenon blocks in patients undergoing cataract surgery.
Material and Methods
After approval from the local medical ethical committee of our institute (IRB 8/8/2020 ANET4) was procured and the study was registered at ClinicalTrial.gov. (NCT04668456), written informed consents from the participants were obtained. Seventy-five patients from both sexes with ASA grades I–II and aged 18–70 years scheduled for elective cataract surgery with subtenon’s anesthesia were enrolled in this randomized blind study. The exclusion criteria included severe cardiopulmonary diseases, and the common contraindications for regional anesthesia were: refusal of the patient, coagulation abnormalities, and impaired mental status, as well as uncontrolled glaucoma and recent surgery in the same eye.
A peripheral IV cannula was inserted, and monitoring included continuous electrocardiography, pulse oximetry, and automated noninvasive blood pressure measurement. Benoxinate hydrochloride (0.4%) drops were administered before the subtenon block. The Pharmacy Department supplied the infusions to the Anesthesia Department prior to the planned surgeries. Both the anesthesia provider and the assessors were blind to the contents of the infusion. The sealed opaque envelopes were only opened by the pharmacist to allocate the patients to their groups. All patients received 2.5 ml of the local anesthetic mixture through subtenon block and IV infusion of the drugs through a 50 ml syringe as follows:
-
a)
Group I (control group): subtenon LA mixture of 0.5% bupivacaine (1 ml) + 2% lidocaine (1 ml)+ 0.9% saline (0.5 ml) and IV infusion of 50 ml 0.9% saline for over 10 min. before the subtenon block.
-
b)
Group II (subtenon dexmedetomidine): subtenon LA mixture of 0.5% bupivacaine (1 ml) + 2% lidocaine (1 ml) + 0.5 μg/kg dexmedetomidine (0.5 ml) and IV infusion of 50 ml 0.9% saline for over 10 min. before the subtenon block.
-
c)
Group III (IV dexmedetomidine): subtenon LA mixture of 0.5% bupivacaine (1 ml) + 2% lidocaine (1 ml) + 0.9% saline (0.5 ml) and IV infusion of 0.5 μg/kg dexmedetomidine in 50 ml 0.9% saline for over 10 min. before the subtenon block.
The subtenon block was performed using a 25-gauge needle. The needle was inserted in the conjunctiva between the eyeball and semilunaris fold with the bevel directed toward the globe. The needle was then shifted slightly medially, displacing the semilunaris fold and caruncle away from the eyeball. Thereafter, the needle was advanced in an anteroposterior direction, with the globe directed slightly medially by the needle until a ‘click’ was perceived. Thereafter, the globe returned to the primary gaze position. In each group, the local anesthetic solution was injected after a negative aspiration test. Demographic data including age, gender, and weight, along with the duration of surgery were recorded. The onset and duration of sensory and motor blocks were recorded. The patients rated their level of pain during the injection of anesthetics using a verbal analog scale with scores ranging from 0 to 4 (grade 0, no pain; grade 1, mild pain; grade 2, moderate pain; grade 3, severe pain; and grade 4, maximum pain). Furthermore, the hemodynamic parameters (HR and MAP) were recorded before surgery, at 1, 10, and 20 min after injection and after the surgery. Sensory block duration, defined as the time from injection of the local anesthetic mixture to the time of the first analgesic request, was measured and recorded. Similarly, motor block duration, defined as the time from injection of a local anesthetic to complete recovery of motor function in all ocular muscles, was measured and recorded. Then, each patient’s level of sedation was assessed using the inverted observer’s assessment of alertness/sedation scale,[6] with a score of 1 = completely awake, 2 = awake but drowsy, 3 = asleep but responsive to verbal commands, 4 = asleep but responsive to tactile stimulus, 5 = asleep and not responsive to any stimuli.
Sample size calculation
In designing the study, we assumed that the differences in sensory block duration between the dose groups and the SDs would be 25% based on a preliminary pilot study that was conducted on 15 patients (five per group). Setting the alpha to 0.05 and the beta to 20%, we calculated that an appropriate group size would require 20 patients. We planned to include 25 patients per group (n = 75) to allow for potential dropouts or protocol violations. We utilized the GraphPad Stat Mate version 2 statistics program for power analysis.
