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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094On-line version ISSN 1806-907X

Rev. Bras. Anestesiol. vol.55 no.6 Campinas Nov./Dec. 2005 



Levobupivacaine 0.5%, 50% enantiomeric excess bupivacaine and racemic bupivacaine in epidural anesthesia for lower abdominal procedures. Comparative study*


Estudio comparativo entre soluciones a 0,5% de levobupivacaína, bupivacaína en exceso enantiomérico del 50% y bupivacaína racémica en anestesia peridural para cirugía de abdomen inferior



Pedro Paulo Tanaka, TSA, M.D.I; Mário Ogleari, M.D.II; Paulo Valmorbida, M.D.II; Maria Aparecida A Tanaka, M.D.III

IProfessor Adjunto da Disciplina de Anestesiologia da UFPr; Co-Responsável do CET do Hospital de Clínicas da UFPr
IIME2 do CET do Hospital de Clínicas da UFPr
IIIAnestesiologista do Hospital de Clínicas da UFPr

Correspondence to




BACKGROUND AND OBJECTIVES: With the purpose of finding a local anesthetic agent safer than racemic bupivacaine, several animal studies have been performed with its isomers. This study aimed at evaluating, for one hour after injection, the efficacy of 50% enantiomeric excess bupivacaine as compared to levobupivacaine and racemic bupivacaine for epidural anesthesia in patients submitted to lower abdominal procedures.
METHODS: After the Research Ethics Committee approval, 87 patients aged 18 to 65 years, physical status ASA I and II, undergoing lower abdominal procedures were included in this randomized double-blind study. Patients were distributed in three groups which received 27 mL (including test dose) of local anesthetics with epinephrine (1:200,000) and fentanyl (100 µg) solutions. Group I was given 0.5% levobupivacaine, group II received 50% enantiomeric excess 0.5% bupivacaine, and group III received 0.5% bupivacaine. Monitoring consisted of pulse oximetry, cardioscopy and noninvasive blood pressure. Motor and sensory block profiles were evaluated, in addition to the incidence of side effects. Unidentified local anesthetic vials were numbered, and the randomized distribution list was opened only at the end of the experiment.
RESULTS: There were no significant differences regarding height and physical status between groups. There was a significant age difference in group I. Hemodynamic parameters were similar between groups. Motor block intensity was significantly lower in group I as compared to groups II and III.
CONCLUSIONS: All groups presented adequate motor and sensory block for surgery, with few side effects, suggesting that these solutions are effective for epidural anesthesia for lower abdominal procedures. Levobupivacaine produced less motor block as compared to the other compounds.

Key words: ANESTHETICS, Local: bupivacaine, bupivacaine isomers, levobupivacaine; ANESTHETIC TECNIQUES, Regional: epidural


JUSTIFICATIVA Y OBJETIVOS: Con la finalidad de encontrar un anestésico local más seguro que la bupivacaína, varios estudios en animales fueron realizados con sus isómeros. Este estudio tuvo como objetivo evaluar la eficacia de la bupivacaína en exceso enantiomérico del 50%, comparada a la levobupivacaína y a la bupivacaína racémica, en la anestesia peridural en pacientes sometidos a la cirugía de abdomen inferior, por el período de una hora después de la inyección de las soluciones.
MÉTODO: Después de la aprobación por el Comité de Ética en Pesquisa, participaron de este estudio, eventual y doblemente encubierto, 87 pacientes con edad entre 18 y 65 años, estado físico ASA I y II sometidos a cirugía del abdomen inferior. Fueron distribuidos en tres grupos que fraccionadamente recibieron solución conteniendo 27 mL (incluyendo la dosis-test) de anestésico local con adrenalina (1:200.000) y fentanil (100 µg). El grupo I recibió solución de levobupivacaína a 0,5%, el grupo II recibió solución de bupivacaína en exceso enantiomérico del 50% a 0,5% y el grupo III recibió solución de bupivacaína a 0,5%. Los pacientes fueron monitorizados por medio de oxímetro de pulso, cardioscopio y presión arterial no invasiva. Fueron investigadas las características motoras y sensitivas del bloqueo anestésico, bien como la incidencia de efectos colaterales. Los frascos de anestésico local fueron preparados sin identificación, numerados y solamente al final del estudio la lista de distribución eventual fue abierta.
RESULTADOS: No se observaron diferencias significativas con relación a la altura y estado físico. Diferencia demográfica significativa fue encontrada con relación a la edad en el grupo I. Los parámetros hemodinámicos fueron semejantes entre los grupos. Hubo una diferencia significativa con relación a la intensidad del bloqueo motor relatado entre los grupos estudiados (menor intensidad en el grupo I comparada a los grupos II y III).
CONCLUSIONES: Fue observado un adecuado bloqueo motor y sensitivo para la realización de la cirugía en los grupos estudiados con pocos efectos colaterales, sugiriendo que las soluciones son eficaces en la anestesia peridural para cirugía de abdomen inferior. La levobupivacaína presentó menor bloqueo motor que los otros dos grupos.




