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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094

Rev. Bras. Anestesiol. vol.51 no.5 Campinas Sept./Oct. 2001 



Comparative study of 0.5% levobupivacaine and 0.5% racemic bupivacaine associated to sufentanil in epidural anesthesia for cesarean delivery*


Estudio comparativo entre levobupivacaína a 0,5% y bupivacaína racémica a 0,5% asociadas al sufentanil en la anestesia peridural para cesárea



João Batista Santos Garcia, TSA, M.D.I; José R Oliveira, M.D.II; Elismar P A Silva, M.D.III; Marcelo S Privado, M.D.III; Américo M Yamashita, TSA, M.D.IV; Adriana M Issy, M.D.V

IProfessor Adjunto de Anestesiologia da UFMA
IIAnestesiologista do Hospital Universitário Materno Infantil da UFMA
IIIAnestesiologista colaborador
IVProfessor Assistente de Anestesiologia da Universidade Federal de São Paulo, UNIFESP, São Paulo, SP
VProfessora Adjunta de Anestesiologia da Universidade Federal de São Paulo, UNIFESP, São Paulo, SP





BACKGROUND AND OBJECTIVES: Although the widespread use of local anesthetics in surgery and obstetrics, racemic bupivacaine is associated to potentially fatal cardiotoxicity. Data suggest that levobupivacaine has local anesthetic effects similar to racemic bupivacaine with the advantage of less central nervous system and cardiovascular toxicity. Studies have shown that epidural anesthesia with racemic bupivacaine and sufentanil for cesarean sections results in a better quality of anesthesia. This study aimed at comparing the efficacy of 0.5% racemic bupivacaine and 0.5% levobupivacaine, both associated to sufentanil, for epidural anesthesia in parturients undergoing cesarean delivery.
METHODS: Participated in this double-blind study 52 obstetric patients submitted to elective cesarean delivery under epidural anesthesia. Patients were randomized to receive 27 ml of 0.5% levobupivacaine and 30 µg sufentanil (Group I n=26) or 27 ml of 0.5% bupivacaine and 30 µg sufentanil (Group II n=26). Characteristics of sensory and motor block, time for analgesics request in the postoperative period and the incidence of side effects were investigated.
RESULTS: Sensory and motor block, time for analgesics request and adverse effects did not differ between groups. However, motor block was significantly longer with levobupivacaine as compared to racemic bupivacaine (p < 0.05).
CONCLUSIONS: Although a longer motor block duration with 0.5% epidural levobupivacaine associated to sufentanil, the efficacy of both local anesthetics associated to sufentanil for cesarean delivery was similar.

Key words: ANALGESICS, Opioids: sufentanil; ANESTHETICS, Local: bupivacaine, levobupivacane; ANESTHETIC TECHNIQUES, Regional: epidural; SURGERY, Obstetric: cesarean section


JUSTIFICATIVA Y OBJETIVOS: A pesar del uso frecuente de anestésicos locales en procedimientos quirúrgicos y obstétricos, la bupivacaína racémica es asociada a la cardiotoxicidad potencialmente fatal. Estudios sugieren que la levobupivacaína presenta acción anestésica local semejante a la bupivacaína racémica, con la ventaja de menor toxicidad tanto en el sistema nervioso central como cardiovascular. Los trabajos han demostrado mejor calidad anestésica con el uso de bupivacaína racémica asociada al sufentanil, vía peridural para cesárea. El presente estudio compara la eficacia de la bupivacaína racémica 0,5% con levobupivacaína 0,5%, ambas asociadas al sufentanil, vía peridural, en parturientas sometidas a cesárea.
MÉTODO: Fueron investigadas 52 mujeres embarazadas, sometidas a anestesia peridural para cesárea electiva. En este estudio duplamente encubierto, las pacientes fueron distribuidas aleatoriamente en dos grupos: Grupo I (n = 26): recibieron 27 ml de levobupivacaína 0,5% y 30 µg de sufentanil, Grupo II (n = 26) recibieran 27 ml de bupivacaína 0,5% y 30 µg de sufentanil. Fueron evaluadas las características de los bloqueos motor y sensorial, el tiempo necesario para solicitación de analgésicos y la incidencia de efectos adversos en el período pós-operatorio.
RESULTADOS: Los bloqueos motor y sensorial, el tiempo para solicitación de analgésicos y los efectos adversos no divergieron entre los grupos. Entretanto, cuando se comparó la duración del bloqueo motor de la levobupivacaína con el de la bupivacaína racémica, se observó duración significantemente prolongada para levobupivacaína (p < 0,05).
CONCLUSIONES: A pesar de la duración del bloqueo motor ser más prolongado para la levobupivacaína asociada al sufentanil, la eficacia anestésica de ambos anestésicos locales investigados, asociados al sufentanil en cesárea por vía peridural, fueron iguales.




