The S(−)-enantiomer of bupivacaine, levobupivacaine, has a favourable cardiovascular and neurological toxicity profile [1,2] and its use as a local anaesthetic has become more widespread, including in ophthalmic surgery . Topical anaesthesia is routinely used for planned cataract surgery, because when compared to injected local anaesthesia it causes only minimal pain during administration and has fewer complications [3,4]. The three main methods for administering topical anaesthesia for cataract surgery are eye drops, eye drops plus intracameral anaesthesia and gel anaesthesia [5,6]. Considering that lidocaine drops is one of the most widely used local anaesthetics for this type of application, it is not surprising that studies regarding the use of topical levobupivacaine are lacking. We compared the efficacy of levobupivacaine 0.75% drops to lidocaine 4% drops for topical anaesthesia in cataract surgery not in terms of equipotency but with the purpose of evaluating the adequacy of levobupivacaine [7,8]. In particular, we assessed the rapidity of onset, efficacy, duration and quality of anaesthesia in order to provide a valid comparison of these two anaesthetics.
A randomized, double-blind study was performed on 203 patients (110 females, 93 males; ASA class I–IV) undergoing corrective cataract surgery by phacoemulsification during the period from July to November 2005. The average age of the patient cohort was 67 yr. Exclusion criteria were unwillingness to participate in the study, known allergy to an amide anaesthetic, communication or language problems, a single functional eye or glaucoma. Patients were randomized using computer-generated random numbers (Microsoft Excel) into two groups to receive either levobupivacaine 0.75% 1.5 mg (102 patients) or lidocaine 4% 8 mg (101 patients). The study was approved by the local Ethics Committee and informed written consent was obtained from all patients, who were admitted to the hospital for 12 h. All surgery was performed by the same surgeon who was blinded to the anaesthetic used. After intravenous access was established and without premedication, four drops of anaesthetic of either levobupivacaine 0.75% 1.5 mg (Chirocaine 0.75%, 10 mL vial, Abbott Laboratories, Abbott Park, IL, USA) or lidocaine 4% 8 mg (lidocaina cloridrato, 0.5 mL vial, Alfa Intes, Industria Terapeutica Splendore via Fratelli Bandiera 26 Casoria (NA), Italy) were instilled on the cornea and conjunctiva.
The following parameters were evaluated: onset time of sensory block, application, intraoperative and postoperative subjective pain using a verbal pain score on a scale from 0 (no pain) to 10 (worst pain imaginable), sensory offset time at beginning of discomfort, overall satisfaction of patients and surgeon (from 0 to 10), rate of supplemental peribulbar anaesthesia and complications. Effectiveness of anaesthetic block was assessed by forceps on the conjunctiva and scored as follows: 0, normal sensitivity; 1, mild sensitivity; 2, total absence of sensitivity. The onset of sensitivity was evaluated at 90 s after instillation and at 1-min intervals until a score of 2 was reached, necessary for initiation of surgery. Monitoring was nonetheless carried out for a total of 10 min. In the case of a sensitivity score of 0 or 1 at 10 min, the protocol required that an additional peribulbular block be used. Sensory evaluations were performed always in the same manner and every hour post-surgery by a trained observer who was blinded as to which anaesthetic the patient had received. Pulse oximetry (SPO2), electrocardiogram and non-invasive blood pressure were continuously monitored.
Twelve cases were excluded from the statistical analysis (five in the levobupivacaine group and seven in the lidocaine group) as supplemental peribulbar injection was required. We analysed data from 191 patients, 97 of which were treated with levobupivacaine 0.75% and 94 with lidocaine 4%. Statistical analysis was performed with Statistica 6.0 (StatSoft Inc., Tulsa, OK, USA). To evaluate the effect of treatment on dependent variables (time of onset and satisfaction levels of the patient and surgeon), we performed a one-way ANOVA and the differences were further analysed by Fishers's exact test. A χ2-test was also carried out to match the administration frequencies of supplementary peribulbar injection of the anaesthetic mixture in the two experimental groups to obtain the correct level of anaesthetic block. We used ANOVA for repeated measures to examine the pain score data.
One-way ANOVA showed that the two anaesthetics had significant differences and, in particular, the mean time of onset was longer in the levobupivacaine group when compared with the lidocaine group (2.1 min ± 20 s, 1.6 min ± 24 s, respectively; P < 0.01). The offset time was also significantly different (59.3 min ± 7.6 min, 23.4 ± 4.4 min, respectively; P < 0.01). The mean patient satisfaction scores were 9.0 ± 0.7 in the levobupivacaine group and 8.8 ± 0.7 in the lidocaine group (P < 0.01). The mean surgeon satisfaction scores were 8.9 ± 0.7 in the levobupivacaine group and 8.2 ± 0.7 in the lidocaine group (P < 0.01). The analysis of pain scores revealed a significant effect of treatment (F1,189 = 321.2; P < 0.01) and of time (F2,378 = 68.7; P < 0.01). As seen from Figure 1, the pain score post hoc tests revealed that the difference between the two drugs was present at all stages. There were no differences between the administration frequencies of supplementary peribulbar injections between the two groups (χ2-test). Lastly, no adverse effects were observed in either group of patients.
Our results permit several interesting considerations. First, both anaesthetics are effective for topical anaesthesia in cataract surgery. While the efficacy of lidocaine has been previously documented [3,5] and also compared with other anaesthetics [6,9], this is the first study examining the use of levobupivacaine drops in cataract surgery although previous studies exist concerning the use of levobupivacaine for peribulbar [10–12] and sub-Tenon's block . Even though a direct comparison with previous investigations would be rendered difficult due to differences in methodology [3,5,6,9–12], our results show that 0.75% levobupivacaine provides a significantly longer mean onset time, even if not relevant in a clinical context. However, the offset time was higher for levobupivacaine, and in fact the pain score, even if low in both treatment groups, was significantly greater at all times measured (at application, intraoperative and 2 h postoperative) for lidocaine. The number of patients subjected to additional anaesthesia (peribulbar block) was greater in the lidocaine group, although this difference did not reach statistical significance.
It should be noted that satisfaction of both patients and surgeons was significantly higher in the levobupivacaine group, which appears to be reflected in lower pain scores and a greater duration of anaesthesia. This indicates a greater degree of comfort and compliance by the patient and could thus justify its use by the surgeon, who would feel less pressured by time considerations when compared with lidocaine.
The cost of the two drugs in Italy is similar (0.119 euro for one drop of levobupivacaine 0.75%; 0.123 euro for one drop of lidocaine 4%), although the differences in pharmaceutical formulations do not permit a complete comparison.
In conclusion, this study has shown that levobupivacaine 0.75% drops are suitable and provide a valid choice for topical anaesthesia in cataract surgery and may even have more favourable properties than lidocaine 4%. No safety or tolerability considerations were raised, even in elderly patients with elevated anaesthetic risk.
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