Postoperative Analgesic Efficacy of Sub-Tenon's Block with Levobupivacaine in Retinal Surgery under General Anesthesia.

BACKGROUND: Vitreoretinal surgery is associated with undesirable intraoperative and postoperative complications including pain, postoperative nausea and vomiting, and oculocardiac reflex (OCR). Systemic analgesics have side effects and are contraindicated in some cases. We hypothesized that the preoperative sub-Tenon's injection of levobupivacaine with general anesthesia would decrease postoperative pain and intraocular pressure as well as the incidence of complication.
METHODS: Eighty patients who were presented for vitreoretinal surgery, aged 30-60 years, were enrolled in the study. General anesthesia was administrated to all patients; then, they were randomized into two equal groups (40 each) - Group I: patients received 5 mL placebo solution for sub-Tenon's block and Group II: patients received 4 mL levobupivacaine 0.5% in 1 mL saline for sub-Tenon's block. Postoperative pain was evaluated using a verbal pain scale. Surgeon satisfaction, postoperative analgesic consumption, and perioperative hemodynamics were also reported.
RESULTS: Verbal rating pain scores were significantly lower at the first 6 h postoperative in Group II (sub-Tenon's levobupivacaine) compared to Group I (sub-Tenon's placebo). First analgesic rescue time and total dose of analgesic consumption were significantly reduced in Group II compared to Group I. There was a lower incidence of OCR with sub-Tenon's levobupivacaine (Group II), also surgeon satisfaction was significantly superior in the same group.
CONCLUSION: The combination of general anesthesia with sub-Tenon's block using levobupivacaine in retinal surgery patients reduces pain scores after surgery; total analgesia requirement also decreases the incidence of OCR. Copyright:

INTRODUCTION

Vitreoretinal surgery is mostly associated with a high incidence of postoperative complications including pain and hemodynamic changes attributed to the oculocardiac reflex (OCR) during ocular manipulation.

Vitreoretinal surgery is usually performed under general anesthesia rather than regional block. The preference of general anesthesia is because of lack of adequate akinesia and patient discomfort with prolonged surgery performed under the regional block.[1]

Pain may be due to the traction on the ocular muscles and sclera. Increased intraocular pressure (IOP) due to expansion of the gas bubble or tight buckling is another explanation of postoperative pain.[2]

Moreover, traction on ocular muscles during vitreoretinal surgeries evokes OCR causing arrhythmias, extrasystole, ventricular fibrillation, or asystole. These events could be dramatically serious, especially in fragile patients with other medical comorbidities.[3]

Numerous studies showed that sub-Tenon's irrigation with local anesthetic in retinal detachment cases under general anesthesia is superior to general anesthesia alone in relieving postoperative pain. Sub-Tenon's block is suitable for most of ophthalmic operations and had long-term postoperative pain management effect.[4]

The most common drug used in sub-Tenon's block is bupivacaine. However, the evident noxious effects of bupivacaine on the central nervous system and the cardiovascular system were the main reasons for the development of different local anesthetics as ropivacaine and levobupivacaine.[5] Levobupivacaine is the isolated stereoisomer of the racemic mixture bupivacaine and is also a long-acting amino-amide local anesthetic drug that has proved to be significantly less toxic than bupivacaine.[6]

In this study, we hypothesized that the sub-Tenon's injection of levobupivacaine as an analgesic in combination with general anesthesia may decrease the incidence of postoperative pain and postoperative analgesic consumption with minimal effect on patient hemodynamics.

METHODS

After approval of the Institutional Research Board of Anesthesia Department, Faculty of Medicine, Mansoura University(R1908574), informed written consent was obtained from all patients before inclusion in this study. This prospective, randomized, double-blind study was carried out in Ophthalmology Center, Mansoura University, in the period between May 2017 and December 2018. Randomization was carried out through sealed opaque envelops to avoid bias.

Inclusion criteria

A total number of 80 patients of either sex, aged 30–60 years old, and belonged to the American Society of Anesthesiologists (ASA) physical status Class I and II who were listed to elective vitreoretinal surgery were included in the study.

Exclusion criteria

Patients with bleeding disorders, deafness, endophthalmitis, contraindications to sub-Tenon's block as patient refusal, history of sensitivity to local anesthetic, or infection at the site of injection were excluded from the study.

