|Year : 2000 | Volume
| Issue : 4 | Page : 285-9
Sodium bicarbonate - An alternative to hyaluronidase in ocular anaesthesia for cataract surgery
M Srinivasan, M Vamshidhar, R Gopal, Banushree
Aravind Eye Hospital & Postgraduate Institute of Ophthalmology, 1, Anna Nagar, Madurai-625 020, India
Aravind Eye Hospital & Postgraduate Institute of Ophthalmology, 1, Anna Nagar, Madurai-625 020
Source of Support: None, Conflict of Interest: None
Keywords: Adult, Aged, Anesthesia, Local, methods, Anesthetics, Local, administration & dosage, Cataract Extraction, Comparative Study, Double-Blind Method, Drug Combi
|How to cite this article:|
Srinivasan M, Vamshidhar M, Gopal R, Banushree. Sodium bicarbonate - An alternative to hyaluronidase in ocular anaesthesia for cataract surgery. Indian J Ophthalmol 2000;48:285
The goals of safe and effective anaesthetic preparation for intraocular surgery are to obtain adequate anaesthesia and akinesia without complications including a significant rise in intraocular pressure (IOP). Traditionally the anaesthetic solution uses a mixture of 30 ml of 2% lidocaine with a 1:200,000 dilution of epinephrine and 450 units (15U / ml) hyaluronidase. Hyaluronidase is an enzyme which catalyzes the depolymerisation of hyaluronic acid to a tetrasaccharide. It improves the efficacy of the local anaesthetic by breaking down interstitial cell barriers, thereby facilitating diffusion of the anaesthetic solution.
Galindo et al reported that by altering the pH of the local anaesthetic solution with sodium bicarbonate, in a 1:10 mixture with lidocaine or bupivicaine, the time of onset and the spread of neural blockade could be enhanced significantly. Buffering is both simple and inexpensive. The objective of this prospective study was to determine the efficacy and safety of sodium bicarbonate buffered local anaesthetic as an alternative to hyaluronidase-mixed local anaesthetic to achieve complete ocular akinesia and anaesthesia in cataract surgery.
| Materials and Methods|| |
The study was conducted in two parts. In Part I, we evaluated the safety and efficacy of sodium bicarbonate buffered lidocaine mixture in patients scheduled for cataract surgery. In Part II, we compared the efficacy of sodium bicarbonate buffered lidocaine and hyaluronidase-mixed lidocaine.
| Part I|| |
One hundred and twelve consecutive patients [53 (42.6%) males and 59 (47.3%) females] electively undergoing cataract extractions with intraocular lens (IOL) implantation over a period of three months from October to December 1998 entered into the study. All patients were recruited with informed consent, and the study was approved by the institute ethics committee. The exclusion criteria were; (a) patients on preoperative sedatives, analgesics or anxiolytics; (b) patients with profound cognitive impairments who would be unable to understand the grading for pain or give informed consent; and (c) patients with documented allergies to lidocaine or hyaluronidase.
Two mixtures of local anaesthetic were prepared; the first contained 30 ml of 2% lidocaine with 1:200,000 epinephrine and 1 ml of 7.5% sodium bicarbonate (0.299mmol/ml). The pH of this mixture was 7.2. A similar mixture without epinephrine was administered to patients with a history of hypertension or ischaemic heart disease. After explaining the procedure of retrobulbar anaesthesia, the patient was placed in a supine position on a couch and asked to fixate in primary position. A 22G, 40 mm reusable sterile blunt needle with the bevel up was introduced just superior to and at the junction of the lateral one-third to medial two-thirds of the inferior orbital rim. The needle was passed straight back through the skin of the lower lid for 1cm going through the orbital septum, and then angled at 45° to follow the lateral wall of the orbit to the apex. An attempt was made to place the anaesthetic solution in the muscle cone. The facial nerve block was given using 4ml of a 2% lidocaine with 1:200,000 epinephrine adopting O'Brien's technique.
The first 25 patients had electrocardiograms, (ECG) and all patients had blood pressure (BP) recordings taken before and after (15-30 minutes) the retrobulbar injection. The physician who had administered the block assessed akinesia and anaesthesia. [Table - 1] shows the grading system used.
Patients with grade 3 anaesthesia had a supplement injection of the same mixture. The standard microsurgical procedure was performed as extracapsular cataract extraction with posterior chamber intraocular lens implantation (ECCE with PCIOL) except for one case in which a combined trabeculectomy and planned ECCE with PCIOL implantation was done. The procedure lasted 15-45 minutes, depending on the experience of the surgeon. All the operated patients had routine postoperative medication consisting of topical antibiotic - steroid eye drops three times a day; and 1% cyclopentolate once a day. On the first and second postoperative day all patients were examined under slitlamp biomicroscope, looking specifically for any adverse anaesthetic effects, such as chemosis, conjunctival congestion and lid oedema. Fundi were examined using direct ophthalmoscope and with +90D lens at slitlamp biomicroscope. Pinhole visual acuity was recorded using Snellen's chart on day two before discharge. Follow-up examination was done at 4, 8, and 12 weeks in all patients. Routine slitlamp biomicroscopy, visual acuity with pinhole and a detailed fundus examination were done at this time. Retinoscopy was done only during 8 weeks and 12 weeks follow up, and the best corrected visual acuity (BCVA) was measured.
