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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.55 no.3 Campinas May/June 2005
Minimum anesthetic volumes for extraconal retrobulbar block: comparison between 0.5% racemic bupivacaine, levobupivacaine and enantiomeric mixture S75/R25 bupivacaine*
Volumen anestésico mínimo para bloqueo retrobulbar extraconal: comparación entre soluciones a 0,5% de bupivacaína racémica, de levobupivacaína y de la mezcla enantiomérica S75/R25 de bupivacaína
Luiz Fernando Soares, TSA, M.D.I; Ana Claudia de Melo Barros, M.D.II; Gustavo Paiva Almeida, M.D.II; Gustavo Luchi Boos, M.D.III; Getúlio Rodrigues de Oliveira Filho, TSA, M.D.IV
Chefe do Núcleo de Educação e Pesquisa em Anestesia para
Oftalmologia, CET/SBA Integrado de Anestesiologia da SES-SC
IIME2, CET/SBA Integrado de Anestesiologia da SES-SC
IIIME3, CET/SBA Integrado de Anestesiologia da SES-SC
IVResponsável, CET/SBA Integrado de Anestesiologia da SES-SC
BACKGROUND AND OBJECTIVES: Minimum anesthetic
volume (MAV) of local anesthetics corresponds to the effective volume for regional
anesthesia in 50% of patients. In this study, MAV of 0.5% racemic bupivacaine,
0.5% levobupivacaine and enantiomeric S75/R25 bupivacaine were calculated and
METHODS: This study involved two series of patients undergoing cataract extraction. Series 1 patients received either 0.5% racemic bupivacaine (n = 9) or 0.5% levobupivacaine (n = 11). Series 2 patients received either 0.5% racemic bupivacaine (n = 11) or 0.5% enantiomeric S75/R25 bupivacaine (n = 10). Blockades were achieved by single-injection and inferior-lateral approach. Motility of each rectus muscle was assessed 10 minutes later as: 0 (absent), 1 (decreased) or 2 (normal). Total muscle scores represented total eye motility score (TMS). Local anesthetic volume administered to the first patient of each group was 7.4 mL. Subsequent patients received volumes corresponding to 0.1 higher natural logarithm unit (if TME > 2) or lower (if TME < 2) as compared to natural logarithm of preceding volume. Massey and Dixon's formulae were used for MAV calculations.
RESULTS: MAVs of bupivacaine in both series were 6 mL and 6.2 mL, respectively. MAVs of levobupivacaine and enantiomeric S75/R25 bupivacaine were 5.7 mL and 5.8 mL, respectively. There were no differences between groups in effective anesthetic volumes.
CONCLUSIONS: Similar volumes of 0.5% racemic bupivacaine, 0.5% levobupivacaine and enantiomeric S75/R25 bupivacaine are needed for extraconal retrobulbar anesthesia.
Key words: ANESTHETICS, Local: bupivacaine, enantiomeric mixture S75/R25 bupivacaine, levobupivacaine; ANESTHETIC TECHNIQUES, Regional: extraconal retrobulbar block
JUSTIFICATIVA Y OBJETIVOS: El volumen
anestésico mínimo (VAM) de un anestésico local es el volumen
efectivo para anestesia regional en un 50% de los pacientes. El objetivo de
éste fue calcular los volúmenes anestésicos mínimos
de las soluciones a 0,5% de bupivacaína racémica, de levobupivacaína
y de la mezcla enantiomérica S75/R25 de bupivacaína para anestesia
MÉTODO: Fueron estudiadas dos series de pacientes sometidos a extracción de catarata. En la serie 1, los pacientes recibieron bupivacaína a 0,5% (n = 9) ó levobupivacaína a 0,5% (n = 11). En la serie 2, los pacientes recibieron bupivacaína racémica a 0,5% (n = 11) ó la mezcla enantiomérica S75/R25 de bupivacaína a 0,5% (n = 10). Los bloqueos fueron realizados por una inyección única ínfero-lateral. La movilidad de cada músculo recto fue evaluada después de 10 minutos como: 0 (ausente), 1 (diminuida) ó 2 (normal). La suma de los resultados constituyó el resultado total de movilidad (ETM) del globo ocular. El volumen inicial fue de 7,4 mL. Los volúmenes utilizados en pacientes subsiguientes correspondieron 0,1 unidad logarítmica mayor (ETM > 2) ó menor (ETM < 2) que el logaritmo natural del volumen precedente. Fueron utilizadas las fórmulas de Massey y Dixon para cálculos de los VAM.
RESULTADOS: Los VAM de la bupivacaína racémica fueron 6 mL y 6,2 mL, el de la levobupivacaína fue 5,7 mL y el de la mezcla enantiomérica de bupivacaína S75/R25 fue 5,8 mL. No hubo diferencia entre los grupos en lo referente a los volúmenes anestésicos efectivos.