Sample size calculation

The power of this study was calculated using G*Power analysis (program version 3: Faul F., Erdfelder E., LangAG2007, Universitat Dusseldorf). Assuming alpha (Type I error) = 0.05 and beta (Type II error) = 0.2, (power = 80%) 36 patients were required in each group to detect a difference of 30% between the two groups. Hence, we added four patients in each group to be forty patients for the possibility of any missing data.

Preoperative preparation

Routine investigations were done in the form of complete blood count, serum creatinine, random blood glucose, and electrocardiogram (ECG).

On the night of the surgery, oral premedication was administrated in the form of 3 mg bromazepam tablets (calmepam 3 mg, GlaxoSmithKline ). Fasting strategy of our institute ensures 8 h fasting for patients scheduled for surgery.

In the anesthetic room, an intravenous (i.v.) line was secured for i.v. administration of fluids and drugs.

Basic monitoring was applied in the form of 3-lead ECG, pulse oximetry, capnography, and noninvasive blood pressure using Datex-Ohmeda Cardiocap II (Helsinki, Finland) monitoring system, and the basal values were recorded.

Patients were preoxygenated for 3 min, and induction of anesthesia was done with fentanyl (1 μg.kg) and propofol (2 mg.kg-1). Atracurium (0.5 mg.kg-1) was used to facilitate endotracheal intubation, and controlled mechanical ventilation was applied to maintain end-tidal CO2 around 35 mmHg. Anesthesia was maintained within sevoflurane (2%) and top-up doses of atracurium (20%) of the intubating dose; patients were infused with i.v. normal saline solution (5–6 mg.kg-1.h-1) intraoperative.

Patients were randomly allocated into two equal groups:

Group (I) – Forty patients received sub-Tenon's block with placebo solution (5 mL saline) following general anesthesia.

Group (II)– Forty patients received sub-Tenon's block with levobupivacaine (4 mL) 0.5% in 1 mL normal saline following general anesthesia.

Sub-Tenon's block was given to the patients under vision with the microscope. The anesthesiologist and surgeon were blind to the nature of the injected solution. A Lieberman lid speculum was placed, and the conjunctiva was sterilized with 4% povidone-iodine. An opening in the conjunctiva and Tenon's fascia in the inferonasal part of the eye was done using blunted tip Westcott scissors to bare the superficial part of the sclera prior to making a posterior tunnel using curved Stevens scissors to create a slight passage in the sub-Tenon's space. A blunted tip sub-Tenon's cannula was introduced into the sub-Tenon's space, and the studied drug was introduced slowly into the space. Surgery was started 5 min after the sub-Tenon's injection.

During the surgery, any decrease in heart rate (HR) >25% from the baseline value was considered to be an OCR and the surgeon requested to discontinue any stimuli if this discontinuation was insufficient or HR was <50 beats/min; i.v. atropine at a dose of 0.01 mg.kg-1 was given. If hypotension occurred (mean arterial pressure [MAP]: <25% from the baseline), i.v. 200 mL normal saline bolus was given; but if this was insufficient or MAP was <60 mmHg, i.v. ephedrine at a dose 5 mg was administered. Hypertension or tachycardia (MAP and HR more than 25% from the baseline) was treated by i.v. propranolol boluses at a dose of 0.5 mg.

At the end of the operation, reversal of the neuromuscular block was done using neostigmine at a dose of 0.04 mg.kg-1 and atropine at a dose of 0.02 mg.kg-1. Extubation was performed after the appearance of satisfactory spontaneous breathing and the patients fulfilled all the criteria of the extubation; extubation was done and 100% oxygen was given through a face mask. Subsequently, patients were transferred to the post-anesthesia care units (PACUs) to be observed for 2 h and then were transferred to the ward where they were observed for 24 h.

These data were collected:

The intensity of pain using 10-point verbal rating scale (VRS) with 0 = no pain and 10 = the most terrible pain; it was recorded on arrival to PACU, 1 h, 2 h, 6 h, 12 h, and 24 h following surgery

IOP was measured using Schiotz tonometer basal, after endotracheal insertion, after sub-Tenon's block, then at the end of surgery

The time of the first demand for analgesia and the total analgesic consumption were documented in the first 24 h following surgery. Postoperative analgesic used was diclofenac which was given if VRS was ≥4 or on patient's demand. It was given i.v. at a dose 37.5 mg over 15 s with the maximum dose of 150 mg/day

Surgeon satisfaction was assessed using 3-point scale: 0 (not satisfied), 1 (moderately satisfied), and 2 (satisfied).

