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Revista Brasileira de Anestesiologia

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

Rev. Bras. Anestesiol. vol.56 no.1 Campinas Jan./Feb. 2006 



Racemic 0.25% bupivacaine and 50% enantiomeric excess (S75-R25) 0.25% bupivacaine associated to fentanyl for labor analgesia with patient’s ambulation. Comparative study*


Estudio comparativo entre bupivacaína racémica a 0,25% y bupivacaína con exceso enantiomérico de 50% (S75-R25) a 0,25% asociadas con fentanil para analgesia de parto con deambulación de la gestante



Carlos Alberto Figueiredo Côrtes, TSAI; Luis Fernando Lima Castro, TSAI; Maurício Marsaioli Serafim, TSAI; Amaury Sanchez Oliveira, TSAII; Marcelo GelminiIII; Rodrigo Betiol PetriIII

ICo-Responsável pelo CET/SBA
IIResponsável pelo CET/SBA
IIIME no período de 2002-2003

Correspondence to




BACKGROUND AND OBJECTIVES: Clinical studies with levogyrous enantiomers of local anesthetics have shown better safety due to lower cardiotoxicity. Parturients ambulation during labor may be able to shorten it. This study aimed at comparing anesthetic quality and maternal and fetal repercussions, as well as patients’ ambulation and spontaneous micturition ability with continuous epidural racemic or 50% enantiomeric excess (S75-R25) 0.25% bupivacaine, associated to fentanyl during labor.
METHODS: Participated in this study 40 parturients, physical status ASA I and II, single fetus and in labor, submitted to continuous epidural analgesia, who were divided in two groups: Group I received 8 mL (20 mg) of 0.25% bupivacaine (S75-R25) and epinephrine, associated to 100 mg fentanyl; and Group II received racemic 0.25% bupivacaine and epinephrine associated to 100 mg fentanyl. The following parameters were evaluated: onset time, sensory block level, motor block level, Romberg’s test, ambulation and spontaneous micturition ability, labor and delivery time, maternal hemodynamic and respiratory changes in addition to neonates vitality.
RESULTS: There were no statistically significant differences between groups in all evaluated parameters. All parturients presented with muscle strength and ambulation ability and when this was not observed, the reason was Cesarean delivery indication (1 in Group II) or delivery before the time needed to observe such parameter (4 in Group I and 5 in Group II).
CONCLUSIONS0: Both racemic and S75-R25 0.25% bupivacaine associated to fentanyl were effective for labor analgesia.

Key Words: ANALGESIA, Obstetric: labor; ANALGESICS, Opioids: fentanyl; ANESTHETICS, Local: racemic bupivacaine, 50% enantiomeric excess bupivacaine (S75-R25); ANESTHETIC TECHNIQUES, Regional: continuous epidural


JUSTIFICATIVA Y OBJETIVOS: Estudios clínicos con enantiómeros levógiros de los anestésicos locales demostraron mayor seguridad debido a la menor cardiotoxicidad. La deambulación de la gestante durante el trabajo de parto por lo que puede abreviar la duración del parto. Este estudio compara la calidad de la analgesia y las repercusiones materno fetales así como la capacidad de deambular y de orinar en forma espontánea de las gestantes, usando bupivacaína a 0,25% y bupivacaína con exceso enantiomérico de 50% (S75-R25) a 0,25% asociadas con fentanil por vía peridural continua durante el trabajo de parto.
MÉTODO: Fueron evaluadas 40 gestantes, estado físico ASA I y II, con feto único y en trabajo de parto, que recibieron analgesia peridural continua, divididas en 2 grupos. En el grupo I recibieron  8 mL (20 mg) de bupivacaína (S75-R25) a 0,25% con epinefrina asociados a 100 µg de fentanil. En el grupo II recibieron 8 ml (20 mg) de bupivacaína racémica a 0,25% con epinefrina asociados a 100 µg de fentanil. Los siguientes parámetros fueron evaluados: tiempo de latencia, altura del bloqueo sensitivo, grado de bloqueo motor, examen de Romberg, capacidad de deambular y orinar en forma espontánea, duración del trabajo de parto y del período expulsivo, variables maternas respiratorias y hemodinámicas y la vitalidad de los neonatos.
RESULTADOS: No hubo diferencia estadística entre los grupos en los parámetros evaluados. Todas las gestantes tenían fuerza muscular y capacidad para deambular, pero esto no ocurrió en un caso del grupo II por indicación de cesárea y en 4 casos del grupo I porque el parto ocurrió antes de iniciar la evaluación motora.
CONCLUSIONES: Tanto la bupivacaína a 0,25% como la bupivacaína (S75-R25) a 0,25% asociadas con fentanil demostraron ser una buena opción para analgesia de parto.




