Postoperative analgesia in pediatric patients: comparative study among local anesthetics, opioids and non-steroidal anti-inflammatory drugs

Abstracts

JUSTIFICATIVA E OBJETIVOS: O tratamento da dor pós-operatória em crianças tem merecido atenção especial nas últimas décadas. O propósito deste estudo foi analisar a analgesia pós-operatória de crianças no que se relaciona à qualidade e à duração da analgesia, à confiabilidade dos métodos de avaliação e à incidência de efeitos colaterais decorrentes das diferentes técnicas de analgesia utilizadas. MÉTODO: Participaram do estudo 100 crianças com idades entre 2 e 12 anos alocadas em 5 grupos de 20 crianças cada, que receberam, logo após a indução da anestesia, os seguintes tratamentos de analgesia: grupo B, bupivacaína a 0,25%, com vasoconstritor, 0,5 a 1 ml.kg-1; grupo F, fentanil, 1,5 µg.kg-1; grupo M, morfina, 30 µg.kg-1, grupo S, sufentanil, 0,3 µg.kg-1, todos por via peridural caudal e o grupo D, que recebeu diclofenaco potássico (1 mg.kg-1) por via retal. A dor foi avaliada por 2 métodos distintos: um predominantemente comportamental, objetivo e o outro de auto-avaliação, subjetivo, durante as primeiras 4 horas e a partir deste momento até a 24ª hora. Efeitos colaterais foram observados e tratados. RESULTADOS: Nas primeiras 4 horas os pacientes dos grupos B, F, M e S apresentaram comportamentos semelhantes, com mínimas necessidades de analgesia complementar. Nas 20 horas restantes o maior tempo de analgesia foi o observado no grupo S, não diferindo dos grupos F e M, mas sendo significativamente superior ao tempo dos grupos B e D. Diclofenaco retal não promoveu alívio efetivo da dor. Maior incidência de efeitos colaterais ocorreu no grupo M que não diferiu do grupo S, mas foi significativamente superior aos grupos F, B e D. Houve correlação positiva e significativa entre os escores das 2 escalas de avaliação de dor. CONCLUSÕES: Os opióides espinhais mostraram-se seguros e efetivos na analgesia pós-operatória em crianças, porém quando comparados à bupivacaína não apresentaram diferenças relevantes e apresentaram maior incidência de efeitos colaterais. O diclofenaco por via retal não se mostrou efetivo como analgésico único quando comparado às outras técnicas.

ANALGÉSICOS, Opióides; ANALGÉSICOS, Opióides; ANALGÉSICOS, Opióides; ANALGÉSICOS, Opióides; ANESTESIA, Pediátrica; ANESTÉSICOS, Local; DOR, Aguda; TÉCNICAS ANESTÉSICAS, Regional

SCIENTIFIC ARTICLE

Postoperative analgesia in pediatric patients: comparative study among local anesthetics, opioids and non-steroidal anti-inflammatory drugs^*

Analgesia pós-operatoria en pacientes pediátricos: estudio comparativo entre anestésico local, opioides y antiinflamatorio no esteróide

Miriam Seligman Menezes, TSA, M.D.^I; Judymara Lauzi Gozzani, TSA, M.D.^II

^IProfessora Adjunta da Disciplina de Anestesiologia da UFSM; Doutorado em Anestesiologia pela UNIFESP; Responsável pelo CET Prof. Manoel Alvarez - UFSM

^IIMestrado em Biologia Molecular pela UNIFESP; Doutorado em Anestesiologia pela UNIFESP

^{Correspondence}

SUMMARY

BACKGROUND AND OBJECTIVES: The treatment of postoperative pain in children has been given special attention in the last decades. This study aimed at analyzing postoperative analgesia in children, considering analgesia quality and duration, evaluation methods reliability and the incidence of side effects resulting from different analgesia techniques.

