Low back pain: comparison of epidural analgesia with bupivacaine associated to methylprednisolone, fentanyl and methylprednisolone plus fentanyl

Abstracts

JUSTIFICATIVA E OBJETIVOS: Os corticosteróides têm sido empregados no espaço peridural, como alternativa de tratamento da lombalgia refratária às medidas conservadoras. Os opióides têm efeito analgésico através da ligação a receptores da medula espinhal e poderiam ter efeito somatório. Este estudo teve como objetivo avaliar a eficácia, os efeitos colaterais e as complicações de opióide e corticosteróide associados ao anestésico local, para tratamento da lombalgia e lombociatalgia aguda, provocadas por hérnia de disco. MÉTODO: Foram avaliados 45 pacientes adultos portadores de hérnia de disco. O grupo G-I recebeu 8 ml de bupivacaína a 0,25% com metilprednisolona (80 mg); o grupo G-II, 8 ml de bupivacaína a 0,25% com fentanil (100 µg) e o grupo G-III, 6 ml de bupivacaína a 0,25% com fentanil (100 µg) e metilprednisolona (80 mg). Havendo necessidade de repetição, nova injeção foi feita após 1 semana e 2 semanas no espaço intervertebral, ou próximo ao da localização da hérnia de disco. O efeito analgésico foi mensurado através de escala verbal. RESULTADOS: Aos 30 minutos, 6, 12 e 24 horas após o procedimento não houve diferença entre os grupos quanto ao alívio da dor. No quarto, sétimo e 14º dias, os grupos GI e GIII mostraram melhor alívio da dor, não havendo diferença estatística entre esses grupos. No grupo GII houve maior necessidade para repetir a injeção no 7º dia (GI= 33,3%; GII= 100% e GIII= 33,3%), e no 14º dia (GI= 6,6%; GII= 86,6% e GIII= 6,6%). A utilização de tramadol foi maior no GII. No GI, houve cefaléia (1 paciente); no GII, sonolência (2 pacientes) e prurido (1 paciente) e no GIII, prurido (1 paciente) e sonolência (1 paciente). CONCLUSÕES: O citrato de fentanil não tem efeito duradouro no controle da dor da hérnia de disco e não melhora o efeito analgésico quando associado a bupivacaína e metilprednisolona por via peridural.

ANALGÉSICOS, Opióides; DOR, Aguda; DROGAS, Corticosteróides

SCIENTIFIC ARTICLE

Low back pain: comparison of epidural analgesia with bupivacaine associated to methylprednisolone, fentanyl and methylprednisolone plus fentanyl^*

Lumbociatalgia: comparación de la analgesia entre metilprednisolona, fentanil y metilprednisolona con fentanil, asociados a la bupivacaína, por vía peridural

Quitéria Maria Wanderley Rocha, M.D.^I; Rioko Kimiko Sakata, TSA, M.D.^II; Adriana Machado Issy, TSA, M.D.^II

^IAnestesiologista, Doutora da Disciplina de Anestesiologia, Dor e Terapia Intensiva da UNIFESP - EPM, São Paulo, SP

^IIProfessora Adjunta da Disciplina de Anestesiologia, Dor e Terapia Intensiva da UNIFESP - EPM, São Paulo, SP

Correspondence

SUMMARY

BACKGROUND AND OBJECTIVES: Epidural steroids are used as an alternative for the treatment of low back pain refractory to conservative measures. Opioids exert their analgesic effect through binding to spinal cord receptors and may have an additive effect. This study aimed at evaluating efficacy, side-effects and complications of opioids and steroids associated to local anesthetics in the treatment of acute low back pain caused by herniated disks.

METHODS: Participated in this study 45 adult patients with acute herniated disks. G-I received 8 ml of 0.25% bupivacaine with methylprednisolone acetate (80 mg); G-II received 8 ml of 0.25% bupivacaine with fentanyl (100 µg) and G-III received 6 ml of 0.25% bupivacaine with fentanyl (100 µg) and 80 mg methylprednisolone acetate. When needed, a new injection was administered after 1 week and 2 weeks into the herniated disk interspace or close to it. Analgesic effects were evaluated through a verbal scale.

