Introduction
Regional anesthesia blocks are commonly used for ophthalmic surgery because of its safety, ease, and less invasiveness. They are inexpensive and provide efficient ocular anesthesia for most ophthalmic surgeries. These blocks are associated with lesser complications such as hemodynamic instability, respiratory depression, postoperative pain, and nausea/vomiting than general anesthesia.[1 2 3
To enhance the onset, duration and efficacy of local anesthetics, various adjuvants are being used with local anesthetics. The most commonly used adjuvants are opioids,[4 5 6 7 8 9 10 11
In 1992, Stevens described the technique of subtenon anesthesia, passing a blunt cannula into the sub-Tenon space. Local anesthetic is injected at this site, which distributes into the subtenon space and subsequently diffuses into the retrobulbar area and surrounding tissues.[12 13 14
Ever since the study of magnesium sulfate in clinical anesthesia began in 1996, it has drawn attention in the field of anesthesia and pain medicine.[15 16 2
Magnesium sulfate has been investigated as adjuvant with local anesthetics in a variety of regional blockages and routes of administration[17
It has also been used in ophthalmic peribulbar anesthesia and found to reduce the time to the onset of action, prolonged duration, and improved quality of block. It is a safe drug, and most studies showed no side effects with its use at the single dose of 50 mg.[2 4 6 18
The aim of this study was to evaluate the efficacy and safety of the addition of 50 mg of magnesium sulfate as an adjuvant to the local anesthetic mixture using subtenon block for phacoemulsification cataract surgery with intraocular lens implant. In addition, we looked for the possible complications and satisfaction of patient's and surgeon's.
Material and Methods
It was a prospective, randomized, double-blind, controlled trial of patients scheduled to undergo phacoemulsification cataract surgery with intraocular lens implant. Institution Ethical committee approved this study (# 2013 P) on February 4, 2020. A total of 200 patients operated between February and April, 2021 were our study population. Written informed consents were obtained from all participants after explaining the research protocol. Participation of all patients in this study was voluntary.
To calculate the sample size, we assumed that analgesic and akinetic effect 10 minutes after the injection will be present in 80% of the subjects in the control group while it will be 95% in the study group using MgSO4 as adjuvant to the local anesthetic mixture.[2 19
A clinical pharmacist was consulted regarding the feasibility, safety, and possible side effects of the added magnesium sulfate to the local anesthetic mixture. Patients of both genders, aged 40–80 years and American Society of Anesthesiologists (ASA) status ranging from grade I (a normal healthy patient) to grade III (patient with moderate systemic involvement) were included in the study. Patients with any contraindication to the sub-Tenon block, for instance degenerative diseases of the central nervous system, severe hearing loss, previous surgery in the same eye, one-eyed patients or any other pathology such as hyper mature cataract, synechia, or need for unusual manipulation of pupil in the target eye were excluded. Similarly, patients having known allergy to any of the constituent drugs of the anesthetic mixture were also excluded from the study.
All patients were kept fasting for 6 hours and premedicated with 1 gram of paracetamol orally 1 hour before surgery. Standard noninvasive monitoring was applied to all patients in the holding area before and during the ophthalmic block, including an electrocardiogram, pulse oximeter and a noninvasive blood pressure recording. A 22-gauge intravenous cannula was inserted into all patients at the dorsum of right hand.
All patients received the standard mixture of 3 ml of 0.5% bupivacaine +2 ml of 2% lidocaine +25 IU hyaluronidase in every 5 ml of the solution. Patients were randomized into two groups: Group magnesium sulfate (MS) received 50 mg/0.5 ml of magnesium sulfate and Group normal saline (NS) received 0.5 ml of normal saline added to the standard mixture, respectively. One senior recovery room nurse prepared the solution, assigned a code for the type of solution using simple randomization and delivered it to the anesthesiologist in a blind manner without a label. She kept a record of the codes used for each type of solution given to the patient and filled it out in the assigned sheet. The anesthesiologist who injected the medication did not know about the content of the mixture or the group assignment of the patients.
Before performing the block, 1–2 drops of 0.4% oxibuprocaine were instilled for topical anesthesia every minute for 3 minutes. This was followed by a drop of Iodine 5% solution for disinfection.