| Part II|| |
The second part of the study was undertaken to compare the efficacy of sodium bicarbonate buffered lidocaine and hyaluronidase mixed lidocaine. This study was conducted as a randomized, double blind clinical trial. One hundred and twenty patients admitted for cataract surgery during the same period were randomly allocated to one of the two groups, group A and B of 60 each. The same protocol and exclusion criteria were adopted as in Part I. Anaesthetic mixtures and bottles were labeled A or B by an independent observer. The physician giving anaesthesia and the surgeons were masked from the study. All retrobulbar blocks were administered and assessed using the same technique and grading system as described in Part I. Group-A patients received anaesthetic solution from bottle A and Group B from the bottle-B. At the end of the study, the code was broken.
After the study, it was determined that Group A had received a mixture of 2ml of 2% lidocaine with 1:200,000 epinephrine and 1ml of 7.5% sodium bicarbonate, (0.299 mol / ml) with the mean pH value being 7.2. Group B had received mixture of 2 ml of 2% lidocaine with 1:200,000 epinephrine and 450 units of hyaluronidase (15U / ml) with the pH at 4.6. Facial block was similar to that used in Part I.
| Results|| |
The characteristics of the subjects in Part I of the study are as follows. The 112 consecutive patients (53 males and 59 females) had a mean age of 58.2 I 10.03 (Range 20-79) years. One hundred (89.2%) patients were healthy and free from systemic diseases; seven (6.2%) had diabetes mellitus, two (1.7%) had asthma, one (0.89%) each had epilepsy, hypertension, and ischaemic heart disease. Two patients had coexisting ocular disease, one with neovascular glaucoma secondary to diabetic retinopathy and the other with primary open angle glaucoma. One patient out of the 112 did not come for postoperative review.
| Systemic safety variables|| |
There were no differences in the heart rate, mean systolic BP (Pre-block: 131.34 Hg ± 12.85; Post-block 135.34 mm Hg ± 14.25) and diastolic BP (pre-block: 79.91 mmHg ± 7.85 and post-block: 82.91 mm Hg ± 9.82) between pre-anaesthetic and post-anaesthetic (15-30 minutes post-block) recordings. There were no untoward events during the surgery or postoperative period.
| Ocular safety variables|| |
There were no anaesthetic adverse effects such as lid oedema, chemosis and congestion during the postoperative period. Fundus examination revealed neither damage to the optic nerve nor retinal toxicity.
One hundred and twenty patients were included in Part II of the study. Sixty patients were randomized to receive sodium bicarbonate-buffered local anaesthetic and the remaining sixty received hyaluronidase mixed local anaesthetic.
The analysis for Part II of the study is shown in [Table - 2]. In Group A, of 60 eyes, 47 (78.3%) achieved adequate anaesthesia in the first attempt, while the remaining patients (21.7%) needed a supplementary block. Thus the reblock rate was 21.6%. Thirty-one (51.5%) eyes achieved complete akinesia and anaesthesia within 5 minutes. One patient developed subconjunctival haemorrhage in the inferior fornix, which did not affect the surgical procedure.
In Group B of 60 eyes, 49 (81.6%) achieved complete akinesia and anaesthesia in the first attempt. Eleven patients (18.4%) required supplemental injection; the reblock rate was 18.3%. Thirteen (21.6%) eyes attained complete anaesthesia and akinesia within 5 minutes. No patient complained of pain or discomfort during the surgical procedure in either group.
After 12 weeks, a final follow-up evaluation was done for the patients included in Part I of the study. The BCVA measure 12 weeks postoperatively showed that 99 (88.39%) patients had vision ≥ 6 / 18 [82 (73.21% - ≥ 6 / 12] (6.25%) had vision between 6 / 18 - 6 / 36 and 5 (4.46%) had a significantly low visual acuity of 6 / 60 or worse. The causes of poor vision in the last 5 patients were: in one each geographic helicoid peripapillary choriodopathy with macular degeneration, decentered IOL, and high with-the-rule astigmatism due to corneal scar; and marked glaucomatous disc changes in two patients.
| Discussion|| |
More than a hundred years ago, in 1884 Knapp described the technique of retrobulbar anaesthesia. Six and half decades later, in 1949, Atkinson reported the advantages of hyaluronidase in anaesthetic solution to allow for injection of large volumes of local anaesthetic agent, and at the same time to achieve early akinesia and anaesthesia. Hyaluronidase has a long record of safety and efficacy without any untoward reactions. However, there have been occasional problems with availability of hyaluronidase both in India and elsewhere. Therefore, sodium bicarbonate, if found as effective as hyaluronidase, would provide a readily available and cost-effective alternative.