Epidural anesthesia for labor analgesia is an effective technique for pain relief and is the most widely used in different countries1-3.

Epidural bupivacaine for labor pain relief and delivery anesthesia is very popular due to its high potency and long duration4. However, motor block intensity is among its limitations with regard to maternal and fetal safety, because it may interfere with labor mechanisms, in addition to being highly cardiotoxic5,6.

Since 1972, one of bupivacaine’s isomers, the dextrogyrous component with narrow safety margin, was already recognized as the major responsible for neurocardiotoxicity7. Clinical studies with levogyrous enantiomers of local anesthetics have shown higher clinical safety as a function of lower central nervous and cardiovascular systems toxicity7-9.

On the other hand, epidural analgesia with patient’s ambulation is being increasingly accepted for promoting increased uterine contractions, preventing inferior vena cava compression by the gravid uterus, helping lowering fetal head and relaxing pelvic muscles10,11.

Currently, anesthetics are prepared by associating low concentrations of opioid agonists, such as fentanyl or sufentanil, to local anesthetics, such as ropivacaine, bupivacaine or levobupivacaine, aiming at obtaining more prolonged analgesia with the lesser possible maternal-fetal effects and with lower changes in delivery dynamics, resulting in more vaginal deliveries and ambulation ability3,12-15.

This study aimed at evaluating the efficacy of epidural enantiomeric (S75-R25) and racemic 0.25% bupivacaine associated to fentanyl for labor analgesia, in terms of quality of analgesia, motor block level, ambulation and spontaneous micturition ability, labor duration, maternal hemodynamic changes and neonates’ vitality.



After the hospital’s Ethics Committee approval and their formal consent, participated in this study 40 primiparous patients, physical status ASA I and II, in labor, with minimum 5 cm cervical dilatation, cephalic presentation and single fetus.

All patients were submitted to continuous epidural analgesia and were randomly distributed in two groups:

· Group I (n = 20): 8 mL (20 mg) 50% enantiomeric excess 0.25% bupivacaine (S75-R25) with 1:200 000 epinephrine, associated to 100 µg fentanyl;

· Group II (n = 20): 8 mL (20 mg) racemic 0.25% bupivacaine with 1:200 000 epinephrine, associated to 100 µg fentanyl.

Maintenance local anesthetic dose (10 mg) was administered to parturients who 15 minutes after analgesia referred pain above 3 by the Visual Analog Scale (VAS). Perineal 20 mg dose was administered to all patients.

After venous puncture with 18G catheter and lactated Ringer’s solution infusion until 10, lumbar puncture was performed in L3-L4 interspace with patients in the sitting position using 17G Tuohy needle. Epidural space was identified by the loss of resistance to air technique and was followed by slow and fractional anesthetic solution administration and epidural catheter insertion in the cephalad direction and introduction of approximately 3 cm. Then, patients were placed in the supine position with the uterus displaced to the left using Crawford’s wedge.

Patients were initially monitored with ECG at DII lead, pulse oximeter, noninvasive blood pressure and heart rate at 5-minute intervals until the 30th minute. Then, due to ambulation, parameters were evaluated at 15-minute intervals.

The following parameters were also evaluated:

1. Demographics data: age, weight, height and body mass index, looking for homogeneity between groups;

2. Gestational age;

3. Cervical dilatation and height of presentation;

4. Pain evaluation by the Visual Analog Scale (VAS) before analgesia and then at 5-minute intervals until the 30th minute;

5. Thermal sensory block level: evaluated by cotton soaked in ether 30 minutes after local anesthetic injection;

6. Ambulation ability: evaluation through motor block level, lower limbs muscle strength, ability to raise the hip from the labor table, and by Romberg’s test with static balance, 30 minutes after local anesthetic injection;

7. Ambulation and spontaneous micturition ability and pain relief at 30 minutes;

8. Time between beginning of analgesia and complete cervical dilatation;

9. Delivery duration;

10. Heart rate, blood pressure and oxygen hemoglobin saturation;

11. Apgar score at 1 and 5 minutes;

12. Neonate weight.

Mann-Whitney test was used for statistical analysis of non-parametric data, and Chi-square test (X2) was used for parametric parameters, being significant p £ 0.05.



