- Email: [email protected]
Aqueous humor levels of topically applied bupivacaine 0.75% in cataract surgery1
Aqueous humor levels of topically applied bupivacaine 0.75% in cataract surgery Ruby Lagnado, FRCOphth, Jennifer Tan, FRCS(Ed), Richard Cole, Raghavan Sampath, FRCOphth Purpose: To measure the intraocular levels of bupivacaine 0.75% topically applied before phacoemulsification and to develop standards for topical anesthesia in cataract surgery. Setting: Department of Ophthalmology, University Hospitals of Leicester, Leicester, United Kingdom. Methods: Forty eyes having phacoemulsification for senile cataract under topical anesthesia without sedation were randomly assigned to 1 of 2 preoperative topical anesthesia regimens. Bupivacaine 0.75% was applied in 0.1 mL drops 3 times in the 30 minutes before surgery in 18 eyes and 6 times in the 60 minutes before surgery in 22 eyes. Aqueous humor and serum samples were taken at the start of surgery and the bupivacaine levels measured. A visual analog pain score scale was used to indicate intraoperative pain. Results: The mean aqueous humor level of bupivacaine was 5.9 g/mL ⫾ 4.3 (SD) after 3 drops and 5.7 ⫾ 4.0 g /mL after 6 drops. The blood levels were less than 1.0 g/mL. There was no statistically significant difference in the intraocular level of bupivacaine between the 2 groups. There was no difference in the age or sex distribution between the 2 groups, although there was an increase in the intraocular level of bupivacaine with age (approximately 1.4 g/mL per decade; P ⫽ .048). There was no clear pattern associating the pain score with age, sex, or intraocular level of bupivacaine. Conclusions: A 3-drop regimen of bupivacaine 0.75% in the half hour before cataract surgery penetrated the eye as effectively as 6 drops in the 1 hour before surgery and provided good analgesia for phacoemulsification. Bupivacaine 0.75% penetrated the eye increasingly effectively with increasing age. J Cataract Refract Surg 2003; 29:1767–1770 © 2003 ASCRS and ESCRS
A
nesthesia for cataract surgery appears to have come full circle, with the most recent interest in topically applied agents.1–5 More than 100 years ago, topically applied cocaine for cataract surgery was described.6 With the subsequent development of retrobulbar, peribulbar, and sub-Tenon’s anesthesia, there is renewed interest in topical anesthesia for small-incision cataract surgery.1,7 This technique is a safe and effective alterna-
Accepted for publication December 18, 2002. Reprint requests to Raghavan Sampath, FRCOphth, Department of Ophthalmology, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom. © 2003 ASCRS and ESCRS Published by Elsevier Inc.
tive to retrobulbar and peribulbar anesthesia.8 –10 A principal advantage is that topical anesthesia eliminates the risk for globe perforation. Topical anesthetic agents used include proparacaine, tetracaine, lidocaine, and bupivacaine.11 Desirable properties of a topical agent include rapid onset, no toxicity, and good analgesia for the duration of surgery.9,12 There are no outlined standards for topical anesthesia in cataract surgery and few quantitative studies evaluating intraocular penetration.3,13,14 This study measured the intraocular penetration of bupivacaine 0.75% applied topically before cataract surgery. A visual analog scale was used to score intraoperative pain. 0886-3350/03/$–see front matter doi:10.1016/S0886-3350(03)00070-1
INTRAOCULAR LEVELS OF TOPICAL BUPIVACAINE IN PHACOEMULSIFICATION
Patients and Methods
Results
