Minimum analgesic concentration of bupivacaine after continuous epidural infusion following spinal anesthesia in the postoperative period of leg, ankle and foot surgery

Abstracts

JUSTIFICATIVA E OBJETIVOS: A concentração analgésica mínima de um anestésico local (CAM-AL) corresponde à concentração efetiva em 50% das pacientes durante o primeiro estágio do trabalho de parto. Pode ser utilizada para determinar a potência relativa de diferentes agentes e estimar o efeito de drogas analgésicas co-administradas no espaço peridural. O objetivo deste estudo foi o de determinar a CAM-AL da bupivacaína para analgesia peridural de cirurgias ortopédicas. MÉTODO: Foi aplicada a técnica de alocação seqüencial não aleatória duplamente encoberta a 23 adultos submetidos a cirurgias ortopédicas sobre a perna, tornozelo ou pé. A anestesia constou de bloqueio subaracnóideo lombar com bupivacaína hiperbárica. Um cateter peridural colocado em L4-L5 foi avançado 3 a 5 cm em direção cefálica. No período pós-operatório imediato, foram administrados 20 ml de bupivacaína seguida de infusão de 0.15 ml.kg-1.h-1, na concentração apropriada. Escores analógicos visuais de dor e de Bromage foram registrados após 4, 8 e 12 horas. A concentração foi considerada eficaz quando os escores de dor foram inferiores a 10 mm em todas as avaliações. A concentração inicial foi de 0,3% e diminuiu ou aumentou 0,1% caso a resposta do paciente anterior tenha sido ineficaz ou eficaz, respectivamente. A CAM-AL foi calculada pela fórmula de Massey e Dixon. RESULTADOS: A CAM-AL da bupivacaína (limites de 95% de confiança) foi de 0,16% (0,11% e 0,21%). Bloqueio motor intenso foi observado na maioria dos pacientes. CONCLUSÕES: Para uma taxa de infusão de 0.15 ml.kg-1.h-1, a CAM-AL da bupivacaína foi de 0,16%. No entanto, o modelo utilizado pode não ter sido adequado para a avaliação dos efeitos motores das concentrações testadas.

ANALGESIA; ANESTÉSICOS, Local; TÉCNICAS ANESTÉSICAS, Regional; TÉCNICAS ANESTÉSICAS, Regional

SCIENTIFIC ARTICLE

Minimum analgesic concentration of bupivacaine after continuous epidural infusion following spinal anesthesia in the postoperative period of leg, ankle and foot surgery^*

Concentración analgésica mínima de la bupivacaína durante infusión peridural continua después de bloqueo subaracnóideo en el período pós-operatorio de cirugías ortopédicas de la pierna, tobillo y pie

Getúlio Rodrigues de Oliveira Filho, TSA, M.D.^I; Nilton Gesser, TSA, M.D.^II; Márcia Regina Ghellar, TSA, M.D.^II; Ranulfo Goldschmidt, TSA, M.D.^II; Adilson José Dal Mago, TSA, M.D.^II

^IResponsável pelo CET/SBA

^IIInstrutor do CET/SBA

Correspondence

SUMMARY

BACKGROUND AND OBJECTIVES: Minimum analgesic concentration of a local anesthetic (MAC-LA) is the effective concentration for 50% of patients (EC₅₀) during the first stage of labor. It may be used to determine relative analgesic potency and to estimate the effects of co-administered epidural analgesics. This study aimed at determining epidural bupivacaine's MAC-LA for orthopedic surgery.

METHODS: A double-blind non randomized sequential allocation method for MAC calculation was applied to 23 adult patients undergoing orthopedic leg, ankle or foot surgeries. Anesthesia was obtained with lumbar spinal hyperbaric bupivacaine. An epidural catheter placed at L₄-L₅ level was inserted 3 to 5 cm in the cephalad direction. Postoperatively, a 20 ml epidural bupivacaine bolus followed by 0.15 ml.kg^-1.h^-1 infusion were administered at the appropriate concentration. Pain and Bromage scores were recorded after 4, 8 and 12 hours. Bupivacaine concentration was considered effective when visual analog pain scores were below 10 mm in all evaluations. Initial concentration was 0.3% and was subsequently decreased or increased by 0.1% for next patient when previous response was effective or ineffective, respectively. MAC-LA was calculated by Dixon and Massey's formula.