Levobupivacaine is a bupivacaine's pure enantiomer (S-) recently introduced in the therapeutic armamentarium for regional blocks. It is strongly bound to plasma proteins with high clearance rate and shorter half-life as compared to its enantiomer (R+). Enantiomers (S-) seem to cause less systemic cardiotoxicity, with a lower incidence of central nervous system and cardiovascular toxicity according to pre-clinical studies 1-3.

Clinical studies have shown that epidural levobupivacaine promotes sensory and motor block similar to bupivacaine (with lower toxicity) in patients needing surgical anesthesia 4. These characteristics make levogyrous bupivacaine attractive for obstetric anesthesia since pregnant women have a high toxicity risk due to physiological adaptations.

The association of long-lasting epidural anesthetics and liposoluble or hydrosoluble opioids, in addition to improving peri and postoperative analgesia, allows for the use of lower local anesthetic doses 5-9.

This study aimed at evaluating the efficacy of epidural 0.5% racemic levobupivacaine and bupivacaine, both associated to sufentanil (30 µg) in patients submitted to cesarean delivery.



After the Hospital's Ethics Committee approval and their formal consent, participated in this double-blind study 52 patients, physical status ASA I or II, aged 16 to 39 years, submitted to elective cesarean delivery under epidural anesthesia.

Patients were randomly distributed in two groups of 26 patients each. Group I received 27 ml (135 mg) of 0.5% levobupivacaine associated to 3 ml sufentanil (30 µg) and Group II received 27 ml (135 mg) of 0.5% racemic bupivacaine associated to 3 ml sufentanil (30 µg), both in a single dose. No vasoconstrictor was associated for both groups. Drugs were distributed by the laboratory in numbered vials which were decoded at the end of the study.

Venoclysis was followed by volume expansion with 500 ml lactated Ringer's. Lumbar epidural block was performed at L3-L4 interspace using the loss of resistance to air technique. After injection, patients were placed in the supine position with manual uterus displacement to the left.

Monitoring consisted of non-invasive blood pressure, heart rate and rhythm and oxygen peripheral saturation. Blood pressure and heart rate were evaluated in different moments: before blockade (T0), 5 (T5), 10 (T10), 15 (T15), 20 (T20), 30 (T30), 45 (T45), 60 (T60), 90 (T90), 120 (T120), 180 (T180) and 240 (T240) minutes after epidural injection.

Parameters related to blockade installation, in addition to intercurrences and complications were observed. For installation, paresthesias (patients subjective information), sensory onset (by clamping the sensitive area corresponding to puncture site), time for maximum sensory block and metameric level of T6, in addition to time for maximum muscular relaxation (confirmed by abdominal muscles relaxation test - AMR, described by Van Zudert) 10 were measured and recorded.

To evaluate blockade duration, times for the following parameters were studied:

• surgical anesthesia evaluated by the clamping test, in the same area used to check initial sensitivity (puncture level);

• muscular relaxation, reverted with total motility recovery;

• regression of two metamers, evaluated by the time needed for the blockade to regress two segments, as compared to the highest blockade obtained;

• analgesia duration, when the patient would voluntarily ask for analgesics due to pain on surgery site.

Those parameters were analyzed as from anesthetic solution injection.

Intercurrences, such as hypotension (20% below initial systolic blood pressure), bradycardia (HR < 50 bpm), nausea and vomiting, pruritus, somnolence, shivering, pain on anesthetic injection site and at fetal extraction, were recorded during the whole study. Hypotension was treated with fractionated doses of 10 mg ephedrine.

For statistical analysis of results Student's t test for parametric variables and Mann-Whitney test for non-parametric variables were applied. Friedman's analysis of variance by posts was used to compare heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) within each group along time. Chi-square or Fisher exact test were applied to study complications and intercurrence associations within groups 11,12. Null hypothesis rejection level was established as 0.05 or 5%.