RESULTS: At 30 minutes, 6, 12 and 24 hours there were no differences among groups as to pain relief. In days 4, 7 and 14, groups G-I and G-III had better pain relief without statistical differences between them. Group II needed more repeated injections in days 7 (G-I = 33.3%; G-II = 100% and G-III = 33.3%) and 14 (G-I = 6.6%, G-II=86.6% and G-III = 6.6%). Tramadol was more frequently used in G-II. G-I referred headache (1 patient), G-II somnolence (2 patients) and pruritus (1 patient) and G-III pruritus (1 patient) and somnolence (1 patient).

CONCLUSIONS: Fentanyl did not improve analgesia when associated either to epidural bupivacaine plus methylprednisolone or to plain bupivacaine.

Key words: ANALGESICS, Opioids: fentanyl; DRUGS, Steroids: methylprednisolone; PAIN, Acute: low back pain

RESUMEN

Justificativa y Objetivos: Los corticosteroides han sido empleados en el espacio peridural, como alternativa de tratamiento de la lumbalgia refractaria a las medidas conservadoras. Los opioides tienen efecto analgésico a través de la ligación a receptores de la médula espinal y podrían tener efecto de suma general. Este estudio tuvo como objetivo evaluar la eficacia, los efectos colaterales y las complicaciones de opioide y corticosteroide asociados al anestésico local, para tratamiento de la lumbalgia y lumbociatalgia aguda, provocadas por hernia de disco.

Método: Fueron evaluados 45 pacientes adultos portadores de hernia de disco. El grupo G-I recibió 8 ml de bupivacaína a 0,25% con metilprednisolona (80 mg); el grupo G-II, 8 ml de bupivacaína a 0,25% con fentanil (100 µg) y el grupo G-III, 6 ml de bupivacaína a 0,25% con fentanil (100 µg) y metilprednisolona (80 mg). Habiendo necesidad de repetición, nueva inyección fue hecha después de 1 semana y 2 semanas, en el espacio intervertebral, o próximo al de la localización de la hernia de disco. El efecto analgésico fue medido a través de escala verbal.

Resultados: A los 30 minutos, 6, 12 y 24 horas después del procedimiento no hubo diferencia entre os grupos cuanto al alivio del dolor. En el cuarto, séptimo e 14º días, los grupos GI y GIII mostraron mejor alivio del dolor, no habiendo diferencia estadística entre esos grupos. En el grupo GII hubo mayor necesidad para repetir la inyección en el 7º día (GI= 33,3%; GII= 100% y GIII= 33,3%) y en el 14º día (GI= 6,6%; GII= 86,6% y GIII= 6,6%). La utilización de tramadol fue mayor en el GII. En el GI, hubo cefalea (1 paciente); en el GII, somnolencia (2 pacientes) y prurito (1 paciente) y en el GIII, prurito (1 paciente) y somnolencia (1 paciente).

Conclusiones: El citrato de fentanil no tiene efecto duradero en el control del dolor de la hernia de disco y no mejora el efecto analgésico cuando asociado a bupivacaína y metilprednisolona por vía peridural.

INTRODUCTION

Acute herniated disk is a very frequent disease and represents a major part of a Pain Clinic work. Pain is in general severe leading to the intake of large amounts of analgesics not always with adequate relief.

Epidural steroids have been used as an alternative for low back pain refractory to conservative measures.

The presence of opioid receptors in the gelatinous substance of the spinal chord dorsal horn and the strong analgesic effect of epidural opioids have openned new perspectives for pain treatment ¹.

This study aimed at comparing efficacy, side-effects and complications of epidural fentanyl and steroids associated to local anesthetics for relief of low back pain induced by acute herniated disk.

METHODS

After the Medical Ethics Committee approval and patient's informed consent, 45 low back pain patients due to herniated disk (less than 30 days of symptoms), with moderate or severe pain participated in this study. The diagnosis was based on history, physical evaluation and radiological results. Exclusion criteria were gastroduodenal ulcer, heart disease, coagulopathy, diabetes, non-controlled hypertension, facet syndrome, vertebral canal stenosis, herniated disk with sphincter incontinence or lower limb paralysis and patients submitted to laminectomy. Pregnant or breast-feeding women were also excluded from the study.

Patients were asked not to take analgesics 6 hours before the injection.

