Issuu on Google+

Anaesthesia, 2000, 55, pages 334±337 ................................................................................................................................................................................................................................................

Use of diclofenac in children with asthma J. A. Short,1 C. A. Barr,1 C. D. Palmer,1 J. M. Goddard,2 C. G. Stack2 and R. A. Primhak3 1 Specialist Registrar, Department of Anaesthesia, 2 Consultant, Department of Anaesthesia, and 3 Senior Lecturer, Division of Child Health, Shef®eld Children's Hospital, Western Bank, Shef®eld S10 2TH, UK Summary

This study investigated the effect of diclofenac on the lung function of 70 children aged 6±15 years with a diagnosis of asthma, recruited from a hospital respiratory clinic. Peak ¯ow and a forced expiratory ¯ow-volume loop were measured and the patients were then given 1±1.5 mg.kg 1 effervescent diclofenac orally. Spirometry was repeated at 10, 20 and 30 min, a 15% decrease in results being considered a signi®cant reduction in lung function. No patient demonstrated a consistent reduction in lung function of > 15% during the study and there were no reports of wheezing or increased bronchodilator use after completion of the spirometry. In conclusion, we studied a group of genuine asthmatics and found no clinically signi®cant incidence of bronchospasm with the use of a single therapeutic dose of diclofenac. Keywords Lung: asthma. Analgesics: diclofenac. Analgesia: postoperative. Complications: asthma. ...................................................................................... Correspondence to: Dr J. A. Short Accepted: 27 October 1999

Attempts to provide adequate postoperative analgesia, particularly after day case surgery, are hampered in children with asthma by the recommendation to avoid nonsteroidal anti-in¯ammatory drugs (NSAIDs) [1]. The avoidance of this class of drugs is based on the risk of NSAID-induced bronchospasm, a complication with a 5±10% incidence in adult-onset asthmatics [2]. Because the incidence of childhood asthma is estimated at 13.1% in Great Britain [3], a large number of children undergoing surgery are denied a class of drugs that would otherwise form a major part of their pain management. Diclofenac has been used cautiously for postoperative pain relief in asthmatic children for some years in this hospital. We are unaware of any signi®cant episodes of bronchospasm associated with its use in this group of patients. We therefore formed the impression that diclofenac-induced bronchospasm has a considerably lower incidence in children than that reported in adult asthmatics. This study was carried out to test this hypothesis. Methods

Local research ethics committee approval was granted for the study and participants and parents gave informed consent. Children aged 6±15 years with a diagnosis of asthma and taking regular prophylactic medication were 334

recruited on attendance at a hospital respiratory clinic (90%) or at presentation for day case surgery (10%). Exclusion criteria included: a previous adverse reaction to NSAIDs, known renal disease or risk of gastro-intestinal bleeding, current deterioration in lung function (FEV1 < 80% predicted) and medication with theophyllines or leukotriene receptor antagonists. Patients taking longacting b2 agonists were asked to omit the medication for 12 h before the study. A questionnaire, based on the International Study of Asthma and Allergies in Childhood (ISAAC) [4], allowed assessment of the type and severity of asthma, the incidence of atopy and a review of current medication. Asthma was categorised as `severe' if there were more than 12 episodes of wheezing in the last year or if speech had been limited to only one or two words between breaths, and `moderate' if there were fewer than 12 episodes of wheezing in the last year, but wheezing occurred in the absence of viral symptoms. If wheezing occurred only in association with a viral illness, the category was `viral episodic', and children who presented with a dry cough in the absence of infection had `cough variant' asthma. After the children had been instructed in the appropriate techniques, peak expiratory ¯ow rate (PEFR) was measured using a Wright peak ¯ow meter and a forced expiratory ¯ow-volume loop [forced expiratory volume in Q 2000 Blackwell Science Ltd


Anaesthesia, 2000, 55, pages 334±337 J. A. Short et al. · Use of diclofenac in children with asthma ................................................................................................................................................................................................................................................

the ®rst second (FEV1) and forced vital capacity (FVC)] was measured using a Micro Medical turbine spirometer. The best of three effective manoeuvres was taken as representative. The patients were then given 1±1.5 mg.kg 1 effervescent diclofenac orally (the recommended dose adjusted to the nearest convenient dose as in normal clinical practice). Spirometry was repeated at 10, 20 and 30 min, a 15% decrease in FEV1 or PEFR being considered a signi®cant reduction in lung function. Arrangements were made to detain patients in the respiratory clinic for observation and treatment if any adverse effects were apparent. Parents were asked to report any subjective increase in wheezing or increased use of bronchodilator drugs over the next few hours. Results