After 5 minutes, the eyelid speculum was placed. The conjunctiva was raised with Thorpe forceps in the inferonasal quadrant, midway between the insertions of the medial and inferior rectus muscles, at about 5 mm from the corneal limbus and a micro incision was made with Westcott scissors. The incision was dissected deeper about 3–5 mm with the tip of the scissors and a blunt metallic 19-gauge curved needle (Steven's needle) was advanced according to the contour of the globe to enter the subtenon's capsule. Anesthetic mixture was slowly injected. The speed of injection was further slowed down if marked proptosis was observed quickly to avoid a speedy rise in the intraocular pressure. The cannula was withdrawn after the injection in the same pattern. Gentle external compression was applied for about 2 minutes to achieve a better distribution of the local anesthetic after the block without using a Honan balloon.
The eye opening score was assessed at 2, 5, and 10 minutes by an independent observer after the block using a 3 points scoring system: 0 = unable to open the eye, 1 = partial opening the eye, and 2 = full ability to open the eye. Similarly, globe akinesia score was also assessed at 2, 5, and 10 minutes after the block in the four quadrants using a similar three point scoring system: 0 = complete akinesia, 1 = partial akinesia, and 2 = normal movement (no akinesia), giving a maximal score of 8 for the four directions (superior, inferior, medial, and lateral). A total akinesia score of 0–1 was taken as a successful block. In case of an inadequate motor blockade by 5 minutes, a supplementary injection was given through the same track using 3 ml of the standard anesthetic mixture.
A single experienced anesthesiologist performed all the blocks, and two coresearchers recorded the data in a predesigned data collection sheet. The anesthesiologist, surgeon, patient and the data collectors were all blind to the contents of the mixture used.
The start time of surgery was recorded when the first incision was made. The protocol included giving intraoperative sedation with midazolam 0.5–2 mg and/or analgesia with Fentanyl 10–30 mg I/V if needed. Similarly, topical drops of 0.4% oxybuprocaine would have also been given if the patient would complain of pain in the eye. The surgery was considered finished as soon as the eyelid speculum was removed. Postoperative analgesia was assessed by using Visual Analogue Score (VAS) as 0 (no pain) to 10 (maximum pain imaginable) at the end of the surgery and then every hour for 4 hours. If the VAS would be 4 or more, oral paracetamol one gram would be given to the patient. The most common adverse effects such as subconjunctival hemorrhage, chemosis, nausea, vomiting, bradycardia, and hypotension were recorded. Surgeon's and patient's satisfaction was asked and scored at the end of surgery using a scale of 0–10, where 0 meant total dissatisfaction while 10 meant total satisfaction. Patients were discharged home 4 hours after surgery if there was no other indication to keep them in hospital.
Statistical analysis
Data were entered using Microsoft Access 2010 (Microsoft Corporation, Redmond, Washington) and analyzed using STATA 17.0 (Stata Corp LLC, College Station, TX, USA). Categorical data were presented as counts and percentages while continuous data were presented as means with standard deviation or medians with interquartile range (IQR). Proportions were compared using the Chi-squared test or exact test. Continuous data were compared using Student's t -test or Mann–Whitney U-test, as appropriate. We used generalized estimating equations (GEEs) to compare eye opening (yes/no) between the MS and NS groups over time.
Odds ratios with 95% CIs were calculated. Three models were developed: Model 1 included type of anesthesia and time as covariants, Model 2 included these two covariants as well as their interaction terms while in Model 3 the odds ratios for the type of anesthesia and time were adjusted for age and sex. A P value of less than 0.05 was considered statistically significant.
Results
A total of 200 who patients randomly received either magnesium sulfate (50 mg/0.5 ml) or normal saline (0.5 ml) as an adjuvant to the standard local anesthetic mixture, were included in the analyses: 98 patients in the MS Group and 102 in the NS Group. The duration of surgery was comparable between the two groups as an average of 43 versus 39 minutes (P = 0.09). The mean ages in the two groups were similar: 62.65 ± 8.11 years in the MS Group and 62.93 ± 7.60 years in the NS Group (P = 0.802). There was a significantly higher proportion of women in the MS Group than in the NS Group (58.2% vs. 41.2%, [P = 0.016]). The side of the eye blocked (right or left) was comparable between the two groups (P = 0.255). There was no difference in the ASA physical score distribution in the two arms (P = 0.820) with approximately two-thirds of the patients in either group falling in the ASA II category [Table 1 ].