Racemic 0.5% bupivacaine has been successfully used in epidural anesthesia for abdominal procedures, producing excellent sensory anesthesia and muscle relaxation. However, greater emphasis have been given to lower systemic toxicity promoted by levogyrous bupivacaine 1, though its anesthetic effectiveness has been questioned in some reports 2.

Starting from purified local anesthetic molecule isomers, it is possible to manipulate the enantiomeric ratio of a racemic compound. This might contribute to its effectiveness and lower potential toxicity, with increased therapeutic index 3.

The purpose of this study was to compare the anesthetic characteristics (sensory and motor block) and hemodynamic repercussions of 50% enantiomeric excess 0.5% bupivacaine, 0.5% levobupivacaine and 0.5% racemic bupivacaine in the epidural space for lower abdominal procedures, during one hour after local anesthetic injection.



After the Research Ethics Committee, Hospital de Clinicas, Universidade Federal do Paraná approval, 87 patients aged 18 to 65 years, physical status ASA I and II, undergoing lower abdominal procedures, were included in this randomized double-blind study. Exclusion criteria were peripheral neuropathy, hypersensitivity to bupivacaine, sepsis, spinal deformities and uncontrolled hypovolemia.

Patients were distributed into three groups according to the administered drug: group I - 0.5% levobupivacaine; group II - 50% enantiomeric excess 0.5% bupivacaine; group III - 0.5% racemic bupivacaine. Preoperative evaluation was performed the night before surgery when physical conditions were assessed and permission to participate in the study was requested. Monitoring consisted of ECG at DII lead, noninvasive blood pressure and pulse oximetry. Local anesthetic solutions used in this study were supplied by Laboratório Cristália in 30 ml unidentified and numbered vials. Groups were identified at the end of the study.

Epidural puncture (L3-L4 interspace) was performed with patients in the sitting position with a 18G Tuohy needle, preceded by superficial tissues infiltration with 1% plain lidocaine. Epidural space was identified by the loss of resistance to air technique. After negative aspiration, 150 mg epinephrine were added to 30 ml of the local anesthetic solution to be injected, and 3 ml of this solution were used as test dose. After that, 100 µg fentanyl were added to the remaining solution, 24 ml of which were injected fractionally. The total amount administered was 27 ml (3 ml test dose plus 24 ml solution). An epidural catheter was inserted after the solution injection and intravenous midazolam was allowed during the surgery. 

After the epidural injection, the following parameters were evaluated: systolic and diastolic blood pressure, heart rate, upper sensory block level (involved dermatomes), and motor block degree by Bromage scale 4 for 30 minutes before surgery. The same parameters were evaluated during the next 30 surgical minutes.

All perioperative complications and intercurrences were recorded. Additional 5 ml solution dose was allowed for patients in whom the initial dose was insufficient for the procedure. Mediate complications were defined as muscle movements, tinnitus, sleepiness, psychomotor agitation, arrhythmia, seizure, hypotension (30% or more decrease in baseline systolic pressure) and heart rate fall below 50 beat.min-1. Data to be statistically analyzed were initially submitted to distribution evaluation through normality tests, variation coefficient and histogram analysis. Statistical tests were selected according to variables distribution and their dependent or independent character, according to the previously performed analyses.

To evaluate possible differences in anesthetic efficiency, sensory and motor block quality and toxicity (0, 10, 20, 30, 45 and 60 minutes after blockade) between the three anesthetics used, Analysis of Variance (ANOVA) for repetitive measures was applied, considering the observational nature of the study and the normal distribution of variables. To perform the same analysis between 2 anesthetics, Student's t parametric test for independent samples was applied, complying with normality and homocedasticity assumptions.

Mantel-Haenszel test was used to evaluate possible differences between groups in sensitivity and muscle strength during evaluated moments.

Two-tailed approaches were used for all tests, considering that differences could be distributed to both sides of the curve, with significance level established to 5%.

Sample size was calculated considering 5% type I error (alpha) and 10% type II error, with minimum estimated test power of 90%.



Patients were randomly distributed in three groups: group I - blockade with 0.5% levobupivacaine (n = 35); group II - blockade with 50% enantiomeric excess 0.5% bupivacaine (n = 33); group III - blockade with 0.5% racemic bupivacaine (n = 19). Table I shows demographic data of studied population.

It was observed a statistically significant age difference between groups (p = 0.005).

Regarding physical status, 22.86% of group I patients were classified as ASA I and 77.14% as ASA II. These values were 48.48% and 51.52% for group II and 57.89% and 42.11% for group III, respectively. Group I had higher incidence of physical status ASA II, different from groups II and III where distribution of physical status I and II was more equivalent (p = 0.02).

Most frequent procedures were abdominal hysterectomy (75.59%) and tubal ligature (14.92%). Most frequent associated disease was systemic hypertension, present in 31.03% of patients.

