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Brief Reports Indian Pediatrics 2002; 39:178-182 |
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Efficacy of Nimesulide in Pain Relief After Day Care Surgery |
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J. Harish S.K. Chowdhary K.L. Narasimhan J.K. Mahajan K.L.N. Rao
Day care surgery is cost effective, it reduces the incidence of hospital acquired infections and allows for early return to normal activity. Adequate post operative pain relief is essential for parents to feel confident of looking after their child at home. Today, a significant number of children the world over with minor surgical problems are managed as day care patients. Our Center at the Postgraduate Institute of Medical Education and Research, Chandigarh has a day care unit functioning since the last fifteen years. Postoperative pain in pediatric patients is inadequately evaluated and apparently under-treated(1). Post-operative caudal anesthesia is very effective in pain relief in the immediate post-operative period. NSAIDs are important agents in the surgeons armamentarium for post-operative pain relief especially useful in ambulatory patients. However, the available safe option for pain relief in children in terms of safety, which can be administered at home has traditionally been acetaminophen (para-cetamol)(2). Nimesulide is a new nonsteroidal anti-inflammatory drug (NSAID) of the sulfonanilide class. It has a unique pharma-cological profile within the currently available NSAIDs as it is highly selective cyclo-oxygenase-2 inhibitor not interfering with the physiological production of prostaglandins in the stomach and kidney (regulated by cyclo-oxygenase-1) and, as a consequence, it causes less local gastrointestinal toxicity(3). It is administered orally and is rapidly absorbed reaching peak plasma concentration within 2 hours. Clinical studies have established the analgesic, anti-inflammatory and antipyretic effectiveness of nimesulide(4). However, there are limited studies on the therapeutic efficacy of nimesulide in children. This study was designed as a double blind prospective controlled clinical trial on children with minor surgical problems undergoing day care surgery at our Pediatric day care surgical unit. We conducted this study to evaluate the therapeutic efficacy of nimesulide suspension for day care patients, in a controlled group of children. Subjects and Methods One hundred children with minor surgical problems like hernia, undescended testis, phimosis, soft tissue swellings, etc. were included in this controlled clinical trial, 50 each in either group. Only children in the age group of 3-12 years were included in the study. Informed parental consent was obtained. Children with a known allergy to NSAIDs, liver or renal disease, gastric ulcers and G-6-PD deficiency were excluded from this trial. Parents, guardians were given the option of withdrawing from this study. The investigators, surgeons and parents were unaware of the pharmacological content of drug-A and drug-B. The dose of the drugs used was 5 mg/kg/day for Drug-A (Nimesulide) and 10 mg/kg/dose for Drug-B (Paracetamol). No other NSAIDs were used during the treatment period. Efficacy of the treatment was assessed by the evaluation of the following parameters: (i) Physiological response: recording of heart rate, blood pressure, respiratory rate, tempera-ture and diaphoresis; (ii) Wound hyperemia; (iii) Pain behavior: this was recorded 30 minutes before and 30 min following anal-gesic medication. Facial expression scoring was done on 1-7 scale, based on the modified happy sad facial scales(5): (1) brows furrowed; (2) eyes tightly closed; (3) nasal root broad and bulged; (4) mouth angular; (5) lips open; (6) taut tongue; (7) chin quiver; (iv) Tolerance: presence/absence of epigastric pain, jaundice, hematemesis, melena, ano-rexia and nausea. The pain relief was recorded as per the protocol explained for each child by the same investigator, and the record was entered in a clinical database. Pain score was recorded 30 min before and 30 min after administration for both Drug-A and Drug-B. Pain medication with Drug-A or Drug-B was given for a mean of 3 days. The data was evaluated and analyzed for statistical signi-ficance. The therapeutic efficacy in terms of pain relief was analyzed by the pain score. The statistical tests used were two tailed t tests. The difference in pain intensity and related variables were analyzed by non-parametric method at p <0.05 level of significance. On the basis of messages sent by letters, 2 months after surgery each patient was called back for a clinical assessment. Results One hundred consecutive children for the day care surgery unit were recruited in the study between 3-12 years of age. They were allotted to Drug-A for the first 50 followed by Drug-B group for the next 50. The 50 children allotted to each group were matched for ages. The average age of children entering the trial of Drug-A was 5.23 years (range 3-12 years). The mean age of children entering the trial for Drug-B was 5.41 yr (range 3-11 yr). The subjects of study underwent operative procedures, which were comparable in terms of operative trauma and infliction of pain. The commonest operation was herniotomy for children for both groups A and B. The distribution of operation in either group in terms of age and operation is shown in Table I. Surgeons in training under consultant supervision performed all operations. The distribution of patients into group-A and Group-B in terms of age, surgical condi-tion and operation conducted were compar-able (Table I). None of the 100 children operated in day care surgery unit were admi-nistered any other kind of medication for pain either intravenously or while they were on oral analgesic other than the test drugs A and B. At the end of the clinical trial and the evaluation of the results, it was revealed to the investigators that drug A was Nimesulide and drug B was paracetamol. The mean difference between scores before and after pain relief in the nimesulide and paracetamol group was 17.42 and 8.75, respectively (p = 0.033). Two months after surgery, a postal request was sent to all parents to return for a clinical assessment. During the period of follow up no child either in group-A or B returned for any clinical complaints of jaundice or gastrointestinal problems. Forty-two (42%) children returned for follow up, 20 (40%) children from Group-A and 22 (44%) from Group-B.