Results were obtained from 70 patients, 47 males and 23 females. The mean age was 9.6 years (range 6±15.5 years). A history of atopy (hay fever or eczema) was noted in 43% and the classi®cation of asthma was as follows: 21 (30%) severe, 27 (39%) moderate, 19 (27%) viral episodic and three (4%) cough variant. All patients used regular inhaled steroids and bronchodilators as required. In addition, 30% were treated with long-acting b2 agonists and 17% required intermittent oral steroids, although no one was taking them at the time of the study. No patients demonstrated a consistent decrease in PEFR or FEV1 > 15% during the study, and there were no reports of wheezing or increased bronchodilator use after completion of the spirometry. The PEFR and FEV1 values are shown in Tables 1 and 2, respectively. It can be seen from the range of the values recorded, that there was an isolated decrease in PEFR of 16% at 20 min and an isolated decrease in FEV1 of 25.4% at 10 min. These values were obtained from two different 6-yr-old children who were performing spirometry for the ®rst time. Neither child was clinically wheezy at any stage and in both cases, the lung function at 30 min showed an improvement as seen in Fig. 1. The rather haphazard results from these two children were felt to be a re¯ection of poor spirometry technique rather than a reaction to diclofenac. From the Table 1 Per cent changes in peak expiratory ¯ow rate (PEFR)

from baseline with time (n ˆ 70)

Time; min

10

20

30

Maximum Minimum Mean SD SEM

‡ 37.5 12.3 ‡ 1.2 7.2 0.9

‡ 40.6 16.0 ‡ 1.3 7.7 0.9

‡ 40.6 13.6 ‡ 1.8 8.5 1.0

Q 2000 Blackwell Science Ltd

Table 2 Per cent changes in FEV1 from baseline with time

(n ˆ 70)

Time; min

10

20

30

Maximum Minimum Mean SD SEM

‡ 8.8 ± 25.4 ± 0.5 5.5 0.7

‡ 13.4 ± 7.5 ‡ 0.9 4.0 0.5

‡ 8.5 ± 8.5 ‡ 0.7 4.4 0.5

Tables, it can be seen that the mean changes in both PEFR and FEV1 remain very close to the baseline throughout the study. There was no signi®cant difference between the changes seen in the different asthma category groups. Discussion

Aspirin intolerance is thought to be a problem mainly of adult intrinsic asthma, presenting in the third or fourth decade of life, often after previous uneventful ingestion of aspirin. A classic triad of symptoms has been described: aspirin-induced bronchospasm presenting in a patient with asthma and nasal polyps [2]. However, after the publication of a report of several cases of aspirin-induced bronchospasm in children with asthma in 1973 [5], several studies investigating the incidence of this complication in children were carried out, reporting a wide range of results. A population study of asthmatic children in Denver in 1973, showed a 1.9% incidence of aspirin intolerance [6] and a subsequent retrospective study reported an incidence of 1.4% [7]. These results contrast with two aspirin-challenge studies on highly selected groups of asthmatic children, which indicated an incidence of 13±28% [8, 9]. A further study detected no aspirin intolerant patients among 32 asthmatic children given an oral challenge test [10]. The true incidence of aspirin intolerance in the paediatric population with asthma is therefore dif®cult to estimate. Since an association has been demonstrated between the use of aspirin and the development of Reye's syndrome in some children, aspirin is no longer recommended for use in children under 12 years of age, and alternative analgesics must be considered [11]. It has been shown that NSAID intolerance is related to the cyclo-oxygenase inhibiting activity of the drugs in vitro, and that adult patients with aspirin-induced bronchospasm show similar intolerance to other NSAIDs [12, 13]. The exact aetiology of this idiosyncratic reaction to NSAIDs remains unclear, however, and the in¯uence of other factors, such as chronic viral infection, may help to explain the unpredictability of onset [14]. Children have differing patterns of asthma from those seen in the adult population and no study has previously assessed the incidence of diclofenac-induced 335


J. A. Short et al. · Use of diclofenac in children with asthma Anaesthesia, 2000, 55, pages 334±337 ................................................................................................................................................................................................................................................