METHODS: Participated in this study 100 children, aged 2 to 12 years, allocated in 5 groups of 20 children each, who received, right after anesthesia, the following analgesics: group B, 0.25% bupivacaine with epinephrine (1:400,000) 0.5 to 1 ml.kg^-1; group F, 1.5 µg.kg^-1 fentanyl; group M, 30 µg.kg^-1 morphine; group S, 0.3 µg.kg^-1 sufentanil, all by epidural caudal block and group D, who received rectal diclofenac (1 mg.kg^-1). Pain was evaluated by two different methods: one, predominantly behavioral and objective and the other subjective and self-evaluated, during the first 4 hours and then up to the 24^th hour. Side effects were observed and treated.

RESULTS: In the first 4 hours, groups B, F, M and S patients presented similar behavior, with a minimum need for complementary analgesia. In the remaining 20 hours, the longest analgesia duration was seen in group S, which did not differ from groups F and M, but was significantly longer than for groups B and D. Rectal diclofenac has not promoted effective pain relief. There has been a higher incidence of side-effects in group M, which did not differ from group S, but was significantly higher than for groups F, B and D. There has been a positive and significant correlation between both pain scales.

CONCLUSIONS: Spinal opioids are safe and effective for postoperative analgesia in children, but when compared to bupivacaine, there have been no significant differences and a higher incidence of side effects. Rectal diclofenac was not effective as a single analgesic as compared to other techniques.

Key words: ANALGESICS, Opioids: fentanyl, morphine, sufentanil, Anti-inflammatory: diclofenac; ANESTHESIA, Pediatric; ANESTHETICS, Local: bupivacaine; ANESTHETIC TECHNIQUES, Regional: caudal epidural; PAIN, Acute: postoperative

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: El tratamiento del dolor pós-operatoria en niños ha merecido atención especial en las últimas décadas. El propósito de este estudio fue analizar la analgesia pós-operatoria de niños en lo que se relaciona a la calidad y a la duración de la analgesia, la confianzabilidad de los métodos de evaluación y la incidencia de efectos colaterales decurrentes de las diferentes técnicas de analgesia utilizadas.

MÉTODO: Participaron del estudio 100 niños con edades entre 2 y 12 anos distribuidos en 5 grupos de 20 niños cada, que recibieron, luego después la inducción de la anestesia, los siguientes tratamientos de analgesia: grupo B, bupivacaína 0,25%, con vasoconstritor, 0,5 a 1 ml.kg^-1; grupo F, fentanil, 1,5 µg.kg^-1; grupo M, morfina, 30 µg.kg^-1, grupo S, sufentanil, 0,3 µg.kg^-1, todos por vía peridural caudal y el grupo D, que recibió diclofenaco potásico (1 mg.kg^-1) por vía retal. El dolor fue evaluada por 2 métodos distintos: uno predominantemente comportamental, objetivo y el otro de auto-evaluación, subjetivo, durante las primeras 4 horas y a partir de este momento hasta la 24ª hora. Fueron observados efectos colaterales y fueron tratados.

RESULTADOS: En las primeras 4 horas los pacientes de los grupos B, F, M y S presentaron comportamientos semejantes, con mínimas necesidades de analgesia complementar. En las 20 horas restantes el mayor tiempo de analgesia fue observado en el grupo S, no divergiendo del grupo F y M, más siendo significativamente superior al tiempo de los grupos B y D. Diclofenaco rectal no promovió alivio efectivo del dolor. Mayor incidencia de efectos colaterales ocurrió en el grupo M que no divergió del grupo S, más fue significativamente superior a los grupos F, B y D. Hubo correlación positiva y significativa entre los resultados de las 2 escalas de evaluación del dolor.

CONCLUSIONES: Los opioides espinales se mostraran seguros y efectivos en la analgesia pós-operatoria en niños, más cuando comparados a la bupivacaína no presentaron diferencias relevantes y presentaron mayor incidencia de efectos colaterales. El diclofenaco por vía retal no se mostró efectivo como analgésico único cuando comparado a las otras técnicas.