The results in 40 eyes having phacoemulsification for senile cataract without sedation were evaluated. The study received local ethics committee approval and license from the Medicines Control Agency UK for the use of bupivacaine outside its product license. After providing informed consent, the patients recruited into the study were randomly assigned to 1 of 2 preoperative anesthesia regimens. Group 1 (n ⫽ 18) received 3 drops, each 0.1 mL, 3 times at 10-minute intervals in the half hour before surgery. Group 2 (n ⫽ 22) received 6 doses, each 0.1 mL, at 10-minute intervals in the 60 minutes before surgery. The difference in the number of patients between the 2 groups was the result of lost samples and conversion to peribulbar anesthesia during surgery. The mean age was 73 years (range 49 to 89 years) in Group 1 and 72 years (range 58 to 90 years) in Group 2. There were no statistically significant differences in age or sex distribution between the 2 groups. All surgery was done by 1 surgeon experienced in phacoemulsification (R.S.) using topical anesthesia. No sedation was given during surgery. Immediately before surgery, a blood sample was taken. Aqueous humor samples of 0.1 to 0.2 mL were obtained via a paracentesis and an insulin syringe with a 30-gauge needle before the corneal incision was made. The anterior chamber was reformed with viscoelastic material, and surgery proceeded with a temporal corneal incision and the phaco-chop technique. A 3.2 mm foldable acrylic intraocular lens was placed in the bag. The wound was not sutured. Topical cefuroxime 75 mg and betamethasone 2 mg (Betnesol威) were given to all patients at the end of surgery. The aqueous humor level of bupivacaine was measured by 1 person (R.C.) using high-performance liquid chromatography (HPLC). Bupivacaine and an internal standard (lignocaine) were extracted from the serum or aqueous humor into ethyl acetate at pH 10. The ethyl acetate layer was dried down and reconstituted in the mobile phase, which was then injected into the HPLC system. The pH of the bupivacaine 0.75% was 5.7. After surgery, patients were asked to score their operative pain from 0 to 10 on a visual analog scale. The questionnaire also asked patients whether they were troubled by the microscope light during surgery, the sense of touch, or their ability to move the eye during surgery. They were asked whether they had had cataract surgery in their other eye under different anesthesia and if so, how it compared and whether they would recommend topical anesthesia to a friend. Finally, patients were asked to describe what they saw during surgery. Data were analyzed as means and standard deviations. Statistical analysis was by the 2-sample Student t and chisquare tests.
After 3 doses of bupivacaine 0.75%, the mean aqueous humor level was 5.9 ⫾ 4.3 g/mL (range 1.3 to 13.9 g/mL). After 6 doses of bupivacaine 0.75%, the mean aqueous level was 5.7 ⫾ 4.0 g/mL (range 1.0 to 13.7 g/mL) (Figure 1). There was no statistically significant difference in the intraocular level of anesthetic agent between the 2 groups (P ⫽ .88). There was an increase in the intraocular level of bupivacaine with increasing age of approximately 1.4 g/mL per decade (P⬍.05). There was no clear pattern associating pain scores with the intraocular level of bupivacaine 0.75% or the patient’s age or sex. The mean perioperative pain score in Group 1 was 0.86 and in Group 2, 1.70. The mean blood level of bupivacaine was less than 1.0 g/mL. No patient reported disturbing visual experiences. Ninetyseven percent of patients would recommend topical anesthesia. The other patient, the oldest in the study (90 years), had reservations and said she might recommend topical anesthesia to younger friends; this patient had not had previous cataract surgery.
1768
Discussion In our study, a 3-drop regimen of topically applied bupivacaine 0.75% penetrated the eye as effectively as 6
Figure 1. (Lagnado) Box plots of aqueous humor level of bupivacaine after 3 drops and 6 drops. Solid line inside the box indicates mean; the length of the box is the interquartile range with the highest and lowest values shown.