Patients were divided in 3 groups: G-I (n=15) received 8 ml of 0.25% bupivacaine associated to methylprednisolone acetate (80 mg); G-II (n=15) received 8 ml of 0.25% bupivacaine associated to 2 ml fentanyl (100 µg); and G-III (n=15) received 6 ml of 0.25% bupivacaine associated to 2 ml fentanyl (100 µg) and 2 ml methylprednisolone acetate (80 mg).

A 20G catheter was inserted in a peripheral vein and lactated Ringer's infusion was started. Epidural injection was performed at the level of the herniated disk or at an interspace close to it, by the loss of resistance technique using a 12G Tuohy needle.

Patients were evaluated for 6 hours. Pain was evaluated by a verbal scale (pain intensity: absent, mild, moderate and severe). At hospital discharge, patients received a form where they should record pain intensity 12 and 24 hours and 4 days after injection. Patients should also record any side-effect. When returning, seven days after, patients referring no pain or moderate pain were told to return in the 14^th day. Patients with moderate or severe pain received a second epidural injection of the same substance of the first injection. Patients were then told to return in the 14^th day for a new evaluation; when pain was absent or mild, the approach was the same as the 7^th day. If patients referred moderate or severe pain, a third epidural injection was applied.

Patients were oriented to take up to 2 tablets of 500 mg paracetamol every 4 hours in case of mild or moderate pain. If there was no pain relief or if it was severe, they were allowed to take 50 to 100 mg tramadol p.o. each 4 hours on a as needed basis.

Results were submitted to statistical analysis using Mann-Whitney test to compare demographics among groups, Kruskal-Wallis and Multiple Comparisons tests to compare pain intensity in all groups in the initial period and different times, and chi-square test was used to compare the need for repeated injections among groups.

RESULTS

Mean age and gender distribution were similar in all groups: G-I patients 45.4 years (9 males and 6 females); G-II 45.9 years (9 males and 6 females); and G-III 43.6 years (8 males and 7 females).

L₃-L₄ interspace hernias were found in 6 patients (2 in G-I, 3 in G-II and 1 in G-III); L₄-L₅ interspace hernias occurred in 23 patients (8 in G-I, 8 in G-II and 7 in G-III); and L₅-S₁ interspace hernias were found in 22 patients (6 in G-I, 7 in G-II and 9 in G-III).

All patients complained of low back pain. Pain had a sudden onset in 12 patients, was irradiated to lower limbs in 40, caused paravertebral muscles contracture in 42, atrophy of thigh and calf muscles in 3, painful palpation of the sciatic nerve pathway in 40 patients, lower limb hypoesthesia in 27, abnormal Achilles reflex in 14 and patellar reflex in 4, positive Lasègue signal in 36 and Néri signal in 26 and decreased foot and halux flexion strength in 30 patients.

The mean symptoms duration were similar in all groups (G-I - 15.87 days; G-II - 20.63 days and G-III - 22.37 days). Initial pain intensity was similar in all groups: moderate (60% in G-I, 73.3% in G-II and 60% in G-III) and severe (40% in G-I, 26.7% in G-II and 40% in G-III).

There were no significant differences in pain intensity at 30 minutes, 6 hours, 12 hours and 24 hours among groups. (Table I). In days 4, 7 and 14, there were more G-II patients with moderate and severe pain as compared to groups I and III, without differences between groups I and III (Figure 1).

Brazilian Journal of Anesthesiology, 2001; 51: 5: 407-413

Low back pain: comparison of epidural analgesia with bupivacaine associated to methylprednisolone,

fentanyl and methylprednisolone plus fentanyl

Quitéria Maria Wanderley Rocha; Rioko Kimiko Sakata; Adriana Machado Issy

Brazilian Journal of Anesthesiology, 2001; 51: 5: 407-413

Low back pain: comparison of epidural analgesia with bupivacaine associated to methylprednisolone,

fentanyl and methylprednisolone plus fentanyl

Quitéria Maria Wanderley Rocha; Rioko Kimiko Sakata; Adriana Machado Issy

The use of paracetamol as rescue analgesic medication was the same in all moments studied for the three groups. Tramadol, however, was needed in three patients in the GI group at 6 hours.