INTRODUCTION

After having been proven that children perceive, respond and remember pain similarly to adults, several analgesic techniques, especially for postoperative pain relief, have been proposed aiming at protecting children against metabolic, hemodynamic and psychological changes caused by surgical procedures ^1-5.

Pain evaluation has been considered a major difficulty in handling postoperative pain in children below 6 years of age, and this has led anesthesiologists to chose techniques that would promote analgesia even before emergence, thus helping this evaluation ^6-8.

Systemic analgesics administered by different routes and loco-regional blockades are common techniques for children’s postoperative pain control, but still today, medical and nursing teams are concerned with the pediatric use of opioids due to the risk of side-effects.

This study aimed at evaluating and comparing different techniques of postoperative analgesia in children. Drugs studied were epidural caudal bupivacaine, morphine, fentanyl and sufentanil, and rectal diclofenac administered after anesthesia induction. Quality of analgesia was evaluated in the first 4 hours by two different pain evaluation methods, and evaluation methods reliability, total analgesia duration and side-effects during the first 24 postoperative hours were observed.

METHODS

After the Ethical Committee approval and written consent of parents or guardians, participated in this study 100 children of both genders, aged 2 to 12 years, physical status ASA I, II and III scheduled for lower limb orthopedic surgeries, urogenital, anal and infraumbilical procedures, who were systematically included, that is, the first two children would belong to Group B, the next two to Group F, and so on, until a total of 20 patients per group.

When needed, patients were premedicated with oral or nasal midazolam (0.5 mg.kg^-1) 20 or 30 minutes before the procedure. Anesthesia was induced with halothane in increasing concentrations and nitrous oxide:oxygen (1:1), or with intravenous thiopental; the same inhaled agents were used for maintenance through tracheal tube, laryngeal mask or oropharyngeal airway with assisted or controlled ventilation in a system without CO₂ reabsorber. Succinylcholine, atracurium or deep inhalation anesthesia were used to help tracheal intubation. Monitoring consisted of cardioscope, pulse oximetry, pre-cordial stethoscope and non-invasive blood pressure.

Soon after anesthetic induction, epidural caudal block was performed in group B with 0.25% bupivacaine with epinephrine (1:400,000) 0.5 to 1 ml.kg^-1 according to the incision area; epidural caudal block was performed in group F with fentanyl (1.5 µg.kg^-1) in 10 ml saline; group M patients received epidural caudal morphine (30 µg.kg^-1) in 10 ml saline; by the same route, Group S patients received sufentanil (0.3 µg.kg^-1) in 10 ml saline. Group D patients received rectal 1 mg.kg^-1 diclofenac.

All patients received oxygen under mask in the immediate postoperative period and were monitored with pulse oximetry. Two different pain evaluation scales were used during the first 4 postoperative hours: Pain and Discomfort Evaluation Scale (PDES) ⁹ shown in table I and Self-Evaluation Scale (SES) ¹⁰, according to figure 1. Evaluations were performed at 15-minute intervals for one hour and then at every 60 minutes for four hours, and oral analgesics were administered whenever children reached scores equal to 7 or above in the Pain and Discomfort Evaluation Scale. From this period on, children were evaluated by the nursing team or by the parents based on changes in children’s behavior and/or position and trying to relate these events to the presence of pain and need for analgesic complementation. Oral acetominophen (10 to 15 mg.kg^-1), intravenous metochlopramide (0.15 mg.kg^-1) and/or naloxone (0.5 to 4 µg.kg^-1) were preconized for pain, nausea and/or vomiting and other opioid-related side-effects.

Brazilian Journal of Anesthesiology, 2002; 52: 2: 175-184

Postoperative analgesia in pediatric patients: Comparative study among

local anesthetics, opioids and non-steroidal anti-inflammatory drugs

Miriam Seligman Menezes; Judymara Lauzi Gozzani

Brazilian Journal of Anesthesiology, 2002; 52: 2: 175-184

Postoperative analgesia in pediatric patients: Comparative study among

local anesthetics, opioids and non-steroidal anti-inflammatory drugs

Miriam Seligman Menezes; Judymara Lauzi Gozzani

Statistical analysis was performed by the F and Chi-square tests to compare demographics among groups; Kruskal-Wallis test was used to compare pain scores and mean analgesia duration among groups; Chi-square test was used to evaluate the need for analgesics during the first 4 hours and the incidence of side-effects in each group; Pearson correlation study was used to evaluate the correlation between both pain evaluation scales. P < 0.05 was considered statistically significant.