J CATARACT REFRACT SURG—VOL 29, SEPTEMBER 2003
INTRAOCULAR LEVELS OF TOPICAL BUPIVACAINE IN PHACOEMULSIFICATION
drops and provided good analgesia during phacoemulsification. The bupivacaine levels in the aqueous humor were higher in older patients. Commonly used topical anesthetic agents include tetracaine, lidocaine 4%, and bupivacaine. Bupivacaine is an amide-linked local anesthetic agent. Because it is an extremely lipid soluble, it is a potent anesthetic agent and its protein binding determines the duration of anesthetic action. Rabbit studies show it has low corneal epithelial toxicity.15 Bupivacaine blocks sensory nerves by binding to receptor sites of nerve membranes and decreasing sodium permeability. This prevents depolarization and nerve-conduction action. We have shown that topically applied bupivacaine is not systemically absorbed to a level that would have a toxic effect on the heart or central nervous system. Topical bupivacaine blocks the subepithelial plexus of the cornea; the nonionized form of the drug penetrates the corneal epithelium and diffuses into the plexus axons. Increasing the pH of an anesthetic agent increases its duration of action16 by increasing the nonionized portion of the agent.17 An in vitro study of lidocaine found that increasing the pH from 5 to 7 significantly increased the corneal permeability of topically applied lidocaine 4%.14 Although adjusting the pH of the bupivacaine may have resulted in higher aqueous concentrations, it may not have reduced the pain levels if there was supramaximal saturation of the nerve fibers during the short duration of surgery.18 Bupivacaine has a 9-minute longer duration of action than other agents.19 There have been few quantitative studies of aqueous humor levels of topically applied anesthetic agents, and both were of lidocaine.3,14 To make our study comparable, we used the regimen described by Bellucci et al.3 However, our study differed in that we used a visual analog pain score scale from 1 to 10. This allowed a more quantitative assessment of pain and demonstrated that the lower dosage regimen was equally effective in terms of analgesia for the duration of surgery. This is in contrast to lidocaine, with which a good level of analgesia can only be consistently achieved with 6 drops. Also, our questionnaire included additional questions to broaden the assessment of the patient’s entire experience of cataract surgery under topical anesthesia. All our patients said they had pleasant visual experiences during surgery, which many described as scenes of a changing sky. We inform all patients scheduled for
cataract surgery under topical anesthesia that they will have visual sensations during surgery. It is possible that because of this and the absence of intravenous sedation during surgery, no patient reported disturbing visual experiences, as in a previous report20 whose findings are in contrast to those in another study.21 Our protocol allowed us to directly compare the results of bupivacaine 0.75% as a topical anesthetic agent in phacoemulsification with those in other studies. Our results quantitatively show the high corneal permeability of bupivacaine and that a lower dose provides good analgesia during surgery. Furthermore, the finding of higher levels of aqueous bupivacaine with increasing age may explain the results in a previous study that found a positive correlation between the duration of anesthesia and age with topical bupivacaine 0.5%.19 Bupivacaine 0.75% has been our standard agent for topical anesthesia for phacoemulsification surgery with good effect and no toxicity. Further studies of different regimens will clarify the standards.