Epidural injection had to be repeated in 5 G-I, 15 G-II and 5 G-III patients (Table II). Statistical analysis has shown a higher frequency of epidural injections in G-II without significant differences between groups I and III. A third injection was more frequent in G-II, without difference between groups I and III. One G-I patient referred headache. Two G-II patients referred somnolence and one pruritus. One G-III patient referred pruritus and one somnolence.

Brazilian Journal of Anesthesiology, 2001; 51: 5: 407-413

Low back pain: comparison of epidural analgesia with bupivacaine associated to methylprednisolone,

fentanyl and methylprednisolone plus fentanyl

Quitéria Maria Wanderley Rocha; Rioko Kimiko Sakata; Adriana Machado Issy

DISCUSSION

Only patients with acute low back pain were studied because psychological alterations, which are frequent in chronic painful syndromes could interfere in the results.

Patients received steroids, opioids or an association of both drugs to verify potentiation of the analgesic effect by drugs with different mechanisms of action. A weekly repetition was adopted because it is known that there is a decrease in epidural methylprednisolone plasma levels after this period. Benzon ² believes that more than three injections are not justificable when there is no pain relief.

Paracetamol was used for rerscue analgesia in patients with mild or moderate pain because it has no anti-inflammatory effect thus interfering less on the results, and tramadol was used in case of severe pain for being an opioid not causing respiratory depression ^3-5. This is important because epidural fentanyl was used and it is known that the association of opioids increase the possibility of respiratory depression ⁶.

Although no significant differences in pain intensity were observed either at 30 minutes or 6 hours after epidural injection, groups receiving fentanyl showed a tendency for better pain relief as compared to the group receiving local anesthetics and steroids alone, probably due to the additive effect of local anesthetics plus opioids.

Some mechanisms are suggested to explain the synergy of the association of opioids and local anesthetics⁷. Low bupivacaine doses facilitate opioids binding to receptors and the depolarization decrease caused by local anesthetics changes calcium channels activation, thus facilitating the opioid effect ⁹.

After 12 and 24 hours, most patients referred moderate or severe pain, probably due to the end of local anesthetics and opioids action.

When evaluating patients at the 4^th. and the 7^th. day after injection, there was a significant decrease in pain intensity in groups I and III, probably due to methylprednisolone. Some authors have observed that steroid effects increase gradually between 1 and 6 days after injection ^10,11. In the 14^th. day, patients receiving steroids had better results showing that steroids alone could maintain analgesia for longer periods.

Steroid pain relief is caused by the anti-inflammatory effect as a consequence of phospholipase A₂ inhibition and decrease of free fatty acids release, prostaglandins and leucotriens precursors. Some authors believe that steroids may modulate n-methyl-D-aspartate (NMDA) receptors ^12,13

The addition of fentanyl to steroids and local anesthetics did not change the frequency of epidural injections, showing that, although having a different mechanism of action, opioids did not improve the effect of epidural steroid injections.

REFERENCES

• 01. Snyder SH - Opiate receptors and internal opiates: Sci Am, 1977;44-56.
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• 10. Dilke FW, Burry HC, Grahame R - Epidural corticosteroid injection in management of lumbar nerve root compression. Br Med J, 1973;2:635-637.
• 11. Haddox JD - Lumbar and cervical epidural steroid therapy. Anaesth Clin Nosth Am 1992;1: 179-203.
• 12. Irwin RP, Rogawski MA, Purdy RH et al - Steroid potentiation and inhibition of N-Methil-D-Aspartato receptor-mediated intracelular Ca⁺⁺ responses: struture-activity studies. J Pharmacol Exp Ther, 1994;677-682.
• 13. Mathis C, Paul SM, Crawley JN - The neurosteroid pregnenolone sulfate blocks NMDA antagonist-induced deficits in a passive avoidance memory task. Psychopharmacology, 1994;116: 201-206.

Endereço para correspondência:

Dra. Rioko Kimiko Sakata

R. Três de Maio 61/51 - Vila Clementino

04044-020 São Paulo, SP

*

Recebido da Disciplina de Anestesiologia, Dor e Terapia Intensiva da Universidade Federal de São Paulo da Escola Paulista de Medicina (UNIFESP - EPM), São Paulo, SP

Publication Dates

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

History

• Accepted
  19 Mar 2001
• Received
  04 Jan 2001