RESULTS

There were no significant demographic differences among all groups (Table II).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 175-184

Postoperative analgesia in pediatric patients: Comparative study among

local anesthetics, opioids and non-steroidal anti-inflammatory drugs

Miriam Seligman Menezes; Judymara Lauzi Gozzani

There were significant differences in mean pain scores among groups in both scales until 60 minutes of evaluation; after this, pain scores did not significantly differ. Group D pain scores were higher as compared to other groups during the first 30, 45 and 60 minutes of evaluation (Table III).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 175-184

Postoperative analgesia in pediatric patients: Comparative study among

local anesthetics, opioids and non-steroidal anti-inflammatory drugs

Miriam Seligman Menezes; Judymara Lauzi Gozzani

Groups B, F, M and S presented a similar behavior with regard to decreased analgesia needs during the first evaluation hours, significantly differing (p < 0.05) from Group D patients who had a very high need for analgesics during the first 4 hours (Figure 2).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 175-184

Postoperative analgesia in pediatric patients: Comparative study among

local anesthetics, opioids and non-steroidal anti-inflammatory drugs

Miriam Seligman Menezes; Judymara Lauzi Gozzani

Total analgesia duration during 24 hours was decreased in Group D with statistically significant differences as compared to other groups (Figure 3). Analgesia was longer in Group S without significant differences as compared to groups F and M, but significantly different as compared to Groups D and B. There were no significant differences in analgesia duration among groups M, F and B.

Brazilian Journal of Anesthesiology, 2002; 52: 2: 175-184

Postoperative analgesia in pediatric patients: Comparative study among

local anesthetics, opioids and non-steroidal anti-inflammatory drugs

Miriam Seligman Menezes; Judymara Lauzi Gozzani

Side-effects were more frequent in patients using opioids with a higher incidence in groups M and S (Figure 4).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 175-184

Postoperative analgesia in pediatric patients: Comparative study among

local anesthetics, opioids and non-steroidal anti-inflammatory drugs

Miriam Seligman Menezes; Judymara Lauzi Gozzani

There has been a positive and significant correlation (p < 0.05) between both pain evaluation scales in similar moments, as from 30 minutes until the 4^th evaluation hour (Table IV).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 175-184

Postoperative analgesia in pediatric patients: Comparative study among

local anesthetics, opioids and non-steroidal anti-inflammatory drugs

Miriam Seligman Menezes; Judymara Lauzi Gozzani

DISCUSSION

Although several methods to prevent and safely and effectively treat postoperative pediatric pain, it is known that they are not being used and that pediatric pain is still underestimated and neglected by medical and nursing teams ^3,11,12.

There are many reasons to explain this inadequate pain treatment in children, as compared to postoperative pain control in adults, which more often related to fear of opioid-induced side-effects and to the widely spread belief that children have decortication-type reactions after noxious stimuli, not localizing pain stimuli, not memorizing painful experiences and being neurologically immature to integrate noxious perception to the cortex ^8,13.

As from the late 80s, literature has contributed to revert this situation showing that painful experiences are a very early sensation in human development ^3,5,14 and that pain relief, in any age-even if followed by some side-effects, is the only means to attenuate postoperative pain damages⁴.