Statistical analysis

The recorded values were coded, processed, and examined by the SPSS program version 22 for Windows (IBM corporation, Armonk, NY, USA). Normal numerical values’ distribution was processed by the Kolmogorov–Smirnov test. Normal distribution of the data was expressed as mean and standard deviation and was matched in variable groups with one-way ANOVA using post hoc Bonferroni test, and in the similar group, using repeated-measures ANOVA with post hoc Dunnett's test. Nonnormal distribution of the data was expressed as median and range and was compared nonparametrically using Kruskal–Wallis test, then by Mann–Whitney U-test. Categorical data were expressed as numbers and percentage and were matched by the Chi-square test. All values were statistically significant if P ≤ 0.05.

RESULTS

There were no significant differences between the studied groups as regards patients’ demographic data (age, gender, body mass index, and ASA physical status) duration of operation, and anesthesia [Table 1].

Table 1

Patients demographic data (age, gender, and body mass index), duration of surgery, and duration of anesthesia (minutes) of the studied groups

	Group I (n=40)	Group II (n=40)	P
Age (years)	53.4±10.6	54.4±9.4	0.81
Gender (male/female)	29/11	27/13	0.26
BMI (kg/m2)	27.7±4.6	26.5±3.7	0.71
ASA (I/II)	23/17	18/22	0.49
Anesthesia duration (min)	75.7±22.6	78.5±16.2	0.6
Surgery duration (min)	63.8±21.9	66.1±17.3	0.68

Data are expressed as mean±SD. Gender and ASA data expressed as numbers. BMI=Body mass index, ASA=American society of anesthesiologist, SD=Standard deviation

VRS at 1, 2, and 6 h was significantly lower in Group II (levobupivacaine group) after surgery compared to Group I (placebo group) (P = 0.01, 0.001, and 0.008, respectively) as shown in Table 2.

Table 2

Pain score in the postoperative period by verbal rating scale

Time	Group I (n=40)	Group II (n=40)	P
Arrival to PACU	1 (0-3)	1 (0-2)	0.20
1 h	2 (0-4)	1 (0-2)*	0.01
2 h	3 (1-5)	2 (1-3)*	0.001
6 h	4 (1-6)	3 (2-4)*	0.008
12 h	3 (2-6)	3 (2-4)	0.28
24 h	2 (2-4)	2 (1-4)	0.85

Data are expressed as median (range). *Significant Group II compared with Group I. P<0.05 is significant. PACU=Post anesthesia care unit

The results showed statistically significant attenuation in IOP values in Group II (levobupivacaine group) relative to Group I (placebo group) after intubation and at the end of the surgery (P = 0.001, and 0.01, respectively). Compared to basal value, significant decrease in IOP was noticed in both the groups after the intubation, while at the end of surgery, the decrease was in Group II only [Table 3].

Table 3

Intraocular pressure changes in the perioperative period in the studied groups

Time	Group I (n=40)	Group II (n=40)	P
Basal	15.1±2.4	15.2±2.5	0.55
Before induction	15.1±2.4	14.8±1.9	0.1
After intubation	14.8±3.5#	13±2.2*,#	0.001
End of surgery	15.9±2.5	11.7±1.9*,#	0.01

Data are expressed as mean±SD. *Significant Group (II) compared with Group (I), #Significant compared with the baseline. P<0.05 is significant. SD=Standard deviation

Table 4 shows statistically significant delay in the time of first analgesic requirement in Group II (235.1 ± 81.8) compared to Group I (154.2 ± 82.9) with P = 0.001, the total analgesic requirement showed statistical significant decrease in Group II (71.3 ± 26.3) compared to Group I (94.4 ± 31.8) (P = 0.03), and the incidence of OCR was less in Group II compared to Group I but not statistically significant. However, Group II showed better surgeon satisfaction compared to Group I (P = 0.01).