RESULTS: Bupivacaine's MAC-LA (95% confidence limits) was 0.16% (0.11% and 0.21%). Intense motor blockade was observed in most patients.

CONCLUSIONS: For a 0.15 ml.kg^-1.h^-1 infusion rate, bupivacaine's MAC-LA was 0.16%. However, the model may have not been suitable for the evaluation of motor effects of tested concentrations.

Key words: ANALGESIA: postoperative; ANESTHETICS, Local: bupivacaine; ANESTHETIC TECHNIQUES, Regional: continuous epidural, spinal block

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La concentración analgésica mínima de un anestésico local (CAM-AL) corresponde a la concentración efectiva en 50% de las pacientes durante la primera parte del trabajo de parto. Puede ser utilizada para determinar la potencia relativa de diferentes agentes y estimar el efecto de drogas analgésicas co-administradas en el espacio peridural. El objetivo de este estudio fue el de determinar la CAM-AL de la bupivacaína para analgesia peridural de cirugías ortopédicas.

MÉTODO: Fue aplicada la técnica de alocación secuencial no aleatoria doblemente encubierta a 23 adultos sometidos a cirugías ortopédicas sobre la pierna, tobillo o pie. La anestesia constó de bloqueo subaracnóideo lumbar con bupivacaína hiperbárica. Un catéter peridural colocado en L₄-L₅ fue avanzado 3 a 5 cm en dirección cefálica. En período pós-operatorio inmediato, fueron administrados 20 ml de bupivacaína seguida de infusión de 0.15 ml.kg^-1.h^-1, en la concentración apropiada. Puntos analógicos visuales de dolor y de Bromage fueron registrados después 4, 8 y 12 horas. La concentración fue considerada eficaz cuando los puntos de dolor fueron inferiores a 10 mm en todas las evaluaciones. La concentración inicial fue de 0,3% y disminuyó o aumentó 0,1% caso la respuesta del paciente anterior haya sido ineficaz o eficaz, respectivamente. La CAM-AL fue calculada por la fórmula de Massey y Dixon.

RESULTADOS: La CAM-AL de la bupivacaína (límites de 95% de confianza) fue de 0,16% (0,11% y 0,21%). Bloqueo motor intenso fue observado en la mayoría de los pacientes.

CONCLUSIONES: Para una tasa de infusión de 0.15 ml.kg^-1.h^-1, la CAM-AL de bupivacaína fue de 0,16%. No obstante, el modelo utilizado puede no haber sido adecuado para la evaluación de los efectos motores de las concentraciones testadas.

INTRODUCTION

Minimal analgesic concentration of a local anesthetic (MAC-LA) is the median effective concentration of a local anesthetic during the first stage of labor and corresponds to the concentration infused in the epidural space that will induce analgesia in 50% of patients (EC₅₀) ¹. The obstetric MAC-LA calculation model has allowed the establishment of the relative potency of different local anesthetics^1-3 and the effect of simultaneous administration of epidural opioids ^4-7.

MAC-LA is calculated by the non randomized sequential allocation method described by Massey and Dixon and local anesthetic concentration administered to each patient is a function of previous patient's response ^1,8,9-11. Some advantages of this method are a 30% to 70% decrease in sample size as compared to multi-group studies with fixed local anesthetic concentrations, in addition to reducing the number of patients submitted to inadequate analgesia ^1,8.

Lower limb orthopedic surgeries cause moderate to severe postoperative pain, thus justifying continuous or intermittent epidural infusion of local anesthetics associated or not to opioids in the immediate postoperative period. However, the minimum analgesic concentration of local anesthetics for this type of surgery has not yet been defined. Knowing the MAC-LA of such anesthetic agents in lower limb orthopedic surgeries may be useful to compare relative potencies and to study the effects of adjuvant drugs.

This study aimed at determining bupivacaine's MAC-LA for continuous epidural infusion in the postoperative period of lower limb orthopedic surgeries.

A pilot study (Study I) was carried out to determine sample size, postoperative pain visual analog scores for lower limb surgeries and the intervals between bupivacaine concentrations to be used for MAC-LA determination (Study II).

METHODS

Both studies were approved by Hospital Governador Celso Ramos Medical Ethics Committee and the informed consents of all patients were obtained.