Difficulties in evaluating pediatric pain were partially responsible for recent approaches suggested by Ecoffey ¹⁵, who suggests that analgesia should be administered before emergence and that muscular or subcutaneous injections should be avoided whenever possible. Epidural caudal administration in children is very adequate for analgesics administration and several studies were carried out using local anesthetics, especially bupivacaine, with satisfactory results ^16-26. Complex and prolonged surgical procedures have required more effective and long-lasting analgesic techniques and epidural caudal opioids, initially morphine, have become an option to children, similarly to what has been used to adults ^27-34. The lack of spinal morphine dose uniformity in the literature, the fear of complications which could result from this technique and some late respiratory depression reports in children below 12 months of age under high doses have delayed for a long time the widespread use of spinal opioids for pediatric analgesia. Epidural caudal liposoluble opioids in a single dose aiming at promoting postoperative analgesia in children are few in the literature and results are not uniform. Prolonged analgesia after epidural caudal fentanyl in a single dose in children has been observed by some authors ^15,35, while others ³⁶ have not seen differences in analgesia duration with bupivacaine by the same route. Benlabed et al. ³⁷ have administered a single dose of caudal sufentanil in children for postoperative analgesia, and were able to promote fast onset and short duration analgesia.

Non-steroid anti-inflammatory drugs (NSAIDs) for pediatric analgesia is a very popular technique but NSAIDs class, dose, route and administration time to promote optimal postoperative pain relief are not yet well established. Several studies were performed with this drug and most of them ^38-39 have not been able to show its efficacy as a single drug.

In our study, we decided for epidural caudal opioid doses which have shown to be safer and more effective in children in previous studies, and for caudal bupivacaine and rectal diclofenac which are already recognized by the literature. The relevant result of our study was analgesia duration obtained with caudal lipophylic opioids, where sufentanil has promoted more prolonged analgesia and, together with fentanyl, was not different from morphine, a hydrosoluble opioid, thus with more prolonged estimated duration. From the hypotheses raised to explain these results, one may mention the most intense binding of fentanyl and sufentanil to epidural fat, which is abundant in children, with slow and fractionated release for some hours and prolonging analgesia duration; dilution volume (10 ml), important in prolonging liposoluble opioids effect; and the low morphine dose used in this study, supposing that there is a direct relationship between the hydrosoluble opioid dose and analgesia duration.

Similar behavior of groups B, F, M and S during the first 4 postoperative analgesia hours, where only 5% of patients needed analgesic complementation, as compared to 45% of group D patients who needed additional analgesia, has confirmed another study ⁴⁰ which states that anti-inflammatory drugs are not potent enough to relieve immediate postoperative pain.

To check the reliability of the tests used in this study, the presence of correlation between them has been investigated. There has been a positive correlation between both methods after 30 minutes, what has reinforced evaluations consistency.

Patients receiving spinal opioids had more side-effects, although not severe, especially groups S and M. Nausea and vomiting did not differ among the 5 groups and were the only adverse effects in groups D and B.

Other postoperative analgesia studies, especially with spinal opioids, will be needed to determine safer and more effective agents and administration techniques for pediatric patients; however our study has shown that safe epidural caudal morphine doses promote analgesia of the same quality, duration and incidence of side-effects than single fentanyl or sufentanil doses by the same route; that caudal bupivacaine promotes prolonged and effective analgesia with minor incidence of side-effects; and that rectal diclofenac, although with a low incidence of side-effects, does not provide an adequate analgesia even during the first postoperative hours.

REFERENCES

Submitted for publication June 11, 2001

Accepted for publication August 28, 2001

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Correspondence to

Dra. Miriam Seligman Menezes

Rua Estácio de Lemos - 190

97010-150 Santa Maria, RS

^* Received from Hospital São Paulo da Universidade Federal do Estado de São Paulo (UNIFESP) e Hospital Universitário de Santa Maria da Universidade Federal de Santa Maria (UFSM), RS

Received from Hospital São Paulo da Universidade Federal do Estado de São Paulo (UNIFESP) e Hospital Universitário de Santa Maria da Universidade Federal de Santa Maria (UFSM), RS

Publication Dates

• Publication in this collection
  08 Nov 2006
• Date of issue
  Apr 2002

History

• Accepted
  28 Aug 2001
• Received
  11 June 2001