Statistical analysis
Data were input into the computer and analyzed using the IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). The Kolmogorov- Smirnov test was used to verify the normality of distribution of the variables; Comparisons between groups for categorical variables were conducted using a Chi-square test. ANOVA was used to compare the three studied groups, followed by a post-hoc test (Tukey) for pairwise comparison. The Kruskal Wallis test was used to compare quantitative variables that were not normally distributed of the studied groups, followed by post- hoc test (Dunn’s for multiple comparisons test) for pairwise comparison. The significance of the obtained results were judged at the 5% level.
Results
Ninety patients were evaluated for eligibility. Fifteen patients were excluded (eight did not meeting the inclusion criteria, and seven refused to participate in the study). The remaining 75 patients were enrolled in the study and designated into three groups of 25 patients each, as shown in the study flow chart [Figure 1].
Figure 1.
Study flow chart
The demographic data (age, sex, and weight) and the duration of surgery were comparable in all groups [Table 1]. There was a significant decrease in the onset of sensory block and a significant increase in the duration of sensory block in Group II compared to the other two groups, with an insignificant difference in the onset and duration of motor block in all groups [Table 1]. There was a significant difference between group III and the other groups with regard to pain during subtenon injection. Notably, only two patients experienced pain during subtenon injection in group III compared to 16 and 12 in groups I and II [Table 1]. Meanwhile, heart rate showed a significant decrease in the patients who received IV dexmedetomidine (Group III) compared to the other two groups (P < 0.05). MAP showed a significant reduction in group III compared to the other two groups during the first minute after local anesthesia injection, with a non-significant difference among the studied groups during the remaining times [Table 2]. Intraocular pressure showed a significant decrease in group III compared to groups I and II at 1 min after subtenon injection. There was a significant reduction in groups II and III compared to group I after the surgery but without a significant difference between groups II and III [Table 2]. VAS showed a significant decrease in the patients who received subtenon dexmedetomidine (group II) compared to the other two groups at 2, 4, and 8 hours after surgery [Table 3]. The level of sedation increased in the two groups that received dexmedetomidine (groups II and III). In addition the sedation score in group III significantly increased compared to those of the other two groups, but with an insignificant difference between groups I and II [Table 3].
Table 1.
Comparison between the three studied groups according to different parameters
| Group I (n=25) | Group II (n=25) | Group III (n=25) | Test of Sig. | P | |
|---|---|---|---|---|---|
| Sex M/F | 13/12 | 14/11 | 13/12 | χ2=0.107 | 0.948 |
| Age (years) | 61.9±5.2 | 61±5.4 | 60.7±6.2 | F=0.319 | 0.728 |
| Weight (kg) | 79±7.8 | 82.6±6 | 80.3±8.5 | F=1.447 | 0.242 |
| Duration (min) | 28±4.3 | 28.3±4.4 | 27.5±3.2 | F=0.239 | 0.788 |
| Onset sensory | 2.5 (1.5-3.5) | 1.5a (1-2) | 2.5b (1.5-3.5) | F=30.86* | <0.001* |
| Duration sensory | 111.2±12.8 | 207.8a±22 | 114.2b±8.9 | F=310.84* | <0.001* |
| Onset motor | 4.5 (3.5-5.5) | 4.5 (4 – 5) | 4 (4 – 5.5) | H=4.008 | 0.135 |
| Duration motor | 153.4±6.7 | 159.2a±6.8 | 157±7.2 | F=4.434* | 0.015* |
| Pain on injection | |||||
| Grade 0 | 9 (36%) | 13 (52%) | 23 (92%) | ||
| Grade 1 | 12 (48%) | 11 (44%) | 2 (8%) | ||
| Grade 2 | 3 (12%) | 1 (4%) | 0 (0%) | χ2=19.69* | <0.001* |
| Grade 3 | 1 (4%) | 0 (0%) | 0 (0%) | ||
| Grade 4 | 0 (0%) | 0 (0%) | 0 (0%) |
Group I: Control group, Group II: Subtenon Dexmedetomidine group, and Group III: IV. dexmedetomidine group. Data were expressed as Mean±SD, Median (Min. – Max.) or number of patients (%). χ2: Chi-square test, F: F for ANOVA test, H: H for Kruskal Wallis test. *: Statistically significant at P≤0.05. a: Significant with group I, b: Significant with group II
Table 2.