25

PEFR Child 1 FEV1 Child 1 PEFR Child 2 FEV1 Child 2

20 15

% change from baseline

10 5 0 -5 -10 -15 -20 -25 -30 0

10

Time (min)

20

30

Figure 1 Spirometry results from two 6-year-old children.

bronchospasm in a representative sample of children with asthma. This study was designed to investigate the incidence of bronchospasm that might be observed after the use of a therapeutic dose of diclofenac in children with a diagnosis of asthma. The method was based on the standard aspirinchallenge test [15], but the period over which spirometry was performed was truncated, a modi®cation made to encourage recruitment. In previous studies, using aspirin and other NSAIDs formulated in gelatin capsules, patients who were intolerant to the drugs, showed signs of reduced lung function within 15±30 min [8, 9]. As this study used effervescent diclofenac, which is absorbed and reaches peak serum levels much more rapidly than that enclosed in capsules, it was felt that most positive reactions would be evident by 30 min following ingestion of the drug. While we might conceivably have failed to detect some late responders to diclofenac, there were no reports of bronchospasm or wheezing following completion of the spirometry. In a study such as this, in which there has been no detected incidence of the adverse event, the `zero numerator rule' [16] may be used to assess the signi®cance of the result. Thus the 95% con®dence interval of our study shows that the incidence of diclofenac intolerance in this population is less than 4.3%. A study involving thousands 336

of patients would be required to allow a more accurate assessment of the true incidence of this complication of diclofenac use. In the absence of such a practically dif®cult multicentre study, we suggest, based on the results of our study, that a diagnosis of asthma is not a contraindication to the short-term use of NSAIDs in children. Practitioners should, however, remain alert to the possibility of an idiosyncratic reaction and report such reactions appropriately should they occur. In conclusion, we have studied a group of 70 children with asthma and found no clinically signi®cant incidence of bronchospasm with use of a single therapeutic dose of diclofenac. Acknowledgments

We would like to thank N. Butler, R. White, H. Rodgers and the staff of the Respiratory Clinic and the Day Care Ward at the Shef®eld Children's Hospital for their invaluable help in recruitment and care of the patients. References 1 Falliers CJ. Analgesic±antipyretic choices for children with asthma: a review of safety and risk of common preparations. Journal of Asthma 1994; 21: 321±30. Q 2000 Blackwell Science Ltd


Anaesthesia, 2000, 55, pages 334±337 J. A. Short et al. · Use of diclofenac in children with asthma ................................................................................................................................................................................................................................................

2 Frew A. Non-steroidal anti-in¯ammatory drugs and asthma. Prescribers' Journal 1994; 34: 74±7. 3 Strachan DP, Anderson HR, Limb ES, O'Neill A, Wells N. A national survey of asthma prevalence, severity, and treatment in Great Britain. Archives of Disease in Childhood 1994; 70: 174±8. 4 Asher MI, Keil U, Anderson HR, et al. International study of asthma and allergies in childhood (ISAAC); rationale and methods. European Respiratory Journal 1995; 8: 483±91. 5 Yunginger JW, O'Connell EJ, Logan GB. Aspirin-induced asthma in children. Journal of Pediatrics 1973; 82: 218±21. 6 Falliers CJ. Aspirin and subtypes of asthma: risk factor analysis. Journal of Allergy and Clinical Immunology 1973; 52: 141±7. 7 Chafee FH, Settipane GA. Aspirin intolerance: I. Frequency in an allergic population. Journal of Allergy and Clinical Immunology 1974; 53: 193. 8 Rachelefsky GS, Coulson A, Siegal SC, Stiehm ER. Aspirin intolerance in chronic childhood asthma: detected by oral challenge. Pediatrics 1975; 53: 443±8. 9 Vedanthan PK, Menon MM, Bell TD, Bergin D. Aspirin and tartrazine oral challenge: incidence of adverse response

Q 2000 Blackwell Science Ltd

10 11 12

13

14 15 16

in chronic childhood asthma. Journal of Allergy and Clinical Immunology 1977; 60: 8±13. Schuhl JF, Pereyra JG. Oral acetylsalicylic acid (aspirin) challenge in asthmatic children. Clinical Allergy 1979; 9: 83±8. Glen-Bott AM. Aspirin and Reye's syndrome. Medical Toxicology 1987; 2: 161±5. Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G. Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients. British Medical Journal 1975; 1: 67±9. Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G. Clinical patterns of hypersensitivity to non-steroidal antiin¯ammatory drugs and their pathogenesis. Journal of Allergy and Clinical Immunology 1977; 60: 276±84. Power I. Aspirin-induced asthma. British Journal of Anaesthesia 1993; 71: 619±21. Delaney JC. The diagnosis of aspirin idiosyncrasy by analgesic challenge. Clinical Allergy 1976; 6: 177±81. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Journal of the American Medical Association 1983; 249: 1743±5.

337


diclofenaco en niños con asma