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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.54 no.5 Campinas Sept./Oct. 2004
Comparative study of epidural and intravenous fentanyl for postoperative analgesia of orthopedic surgeries*
Estudio comparativo entre fentanil por vías peridural y venosa para analgesia de operaciones ortopédicas
Marcelo Soares Privado, M.D.I; Rioko Kimiko Sakata, TSA, M.D.II; Adriana Machado Issy, M.D.II; João Batista Santos Garcia, TSA, M.D.III
IPós-Graduando da Disciplina
de Anestesiologia, Dor e Terapia Intensiva (UNIFESP)
IIProfessora Adjunta e Responsável pelo Setor de Dor da Disciplina de Anestesiologia, Dor e Terapia Intensiva (UNIFESP)
IIIProfessor Adjunto da Disciplina de Anestesiologia da Universidade Federal do Maranhão
BACKGROUND AND OBJECTIVES: There are controversies
about the action site of lipophylic opioids after epidural injection. Some authors
believe that these drugs act at supraspinal level, while others propose a spinal
action. This comparative study aimed at answering this question by comparing
epidural and intravenous fentanyl for postoperative analgesia of lower limb
METHODS: This was a randomized double-blind study. At postoperative pain complaint, G1 patients (n = 14) received 5 mL epidural solution (100 µg fentanyl in 0.9% saline) and 2 mL of intravenous 0.9% saline; G2 patients (n = 15) received 5 mL epidural 0.9% saline and 2 mL intravenous fentanyl (100 µg). Analgesic complementation with intravenous tenoxicam (40 mg) and epidural 0.25% bupivacaine (5 mL) (when there was no relief with tenoxicam) has been evaluated. Pain intensity was evaluated by numeric and verbal scales in moments M30, M120 and M240 minutes.
RESULTS: Number of patients needing analgesic complementation both with tenoxicam (G1 = 10 and G2 = 15 patients) and bupivacaine (G1 = 2 and G2 = 8 patients) has been higher in G2. There have been no statistical differences in pain intensity between groups in all studied moments.
CONCLUSIONS: In the conditions of our study, effects of epidural fentanyl were better as compared to intravenous fentanyl.
Key Words: ANALGESIA, Postoperative; ANALGESICS, Opioids: fentanyl; ANESTHETIC TECHNIQUES, Regional: epidural, intravenous
JUSTIFICATIVA Y OBJETIVOS: Existen controversias
sobre el local de acción de opioides lipofílicos después de inyección
peridural, y algunos autores acreditan que eses fármacos actúan en
el nivel supra-espinal, en cuanto otros suponen que ocurre acción espinal.
Para tentar esclarecer esa duda fue hecho estudio comparativo de la aplicación
de fentanil por vías peridural y venosa después de operaciones ortopédicas
de miembro inferior.
MÉTODO: El estudio fue aleatorio y duplamente encubierto. Cuando presentaban dolor pos-operatorio, los pacientes del G1 (n = 14) recibieron 5 ml de solución (100 µg de fentanil en solución fisiológica a 0,9%) por vía peridural y 2 ml de solución fisiológica a 0,9% por vía venosa, los del G2 (n = 15) recibieron 5 ml de solución fisiológica a 0,9%, por vía peridural y 2 ml de fentanil (100 µg) por vía venosa. Fue evaluada la necesidad de complementación analgésica con tenoxicam (40 mg) por vía venosa y con bupivacaína a 0,25% (5 ml) por vía peridural (cuando no había alivio con tenoxicam). La intensidad del dolor fue evaluada por las escalas numérica y verbal en los momentos M30, M120 y M240 minutos.
RESULTADOS: El número de pacientes que necesitaron de complementación analgésica, tanto con el tenoxicam (G1 = 10 y G2 = 15 pacientes) cuanto con la bupivacaína (G1 = 2 y G2 = 8 pacientes) fue mayor en el G2. No hubo diferencia estadística en la intensidad del dolor entre los grupos en los tiempos evaluados.
CONCLUSIONES: En las condiciones de este estudio el efecto analgésico del fentanil peridural es mejor que por vía venosa.
After the discovery of spinal cord receptors and the publication of a study reporting prolonged and intense pain relief after spinal morphine injection 1, a new era for the treatment of pain with spinal opioids has started, to control both acute and chronic pain.
Fentanyl has been one of the most used opioid by epidural injection. It has fast onset with satisfactory pain relief and analgesic effects lasting 4 to 8 hours.
There are controversies about fentanyl action site after epidural injection. Some authors believe that it is the spinal cord, while others suggest the supraspinal region due to its high liposolubility, with consequent absorption to the circulation and distribution to brain 2.
Some studies attribute systemic action to epidural fentanyl, because they have shown that plasma concentrations during analgesia are within the so-called "analgesic range". However, other investigators have concluded that fentanyl analgesic action is by spinal action 3,4, because plasma concentration of this drug during moments of comfort and postoperative analgesia is lower as compared to minimum plasma concentration needed for analgesia 5,6. Still others believe in a combination between both mechanisms 7.
This study aimed at comparing epidural and intravenous fentanyl for postoperative analgesia of lower limb orthopedic procedures.