Table 4

First analgesic time (minutes), total analgesic requirements (mg), incidence of oculocardiac reflex (number and %), and surgeon satisfaction

	Group I (n=40)	Group II (n=40)	P
First analgesic time (min)	154.2±82.9	235.1±81.8*	0.001
Total analgesic requirement (mg)	94.4±31.8	71.3±26.3*	0.03
Incidence of OCR, n (%)	6 (15)	3 (7.5)	0.58
Surgeon satisfaction (0/1/2), n (%)	9 (22.5)/5 (12.5)/26 (65)	2 (5)/3 (7.5)/35 (37.5)*	0.01

Data expressed as mean±SD, number and percentage. *Significant Group (II) compared with Group (I), Surgeon satisfaction=0 (not satisfied), 1 (moderately satisfied), 2 (satisfied). P<0.05 is significant. SD=Standard deviation, OCR=Oculocardiac reflex

DISCUSSION

In this prospective study, the results showed that sub-Tenon's block using levobupivacaine in addition to general anesthesia is safe and efficient for perioperative analgesia for patients who had vitreoretinal surgery. The first postoperative analgesic rescue time was significantly prolonged when sub-Tenon's block was done with levobupivacaine. Moreover, sub-Tenon's levobupivacaine leads to the decreased requisite of postoperative analgesics, decreased incidence of OCR, and better surgeon satisfaction. These findings are similar to that of Abouammoh et al.[7] who reported that the combination of sub-Tenon's block and general anesthesia reduced postoperative analgesic requirements and complications.

Parallel to the results of this study, Farmery et al.[8] found that sub-Tenon's block with bupivacaine in addition to general anesthesia leads to a significant decrease in perioperative opioid utilization and improved pain scores and nausea in the first 12 h postoperatively after vitreoretinal surgery.

The result of sub-Tenon's block was prominent in the first 6 h postoperative; this may be due to that the sub-Tenon's block cut down the afferent stimulus resulted from traction on the muscles, which prevent the central neural excitability by injurious stimuli that enhance pain.

Contrary to the result of the current study, Mason et al.[9] found that injection of sub-Tenon's space with local anesthetic drug prior to vitrectomy in generally anesthetized patients did not reduce postoperative pain or analgesic requirement. Furthermore, Ramachandran et al.[10] have shown that sub-Tenon's block following general anesthesia did not reduce the incidence of postoperative pain after squint surgery in pediatric compared to IV fentanyl although there was a lower incidence of OCR and postoperative nausea and vomiting up to 2 h, but this may be due to the presence of emergence delirium that occurs with sevoflurane anesthesia and the use of Children's Hospital of Eastern Ontario Pain Scale which may not be capable of differentiation between emergence delirium and postoperative pain; this discrepancy in the results may be attributed to the use of another local anesthetic in different types of surgery.

In the current study, sub-Tenon's levobupivacaine in combination with general anesthesia was accompanied with better surgeon satisfaction in vitreoretinal surgery, this is in agreement with Aksu et al.[6] who reported similar results when they injected 0.5% levobupivacaine retrobulbar in vitreoretinal operation. In a study that compared 0.75% levopubivacaine with 4% lidocaine as topical anesthesia in cataract operation, they found more patient and surgeon satisfaction in the levobupivacaine group, which is similar to our finding.[11]

The IOP in the present study was lower in Group II compared to Group I and to the basal values after intubation and sub-Tenon's block; also at the end of the surgery, this may be due to the potentiation of the effect of general anesthesia with the local anesthetic used in sub-Tenon's block. Similar finding was reported by Pacella et al.,[12] who noticed lower IOP after peribulbar block with bupivacaine and hyaluronidase enzyme.

In the present study, no serious complications were reported with sub-Tenon's block as it was done under vision and by expertise ophthalmologist which enhance the safety of the block, these were in agreement with Mahfouz and Nabawi.[13] As regards intraoperative OCR incidence, it was decreased in sub-Tenon's levobupivacaine group (Group II) that may be due to the block of the afferent of the reflex arc. Chhabra et al.[14] reported similar results of decreased OCR incidence in sub-Tenon's block in vitreoretinal surgery for pediatric patients.

CONCLUSION

The present study showed that a combination of general anesthesia and sub-Tenon's block with levobupivacaine in adult vitreoretinal surgery resulted in better postoperative analgesia and prolonged the time to first rescue analgesia. It also decreases OCR analgesic consumption which is beneficial for the elderly and outpatient surgery.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.