All patients were classified as physical status ASA I. Patients aged below 18 or above 65 years, non-cooperative, with neurological or psychiatric diseases, drug addicted, with liver or kidney diseases, diabetes mellitus and plaster immobilization of the operated extremity were excluded from the study.

Both studies were prospective and double-blind.

Patients were premedicated with oral diazepam (0.1 to 0.15 mg.kg^-1) 60 to 90 minutes before surgery. Peripheral venoclysis was installed for saline infusion at a rate of 2 ml.kg^-1.h^-1. Monitoring consisted of cardioscope, non invasive blood pressure and pulse oximetry.

Study I

Participated in this study 28 patients aged 19 to 56 years, of both genders submitted to lower limb orthopedic surgeries (hip and femur: 4 patients; knee: 11 patients; leg, ankle and foot: 13 patients). An epidural catheter was placed at L₄-L₅ and advanced 3 to 5 cm in the cephalad direction. Anesthesia was induced with propofol (2 to 2.5 mg.kg^-1) and maintained with 50% nitrous oxide and isoflurane under manually controlled ventilation through a laryngeal mask. At recovery, visual analog scores were recorded on a 100 mm scale (0 = no pain, 100 = the worst imaginable pain), according to previous instruction and training. If the visual analog score was above 10 mm, patients would receive 20 ml bupivacaine in the adequate concentration through the epidural catheter. The first patient received 0.125% bupivacaine and the following received 0.0125% more or less, according to previous patient's response, as described below.

Bupivacaine's analgesic concentration efficacy was evaluated 30 minutes after administration by an observer unaware of the concentration in use, and was classified as:

a) Effective - when pain visual analog score was lower than or equal to 10 mm. In this case, the next patient received bupivacaine in a concentration reduced in 0.0125%;

b) Ineffective - when pain visual analog score was higher than 10 mm. In this case, 15 ml of 2% lidocaine were administered and a new evaluation was performed 30 minutes later.

Case visual analog scores were equal to or lower than 10 mm, bupivacaine's concentration was considered ineffective and the next patient would received 0.0125% more. If the visual analog score remained above 10 mm, the case was rejected and the next patient would receive the same bupivacaine's concentration.

Effective and ineffective concentrations were compared by non paired Student's t test. Pain visual analog scores in operated sites were compared by Kruskal-Wallis test. Significance level was established to 5%.

Study II

Participated in this study 23 patients of both genders, aged 20 to 58 years, submitted to elective leg, ankle or foot orthopedic surgery. Patients were placed in the lateral position over the operated limb and received 12 to 15 mg of 0.5% hyperbaric bupivacaine in the subarachnoid space through a 27G Quincke needle introduced by median access at L₄-L₅ level. A 16G Tuohy needle was introduced in the same place and the epidural space was located by the loss of resistance to saline test. An 18G epidural catheter was then introduced 3 to 5 cm in the cephalad direction. No local anesthetics test dose was administered and catheter patency was confirmed by 1 ml saline injection. An occlusive dressing protected the catheter. Surgery was started and upper sensory block level was tested by pinprick (22G needle) 30 minutes after spinal injection and at 30-minute intervals thereof. Patients were sedated during surgery with repeated doses of 2 mg midazolam.

After a 4-dermatome regression of upper sensory block (HO), 20 ml bupivacaine in the concentration determined by the previous patient's response were injected through the epidural catheter at a rate of 4 ml.min^-1, followed by bupivacaine infusion in the same concentration through a volumetric pump at a rate of 0.15 ml.kg^-1.h^-1. The first patient received 0.3% bupivacaine. The intervals between tested concentrations were 0.1%.

An investigator unaware of the bupivacaine's concentration used evaluated the patients 4 (H4), 8 (H8) and 12 (H12) hours after epidural infusion and the following data were collected:

a) Pain at rest and during ankle and toes movement, measured through a 100 mm pain visual analog score (0 = no pain; 100 = the worst imaginable pain);

b) Bromage scores for active movement of the operated limb: 0 = no movement, 1 = ankle flexion, 2 = ankle and knee flexion, and 3 = ankle, knee and hip flexion.

