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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.57 no.2 Campinas Mar./Apr. 2007
0.5% enantiomeric excess bupivacaine (S75-R25), 0.5% racemic bupivacaine, and 2% lidocaine for facial nerve block by the O'Brien Technique: a comparative study*
Bupivacaína con exceso enantiomérico (S75-R25) a 0,5%, bupivacaína racémica a 0,5% y lidocaína a 2% en el bloqueo del nervio facial por la técnica de O'Brien: estudio comparativo
Luis Henrique CangianiI; Luiz Marciano Cangiani, TSAII; Antônio Márcio de Safim Arantes Pereira, TSAII
do Instituto Penido Burnier e Centro Médico de Campinas
IICo-responsável pelo CET/SBA do Instituto Penido Burnier e Centro Médico de Campinas
OBJECTIVES: Enantiomeric mixtures of bupivacaine in different formulations,
S75-R25 or S90-R10, were proposed aiming at reducing the cardiotoxicity and
with a satisfactory motor blockade. The aim of this study was to compare the
length of time until the appearance of the motor blockade and its degree using
50% enantiomeric excess 0.5% bupivacaine (S75-R25), 0.5% racemic bupivacaine,
and 2% lidocaine for facial nerve block by the O'Brien technique.
METHODS: Forty-five patients, over 60 years old, scheduled for the surgical treatment of cataracts under retrobulbar block preceded by O'Brien paralysis participated in this study. Patients were randomly divided in three groups of 15 patients, according to the anesthetic used for the facial nerve block: Group L (Lidocaine), Group B (Bupivacaine), and Group M (S75-R25). Three milliliters of the solution were administered. The length of time for motor blockade to become apparent and the degree of the motor block (Grades 1, 2, and 3) were evaluated 15 seconds after the injection and every 15 seconds until it reached 180 seconds.
RESULTS: The initial manifestations of the blockade were faster (15 s) in Group L. There were no differences between Groups B and M. Every patient in Group L showed Grade 3 motor block in up to 60 seconds, which was faster than Groups B and M (120 and 135 seconds, respectively). Groups B and M had similar behavior during the study, without any statistically significant difference. At 180 seconds, the incidence of Grade 3 motor block was similar in all three groups.
CONCLUSIONS: The beginning of the motor blockade and its maximal degree were achieved faster with 2% lidocaine. The same degree was achieved by racemic bupivacaine and S75-R25, but it took longer. These two anesthetics showed the same behavior regarding the latency and the maximal degree of motor block, but at the end of 180 seconds there were no differences in the intensity of the blockade among the three groups.
Key Words: ANESTHETICS, Local: bupivacaine, enantiomeric excess mixture (S75-R25), lidocaine; ANESTHETIC TECHNIQUES, Regional: facial nerve block, O'Brien technique.
JUSTIFICATIVA Y OBJETIVOS:
Mezcla de enantiómeros de la bupivacaína en diferentes formulaciones,
S75-R25 o S90-R10, fueron propuestos objetivando una menor cardiotoxicidad y
bloqueo motor satisfactorio. El objetivo de este estudio fue comparar el tiempo
de instalación y el grado de bloqueo motor utilizando la bupivacaína
con exceso enantiomérico de 50% (S75-R25) a 0,5%, la bupivacaína
racémica a 0,5% y la lidocaína a 2% en el bloqueo del nervio facial
por la técnica de O'Brien.
MÉTODO: Participaron del estudio 45 pacientes, con edad por encima de los 60 años, programados para tratamiento quirúrgico de catarata bajo bloqueo retrobulbar, precedido por la acinesia de O'Brien. Los pacientes fueron divididos aleatoriamente en 3 grupos de 15, de acuerdo con la solución anestésica empleada para el bloqueo del nervio facial: Grupo L (Lidocaína), Grupo B (Bupivacaína) y Grupo M (S75-R25). Fueron inyectados 3 mL de la solución. Fueron verificados el tiempo de instalación y el grado del bloqueo motor (Grados 1, 2 y 3) a los 15 segundos después de la inyección y sucesivamente a cada 15 segundos hasta completar los 180 segundos.