References 1. Kershner RM. Topical anesthesia for small incision selfsealing cataract surgery; a prospective evaluation of the first 100 patients. J Cataract Refract Surg 1993; 19:290–292 2. Dillman DM. Topical anesthesia for phacoemulsification. Ophthalmology Clin North Am 1995; 8(3):419 – 427 3. Bellucci R, Morselli S, Pucci V, et al. Intraocular penetration of topical lidocaine 4%. J Cataract Refract Surg 1999; 25:643–647 4. Dutton JJ, Hasan SA, Edelhauser HF, et al. Anesthesia for intraocular surgery. Surv Ophthalmol 2001; 46:172– 184 5. Dinsmore SC. Drop, then decide approach to topical anesthesia. J Cataract Refract Surg 1995; 21:666 –671 6. Knapp H. On cocaine and its use in ophthalmic and general surgery. Arch Ophthalmol 1884; 13:402–408 7. Patel BCK, Burns TA, Crandall A, et al. A comparison of topical and retrobulbar anesthesia for cataract surgery. Ophthalmology 1996; 103:1196 –1203 8. Zehetmayer M, Radax U, Skorpik C, et al. U. Topical versus peribulbar anesthesia in clear corneal cataract surgery. J Cataract Refract Surg 1996; 22:480 –484 9. Manners TD, Burton RL. Randomised trial of topical versus sub-Tenon’s local anaesthesia for small-incision cataract surgery. Eye 1996; 10:367–370 10. Katz J, Feldman MA, Bass EB, et al. Injectable versus topical anesthesia for cataract surgery; patient perceptions of pain and side effects. Ophthalmology 2000; 107: 2054 –2060
J CATARACT REFRACT SURG—VOL 29, SEPTEMBER 2003
1769
INTRAOCULAR LEVELS OF TOPICAL BUPIVACAINE IN PHACOEMULSIFICATION
11. Davis DB, Mandel MR. Anesthesia for cataract surgery. Int Ophthalmol Clin 1994; 34(2):13–30 12. Judge AJ, Najafi K, Lee DA, Miller KM. Corneal endothelial toxicity of topical anesthesia. Ophthalmology 1997; 104:1373–1379 13. Behndig A, Linde´n C. Aqueous humor lidocaine concentrations in topical and intracameral anesthesia. J Cataract Refract Surg 1998; 24:1598 –1601 14. Fuchsja¨ger-Mayrl G, Zehetmayer M, Plass H, Turnheim K. Alkalinization increases penetration of lidocaine across the human cornea. J Cataract Refract Surg 2002; 28: 692–696 15. Liu JC, Steinemann TL, McDonald MB, et al. Topical bupivacaine and proparacaine: a comparison of toxicity, onset of action, and duration of action. Cornea 1993; 12:228 –232 16. Draeger J, Langenbucher H, Bannert C. Efficacy of topical anaesthetics. Ophthalmic Res 1984; 16:135–138 17. DeSantis LM Jr, Patil PN. Pharmacokinetics. In: Mauger TF, Craig EL, eds, Havener’s Ocular Pharmacology, 6th ed. St Louis, MO, Mosby, 1994; 40
1770
18. Zehetmayer M, Rainer G, Turnheim K, et al. Topical anesthesia with pH-adjusted versus standard lidocaine 4% for clear corneal cataract surgery. J Cataract Refract Surg 1997; 23:1390 –1393 19. Carruthers JDA, Sanmugasunderan S, Mills K, Bagaric D. The efficacy of topical corneal anesthesia with 0.5% bupivacaine eyedrops. Can J Ophthalmol 1995; 30(5): 264 –266 20. Newman DK. Visual experience during phacoemulsification cataract surgery under topical anaesthesia. Br J Ophthalmol 2000; 84:13–15 21. Au Eong KG, Low C-H, Heng W-J, et al. Subjective visual experience during phacoemulsification and intraocular lens implantation under topical anesthesia. Ophthalmology 2000; 107:248 –250 From University Hospitals, Leicester, United Kingdom. Presented at the ASCRS Symposium on Cataract, IOL and Refractive Surgery, Philadelphia, Pennsylvania, USA, June 2002. None of the authors has a financial or proprietary interest in any material or method mentioned.
J CATARACT REFRACT SURG—VOL 29, SEPTEMBER 2003
A
nesthesia for cataract surgery appears to have come full circle, with the most recent interest in topically applied agents.1–5 More than 100 years ago, topically applied cocaine for cataract surgery was described.6 With the subsequent development of retrobulbar, peribulbar, and sub-Tenon’s anesthesia, there is renewed interest in topical anesthesia for small-incision cataract surgery.1,7 This technique is a safe and effective alterna-
Accepted for publication December 18, 2002. Reprint requests to Raghavan Sampath, FRCOphth, Department of Ophthalmology, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom. © 2003 ASCRS and ESCRS Published by Elsevier Inc.