Bupivacaine analgesic efficacy was evaluated as follows:

a) Effective when, in all evaluations, visual analog scores were lower than or equal to 10 mm at rest and during movement. In this case, the next patient would receive a bupivacaine's concentration 0.1% lower;

b) Ineffective when, at least in one evaluation, visual analog score at rest or during movement was higher than 10 mm. In this case, 15 ml of 0.5% bupivacaine were administered and a new evaluation was performed after 30 minutes. If pain visual analog score at rest or during movement was equal to or lower than 10 mm, the concentration studied was considered ineffective and the next patient would receive 0.1% more bupivacaine.

Case pain visual analog score persisted above 10 mm, patient was rejected and the same bupivacaine's concentration was administered to the next patient.

Bupivacaine's minimum analgesic concentration was calculated by Massey and Dixon's formula ⁸.

Upper sensory block level and Bromage scores were compared between effective and ineffective concentrations by Mann-Whitney test. Significance level was established to 5%.

RESULTS

Demographics data of both samples are shown in table I.

Brazilian Journal of Anesthesiology, 2001; 51: 5: 385-393

Minimum analgesic concentration of bupivacaine after continuous epidural infusion following

spinal anesthesia in the postoperative period of leg, ankle and foot surgery

Getúlio Rodrigues de Oliveira Filho; Nilton Gesser; Márcia Regina Ghellar;

Ranulfo Goldschmidt; Adilson José Dal Mago

Study I

Figure 1 shows the responses to different bupivacaine concentrations. Bupivacaine's MAC-LA could not be calculated because data did not meet essential Massey and Dixon formula's requirements. There were 6 effective responses, 15 ineffective and 7 rejections. Mean bupivacaine concentration in this sample was 0.18% ±0.05%. Mean effective bupivacaine concentration was 0.19% ±0.07% and mean ineffective concentration was 0.18% ±0.055% (p>0.05). Median pain visual analog score (extremes) before bupivacaine administration was 70 (25 and 100 mm) and did not significantly differ according to the operated site.

Brazilian Journal of Anesthesiology, 2001; 51: 5: 385-393

Minimum analgesic concentration of bupivacaine after continuous epidural infusion following

spinal anesthesia in the postoperative period of leg, ankle and foot surgery

Getúlio Rodrigues de Oliveira Filho; Nilton Gesser; Márcia Regina Ghellar;

Ranulfo Goldschmidt; Adilson José Dal Mago

Study II

Figure 2 shows the responses to the tested bupivacaine's concentrations. There were 11 effective responses, 9 ineffective and 3 rejections. Bupivacaine's concentrations were considered ineffective in 3 patients in H4, 4 patients in H8 and 2 patients in H12. Bupivacaine's MAC-LA (EC₅₀) was calculated in 0.16%, with a 95% confidence interval between 0.11% and 0.21%. EC₉₅ was calculated in 0.26%, with 95% confidence intervals between 0.21% and 0.31%. There were no upper sensory block level differences between patients receiving bupivacaine effective and ineffective concentrations. Effective concentrations produced significantly lower Bromage scores as compared to ineffective concentrations (Tables II and ^III).

Brazilian Journal of Anesthesiology, 2001; 51: 5: 385-393

Minimum analgesic concentration of bupivacaine after continuous epidural infusion following

spinal anesthesia in the postoperative period of leg, ankle and foot surgery

Getúlio Rodrigues de Oliveira Filho; Nilton Gesser; Márcia Regina Ghellar;

Ranulfo Goldschmidt; Adilson José Dal Mago

Brazilian Journal of Anesthesiology, 2001; 51: 5: 385-393

Minimum analgesic concentration of bupivacaine after continuous epidural infusion following

spinal anesthesia in the postoperative period of leg, ankle and foot surgery

Getúlio Rodrigues de Oliveira Filho; Nilton Gesser; Márcia Regina Ghellar;

Ranulfo Goldschmidt; Adilson José Dal Mago

Brazilian Journal of Anesthesiology, 2001; 51: 5: 385-393

Minimum analgesic concentration of bupivacaine after continuous epidural infusion following

spinal anesthesia in the postoperative period of leg, ankle and foot surgery

Getúlio Rodrigues de Oliveira Filho; Nilton Gesser; Márcia Regina Ghellar;

Ranulfo Goldschmidt; Adilson José Dal Mago

DISCUSSION

Although not allowing bupivacaine's MAC-LA calculation in lower limb orthopedic surgeries, study I provided mean and standard deviation estimates needed to calculate study II sample size. Since standard deviation for the whole sample was 0.05% and there has been a 0.1% interval between effective concentrations of case 8 and case 16, this 0.1% interval was adopted in study II. Since there is no method for a priori sample size calculation for the non randomized sequential allocation method, estimates were based on Student's t test for independent samples ⁷. It was established that a significant difference between effective and ineffective concentrations should be higher than the standard deviation and lower than the test interval, that is, between 0.06% and 0.09%. With the above data and considering a = 0.05 and b = 0.2, sample size was estimated between 10 and 18 patients.