RESULTADOS: Las manifestaciones iniciales del bloqueo fueron más rápidas (15 s) en el Grupo L que en los Grupos B y M. No hubo diferencia entre los Grupos B y M. Todos los pacientes del Grupo L presentaron bloqueo motor Grado 3 en hasta 60 segundos, tiempo menor que aquellos observados en los Grupos B y M (120 y 135, respectivamente). Los grupos B y M tuvieron un comportamiento semejante a lo largo del estudio, no habiendo diferencia estadística entre ellos. A los 180 segundos el bloqueo motor Grado 3 fue semejante en los 3 Grupos.
CONCLUSIONES: La instalación del bloqueo motor y el grado máximo de bloqueo se obtuvieron más rápidamente con la lidocaína a 2%. El mismo grado se alcanzó por la bupivacaína racémica y por la S75-R25, pero sin embargo en tiempo mayor. Esos de los anestésicos presentaron el mismo comportamiento en relación a la latencia y al grado máximo del bloqueo motor, siendo que al término de 180 segundos, no había más diferencia en la intensidad de este entre las tres soluciones estudiadas.
Bupivacaine (1-butyl-2;6'-pipecolidilxylidase) is widely used in infiltrative anesthesia, as well as in regional blocks. However, it has a narrow safety margin due to its cardiotoxicity and its pro-arrhythmic potential 1,2.
Bupivacaine has an asymmetric, or chyral, carbon in its structure responsible for the existence of two optical isomers, or enantiomers: levobupivacaine (S(-) bupivacaine) and dextrobupivacaine (R(+) bupivacaine), with independent pharmacological behaviors due to the stereoselectivity 3.
Studies have demonstrated that the dextrorotatory component of bupivacaine is responsible for the cardiotoxicity of racemic bupivacaine (S50-R50) and its refractoriness to cardiopulmonary resuscitation 2,4-8.
In an experimental model of rat sciatic nerve, there were no differences between both enantiomers regarding the anesthetic activity 3. However, another comparative study between levobupivacaine and bupivacaine, using the same experimental model, showed that the latency of the motor blockade was decreased with levobupivacaine, but the intensity and the duration were similar for both formulations 9.
Despite the experimental evidence, in clinical practice 0.5% levobupivacaine did not show the same efficacy as 0.5% bupivacaine regarding the motor blockade, especially with epidural anesthesia 10. This led to the idea of manipulating the enantiomeric ratio, which in the experimental rat sciatic nerve model demonstrated that the motor blockade produced by the 50% enantiomeric excess mixture (S75-R25) was similar to that of the racemic form (S50-R50) 11,12. A comparative study between 0.5% levobupivacaine and S75-R25 bupivacaine in epidural block demonstrated that the latter had better performance regarding the motor blockade 13.
Facial nerve block by the O'Brien technique is widely used in ophthalmologic surgeries, especially intraocular surgeries. In this technique, the facial nerve is blocked below the condyle of the mandible. The blockade aims at paralyzing the orbicularis oculi muscle and blocking the movements of the eyebrow. It is easy to perform and has a high efficacy rate when 2 to 3 mL of the anesthetic solution is used, especially 2% lidocaine 14,15.
The aim of this study was to verify the degree of the motor blockade and its latency, comparing 0.5% enantiomeric excess bupivacaine (S75-R25), 0.5% racemic bupivacaine, and 2% lidocaine in facial nerve block by the O'Brien technique.
After approval by the Ethics Committee and signing of the informed consent, 45 patients, of both genders, older than 60 years, ASA physical status I and II, scheduled for surgery for cataracts under retrobulbar block preceded by facial nerve block by the O'Brien technique, participated in this study. Obese patients, diabetics, patients with neurological diseases, and those with altered level of conscience were excluded from the study. Patients were randomly divided in 3 groups of 15 patients according to the analgesic solution used for the facial nerve block: Group L (lidocaine), Group B (racemic bupivacaine), and Group M (50% enantiomeric excess, S75-R25). The study population was calculated after a pilot study, where the constancy of the results was verified in non-obese patients older than 60 years in whom the injection site was easily identified.