After the Ethics Committee, Unversidade Federal de São Paulo approval and their informed consent, participated in this randomized double-blind study 29 patients aged 18 to 65 years, physical status ASA I or II, submitted to lower limb orthopedic procedures.
Patients were divided in two groups and exclusion criteria were epidural puncture counterindication (puncture site infection, patients refusal, coagulation disorders) and opioid users.
Patients were premedicated with 10 mg oral midazolam, one hour before surgery.
Epidural anesthesia was induced with lumbar puncture at L3-L4 or L4-L5 interspace, followed by 20 mL of 0.5% bupivacaine with 1:200,000 epinephrine and 1 mL (50 µg fentanyl). Epidural catheter was inserted for analgesic complementation, if needed. Sedation was induced with midazolam, after blockade.
Postoperative analgesia was scheduled as follows: group 1 (n = 14) would receive 5 mL epidural solution with 100 µg fentanyl diluted in 0.9% saline and 2 mL intravenous 0.9% saline; group 2 (n = 15) would receive 5 mL epidural 0.9% saline and 2 mL intravenous fentanyl (100 µg).
Analgesia would be complemented according to patients request, with intravenous tenoxicam (40 mg), and epidural 0.25% bupivacaine (5 mL) in case of no pain relief.
Pain was evaluated at 30 minutes, 2 and 4 hours after analgesic solutions injection, by numeric scale from zero to 10, where zero (0) was no pain and ten (10) the worst imaginable pain.
Results were submitted to Fisher Exact test, Students t test, Chi-square test and Analysis of Variance.
Demographics (gender, age, weight, height and body mass index) were similar between groups (Fisher Exact test; Students t test) (Table I).
Surgical procedures were similar without significant differences in surgery mean length for group 1 (137 minutes) and group 2 (135 minutes) (Table II).
Mean time between beginning of anesthesia and epidural fentanyl injection (G1) was 380 ± 101 minutes and between beginning of anesthesia and intravenous fentanyl injection (G2) was 331 ± 83 minutes, without statistical difference (Students t test, p = 0.170).
Number of patients needing analgesic complementation both with tenoxicam and bupivacaine has been higher in Group 2 (Fisher Exact test) (Table III).
Mean time between fentanyl injection and tenoxicam and bupivacaine complementation has been similar for both groups (Mann-Whitney test, p = 0.2673) (Table IV).
Pain intensity evaluated by numeric scale for both groups in each moment has not shown statistically significant differences, as shown in table V.
There are several clinical studies aiming at explaining the action mechanism of epidural fentanyl 2,3,8,9-20. Although many have concluded that the action is systemic, by absorption to circulation followed by cerebral effect, some have used continuous infusion.
Continuous infusion leads to higher plasma fentanyl concentrations, which may have supraspinal action 3. Plasma concentrations found when patients presented analgesia were close to or above 0.63 ng.mL-1, considered by some studies as minimum plasma concentration for analgesic efficacy 3,5,6. Our study has used fixed epidural fentanyl dose and timing compatible with this opioid kinetics.
In spite of the availability of adequate analytical methods to quantify fentanyl plasma concentrations, these do not reflect the level of binding of opioids in sites of drug effects, such as spinal cord and brain 11. However, all studies aiming at evaluating epidural fentanyl action site do it this way, analyzing fentanyl plasma concentrations, analgesic effect and need for analgesic complementation, due to the difficulty in studying the binding of those drugs to receptors.
Our study has evaluated patients submitted to similar surgical procedures to compare similar pain intensities.
Demographics data were similar between groups, which is an important factor to prevent pharmacological differences.
Surgery length, as well as time between beginning of anesthesia and postoperative intravenous or epidural fentanyl were also similar, resulting in a more homogeneous sample.
Catheter was placed as close as possible to the dermatome corresponding to higher painful stimulation, tactic also adopted by other authors 11,21 and considered important 22,23 because it allows more effective analgesia with less drugs. Although many professionals administer epidural opioids in vertebral interspaces apart from those corresponding to surgical incision dermatome, it is known that, in spite of more extensive spread of these drugs as compared to local anesthetics, higher concentration is seen close to injection site.
Local anesthetics associated to opioid for epidural anesthesia aimed at decreasing both drugs doses, improving anesthesia and decreasing the intensity of side effects of the drugs, which have different action mechanisms with synergistic analgesia 4,6,24,25.
Fentanyl for epidural anesthesia could have interfered with the evaluation. However it is unlikely that this may have happened because after initial opioid use, fentanyl has only been used when patients referred pain.
Although the absence of difference in pain intensity in both groups, results have been influenced by a larger number of patients using analgesic complementation throughout the study and a large number of patients needing more than one analgesic complementation in group 2, where intravenous fentanyl was used.
The need for analgesic complementation has been higher after intravenous fentanyl (100 mg) as compared to epidural injection.
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Dra. Rioko Kimiko Sakata
R Três de Maio 61/51 Vila Clementino
04044-020 São Paulo, Brazil
Submitted for publication October 21, 2003
Accepted for publication April 26, 2004
* Received from Hospital São Paulo, Universidade Federal de São Paulo (UNFESP), São Paulo, SP