tive to retrobulbar and peribulbar anesthesia.8 –10 A principal advantage is that topical anesthesia eliminates the risk for globe perforation. Topical anesthetic agents used include proparacaine, tetracaine, lidocaine, and bupivacaine.11 Desirable properties of a topical agent include rapid onset, no toxicity, and good analgesia for the duration of surgery.9,12 There are no outlined standards for topical anesthesia in cataract surgery and few quantitative studies evaluating intraocular penetration.3,13,14 This study measured the intraocular penetration of bupivacaine 0.75% applied topically before cataract surgery. A visual analog scale was used to score intraoperative pain. 0886-3350/03/$–see front matter doi:10.1016/S0886-3350(03)00070-1
INTRAOCULAR LEVELS OF TOPICAL BUPIVACAINE IN PHACOEMULSIFICATION
Patients and Methods
Results
The results in 40 eyes having phacoemulsification for senile cataract without sedation were evaluated. The study received local ethics committee approval and license from the Medicines Control Agency UK for the use of bupivacaine outside its product license. After providing informed consent, the patients recruited into the study were randomly assigned to 1 of 2 preoperative anesthesia regimens. Group 1 (n ⫽ 18) received 3 drops, each 0.1 mL, 3 times at 10-minute intervals in the half hour before surgery. Group 2 (n ⫽ 22) received 6 doses, each 0.1 mL, at 10-minute intervals in the 60 minutes before surgery. The difference in the number of patients between the 2 groups was the result of lost samples and conversion to peribulbar anesthesia during surgery. The mean age was 73 years (range 49 to 89 years) in Group 1 and 72 years (range 58 to 90 years) in Group 2. There were no statistically significant differences in age or sex distribution between the 2 groups. All surgery was done by 1 surgeon experienced in phacoemulsification (R.S.) using topical anesthesia. No sedation was given during surgery. Immediately before surgery, a blood sample was taken. Aqueous humor samples of 0.1 to 0.2 mL were obtained via a paracentesis and an insulin syringe with a 30-gauge needle before the corneal incision was made. The anterior chamber was reformed with viscoelastic material, and surgery proceeded with a temporal corneal incision and the phaco-chop technique. A 3.2 mm foldable acrylic intraocular lens was placed in the bag. The wound was not sutured. Topical cefuroxime 75 mg and betamethasone 2 mg (Betnesol威) were given to all patients at the end of surgery. The aqueous humor level of bupivacaine was measured by 1 person (R.C.) using high-performance liquid chromatography (HPLC). Bupivacaine and an internal standard (lignocaine) were extracted from the serum or aqueous humor into ethyl acetate at pH 10. The ethyl acetate layer was dried down and reconstituted in the mobile phase, which was then injected into the HPLC system. The pH of the bupivacaine 0.75% was 5.7. After surgery, patients were asked to score their operative pain from 0 to 10 on a visual analog scale. The questionnaire also asked patients whether they were troubled by the microscope light during surgery, the sense of touch, or their ability to move the eye during surgery. They were asked whether they had had cataract surgery in their other eye under different anesthesia and if so, how it compared and whether they would recommend topical anesthesia to a friend. Finally, patients were asked to describe what they saw during surgery. Data were analyzed as means and standard deviations. Statistical analysis was by the 2-sample Student t and chisquare tests.
After 3 doses of bupivacaine 0.75%, the mean aqueous humor level was 5.9 ⫾ 4.3 g/mL (range 1.3 to 13.9 g/mL). After 6 doses of bupivacaine 0.75%, the mean aqueous level was 5.7 ⫾ 4.0 g/mL (range 1.0 to 13.7 g/mL) (Figure 1). There was no statistically significant difference in the intraocular level of anesthetic agent between the 2 groups (P ⫽ .88). There was an increase in the intraocular level of bupivacaine with increasing age of approximately 1.4 g/mL per decade (P⬍.05). There was no clear pattern associating pain scores with the intraocular level of bupivacaine 0.75% or the patient’s age or sex. The mean perioperative pain score in Group 1 was 0.86 and in Group 2, 1.70. The mean blood level of bupivacaine was less than 1.0 g/mL. No patient reported disturbing visual experiences. Ninetyseven percent of patients would recommend topical anesthesia. The other patient, the oldest in the study (90 years), had reservations and said she might recommend topical anesthesia to younger friends; this patient had not had previous cataract surgery.