Patients did not receive premedication. In the operating room, monitoring included cardioscope on the DII derivation, pulse oxymeter for determination of the SpO2, and sphygmomanometer for determination of blood pressure by auscultation. Afterwards, venipuncture in the antecubital fold with a 22G catheter was performed followed by infusion of Ringer's lactate solution (500 mL).
Patients received intravenous sedation, which was titulated from a mixture containing 5 mg of midazolam (1 mL) and 50 µg of fentanyl (1 mL) diluted to 5 mL 16. The mixture was injected in an amount deemed necessary, so the patient would be calm and cooperative, capable of responding commands to open and close the eyes. Oxygen, 2 L.min-1, was administered through a nasal catheter. Facial nerve block was performed using the O'Brien technique with a 13 x 4.5 needle, using 3 mL of the analgesic solution according to each study group: Group L 2% lidocaine; Group B 0.5% bupivacaine; and Group M enantiomeric excess mixture S75-R25. After the injection, digital compression of the site was performed and, afterwards, the patient was asked to open and close his eyes tightly every 15 seconds for 180 seconds. The degree of the motor blockade was evaluated according to the following criteria: Grade 0 Absence of motor blockade; Grade 1 partial incapacity to close the eyes; Grade 2 total incapacity to close the eyes (paralysis of the orbicularis oculi); Grade 3 unable to move the eyebrow.
The comparison with the opposite eye allowed to determine the degree of the blockade.
Afterwards, patients underwent retrobulbar block with a mixture containing equal parts of 2% lidocaine, 0.75% bupivacaine, adrenaline 1:200,000, and 40 UI.mL-1 of hyaluronidase. The volume injected was determined according to the complacency of the eye socket. After retrobulbar block, the surgical procedure was performed. Patients were discharged according to the protocol for outpatient basis surgery.
Groups were compared regarding the length of time necessary for the initial manifestations of the blockade, the degree of the blockade, and the length of time necessary to achieve a Grade 3 blockade.
In the first day (24 hours), and on postoperative days 7, 30, and 60, patients were evaluated for the presence of neurological damage of the facial nerve.
Variables were compared by the test t Student (age, weight, height), Chi-square test (gender and physical status), and Kruskal-Wallis test with Connover post-test (length of time until the beginning of the blockade Grade 1 and degree of the motor blockade). Intra-group comparisons were done using the Friedman test to determine the moment maximal blockade was achieved. A value of p < 0.05 was considered significant.
Both groups were homogenous regarding gender, age, height, weight, and physical status (Table I).
At 15 seconds, in Group L (lidocaine), 11 patients presented grade 1 motor blockade and four, grade 2. In Group B (bupivacaine), eight patients presented grade 1 motor blockade and 7, grade 0. In Group M (S75-R25 bupivacaine), nine patients presented grade 1 motor blockade and six, grade 0. There was a statistically significant difference between Group L and Groups B and M. The length of time until the motor blockade was apparent was smaller in Group L; there were no statistically significant differences between Groups B and M (Figures 1, 2, and 3).
The intragroup analysis showed that the maximal blockade in the lidocaine group was achieved at 60 seconds and, from that moment on, the Friedman test for non-repetitive measures did not show significant differences regarding this parameter (Friedman's statistics = 8.00, p = 0.435) (Figure 1).
The maximal blockade in the racemic bupivacaine group was achieved at 135 seconds and Friedman's statistics from this moment on did not show significant differences (Friedman's statistics = 3.00, p = 0.3916) (Figure 2).
For S75-R25 bupivacaine, the maximal blockade was achieved at 120 seconds, with no statistically significant differences from that moment on (Friedman's statistics = 8.00, p = 0.0916) (Figure 3).