CONCLUSIONES: Volúmenes semejantes de soluciones a 0,5% de bupivacaína racémica, levobupivacaína o de la mezcla enantiomérica S75/R25 de bupivacaína son necesarios para anestesia retrobulbar extraconal.
Minimum local anesthetic volume (MAV), corresponding to the effective volume for regional anesthesia in 50% of patients, was introduced as a research tool to compare 0.5% bupivacaine and 0.5% ropivacaine for femoral nerve block 1. To determine MAV of a certain local anesthetic agent, its concentration has to be constant. The sequential allocation method, dependent on previous patient's response (Massey and Dixon's up-down method), was used to calculate MAV. Its primary advantages are decreased number of patients exposed to anesthetic failures and substantially smaller sample size 2,3.
In addition to allowing comparisons among different local anesthetics 1, MAV may be used to compare differents concentrations of the same agent or the effect of adjuvant drugs on local anesthetic volume for nervous blocks.
Specifically for retrobulbar extraconal block, local anesthetic volume injected in the orbit plays a critical role, since it is directly related to intraocular pressure increase 4.
Racemic bupivacaine is effective for peribulbar block 5. Its major disadvantage is cardiotoxicity primarily triggered by its dextrogyrous enantiomer 6. The levogyrous enantiomer (levobupivacaine) is less cardiotoxic as compared to the racemic mixture 7. Aiming at maintaining bupivacaine potency and decreasing its toxicity, an enantiomeric mixture was developed containing 75% levogyrous enantiomer and 25% dextrogyrous enantiomer (S75/R25), which is less toxic than the racemic mixture 8.
Minimum effective volumes for bupivacaine, levobupivacaine or enantiomeric S75/R25 bupivacaine to induce ocular akinesia and surgical anesthesia in retrobulbar extraconal blocks have not yet been determined. This study aimed at defining and comparing minimum anesthetic volumes of 0.5% racemic bupivacaine, levobupivacaine and enantiomeric S75/R25 bupivacaine for retrobulbar extraconal anesthesia.
After the institutional Ethics Committee approval and their informed consent, participated in this study two series of patients of both genders, aged 18 to 85 years, submitted to elective cataract extraction by extracapsular or phacoemulsification technique. Patients were not premedicated and were monitored with cardioscopy, automatic noninvasive blood pressure and pulse oximetry. A peripheral vein was punctured with 20G catheter in the non-dominant hand for 0.9% saline infusion (2 mL.min-1).
Series 1, aimed at comparing minimum anesthetic volumes of 0.5% racemic bupivacaine and 0.5% levobupivacaine, involved 20 patients receiving 0.5% bupivacaine (n = 9) or 0.5% levobupivacaine (n = 11). Series 2, aimed at comparing minimum anesthetic volumes of racemic bupivacaine and 0.5% enantiomeric S75/R25 bupivacaine, involved 21 patients receiving 0.5% racemic bupivacaine (n = 11) or 0.5% enantiomeric S75/R25 bupivacaine (n = 10). Patients were allocated to each group by electronically randomized numbers. All solutions contained 1:200,000 epinephrine.
Retrobulbar extraconal injection was performed by transcutaneous inferior-lateral approach with 25G 2.5 cm needles. Needle was inserted 1 cm perpendicular to the skin and then was slightly advanced 1.5 cm upwards and inwards toward the orbital apex. After negative blood, CSF and vitreous humor aspiration, predetermined local anesthetic volume was injected. Immediately after, a 600 g oculopression was applied on the eye for 10 minutes. To calculate volumes to be used in each sequence, maximum volume was established as 10 mL, which has been transformed into natural logarithm. From it, 0.1 units were subtracted until 10 posts below. These values were transformed in volumes (mL) by calculating respective antilogarithms. Volume administrated to the first patient of each group was 7.4 mL.
Subsequent volumes were determined according to the response of each previous patient in each group. Motility of every rectus muscles was evaluated 10 minutes after injection and the following scores were attributed to each muscle: 0 (absent), 1 (decreased) and 2 (normal). Total rectus muscles scores represented total eye motility score9. If total motility score was above 2, 3 mL of 0.2% lidocaine were injected by superior-medial or inferior-lateral approach, result was considered a failure and next patient would receive the immediately higher volume. If not, result was considered a success and next patient would receive the immediately lower volume. Minimum anesthetic volumes were calculated using Massey and Dixon's formulae for nominal samples equal to six2,3. The natural logarithms of the volumes associated to blockade success were compared between groups by single factor analysis of variance2, considering significant p < 5%.
Bupivacaine and levobupivacaine standard MAV for series 1 were 6 mL and 5.7 mL, respectively (Figures 1 and 2). Racemic bupivacaine and enantiomeric S75/R25 bupivacaine standard MAV for series 2 were 6.2 mL and 5.8 mL, respectively (Figures 3 and 4). There were no differences among natural logarithms of volumes associated to blockade success (F(2, 24) = 0.5; p = 0.61). Supplemental injection was needed for 7 patients in each group, who are represented by circles on figures. After supplementation, all patients could be submitted to proposed surgical procedures.