1768
Discussion In our study, a 3-drop regimen of topically applied bupivacaine 0.75% penetrated the eye as effectively as 6
Figure 1. (Lagnado) Box plots of aqueous humor level of bupivacaine after 3 drops and 6 drops. Solid line inside the box indicates mean; the length of the box is the interquartile range with the highest and lowest values shown.
J CATARACT REFRACT SURG—VOL 29, SEPTEMBER 2003
INTRAOCULAR LEVELS OF TOPICAL BUPIVACAINE IN PHACOEMULSIFICATION
drops and provided good analgesia during phacoemulsification. The bupivacaine levels in the aqueous humor were higher in older patients. Commonly used topical anesthetic agents include tetracaine, lidocaine 4%, and bupivacaine. Bupivacaine is an amide-linked local anesthetic agent. Because it is an extremely lipid soluble, it is a potent anesthetic agent and its protein binding determines the duration of anesthetic action. Rabbit studies show it has low corneal epithelial toxicity.15 Bupivacaine blocks sensory nerves by binding to receptor sites of nerve membranes and decreasing sodium permeability. This prevents depolarization and nerve-conduction action. We have shown that topically applied bupivacaine is not systemically absorbed to a level that would have a toxic effect on the heart or central nervous system. Topical bupivacaine blocks the subepithelial plexus of the cornea; the nonionized form of the drug penetrates the corneal epithelium and diffuses into the plexus axons. Increasing the pH of an anesthetic agent increases its duration of action16 by increasing the nonionized portion of the agent.17 An in vitro study of lidocaine found that increasing the pH from 5 to 7 significantly increased the corneal permeability of topically applied lidocaine 4%.14 Although adjusting the pH of the bupivacaine may have resulted in higher aqueous concentrations, it may not have reduced the pain levels if there was supramaximal saturation of the nerve fibers during the short duration of surgery.18 Bupivacaine has a 9-minute longer duration of action than other agents.19 There have been few quantitative studies of aqueous humor levels of topically applied anesthetic agents, and both were of lidocaine.3,14 To make our study comparable, we used the regimen described by Bellucci et al.3 However, our study differed in that we used a visual analog pain score scale from 1 to 10. This allowed a more quantitative assessment of pain and demonstrated that the lower dosage regimen was equally effective in terms of analgesia for the duration of surgery. This is in contrast to lidocaine, with which a good level of analgesia can only be consistently achieved with 6 drops. Also, our questionnaire included additional questions to broaden the assessment of the patient’s entire experience of cataract surgery under topical anesthesia. All our patients said they had pleasant visual experiences during surgery, which many described as scenes of a changing sky. We inform all patients scheduled for
cataract surgery under topical anesthesia that they will have visual sensations during surgery. It is possible that because of this and the absence of intravenous sedation during surgery, no patient reported disturbing visual experiences, as in a previous report20 whose findings are in contrast to those in another study.21 Our protocol allowed us to directly compare the results of bupivacaine 0.75% as a topical anesthetic agent in phacoemulsification with those in other studies. Our results quantitatively show the high corneal permeability of bupivacaine and that a lower dose provides good analgesia during surgery. Furthermore, the finding of higher levels of aqueous bupivacaine with increasing age may explain the results in a previous study that found a positive correlation between the duration of anesthesia and age with topical bupivacaine 0.5%.19 Bupivacaine 0.75% has been our standard agent for topical anesthesia for phacoemulsification surgery with good effect and no toxicity. Further studies of different regimens will clarify the standards.