Comparing the intensity of the motor blockade in the three groups at each moment by the Kruskal-Wallis test, there were significant differences among them until 105 seconds. The Conover post-test was used to identify which groups presented the differences. It showed that the motor blockade induced by lidocaine was more intense than the one produced by the other anesthetics until 90 seconds, and even more intense than the one produced by bupivacaine at 105 seconds. The same test showed that there were no significant differences between racemic bupivacaine and S75-R25 bupivacaine at any moment.
At 180 seconds, the results were similar in all three groups.
Since the first reports on the cardiotoxicity of bupivacaine, especially at the 0.75% concentration, physicians have been concerned about using it 2-4. Experimental studies showed that the dextrorotatory component was responsible for the cardiotoxicity; therefore, the use of the levorotatory component was investigated in experimental models and, posteriorly, in humans 2,4-8.
The experimental model using the rat sciatic nerve is considered the starting point for the study of local anesthetics in an intact animal, which, along with the in vitro investigations, composes the pre-clinical phase, before the investigation in humans 9. This model provides the conditions to evaluate the length of time until the beginning of the motor blockade and its duration 17, to quantify the sensitive blockade 18, and to detect the neurotoxicity of local anesthetics 17. An experimental study with levobupivacaine demonstrated its efficacy in both motor blockade and analgesia 9. It also demonstrated that there was a reduction in the length of time until the motor blockade was apparent when compared to the racemic form 9. This can be explained by the enantioselectivity. Animal studies with enantiomeres of local anesthetics showed the difference regarding the duration of the blockade attributed to the stereoselectivity of the levorotatory form for the vessels, causing vasoconstriction and, therefore, prolonging its anesthetic action 3. This was confirmed in infiltrative anesthesia in man 19. Vasoconstriction was also observed with ropivacaine in the same intensity caused by epinephrine 20,24.
In epidural anesthesia, however, the motor blockade of bupivacaine was superior the levorotatory enantiomer, which led to the idea of manipulating the enantiomeric relation between levobupivacaine and dextrobupivacaine (S75-R25 and S90-R10) to produce a motor blockade with low cardiotoxicity 11-13. The 50% enantiomeric excess mixture (S75-R25) showed, in the rat sciatic nerve experimental model, good motor blockade and no neurotoxicity 11-13. In epidural anesthesia it promoted greater motor blockade than levobupivacaine 14.
Considering that the 50% enantiomeric excess mixture (S75-R25) had already been tested in the experimental model and epidural anesthesia, and did not cause neurotoxicity, we decided to study it in the facial nerve block by the O'Brien technique.
The facial nerve block, especially of the temporal branch, is widely used in surgical procedures of the eyes to promote paralysis of the orbicularis oculi muscle and eyebrow, to prevent the patient from closing the eye during the procedure, especially under awake sedation 16.
Facial nerve block by the O'Brien technique is simple to perform and has a high success rate. The local anesthetic is deposited just below the condyle of the mandible, which is easily palpable when the patient opens and closes his mouth 21. The site of the injection is close to the facial nerve, but far enough to avoid puncturing it. Compressing the skin immediately after the injection facilitates the dispersion of the local anesthetic towards the nerve.
In this study, lidocaine, racemic bupivaciane, and 50% enantiomeric excess bupivacaine (S75-R25) were compared; 2% lidocaine was established as the standard due to its great efficacy. The choice of 15-second intervals to determine the degree of the motor blockade was based on the observation that, in most cases, motor blockade starts 15 seconds after the administration of lidocaine. Patients younger than 60 years and obese were excluded from the study to prevent the biological variability from influencing the results.