Study I has also allowed postoperative pain intensity estimates in lower limb orthopedic surgeries. Since median pain visual analog score was 70 mm, reflecting moderate or severe pain, the conclusion was that the model should be abandoned for exposing patients to such severe postoperative pain. For this reason, we decided to study bupivacaine's MAC-LA using postoperative continuous infusion after spinal anesthesia and, since MAC-LA varies according to the painful stimulus intensity ^11,12, study II sample was limited to leg, ankle and foot surgeries.

Although the effective concentration in 95% of patients (EC₉₅) be more relevant for clinical practice, the effective concentration in 50% of patients (EC₅₀) is a more useful research tool due to its position in local anesthetics concentration-response curve. EC₅₀ corresponds to the point were there is a maximum slope so that any factor changing the concentration-response curve position is easily detected by changes in EC₅₀ values. On the other hand, EC₉₅ is located at the upper flat portion of the concentration-response curve in a way that only major changes in its position will be noticed by EC₉₅ analysis.

MAC-LA was calculated by the non randomized sequential allocation method described by Massey and Dixon ⁸. According to this method, the interval between tested concentrations should be lower than two standard deviations (SD). In study II, the interval between tested concentrations was 0.1%, or 1.66 SD. Robustness of test t was estimated as 0.92, so that with the final sample of 20 patients, the possibility of type II error was 0.08.

Among patients receiving ineffective bupivacaine concentrations, upper sensory block level measured by pinprick remained between T₁₀ and L₄, showing that the lack of sensitivity measured by such method does not prevent patients from referring pain in the territory innervated by L₅ and S₁. This is in line with other studies where only high local anesthetic concentrations produced a complete sensory block of L₅ and S₁ roots ^13-16. This is because L₅ and S₁ roots are thicker, thus prolonging sensory and motor block onset and decreasing their intensity ¹⁷. In a previous study, 0.5% bupivacaine, associated or not to epidural or intravenous fentanyl, has not provided total anesthesia and immobility in the territory innervated by L₄, L₅ and S₁ roots ¹⁸.

In studies of first stage labor analgesia, bupivacaine's MAC-LA was estimated between 0.048% and 0.14% ^1-7,10-12. In our study, bupivacaine's MAC-LA was estimated in 0.16%. Reasons for such difference may be the type of pain (somatic in this study and visceral in the others), pain intensity generated by leg, ankle and foot orthopedic surgeries and larger L₅ and S₁ roots as compared to T₁₀ to L₁ roots involved in first stage labor pain.

A large number of patients presented with intense motor block during the observation period, and this was even higher among patients with effective analgesia. This may be due to the cumulative effect of bupivacaine infusion. In other studies, prolonged 0.125% bupivacaine infusions at a rate of 0.15 ml.kg^-1.h^-1 were not associated to a prevalence of motor block similar to our study ^19-21. Although bupivacaine's administration took place during the spinal block recovery period, it might have delayed bupivacaine elimination from the spinal space because it depends on extradural local anesthetic spread and is forced by concentration gradient; at the same time there might have been spinal spread of epidural bupivacaine, thus intensifying spinal block ²² even with no increase in upper sensory block level after epidural bupivacaine administration.

So, although continuous infusion after spinal block having allowed bupivacaine's MAC-LA calculation in leg, ankle and foot orthopedic surgeries, it is possible that this model will not be useful to investigate bupivacaine's minimum analgesic concentration effects on motor block.