Demographics data were evaluated to determine homogeneity between groups. Results are shown in table I, without statistically significant differences between groups.



There were no statistically significant differences between groups in gestational age. Group I mean was 38.99 weeks with standard deviation of 1.651 weeks, and Group II mean was 39.73 weeks, with standard deviation of 1.575.

Most parturients had 6 cm cervical dilatation, with 5 cm in one Group I and four Group II patients.

There were no statistically significant differences in height of fetal head presentation and data are shown in table II.



There were no statistical differences between groups in pain evaluation during studied moments. Initially, all patients had pain intensity between 7 and 10.

At 15 minutes, all Group I patients referred pain equal to or below 3. In Group II, at this moment, one patient referred intensity 5 and all others referred pain below 3.

At 30 minutes, only one Group II patient had pain level 4. All other patients referred pain below 3 or no pain (Table III and Table IV).

Mann-Whitney non-parametric test was applied at every temporal measurement and produced the following results:

Most patients had sensory block at T8, without significant differences between groups (Table V). One Group II patient presented sensory block at T12 and needed maintenance dose.



As to ambulation ability 30 minutes after anesthesia results were as follows: all patients, regardless of group, in whom all parameters could be evaluated, that is, deliveries 30 minutes after analgesia, had motor block level zero, in addition to lower limbs muscle strength and ability to normally raise their hips. In patients where it was possible to evaluate Romberg’s test, results were positive for both groups, that is, patients were placed standing up and had static balance to walk helped by the anesthesiologist or the nurse.

Cases with no ambulation were those where Cesarean delivery was indicated (one Group I patient) or when delivery was before the time needed to measure this variable (four Group I and five Group II patients) (Table VI).



There were no statistically significant differences between groups in spontaneous micturition (Table VII).



Mean time between beginning of analgesia and complete dilatation for Group I was 48.50 minutes, with standard deviation of 15.07 minutes; for Group II time was 54.89 minutes and 21.07 minutes, respectively. There were no statistically significant differences between groups although a higher variability was seen in Group II (Figure 1).



As to delivery duration, there were no statistically significant differences between groups. Group I mean was 11.84 minutes with standard deviation of 3.47 minutes; for Group II, mean was 11.22 minutes with standard deviation of 4.81 minutes (Figure 2).



All patients received 5 Ul oxytocin in 500 mL of 5% glucose solution, in 8 to 12 drops.min-1, indicated by obstetricians.

In terms of hemodynamic parameters, systolic blood pressure was slightly higher in Group II and this difference was maintained throughout the period, except for the last two measurements where both groups were equivalent. Tests have also indicated that time is a significant factor for this variable; systolic blood pressure decreases along time.

Considering the difference between the first and the last systolic pressure measurement, figures show that all patients had decreased or return to baseline systolic blood pressure along time. There were no statistically significant differences between groups in first and last systolic blood pressure (Figure 3).



There were no statistically significant differences in mean diastolic blood pressure, although the result was significant for the time factor (Figure 4).



There was a difference in mean heart rate. Group I started with higher values and remained as such throughout the evaluation period, with increased difference between groups in the last three evaluations.

When comparing first and last heart rate value, one could conclude that there were only cases of heart rate decrease or return to baseline values along time, except for one Group I patient. Tests, however, indicated that mean differences between first and last heart rate values for both groups were not statistically significant. It should be observed that one Group II patient presented atypical heart rate (150 first and 70 last) (Figure 5).



As to mean oxygen hemoglobin saturation there was no statistically significant differences between the techniques, although this variable has increased with time.

There were also no statistically significant differences between first and last mean values of this variable (Figure 6).



Mean neonates weight in Group I was 3,146.93 g with standard deviation of 256.85 g. In Group II, these values were 3,247.67 and 474.71, respectively. There were no statistically significant differences between groups in spite of higher variability in Group II (Figure 7).



All Group II neonates presented with excellent vitality conditions that is Apgar score equal to or above 7 in the 1st minute, remaining with 10 at 5 minutes of life. In Group I, one neonate presented Apgar 3 in the 1st minute and 6 in the 5th minute of life and this child was born from instrumental delivery. All others presented with excellent vitality conditions at birth.



Thirty-five parturients of both groups were primiparous with 6 cm cervical dilatation at analgesia and five parturients had 5 cm cervical dilatation being considered late indications. Early labor analgesia is defined as spinal block with cervical dilatation below 5 cm3,16,17.