Comparison between the three studied groups according to HR, MAP, and IOP
| Group I (n=25) | Group II (n=25) | Group III (n=25) | F | P | |
|---|---|---|---|---|---|
| HR | |||||
| 0 | 73.1±7 | 77.4±8.7 | 76.3±7.3 | 2.105 | 0.129 |
| 1 | 76.7±6.9 | 80.6±8.2 | 70.5ab±7.1 | 11.839* | <0.001* |
| 10 | 73.6±6.5 | 74.1±7.3 | 68.7ab±6.5 | 4.847* | 0.011* |
| 20 | 72.5±6.2 | 72.8±6.4 | 65.2ab±8.9 | 8.768* | <0.001* |
| End | 73.9±6.7 | 74.4±5.3 | 69.7ab±6 | 4.688* | 0.012* |
| MAP | |||||
| 0 | 89.9±5.2 | 83.2a±6.5 | 83.3a±9 | 7.396* | 0.001* |
| 1 | 91.1±4.6 | 88.6±9.4 | 80.6ab±7.5 | 13.781* | <0.001* |
| 10 | 88.6±5.1 | 81.6a±5.8 | 78.6a±7.7 | 16.453* | <0.001* |
| 20 | 87.6±5 | 79.2a±5.2 | 76.2a±7.5 | 24.215* | <0.001* |
| End | 86.8±4.7 | 80.5a±5.2 | 76.5ab±6.5 | 22.199* | <0.001* |
| IOP | |||||
| 0 | 15.4±1.2 | 16.5a±1.4 | 16.4a±1.7 | 4.370* | 0.016* |
| 1 | 16.4±1.5 | 17.7a±1.2 | 14.9ab±1.2 | 27.421* | <0.001* |
| End | 15.1±1.1 | 14.4a±0.7 | 14.3a±0.8 | 6.191* | 0.003* |
Group I: Control group, Group II: Subtenon Dexmedetomidine group, and Group III: IV. dexmedetomidine group. Data were expressed as Mean±SD. F: F for ANOVA test. *: Statistically significant at P≤0.05. a: Significant with group I, b: Significant with group II
Table 3.
Comparison between the three studied groups according to VAS and sedation
| Group I (n=25) | Group II (n=25) | Group III (n=25) | H | P | |
|---|---|---|---|---|---|
| VAS | |||||
| 2 | 3 (2-5) | 2a (0-3) | 3b (2-5) | 37.995* | <0.001* |
| 4 | 4 (3-7) | 2a (0-4) | 4b (3-6) | 36.679* | <0.001* |
| 8 | 5 (3-7) | 3a (2-5) | 5b (3-7) | 28.331* | <0.001* |
| 12 | 4 (3-6) | 4 (3-6) | 4 (3-6) | 1.403 | 0.496 |
| Sedation | |||||
| 0 | 1 (1-2) | 1 (1-2) | 1 (1-2) | 0.311 | 0.856 |
| 1 | 1 (1-2) | 1 (1-2) | 2ab (1-3) | 39.014* | <0.001* |
| 10 | 1 (1-2) | 1 (1-2) | 2ab (1-3) | 40.461* | <0.001* |
| 20 | 1 (1-2) | 1 (1-3) | 3ab (2-4) | 44.600* | <0.001* |
| End of surgery | 1 (1-2) | 1 (1-2) | 2ab (1-3) | 19.468* | <0.001* |
Group I: Control group, Group II: Subtenon Dexmedetomidine group, and Group III: IV. dexmedetomidine group. Data were expressed as Median (Min. – Max.). H: H for Kruskal Wallis test. *: Statistically significant at P≤0.05. a: Significant with group I, b: Significant with group II
Discussion
Postoperative pain in patients after cataract surgery is a common phenomenon that ranges from mild to severe, occurs in the early hours after surgery at hospitals and may persist up to 6 weeks after surgery in the form of ocular irritation. Notably, patients undergoing cataract surgery are usually elderly, and most elderly patients have concomitant diseases and use medications. Therefore, the physiological changes and drug interactions related to age and associated comorbidities should be considered in pain management through analgesics in such patients.[7] This bottleneck can be overcome by using non-opioid adjuvants to subtenon block to provide safe postoperative analgesia to these patients.