Discussion Pain relief in pediatric day care surgery has been traditionally confined to the use of acetaminophen (paracetamol) which is an NSAID acting on the peripheral nervous system. The main mode of action is related to the inhibition of cyclo-oxygenase enzyme resulting in decreased synthesis of prostag-landin. It also inhibits production of metabolities of ararchidonic acid metabolism and thereby reduces the inflammatory responses. Allergic reactions and gastro-intestinal symptoms are the main side effects, but it also has effects on the platelet function, renal and liver functions(6). NSAIDs are being used as the sole agents or as an adjuvant to other analgesics in day care surgery for post-operative pain relief(2). In practice of day care surgery, despite the occasional side effects of NSAIDs it remains the analgesic of choice for administration at home and under limited nursing supervision available at the day care surgery unit. Nimesulide has been proposed to be a drug with superior therapeutic efficacy in terms of analgesic and antipyretic effect based on experimental studies conducted on rats(7). The pharmacokinetic characteristics of the drug allow achieving a peak plasma con-centration within 2 h and this declines over the next 12 h. Therefore, it can be administered in 2-3 times daily doses. Previous studies on adults have also confirmed good results in terms of pain relief. There have been numerous comparative clinical trials with nimesulide and representative NSAIDs in the treatment of inflammatory/painful disease. Nimesulide is more effective than para-cetamol as an antipyretic agent and is safe for use in infants and children(8). It is known to have a good tolerance and has similar side effects as the other NSAIDs. Moreover, it has been known to be well tolerated by patients who are allergic to salicylic acid. Occa-sionally, mild derangement in renal and liver functions has been reported(9). In our study, we included 100 consecutive children, divided into 2 clinically matched groups in terms of age and operation carried out. The pain scoring demonstrated statisti-cally significant efficacy in terms of pain relief in the case of nimesulide (p <0.05). In the immediate postoperative period we did not notice any allergic reaction in any child of either group A and B. None of the children of either group A or B reported to the unit with any complaint of gastrointestinal symptoms, jaundice or symptoms of renal disease. It is unlikely that they have gone elsewhere for treatment. However, in response to our postal request for follow up, 42% returned for clinical assessment. The failure of all children to report for follow up is not an unusual pheno-menon in our country. Randomization of children to either group A or group B, would have added to the accuracy of the study. Similarly, the use of pharmacological for-mulation of both drugs in such a strength so that a similar volume could be administered and a similar colour and viscosity of both drugs would have eliminated any possible bias in the study. In conclusion, nimesulide is an alternative drug to paracetamol, which was well tolerated in children and proved effective as a sole drug for ambulatory pain relief after pediatric day care surgery. In our study, the therapeutic efficacy of nimesulide was more than para-cetamol. Further studies need to be conducted in a larger sample size to confirm its safety. Contributors: JH and SKC conceptualized and designed the study. KLN and JKM drafted the article. KLNR reviewed it critically for the intellectual content and will act as the guarantor for the manuscript. Funding: M/s. Panacea Biotech Limited. Competing interests: Panacea Biotech Limited, manufacturers and markets Nimesulide.
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