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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.51 no.5 Campinas Sept./Oct. 2001
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
IIInstrutor do CET/SBA
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
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
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.
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 anesthetics1-3 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).
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.
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%.
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%.
Demographics data of both samples are shown in table 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.
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).
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.
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Correspondence to: Submitted for publication January
3, 2001 *
Received from Hospital Governador Celso Ramos, CET/SBA Integrado de Anestesiologia
da SES-SC, Florianópolis, SC
Dr. Getúlio Rodrigues de Oliveira Filho
Rua Luiz Delfino 111/902
ZIP: 88015-360 City: Florianópolis, Brazil
Accepted for publication April 27, 2001
Submitted for publication January
* Received from Hospital Governador Celso Ramos, CET/SBA Integrado de Anestesiologia da SES-SC, Florianópolis, SC