Table 1: Profile of cataract patients operated with and without magnesium sulfate as adjunct to the standard anesthetic solution
Figures 1 and 2 summarize the effect of local anesthesia on eye-opening and movement of the globe (globe akinesia) over the time. The proportion of those achieving “No eye-opening” or “No movement of the globe” increased with time. However, the effect was not statistically different across the two groups.
Figure 1: Comparison of eye opening score in patients operated for cataract using subtenon anesthesia with and without magnesium sulfate. X -axis denotes percentage of patients. Y -axis denotes time of assessment
Figure 2: Comparison of the globe akinesia score at different time in patients operated for cataract using subtenon anesthesia with and without magnesium sulfate in four directions of gaze. X -axis denotes percentage of patients. Y -axis denotes time of assessment
In the age and sex adjusted GEE analysis, there was no significant difference in “eye opening score” between MS and NS Groups (adjusted odds ratio, 0.90), but the likelihood of “no eye opening” significantly increased with time (adjusted odds ratio, 1.26 P < 0.001) [Table 2 ].
Table 2: Estimates of effects of anesthesia type on eye opening over time, obtained using generalized estimating equations (GEE)
Chemosis and conjunctival bleeding were the main complications seen in both groups [Table 3 ]. Although chemosis alone was not significantly different across the groups, a significant proportion of conjunctival hemorrhage was seen in the MS Group in comparison to the NS Group (36 of 98 [36.7%] vs. 11 of 102 [10.8%], P < 0.001). Similarly, chemosis combined with subconjunctival hemorrhage was also higher in the MS Group (55 of 98 [56.1%] vs. 39 of 102 [38.2%], P < 0.011) which was statistically significant. Transient bradycardia was seen in only one participant in the MS Group.
Table 3: Adverse events and satisfaction scores in the two anesthesia groups
Few patients (6 vs. 8) needed supplementary anesthesia in MS and NS Group, respectively. They were given 3 ml of the standard mixture of local anesthetic without any adjuvant and no statistically significant difference was found between the groups with regards to the need for supplement (P = 0.65). One patient in MS versus five patients in NS Group needed intraoperative sedation using Midazolam iv 0.5–2 mg but it was also not statistically significant (P = 0.13). None of the patients in either group required intravenous analgesia using Fentanyl as per protocol. Eight versus seven patients in group MS and NS respectively needed additional topical drops (0.4% oxybuprocaine) without any statistically significant difference (P = 0.74). None of the patients required suturing of the conjunctival cut made for sub-Tenon cannula insertion.
Postoperatively, none of the patients needed further topical or intravenous analgesia when evaluated at 1 minute, 1 hour and 2 hours after the surgery. Oral paracetamol 1 g was given to 7 versus 5 patients in MS and NS Groups respectively for mild discomfort in the operated eye. The overall patient's satisfaction score was very good (9 of 10) in either group but statistically slightly less in MS than NS Group (P = 0.00), however, the surgeon's satisfaction score in both groups was not statistically different (median 9 vs. 10 [P = 0.149]).
Discussion
In ophthalmic-regional anesthesia, most of the clinical studies evaluated magnesium sulfate as adjuvant to the local anesthetics comparing with other agents in peribulbar block as standard procedure for cataract surgery.[2 4 6 18
The eye lid dropping (ptosis) and akinesia of the eye globe were considered as a quality of effective anesthesia. The effect on the eye opening after the ophthalmic block is usually the first signs to observe. Impaired eye opening reflects the effectiveness of local anesthetic on the levater palpebrae muscle that is responsible for raising up the upper eye lid. Total upper eyelid drop is considered as an endpoint marker of peribulbar anesthesia.[20
About 50% of our patients were unable to open their eye (score zero) while 90% were either completely or partially unable to open their eye by 2 minutes after the block. This percentage increased to >75% for “no eye opening” and >98% for “complete or partial eye opening” by 5 minutes. Further improvement after 5 minutes of the block was very little. There was no statistically significant difference between the two groups in the eye opening score at 2, 5, and 10 minutes after the block.