Alpha-2 adrenergic receptor agonists have sedative, analgesic, and euphoric effects.[8] Dexmedetomidine is a highly selective α2- adrenergic receptor agonist with a relatively high ratio of α 2/α 1 activity.[9] The sedative and supraspinal analgesic effects of dexmedetomidine are mediated by the hyperpolarization of nonadrenergic neurons, which suppress neuronal firing within the locus cereleus alongside the inhibition of norepinephrine release and activity in the descending medullospinal noradrenergic pathway, secondary to the activation of central α2- adrenergic receptor.[10]
The results elicited from the present study showed a significant increase in the duration of sensory block with a shorter time of onset in group II which received subtenon dexmedetomidine, compared with the other two groups of patients who received LA alone or IV dexmedetomidine. The number of patients who suffered from pain during subtenon injection in group III was significantly lesser than those in the other groups. Furthermore, VAS showed a significant decrease in group II, which received subtenon dexmedetomidine, compared to the other groups. More patients were sedated in groups II and III than in group I, with a significant difference between group III and the other two groups. IOP was significantly decreased after the surgery in both groups of patients who received dexmedetomidine, either subtenon or IV. HR was significantly decreased in the group that received IV dexmedetomidine more than the other two groups, with an insignificant difference in MAP between the studied groups.
The value of adding dexmedetomidine to LA in cataract surgery with subtenon block in the current study was supported by a research of Ghali et al.,[11] who reported that a combination of levobupivacaine and dexmedetomidine in subtenon block provides sedation, as well as decreases the onset time of sensory block and extends its duration. The results also agreed with the findings of Eskandr et al.,[12] who studied the efficacy of dexmedetomidine as an adjuvant to subtenon block in cataract surgery and reported shortened sensory block onset, prolonged sensory block duration, increased sedation level, and decreased IOP. Similarly, the results were in agreement with those of Cabral et al.,[13] who studied the effect of clonidine as an adjuvant to subtenon block in cataract surgery. Similar findings were noticed in other studies that added dexmedetomidine to LA in different ocular surgeries with peribulbar block, such as those by Abdelhamid et al.,[1] and Gujral et al.,[14] or with retrobulbar block such as the research conducted by Ye et al.[15]
Furthermore, in the present study, the IV administration of dexmedetomidine during subtenon block decreased the HR, MAP, and IOP. It also, provided a satisfactory level of intraoperative sedation with a lesser number of patients experienced pain on LA injection. These results are compatible with those of Ghali et al.[11] who studied the effect of dexmedetomidine versus propofol for sedation in patients undergoing vitreoretinal surgery under subtenon’s anesthesia. They noticed that dexmedetomidine has adequate control of HR and BP and decreases IOP, in addition to exerting a sedative effect and improving patient satisfaction. The same results were found by Yoo et al.,[16] who examined the effect of dexmedetomidine sedation on patient and surgeon satisfaction during retinal surgery under subtenon’s anesthesia.
An appropriate sedative effect of dexmedetomidine may lower the IOP and pain on injection. The mechanism of action of dexmedetomidine involves the activation of the receptors in the brain, and the spinal cord inhibits neuronal firing by presynaptic activation of the α-2 adrenoceptor, which inhibits the release of norepinephrine and terminates pain signals transmission. The postsynaptic activation of α-2 adrenoceptors in the central nervous system inhibits sympathetic activity and decreases BP and HR. These effects can produce analgesia and sedation.[1,17]
The effect of dexmedetomidine on the IOP may be due to a reduction of aqueous humor formation through its direct vasoconstrictor effect on the afferent blood vessels of the ciliary body. It may also facilitate the drainage of aqueous humor by reducing the sympathetically mediated vasomotor tone of the ocular drainage system. Finally, the hemodynamic effects of dexmedetomidine may be responsible for the reduction of IOP.[18-20]
A limitation of this study is that it was performed in a single center with a small sample size.
Conclusion
Dexmedetomidine is an effective adjuvant to bupivacaine in subtenon anesthesia with more favorable effects, such as shortened sensory onset time, prolonged sensory block duration, and hemodynamic stability, compared with the IV administration of dexmedetomidine during subtenon block. However, IV dexmedetomidine decreases pain during LA injection and provides a satisfactory level of intraoperative sedation. Future studies focusing on a combination of both subtenon and IV dexmedetomidine to elicit benefits from their concomitant administration are highly recommended.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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