If there is inadequate labor analgesia with low local anesthetic doses without fentanyl or sufentanil, especially in early indications with cervical dilatation between 3 and 5 cm, there may be increased surgical deliveries, as shown in a known study3. Other authors believe that the primary factor causing obstetric dystocias is high fetal presentation in the beginning of analgesia, in addition to neonate weight18. Our study has not shown statistically significant differences between groups in fetal presentation height at analgesia and neonate weight, since these are factors influencing labor under analgesia evolution.

There was just one Cesarean delivery in our study and, considering that patients were primiparous with high presentation in most cases, one may state that analgesia has not interfered with labor dynamics in both groups. In a similar study, the incidence of Cesarean deliveries was 63.1% although authors have not reported the presence of motor block19. There are evidences showing that the obstetric approach is more important for the incidence of surgical deliveries as compared to the type of analgesia19.

Although there were no statistically significant differences between groups in the presence of pain, some patients referred some discomfort or even pain (one patient with VAS 4 in Group II at 30 minutes). This may be justified by fast labor evolution after analgesia with mean delivery time of 48.50 minutes in Group I and 54.89 minutes in Group II, similar to what has been obtained in previous publication20.

With 0.25% bupivacaine or 0.2% ropivacaine alone, other authors have concluded that there has been decreased pushing ability due to muscle relaxation, thus prolonging delivery and increasing the number of Cesarean sections6,10. In our study, groups had extremely short delivery times being 11.84 minutes for Group I and 11.22 minutes for Group II, similar to what has been found in studies with 0.125% or 0.25% bupivacaine3,10,21.

With fast labor evolution and fetal presentation more intensively compressing perineal somatic structures, there is severe pain which may not be abolished by the proposed low initial dose. Upper analgesia level, evaluated by thermal sensation, was higher than that needed to relieve pain during dilatation, considering that 75% of parturients from both groups presented levels equal to or above T8. Only one Group II patient presented upper analgesia at T12, lower than desired, with pain score 4 until 30 minutes after analgesia, needing local anesthetic maintenance dose.

All patients whose deliveries were after 30 minutes could walk and had spontaneous micturition, without any clinically evidenced motor block.

The real benefits of ambulating during labor are controversial22, but dilatation in our study was extremely fast and delivery extremely short, which may be related to this factor. Spontaneous micturition should be evidenced because it may prevent vesical catheterization, depending of course of the obstetrician’s approach and of patient’s will.

In an attempt to show that ambulation is not a privilege of the spinal-epidural technique which produces minimum motor block, but which may present complications such as respiratory depression, fetal bradycardia and pruritus with the use of spinal sufentanil, some authors have studied the effectiveness and parturients’ ability to walk after continuous epidural labor analgesia.

They administered initial 12 mL bupivacaine doses in concentrations of 0.0625% and 0.125% with sufentanil (10 mg), with and without 3 mL lidocaine with epinephrine as test dose. In all groups, continuous 13.5 to 15 mL.h-1 bupivacaine infusions associated to 0.33 µg.mL-1 sufentanil were administered, in addition to 5 mL of 0.25% bupivacaine if pain persisted 15 minutes later.

They concluded that the ability to walk with regional anesthesia is not limited to the combined spinal-epidural technique and that ambulation may be obtained with epidural analgesia with 0.125% bupivacaine without test dose22. Our study has obtained the same satisfactory results with 0.25% bupivacaine associated to fentanyl, using half the initial volume preconized by the previous study, without continuous local anesthetics and opioids infusion, suggesting that total local anesthetics used could be more important than its concentration.

There is low incidence of local anesthetics intoxication, however it is catastrophic and investigations are directed toward obtaining less toxic local anesthetics8,9,23,24. Although labor analgesia doses are low, when there is supplementation to obtain surgical anesthesia for Cesarean delivery, these will be added and in this case bupivacaine (S75-R25) may be advantageous due to its lower toxicity.

We were able to conclude that continuous epidural block with local anesthetics in concentrations and doses used, associated to opioids, was a good option for labor analgesia, providing comfort to patients and pain relief, respecting labor and neonate physiology and not preventing patients’ cooperation who are able to ambulate and push with maintenance of abdominal press during delivery, without significant hemodynamic changes.



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Correspondence to
Dr. Carlos Alberto Figueiredo Côrtes
Address: Av. Orosimbo Maia, 165 - 3º andar
ZIP: 13023-910 City: Campinas, Brazil

Submitted for publication May 2, 2005
Accepted for publication November 17, 2005



* Received from Hospital e Maternidade de Campinas, CET/SBA Integrado de Campinas, Campinas, SP

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