In this study, all three groups were homogenous for age, height, weight, gender, and physical status (Table I). Regarding the motor blockade, one should consider four aspects. First, lidocaine was very effective. At 15 seconds, 11 patients had a grade 1 motor blockade and 4 had a grade 2 blockade. At 60 seconds, a grade 3 blockade was already present. Just one patient presented motor blockade only at 75 seconds. Lidocaine was superior to racemic bupivacaine and S75-R25 when the results were compared. Second, it took longer to achieve a grade 1 blockade with bupivacaine and S75-R25, but both had similar behavior. However, at 15 seconds, 40% of the patients did not present motor blockade (grade 1), which only happened after 30 seconds and was complete at 75 seconds; the difference was not statistically significant. Third, the grade 3 motor blockade was achieved gradually in groups B and M, and at 120 seconds there were no statistically significant differences between bupivacaine and S75-R25. The results showed that both drugs had similar behavior. Fourth, the results at 180 seconds showed no statistically significance among the three groups regarding the degree of the motor blockade.
The results showed that it is possible to achieve a maximal degree of motor blockade with any one of the three drugs studied. However, it takes longer for racemic bupivacaine and 50% enantiomeric excess bupivacaine (S75-R25).
When compared with the experimental model, these results showed that the length of time until the beginning of the motor blockade is shorter. This occurred because in the experimental model, 0.2 mL of the anesthetic solution is used in the peri-articular region of the posterior limb, in the popliteal space of the rat, using the Truant technique 22, and in the facial nerve block by the O'Brien technique, 3 mL of the anesthetic solution were injected. Besides, applying digital compression for five seconds immediately after the injection facilitates the diffusion of the anesthetic, decreasing the length of time until the beginning of the motor blockade.
Regarding the epidural block 13, in this study the length of time until the beginning of the motor blockade was much shorter for the three drugs. This was expected since in the epidural block several nerves, with different distances and calibers, must be reached. Therefore, the variability in the results in epidural block is greater, that is, the techniques are not comparable and they cannot be compared with the experimental model.
It was not possible to study the duration of the blockade because, after the surgery, the operated eye was covered, and the dressing was removed only 24 hours later, at the time of the first postoperative exam. However, facial nerve lesion was not observed in the first postoperative day and in the subsequent exams, 7, 30, and 60 days later.
From what was exposed, and considering the conditions of this study, one can conclude that the beginning, grade 1, and grade 3 of the motor blockade occurred faster with 2% lidocaine. The same degree was achieved with bupivacaine and 50% enantiomeric excess bupivacaine, but it took longer. There were no differences regarding the length of time until the beginning of the blockade and its degree between racemic bupivacaine and enantiomeric excess bupivacaine. At 180 seconds, there were no differences regarding the degree of the motor blockade among the three drugs. Thus, both bupivcaine and 50% enantiomeric excess bupivcaine (S75-R25) are good options to achieve paralysis of the eyelids and eyebrow with facial nerve block by the O'Brien technique.
01. Liu PL, Feldman HS, Giasi R et al. Comparative CNS toxicity of lidocaine, bupivacaine and tetracaine in awake dogs following rapid intravenous administration. Anesth Analg, 1983;62:375-379. [ Links ]
02. Albright GA Cardic arrest following regional anesthesia with etidocaine and bupivacaine. Anesthesiology, 1979;51:285-286. [ Links ]