References 1. Kershner RM. Topical anesthesia for small incision selfsealing cataract surgery; a prospective evaluation of the first 100 patients. J Cataract Refract Surg 1993; 19:290–292 2. Dillman DM. Topical anesthesia for phacoemulsification. Ophthalmology Clin North Am 1995; 8(3):419 – 427 3. Bellucci R, Morselli S, Pucci V, et al. Intraocular penetration of topical lidocaine 4%. J Cataract Refract Surg 1999; 25:643–647 4. Dutton JJ, Hasan SA, Edelhauser HF, et al. Anesthesia for intraocular surgery. Surv Ophthalmol 2001; 46:172– 184 5. Dinsmore SC. Drop, then decide approach to topical anesthesia. J Cataract Refract Surg 1995; 21:666 –671 6. Knapp H. On cocaine and its use in ophthalmic and general surgery. Arch Ophthalmol 1884; 13:402–408 7. Patel BCK, Burns TA, Crandall A, et al. A comparison of topical and retrobulbar anesthesia for cataract surgery. Ophthalmology 1996; 103:1196 –1203 8. Zehetmayer M, Radax U, Skorpik C, et al. U. Topical versus peribulbar anesthesia in clear corneal cataract surgery. J Cataract Refract Surg 1996; 22:480 –484 9. Manners TD, Burton RL. Randomised trial of topical versus sub-Tenon’s local anaesthesia for small-incision cataract surgery. Eye 1996; 10:367–370 10. Katz J, Feldman MA, Bass EB, et al. Injectable versus topical anesthesia for cataract surgery; patient perceptions of pain and side effects. Ophthalmology 2000; 107: 2054 –2060
J CATARACT REFRACT SURG—VOL 29, SEPTEMBER 2003
1769
INTRAOCULAR LEVELS OF TOPICAL BUPIVACAINE IN PHACOEMULSIFICATION
11. Davis DB, Mandel MR. Anesthesia for cataract surgery. Int Ophthalmol Clin 1994; 34(2):13–30 12. Judge AJ, Najafi K, Lee DA, Miller KM. Corneal endothelial toxicity of topical anesthesia. Ophthalmology 1997; 104:1373–1379 13. Behndig A, Linde´n C. Aqueous humor lidocaine concentrations in topical and intracameral anesthesia. J Cataract Refract Surg 1998; 24:1598 –1601 14. Fuchsja¨ger-Mayrl G, Zehetmayer M, Plass H, Turnheim K. Alkalinization increases penetration of lidocaine across the human cornea. J Cataract Refract Surg 2002; 28: 692–696 15. Liu JC, Steinemann TL, McDonald MB, et al. Topical bupivacaine and proparacaine: a comparison of toxicity, onset of action, and duration of action. Cornea 1993; 12:228 –232 16. Draeger J, Langenbucher H, Bannert C. Efficacy of topical anaesthetics. Ophthalmic Res 1984; 16:135–138 17. DeSantis LM Jr, Patil PN. Pharmacokinetics. In: Mauger TF, Craig EL, eds, Havener’s Ocular Pharmacology, 6th ed. St Louis, MO, Mosby, 1994; 40
1770
18. Zehetmayer M, Rainer G, Turnheim K, et al. Topical anesthesia with pH-adjusted versus standard lidocaine 4% for clear corneal cataract surgery. J Cataract Refract Surg 1997; 23:1390 –1393 19. Carruthers JDA, Sanmugasunderan S, Mills K, Bagaric D. The efficacy of topical corneal anesthesia with 0.5% bupivacaine eyedrops. Can J Ophthalmol 1995; 30(5): 264 –266 20. Newman DK. Visual experience during phacoemulsification cataract surgery under topical anaesthesia. Br J Ophthalmol 2000; 84:13–15 21. Au Eong KG, Low C-H, Heng W-J, et al. Subjective visual experience during phacoemulsification and intraocular lens implantation under topical anesthesia. Ophthalmology 2000; 107:248 –250 From University Hospitals, Leicester, United Kingdom. Presented at the ASCRS Symposium on Cataract, IOL and Refractive Surgery, Philadelphia, Pennsylvania, USA, June 2002. None of the authors has a financial or proprietary interest in any material or method mentioned.
J CATARACT REFRACT SURG—VOL 29, SEPTEMBER 2003