There was a post-anesthesia decrease in systolic blood pressure for all groups, especially during the first 20 minutes, with statistically significant difference among groups as compared to baseline values (p = 0.006) (Figure 1).

There was also a diastolic pressure decrease in the first 20 minutes, with no statistically significant difference among groups (p = 0.15) (Figure 2) as compared to baseline values though.

Heart rate analysis (Figure 3) showed that, although group II had a greater increase at 10 minutes, there were no statistically significant differences among groups throughout the post-anesthesia period (p = 0.619).

Muscle relaxation was evaluated by Bromage scale (Figure 4) at 30 minutes after local anesthetic injection. There were statistically significant differences in level 2 blockade in groups II and III as compared to group I.

There was no statistically significant sensory block extension difference between groups along time (Figure 5).

Five group I patients, three group II patients and two group III patients received ephedrine due to blood pressure decrease to predefined levels for treatment. Anesthesia was insufficient for surgery performance in 3 patients in group I, 1 in group II and 2 in group III. Failures were partial, resolved in all patients with additional local anesthetics doses and sedation.



Our study has shown demographic homogeneity among groups, except for older age in group I. Although this is probably a casual finding due to sample size, age alone has minor influence in epidural block of adults, being important for pediatric and elderly populations 5.

There were no statistically significant differences in hemodynamic parameters 10 minutes after local anesthetic injection. Difference in baseline systolic values between groups was probably due to the fact that patients were not premedicated. Heart rate, systolic and diastolic blood pressures had similar decreases, as it was to be expected, due to extensive sympathetic block, as shown by observed sensory block levels. Some patients in each group needed ephedrine to treat hypotension. Results are similar to other studies using 50% enantiomeric excess bupivacaine for lumbar 6 or thoracic 7 epidural anesthesia.

Epinephrine added to local anesthetic solution promotes local vasoconstriction, interfering with the absorption rate of the injected drug, thus allowing it to remain for a longer period in contact with nervous roots 5. However, a study by Newton et al. has shown higher vasoconstrictor activity with the levogyrous isomer, factor considered responsible for long sensory block duration 8. Our study has determined that all solutions should contain the vasoconstrictor agent because investigators were blind to the local anesthetic being used.

According to studies with the levogyrous isomer and 50% enantiomeric excess bupivacaine in patients submitted to cesarean sections 9-11, the association of opioid to local anesthetic potentiates its effects and provides adequate conditions for abdominal procedures. Another tactic described to prevent failures 12 is increasing local anesthetic concentration to obtain the same effect, although this may expose patients to higher anesthetic mass, diminishing the advantages of low systemic toxicity drugs. In our study, fentanyl addition and even the placement of an epidural catheter for further local anesthetic injection have not prevented blockade failures, which may be related to the fact that anesthesia was performed by resident physicians.

Comparing isomers to racemic bupivacaine, an in vitro study 13 has shown that the dextrogyrous one is more potent (1.36), the levogyrous is less potent (0.45) and the 50% enantiomeric excess bupivacaine has similar potency (0.88). However, the clinical use of local anesthetics is more complex than what has been shown in animals, and in vivo potencies do not correlate to in vitro results 14. Local factors affecting anesthetic spread and block extension are of major impact on clinical effects. The clinical use may not require absolute action potential suppression, but just the interruption of information coded by the depolarization pattern. Hence, the relative potency of epidural racemic bupivacaine and levobupivacaine would be the same 15. These data validate the clinical correlation shown in our study in which local anesthetics are clinically comparable in the epidural space in equal concentrations and volumes.

This study has determined that surgery would only start 30 minutes after epidural injection to allow the evaluation of muscle relaxation. Mean time of 20 minutes was needed for motor block to reach the highest degree with racemic and 50% enantiomeric excess bupivacaine 16. In a study by Cox 17, results were similar between levobupivacaine and 0.5% racemic bupivacaine. Differences in motor block intensity in our groups were significant, with more patients presenting Bromage 2 in groups II and III as compared to group I. Delfino et al. 18, studying pure 0.5% levogyrous isomer as compared to 50% enantiomeric excess mixture in patients submitted to varicose vein procedures, have also observed lower degree of relaxation, however difference was significant to Bromage levels 0 and 3. This may be justified by the larger sample size of our study.

In conclusion, both levobupivacaine and 50% enantiomeric excess bupivacaine are local anesthetic solutions suitable for lower abdominal surgeries and clinically comparable to racemic bupivacaine. Levobupivacaine has promoted less motor block as compared to the other two solutions.



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Correspondence to
Dr. Pedro Paulo Tanaka
Address: Rua Justiniano de Mello e Silva, 355
ZIP: 82530-150 City: Curitiba, PR

Submitted for publication December 2, 2004
Accepted for publication August 9, 2005



* Received from Hospital de Clínicas da Universidade Federal do Paraná (UFPr), Curitiba, PR

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