REFERENCES

• 01. Columb MO, Lyons G - Determination of the minimum local analgesic concentrations of epidural bupivacaine and lidocaine in labor. Anesth Analg, 1995;81:833-837.
• 02. Capogna G, Celleno D, Fusco P et al - Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth, 1999;82:371-373.
• 03. Polley LS, Columb MO, Naughton NN et al - Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor: implications for therapeutic indexes. Anesthesiology, 1999;90:944-950.
• 04. Columb MO, Polley LS, Wagner DS et al - Reduction in the minimum local analgesic concentration (MLAC) of bupivacaine by epidural sufentanil is dose dependent. European J Anaesthesiol, 1997;14:549-550.
• 05. Polley LS, Columb MO, Wagner DS et al - Dose-dependent reduction of the minimum local analgesic concentration of bupivacaine by sufentanil for epidural analgesia in labor. Anesthesiology, 1998;89:626-632.
• 06. Polley LS, Columb MO, Lyons G et al - The effect of epidural fentanyl on the minimum local analgesic concentration of epidural chloroprocaine in labor. Anesth Analg, 1996;83: 987-990.
• 07. Polley LS, Columb MO, Naughton NN et al - Effect of intravenous vs epidural fentanyl on the minimum local analgesic concentration (MLAC) of epidural bupivacaine in labor. Anesthesiology, 1999;90:25A.
• 08. Dixon WJ, Massey FJ - Introduction to Statistical Analysis. 4^th Ed, New York, McGraw-Hill, 1983:428-439.
• 09. Wulf HF - Up-down sequential allocation technique to investigate the influence of opioids on the efficacy of epidural local anesthetics in labor pain. Anesthesiology, 1999;90:1788.
• 10. Columb MO, Polley LS - Up-down sequential allocation technique to investigate the influence of opioids on the efficacy of epidural local anesthetics in labor pain. Anesthesiology, 1999;90:1788-1789.
• 11. Columb MO, Lyons G, Polley LS - Bupivacaine requirements for labor analgesia. Anesthesiology, 1999;90:73A.
• 12. Capogna G, Celleno D, Lyons G et al - Minimum local analgesic concentration of extradural bupivacaine increases with progression of labour. Br J Anaesth, 1998;80:11-13.
• 13. Galindo A, Benavides O, De Munos SO et al - Comparison of anesthetic solutions used in lumbar and caudal peridural anesthesia. Anesth Analg, 1978;57:175-179.
• 14. Arendt-Nielsen L, Oberg B, Bjerring P - Quantitative assessment of extradural bupivacaine analgesia. Br J Anaesth, 1990;65:633-638.
• 15. Axelsson K, Nydahl PA, Philipson L et al - Motor and sensory blockade after epidural injection of mepivacaine, bupivacaine and etidocaine: a double-blind study. Anesth Analg, 1989;69:739-747.
• 16. Lund C, Hansen OB, Kehlet H - Effect of epidural 0.25% bupivacaine on somatosensory evoked potentials to dermatomal stimulation. Reg Anesth, 1989;14:72-77.
• 17. Galindo A, Hernandez J, Benavides O et al - Quality of spinal extradural anaesthesia: the influence of spinal nerve root diameter. Br J Anaesth, 1975;47:41-47.
• 18. Oliveira Fş GR, Pederneiras SG, Ghellar MR et al - Qualidade da anestesia das raízes L4, L5 e S1 com bupivacaína 0,5% epidural: efeitos da associação de fentanil por via epidural ou venosa. Rev Bras Anestesiol, 1996;46:CBA013.
• 19. Rygnestad T, Borchgrevink PC, Eide E - Postoperative epidural infusion of morphine and bupivacaine is safe on surgical wards. Organisation of the treatment, effects and side-effects in 2000 consecutive patients. Acta Anaesthesiol Scand, 1997;41: 868-876.
• 20. Scott DA, Beilby DS, McClymont C - Postoperative analgesia using epidural infusions of fentanyl with bupivacaine. A prospective analysis of 1,014 patients. Anesthesiology, 1995;83: 727-737.
• 21. Bogod DG, Rosen M, Rees GA - Extradural infusion of 0.125% bupivacaine at 10 m.h^-1 to women during labour. Br J Anaesth, 1987;59:325-330.
• 22. Stienstra R, Dahan A, Alhadi BZ et al - Mechanism of action of an epidural top-up in combined spinal epidural anesthesia. Anesth Analg, 1996;83:382-386.

*

Recebido do Hospital Governador Celso Ramos, CET/SBA Integrado de Anestesiologia da SES-SC, Florianópolis, SC

Publication Dates

• Publication in this collection
  14 Mar 2011
• Date of issue
  Oct 2001

History

• Received
  03 Jan 2001
• Accepted
  27 Apr 2001