The most common block performed for intraocular surgery is the retrobulbar block. With experience, the surgeon can obtain reliable anaesthesia in 5-10 minutes with a single injection of 2-5 ml of local anesthetic. In excess of one million retrobulbar anaesthetic injections are delivered every year in the United States alone. The majority of these injections are without complications, although vision-threatening and even life-threatening side effects of retrobulbar anaesthesia can occur. To reduce the risks, peribulbar technique was introduced during the mid-1970s. Unfortunately the peribulbar anaesthetic is not without problems: the onset of anaesthesia and akinesia is delayed; a large volume (7-10 ml) is required; it has a longer learning curve; multiple supplement injections are required; intraocular pressure is increased; and finally it is not suitable for high-volume cataract surgeries. Peribulbar technique could also result in globe perforations. We had 7 globe perforations in 20,000 consecutive cataract extractions when we switched to the peribulbar technique during 1995 and 1996 (unpublished data). Since the risk for globe perforation is equal in both techniques, we adopted retrobulbar technique for this study, which has its own merits.
Most local anaesthetics are supplied as acidic salts to avoid precipitation during shipping and storage. It has been demonstrated [8,9] that the alkaline form is the active form of the drug and therefore alkalinisation of the local anaesthetic agent with sodium bicarbonate increases the non-cation form of the drug. It has been postulated [8,9] that the non-cation penetrates through the soft tissue and nerve sheath faster, resulting in a decrease in the duration of onset of action. The ability of pH-adjusted local anaesthetic solution to decrease the onset time for the neural blockade has been described by Hilgier in a study on brachial plexus anaesthesia. In addition, Gros and Ritchie observed that alkalinization of the local anaesthetic decreases the time of onset and increases the potency of anaesthesia [Table - 2].
Although the pH adjustment of the local anaesthesia is very simple and not time consuming, the potential disadvantage is that precipitation may occur when sodium bicarbonate is added to lidocaine as a bolus. This can be avoided by slowly adding sodium bicarbonate to lidocaine. Only fixed volume of alkalinization can result in precipitation and not freshly prepared solution. Eccarius et al reported significant reduction in pain when buffered injections were used compared to unbuffered injection for eyelid anaesthesia. Although a few reports have been published regarding the use of buffered solution in ocular anaesthesia, to the best of our knowledge, this is the first study to evaluate a buffered anaesthetic mixture without hyaluronidase for cataract surgery.
In our study, we have used a mixture of 30ml 2% lidocaine with a 1:200,000 dilution epinephrine and 1ml of 7.5% sodium bicarbonate (0.299mmol / ml). By injecting this mixture we were able to achieve akinesia and anaesthesia in an average 7.51 minutes compared to an average 8.86 minutes with the anaesthetic solution containing 15U/ml of hyaluronidase. The time to onset of akinesia and anaesthesia was not statistically significant, in either anaesthetic mixture, the quality of anaesthesis was also not different. Since there was no similar study to determine the efficacy of pH-adjusted anaesthetic without hyaluronidase, we could not compare our results with any previous reports.
Zahl et al have discussed the effect of bicarbonate on mixtures of lidocaine, bupivocaine and hyaluronidase with or without epinephrine, but not without hyaluronidase.
Previous studies using pH- adjusted local anaesthetic with sodium bicarbonate have not reported on safety issues. In Part I of our study we investigated for any adverse events by having an experienced physician monitor the cardiac function by ERG, BP, pulse and respiratory rate before and after retrobulbar blocks. All the subjects did well without untoward reactions to the anaesthetic mixture.
An ever-increasing demand for hyaluronidase should have logically increased its production and decreased the market price. Unfortunately, the manufacturers have not been able to meet the market demand. Local anaesthesia without hyaluronidase results in suboptimal anaesthetic effect, and hence patients experience more pain during surgery. For an effective anaesthesia 1500 IU of hyaluronidase (Rs.42 / -, Rallis India Ltd, Waluj, India) is mixed with 90ml of 2% lidocaine (16.6 U / ml). By utilising 6 ml of this mixture per patient (2ml for retrobulbar injection and 4ml for facial block), 15 patients can be anaesthetized at the cost of Rs.3 / - per patient. With 7.5% sodium bicarbonate (Rs.5 / - per 10 ml ampoule; Seth Pharmaceuticals Ltd. Vulcan Laboratories, Calcutta, India) mixed with 300 ml of 2% lidocaine (1:30), 50 patients can be anaesthetized, at a cost of 10 paise per patient (30 times less expensive; see [Table - 3]). More than three million cataract surgeries were performed in India during 1998. At the current cost, Rs. 9 million is spent for hyaluronidase alone. If sodium bicarbonate could substitute hyaluronidase, it amounts to a substantial savings of Rs.8.7 million.
In conclusion, pH adjustment of lidocaine with epinephrine using sodium bicarbonate is a safe; well tolerated and painless method, which effectively shortens the onset of ocular anaesthesia and achieves akinesia coomparable to lidocaine and hyaluronidase mixture. Additionally, it provides a reasonable and cost-effective alternative.
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[Table - 1], [Table - 2], [Table - 3]