We found a similar trend in terms of the effect of block on the ocular muscles regarding the onset and degree of akinesia of the globe between the two groups. We saw a relatively faster and denser effect of the anesthetic on superior, inferior and medial rectus muscles (>74% patients) in the first two minutes but the lateral rectus muscle was blocked in less than 63% of patients in the same period of time in both groups. The effect on lateral rectus muscle reached to a comparable level as the other extraocular muscles by 5 minutes and there was no more difference in the akinesia score subsequently. A possible explanation for the relatively delayed effect on the lateral rectus muscle could be the site of injection as we approached the Tenon's capsule through the infero-medial aspect that is closer to the superior, inferior, and medial ocular muscles. In addition, these muscle are supplied by a single nerve (oculomotor nerve). In contrast, the lateral rectus muscle not only falls relatively away from the injection site but is supplied by a different nerve (abducens nerve) and may take relatively longer time to be blocked. The degree of globe akinesia was closely comparable and there was no statistically significant difference across the two groups.
In general, we found that five minutes is a reasonable time to look for the appropriate effect of the block as we observed the maximum effect of the anesthetic in the first 5 minutes and very few patients had further improvement in the block quality beyond this time.
To distribute the anesthetic well around the globe, peribulbar block requires a higher volume of the anesthetic mixture (average 10 ml in our center) that is injected directly into the proximity of the surrounding tissues of the globe which may lead to the immediate uptake of the anesthetic by the nerves and muscles. Many peribulbar blocks requires a supplementary injection from the opposite quadrant as well. The requirement for the supplement may vary between 2% and 44%, depending on the length of the needle.[21
On the other hand, a sub-Tenon block require relatively smaller volume of 3–5 ml.[22
Mogahed et al. [23
Chemosis and localized hemorrhage at the injection site were the most common complications in our study with the overall occurrence of 35.5% and 23.5%, respectively. The reported incidence of chemosis and hemorrhage is 32%–76% and 20%–56% respectively, which varies with the type and length of the subtenon's cannula used.[24 P = 0.591).
The incidence of hemorrhage in our study was comparable (23.5%) to the reported incidence but it was significantly higher in the MS Group than the NS Group (P = 0.001). Magnesium sulfate is well known to prolong bleeding time and cause vasodilation in human studies.[25 26 2 formation which is not only a potent platelet aggregator but a powerful vasoconstrictor as well. Its inhibition may lead to a higher tendency of bleeding.[27
Some other adverse effects of neuraxial use of magnesium sulfate have been reported in isolated cases at higher doses, for instance, bradycardia, hypotension, sedation, headache, disorientation, or periumbilical burning pain.[28 29 30
Our overall patient's satisfaction score was although very good (9/10) in either group but statistically slightly lower in the MS than NS Group (P = 0.001). We mentioned earlier that MS group had a significantly higher incidence of subconjunctival hemorrhage than NS Group. We do not apply any cotton gauze but rather use a transparent shield to cover the eye after the surgery. We believe that a postoperative red eye seen in the mirror may have contributed to the dissatisfaction of some patients.
Surgeon's satisfaction score, on the other hand was very good (9/10) and statistically comparable in both groups (P = 0.149). Few surgeons expressed a little concern over the relatively longer time taken to perform the block that caused a delay while others were unhappy about the localized conjunctival bleeding at the injection site that affected the visual field during surgery.
Conclusion
The dose of 50 mg of magnesium sulfate added to the standard mixture of local anesthetic in sub-Tenon block for cataract surgery does not improve the onset of action, prolong the duration, or the quality of block.
Magnesium sulfate seems to be a safe drug that does not cause any serious complication beside chemosis and mild conjunctival bleeding that happens during the performance of the block. The block is well tolerated with a high satisfaction level among the patients and surgeons.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
Dr Abdul Zahoor and Dr Ingrid Font contributed equally to the work and should be considered co-first authors”. Mr. Arman Zahoor medical student AlFaisal University Riyadh for his role in the data collection and entry. Dr. Syed Khabir Ahmad Chief of Ophthalmic Epidemiology for their role in the statistical analysis.
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