Our results have not shown differences between minimum anesthetic volumes of racemic bupivacaine, levobupivacaine and enantiomeric S75/R25 bupivacaine.
Considering that the potency of a drug is the ratio between mass and effect 10, that the same volume of two solutions with the same concentration of substances with the same molecular weight has the same mass, and that the molecular weight of both bupivacaine enantiomers is 288.4 11, one may conclude that all solutions tested for retrobulbar extraconal block had similar potencies.
Our study has used Massey and Dixon's method for small sample sizes. As compared to logistic regression and Massey and Dixon's method for large sample sizes, this method was powerful and could determine with equal accuracy ED50 of different analgesic agents 3. Its primary limitation is the impossibility of determining effective volumes for 95% of cases 2.
Although being more applicable to the clinic due to its position in the upper plateau of the dose-response logarithmic curve, ED95% is inadequate to compare between different drugs, different concentrations of the same drug or the effect of adjuvant drugs. MAV, however, for its position in the middle of the dose-response ascending logarithmic curve, is adequate for such comparisons 10,12.
Retrobulbar extraconal block deposits local anesthetics beyond the eye equator, close to the cone, being different from peribulbar block in which the needle is tangent to eye equator 13. We have used retrobulbar extraconal block to prevent the need to fraction predetermined local anesthetic volumes between two injection sites.
Our conclusion was that similar volumes of 0.5% racemic bupivacaine, levobupivacaine and enantiomeric S75/S25 bupivacaine are needed for retrobulbar extraconal anesthesia.
01. Casati A, Fanelli G, Magistris L et al - Minimum local anesthetic volume blocking the femoral nerve in 50% of cases: a double-blinded comparison between 0.5% ropivacaine and 0.5% bupivacaine. Anesth Analg, 2001;92:205-208. [ Links ]
02. Dixon WJ, Massey FJ - Introduction to Statistical Analysis. 4th Ed, New York: McGraw Hill, 1983. [ Links ]
03. Lichtman AH - The up-and-down method substantially reduces the number of animals required to determine antinociceptive ED50 values. J Pharmacol Toxicol Methods, 1998;40:81-85. [ Links ]
04. Frow MW, Miranda-Caraballo JI, Akhtar TM et al - Single injection retrobulbar extraconal anaesthesia. Total upper eyelid drop as an end-point marker. Anaesthesia, 2000;55:750-756. [ Links ]
05. Birt DJ, Cummings GC - The efficacy and safety of 0.75% levobupivacaine vs 0.75% bupivacaine for retrobulbar extraconal anaesthesia. Eye, 2003;17:200-206. [ Links ]
06. Valenzuela C, Snyders DJ, Bennett PB - Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation, 1995;92:3014-3024. [ Links ]
07. Mazoit JX, Boico O, Samii K - Myocardial uptake of bupivacaine. Pharmacokinetics and pharmacodynamics of bupivacaine enantiomers in the isolated perfused rabbit heart. Anesth Analg, 1993;77:477-482. [ Links ]
08. Simonetti MPB, Ferreira FMC - Obtenção de novos anestésicos locais através da modificação da relação enantiomérica da bupivacaína racêmica. Rev Bras Anestesiol, 1999;49:(Supl):CBA156. [ Links ]
09. Nicoll JM, Treuren B, Acharya PA et al - Retrobulbar anesthesia: the role of hyaluronidase. Anesth Analg, 1986;65:1324-1328. [ Links ]
10. Ross EM - Pharmacodynamics. Mechanisms of Drug Action and the Relationship between Drug Concentration and Effect, em: Hardman JG, Limbird LE, Molinoff PB et al - Goodman & Gilman's the Pharmacological Basis of Therapeutics, 9th Ed, New York, McGraw-Hill, 1996;29-41. [ Links ]
11. Langerman L, Golomb E, Grant GJ et al - Duration of spinal anaesthesia is determined by the partition coefficient of local anaesthetic. Br J Anaesth, 1994;72:456-459. [ Links ]
12. Sonner JM - Issues in the design and interpretation of minimum alveolar anesthetic concentration (MAC) studies. Anesth Analg, 2002;95:609-614. [ Links ]
13. Edge KR, McClarty CP, Krige SJ et al - Comparison of an extraconal block with a retrobulbar-facial block combination for ocular surgery. A safe alternative technique to the combination of retrobulbar block and facial nerve block. S Afr J Surg, 1995;33:117-119 [ Links ]
Dr. Getúlio Rodrigues de Oliveira Filho
Address: Rua Luiz Delfino 111/902
ZIP: 88015-360 City: Florianópolis, Brazil
Submitted for publication Januay 17, 2005
Accepted for publication February 24, 2005
* Received from Hospital Governador Celso Ramos, CET/SBA Integrado de Anestesiologia da Secretaria de Estado da Saúde de Santa Catarina (SES-SC), Florianópolis, SC