There were no significant differences in mean weight, height, body mass index and age in both groups (Table I).

Mean heart rate variation along time has shown a significant decrease as from 60 minutes for GI and 90 minutes for GII, without significant differences between groups (Figure 1). There has been a significant systolic blood pressure decrease as from 15 minutes for GI and 20 minutes for GII, without significance when comparing both groups (Figure 2). Diastolic blood pressure significantly decreased in both groups as from 20 minutes, also without significance when comparing both groups (Figure 3).

Epidural blockade onset measurements (paresthesias, sensory onset, time for maximum sensory block and relaxation, as well as time for reaching T6) were not significantly different between groups (Table II).

A metameric level above blockade in T4 (mode) was observed in both groups, with variation of T8 to T3 in GI and of T7 to T2 in GII. Highest muscular relaxation level (MRL) was 3 for both groups. The muscular relaxation duration was significantly higher in GI (levobupivacaine) as compared to GII (racemic).

Anesthesia duration, time for two-metamer regression and for analgesic request were not significantly different between groups (Table III).

Intercurrences, which were not significantly different between groups are shown in table IV. Pruritus was the most frequent adverse effect (referred by 11 patients).



Ropivacaine, and subsequently levobupivacaine, new long-lasting local anesthetics, were synthesized to replace bupivacaine in local/regional blocks. Both have less cardiotoxicity and neurotoxicity as compared to bupivacaine 13,14.

Clinical studies have shown that levobupivacaine is equipotent to bupivacaine in terms of anesthetic efficacy 4,15,16.

In line with bupivacaine experiments, early studies with ropivacaine and levobupivacaine have also associated lipophylic opioids aiming at improving anesthesia and decreasing the dose of local anesthetics 5-9,17,18. Clinical trials have not shown significant differences in sensory block, motor block, muscle relaxation and anesthesia quality between groups receiving 0.5% levobupivacaine or bupivacaine 4,16,19,20. Our results were similar, but the motor block  duration was higher in the levobupivacaine group, without clinical significance (Table III).

As to time to epidural block installation, there have been no significant differences between groups in sensory onset, maximum sensory block, maximum muscular relaxation and time to reach T6 (Table II). Our results were similar to other authors' 16,17.

The association of opioids to local anesthetics in spinal blocks decreases blockade onset time and improves anesthesia quality 5,7,21,22. Our study has shown that the association of 0.5% levobupivacaine or bupivacaine (27 ml) to sufentanil (30 µg), has provided an adequate analgesia for the proposed surgery. Only three racemic group patients referred discomfort at fetal extraction. Postoperative analgesia was 355.58 minutes for the levobupivacaine group and 303.35 for the racemic bupivacaine group, and longer as compared to the administration of racemic bupivacaine alone for cesarean delivery.

There have been no significant differences in blockade regression between groups. Similar results were obtained by other authors 16 in a study where no lipophylic opioid was associated to local anesthetics.

Both groups presented a significant heart rate decrease during the study (T0 -T240), but without differences between groups (Figure 1). A significant systolic and diastolic blood pressure decrease was observed during the first 20 minutes in both groups. As from this moment there has been a stabilization of such parameters (Figures 2 and 3). These are common events during regional anesthesia for cesarean delivery and have no clinical significance.

Clinical intercurrences were irrelevant to the point that they did not compromise anesthesia quality. Pruritus was the most frequent complaint, as shown in table IV and was approximately 50% lower than what has been observed by other authors 17 using morphine in addition to lipophylic opioids. Hypotension was present in 15.38% of Group I and 11.54% of Group II patients, without differences between groups and in line with other studies 16,17.

We concluded that epidural 0.5% levobupivacaine (135 mg) associated to sufentanil (30 µg) for cesarean delivery is as effective as the association of 0.5% racemic bupivacaine (135 mg) and sufentanil (30 µg).



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Correspondence to:
Dr. João Batista Santos Garcia
Address: Av. dos Holandeses, 213/701 - Ponta da Areia
ZIP: 65085-150 City: São Luiz, Brazil

Submitted for publication December 4, 2000
Accepted for publication March 21, 2001



* Received from Hospital Universitário da Universidade Federal do Maranhão (UFMA) São Luiz, MA

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