03. Aberg G Toxicological and local effects of optically active isomers of two local anaesthesic compounds. Acta Pharmacol Toxicol, 1972;31:273-286. [ Links ]
04. Clarkson C, Hondeghem L Mechanism for bupivacaine depression of cardiac condution: fast block of sodium channels during the action potencial with slow recovery from block during diastole. Anesthesiology, 1985;62:396-405. [ Links ]
05. Butterworth JF, Brownlow RC, Leith JP et al. Bupivacaine inhibits cyclic-3',5'-adenosine monophosphate production: a possible contributing factor to cardiovascular toxicity. Anesthesiology, 1993;79:88-95. [ Links ]
06. Vanhoute F, Vereecke J, Verbeken N et al. Stereoselective effects of the enantiomers of bupicavaine on the eletctrophysiological properties of the guinea-pig papillary muscle. Br J Pharmacol, 1991;103:1275-1281. [ Links ]
07. Denson DD, Behbehani MM, Gregg RV Enantiomer-specific effect of an intravenously administered arrhythmogenic dose of bupivacaine on neurons of nucleus tractus solitarius and the cardiovascular system in the anesthetized rat. Reg Anesth, 1992;17:311-316. [ Links ]
08. Mazoit JX, Boico O, Samii K Myocardial uptake of Bupivacaine: II. pharmacokinetics and pharmacodynamics of bupivacaine enantiomers in the isolated perfused rabbit heart. Anesth Analg, 1993;77:477-482. [ Links ]
09. Simonetti MPB, Valinetti EA, Ferreira FMC Avaliação da atividade local da S(-) bupivacaína: Estudo Experimental in vivo no nervo ciático do rato. Rev Bras Anestesiol, 1997;47:425-434. [ Links ]
10. Cox CR, Faccenda KA, Gilhhooly C et al. Extradural S(-)bupivacaíne: comparison with racemic RS-bupivacaíne. Br J Anaesth, 1998;80:289-293. [ Links ]
11. Simonetti MPB, Ferreira FMC Does the D-isomer of bupivacaine contribute to the improvement of efficacy in neural block? Reg Anaesth Pain Med, 1999;24;(Supp):43. [ Links ]
12. Simonetti MPB, Ferreira Jr R, Bird RA Optimization of the therapeutic index of bupivacaine through the manipulation of the enantomeric ratio. 12th WCA, 2000, Abstrat, P6.4.05.pg 247. [ Links ]
13. Delfino J, Vale NB Bupivacaína levógira a 0,5% pura versus mistura enantiomérica de bupivacaína (S75-R25) a 0,5% em anestesia peridural para cirurgia de varizes. Rev Bras Anestesiol, 2001;51:474-482. [ Links ]
14. Ferreira AA Bloqueio do nervo facial. Rev Bras Anestesiol, 1995; (Supl. 20):34-36. [ Links ]
15. Cangiani LM Anestesia em Oftalmologia, em: Manica JT Anestesiologia Princípios e Técnicas, 3ª Ed, Porto Alegre, Artmed, 2004;910-922. [ Links ]
16. Cangiani LM, Oliveira AC, Camargo LL et al. Sedação com midazolam ou com a associação midazolam-fentanil em cirurgia oftálmica sob bloqueio retrobulbar. Rev Bras Anestesiol, 1995;45:363-368. [ Links ]
17. Feldman HS, Covino BG Comparative motor blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog. Anesth Analg, 1988;67:1047-1052. [ Links ]
18. Grant GJ, Vermeulen K, Zakowski MI et al. A rat sciatic nerve model for independent assessment of sensory and block induced by local anesthetics. Anesth Analg, 1992;75:889-894. [ Links ]
19. Aps C, Reynolds F An intradermal study of the local anaesthetic and vascular effects of the isomers of bupivacaine. Br J Pharmacol, 1978;6:66-68. [ Links ]
20. Kopacz DJ, Carpenter RL, Mackey DC Effects of ropivacaine on cutaneous capillary blood flow in pigs. Anesthesiology, 1989;7:169-174. [ Links ]
21. Guinard JP, Carpenter RL, Morett RC Effects of local anesthetic concentration on the capillary bood flow in human skin. Reg Anesth, 1992;17:317-321. [ Links ]
22. Truant Ap Studies on pharmacology of meprycaine (orocaine), a local anesthetic. Arch Int Pharmacodyn, 1958;115:483-497. [ Links ]
Dr. Luiz Marciano Cangiani
Av. Princesa D'Oeste, 1090/111 Vila Paraíso
13100-040 Campinas, SP
Submitted em 20
de setembro de 2005
Accepted para publicação em 27 de dezembro de 2006
* Trabalho de Conclusão do Curso de Especialização em Anestesiologia realizado no CET/SBA do Instituto Penido Burnier e Centro Médico de Campinas, Campinas, SP